Freeman May 2012 - American Optometric Association

Transcription

TABLE OF CONTENTS
EDITOR’S PERSPECTIVE
PAUL B. FREEMAN, O.D.
A novel approach to health care?…..159
MEDICAL ABSTRACT
MARC D. MYERS, O.D.
Trends in Use of Ancillary Glaucoma Tests for Patients with Open-Angle Glaucoma from 2001 to
2009.…..160
May 2012
Vol 83, No 5
CLINICAL CARE
MELISSA MISKO, O.D.
Ocular Contusion with Microhyphema and Commotio Retinae…..161
CLINICAL RESEARCH
LORI VOLLMER, O.D., JOSEPH SOWKA, O.D., JOSEPH PIZZIMENTI, O.D., AND XINHA
YU, PH.D., M.S.
Central corneal thickness measurements obtained with anterior segment spectral domain optical
coherence tomography compared to ultrasound pachymetry in healthy subjects…..167
CLINICAL RESEARCH
RICHARD J. ZIMBALIST, O.D.
Normalization of Retinal Nerve Fiber Layer with Stratus Optical Coherence Tomography after
Bilateral Diabetic Papillopathy…..173
CLINICAL RESEARCH
JEFFREY COOPER M.S., O.D., ERICA SCHULMAN, O.D., AND NADINE JAMAL O.D.
Current Status on the Development and Treatment of Myopia….179
CLINICAL RESEARCH
GARY VANDERZEE, O.D., AND DOUGLAS TASSI, O.D.
New trends in early diagnosis of hydroxychloroquine toxic retinopathy…..200
1
Optometry
Optometry
Optometry
Journal of the American Optometric Association!
OPTOMETRY STAFF
OPTOMETRY STAFF
Paul B. Freeman, O.D., Editor-in-Chief
[email protected]
B. Freeman,
O.D., Editor-in-Chief
OPTOMETRY
STAFF
e-mail:
e-mail: [email protected]
REVIEW BOARD
REVIEW BOARD
Sherry J. Bass, O.D., M.S.
Sherry J.K.BOARD
Bass,
O.D.,O.D.,
M.S. M.S., MPH
REVIEW
Norma
Bowyer,
Norma K. Bowyer, O.D., M.S., MPH
Karl Citek, O.D., Ph.D.
Karl Citek, O.D., Ph.D.
O.D.
Paul B. Freeman, O.D., Editor-in-Chief
SherryBradley
J. Bass,Coffey,
O.D., M.S.
Bradley
Coffey,
O.D.
Dawn
K.
DeCarlo,
O.D.
K. DeCarlo,
Shannon,
M.B.A.,
e-mail:Brandie
[email protected]
NormaDawn
K. Bowyer,
O.D.,O.D.
M.S., MPH
Brandie
Shannon,
M.B.A.,Managing
ManagingEditor
Editor
S.
Barry
Eiden,
O.D.
S.
Barry
Eiden,
O.D.
3251
Riverport
Lane
Karl
Citek,
O.D.,
Ph.D.
3251 Riverport Lane
Andrew Gurwood,
O.D.
St. Louis,
MO
63043
BradleyAndrew
Coffey,Gurwood,
O.D. O.D.
St. Louis,
MO
63043
Elizabeth
Hoppe,
O.D.,
Dr.P.H., MPH
Hoppe,
e-mail:
[email protected]
Dawn Elizabeth
K. DeCarlo,
O.D.O.D., Dr.P.H., MPH
e-mail:
[email protected]
Brandie Shannon,
M.B.A., Managing Editor
Robert
N.
Kleinstein,
O.D., Ph.D.,
Ph.D.,MPH
MPH
Robert
N.
Kleinstein,
O.D.,
S. Barry Eiden, O.D.
3251 Stephen
Riverport
Dominick
Maino, O.D.,
O.D., M.Ed.
M.Ed.
Sandra
Lundgren,
Director,Director
Dominick
M.Lane
Wasserman,
Stephen
M.
Wasserman,
Director
Andrew
Gurwood,
O.D.
St. Louis,
MO
63043
Communications/Marketing
Group
Kelly
A.
O.D.
KellyHoppe,
A. Malloy,
AOA
Communications
andand
Membership
AOA
Communications
MembershipGroup
GroupElizabeth
O.D.,O.D.
Dr.P.H., MPH
e-mail:
[email protected]
e-mail:e-mail:
[email protected]
William
O.D., Ph.D.
Ph.D.
William L. Miller, O.D.,
[email protected]
e-mail:
[email protected]
Robert N. Kleinstein, O.D., Ph.D.,
MPH
Scott Schatz,
Schatz, O.D., Ph.D.
Scott
Ph.D.
Dominick Maino, O.D., M.Ed.
Stephen
M.
Wasserman,
Director
Leo
P.
Semes,
O.D.
Bob
Foster,
ELS,
Associate
Director,
Leo P. Semes, O.D.
Bob Foster, ELS, Associate Director,
Kelly A.
Malloy,
O.D.
AOA Publishing/Social
Communications
and
Membership Group
Diana Shechtman,
Shechtman, O.D.
Publishing/Social
Media
Diana
O.D.
Media
William
L. Miller,
O.D., Ph.D.
e-mail:e-mail:
[email protected]
Joseph
P.
Shovlin,
e-mail:
[email protected]
Joseph P. Shovlin, O.D.
O.D.
[email protected]
Scott Schatz,
O.D.,
Ph.D.O.D.
Joseph W.
W.
Sowka,
Joseph
Sowka,
O.D.
Leo P.Irwin
Semes,
O.D. O.D., D.O.S.
Bob Foster,
ELS,
Associate
Director,
Tracy
Overton,
Senior
Editor
B. Suchoff,
Suchoff,
Tracy
Overton,
Senior
Editor
Irwin B.
O.D., D.O.S.
Diana
Shechtman,
O.D.
Publishing/Social
Media
e-mail:
[email protected]
Mark Swanson,
Swanson, O.D.,
Mark
O.D., MSPH
MSPH
Joseph P. Shovlin, O.D.
Bob Pieper, Practice Strategies Editor
Joseph W. Sowka, O.D.
Bob Pieper, Practice Strategies Editor
e-mail: Senior
[email protected]
Tracy e-mail:
Overton,
Editor
Irwin B. Suchoff, O.D., D.O.S.
[email protected]
Mark Swanson, O.D., MSPH
Bob Pieper,DEPARTMENT
Practice Strategies Editor
EDITORS
DEPARTMENT EDITORS
Marc D. Myers, O.D.
Marc
Myers, CPOT
O.D.
JillD.
Luebbert,
DEPARTMENT
EDITORS
Jill G.
Luebbert,
CPOT
Lynn Casto
Mitchell, M.A.S., Statistician
G. Lynn
Mitchell,
M.A.S., Statistician
Byron Casto
Y. Newman,
O.D.
G. Timothy
Petito,
O.D.
Byron
Y. Newman,
O.D.
Marc D. Myers, O.D.
G. Timothy Petito, O.D.
Jill Luebbert, CPOT
G. Lynn Casto Mitchell, M.A.S., Statistician
Byron Y. Newman, O.D.
G. Timothy Petito, O.D.
JANUARY 2012 . VOLUME 83 . NUMBER 1
AOA OFFICERS
AOA OFFICERS
Dori Carlson, O.D., President
Dori
Carlson,
O.D., President
AOA
OFFICERS
Ronald
Hopping,
O.D., MPH, President-Elect
Ronald Hopping, O.D., MPH, President-Elect
Mitchell T. Munson, O.D., Vice President
David
A. O.D.,
Cockrell,
O.D., Secretary-Treasurer
DoriDavid
Carlson,
President
A. Cockrell,
O.D., Secretary-Treasurer
Joe
E.
Ellis,
O.D.,
Immediate
Past
President
Joe E.Hopping,
Ellis, O.D.,
Immediate
President
Ronald
O.D.,
MPH,Past
President-Elect
David A. Cockrell, O.D., Secretary-Treasurer
Joe E.AOA
Ellis,
O.D.,
Immediate Past President
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Samuel
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Samuel
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Hilary Hawthorne, O.D.
Christopher
Quinn,
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Christopher
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Barbara
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OPTOMETRY Editor’s Perspective
A novel approach to health
care?
Paul B. Freeman, O.D.
May has been designated “Older Americans Month.”
Established in 1963, the purpose of this designation was to
“acknowledge the contributions of past and current older
persons to our country, in particular those who defended our
country.”1 I would submit that the contributions of many
older Americans will continue to fashion the fabric of America,
even into the future. As optometrists, to support the goal of
helping older Americans continue to be visually viable, we need
to redouble our efforts at listening to our seniors, and then
addressing their needs.
Interestingly, in any conversation about senior eye care, the
question usually comes up, “What is so different about
evaluating a senior other than, say, evaluating someone who is
middle-aged?” Other than finding the obvious normal aging
vision changes, as well as the potential increased likelihood of
ocular pathology, such as cataracts or macular degeneration,
the difference oftentimes lies in the ability to communicate
effectively.
Although listening to our patients seems obvious, consider
some basic characteristics of doing so carefully. Encourage
older patients to talk, and be prepared to really listen to what
they have to say. In one of my recent editorials, I mentioned
the distinction between asking “How are you doing?’ vs. a
more specific question like “How is your reading?”2 Asking
specific questions is more likely to elicit more well defined
concerns which we can address. But, be prepared to really
listen to the response, as it is sometimes necessary to read
between the lines. Sometimes patients will equate functional
improvement with the expectation of being as visually vibrant
as they were years before, or as sometimes said, “visually
normal.”
After clarifying the needs or problems a patient may have, it
may be helpful to modify the pace or extent of the
examination; with young patients the pace might need to be
quick (and sometimes abbreviated) to keep up with the energy
of the patient, while with seniors, the pace might have to be
slowed down a bit (and sometimes abbreviated), with the
patient directing the pace. Then, once the exam is complete,
we must use whatever we have in our armamentarium to
address the patient’s needs, including lenses, prisms, contact
lenses, vision therapy, low vision rehabilitation, nutritional
counseling, lighting and glare control, etc., or to treat those
pathologies that are within our scope of practice, and, when
necessary, make the appropriate referral for those medical
and/ or functional interventions that we as individual
practitioners do not perform. Care for seniors should all be
done without using age as a limiting criterion for treatment.
senior patient, rather than
initially to a family member,
spouse or caregiver, who might
have accompanied the patient
(although they, too, typically
have an opportunity to “share”
information once the patient’s
concerns are addressed). It
should not be assumed that
aging and the inability to
understand or respond go hand
in hand. That said, however, we
should be cognizant that “…
even when neurological disease
is not present there is a
progressive and gradual loss of
some intellectual functions that
become evident starting from the seventh or eight decade of life
and increasingly evident after the ninth decade.”3 With more
recent information that suggests that “cognitive decline is already
evident in middle age (age 45-49),”4 it should make the doctor, in
the patient- centered interaction, more acutely aware of how best
to address the concerns and questions of the patient. Recognizing
this apparent fact will go a long way to helping a senior patient
understand what the evaluation is about, what options there are
to solve the patient’s chief complaint, and in helping the patient
understand the importance of compliance of treatment options.
This type of care in the larger medical arena has recently been
defined as “Patient- Centered Medicine,” and is carried out by
“focusing on the individual patient’s needs and concerns, rather
than the doctor’s….”5 What a novel approach: listening to the
patient!
Optometrists, by and large, have always embraced the notion of
listening to patients and spending time trying to sort out their
visual needs; now there is actually a term for that. Recognizing
the importance of attending to the visual needs for seniors is not
new and was, I believe, helpful in our gaining Medicare parity, for
as Congressman Claude Pepper (D-FL), commented on HR 3009
and 3010 in 1984, “Vision is the single most important sense upon
which the nation’s elderly depend. Certainly its deterioration or
loss dramatically reduces the quality of life and seriously
threatens the ability of the aged to function independently.” Who
better than optometrists to support the vitality of seniors!
In time, we will each be someone’s patient. As we age, the odds
of that happening go up considerably. The question we must ask
ourselves is “do we want our care to be patient-centered or
doctor-centered?” And then, remember the Golden Rule….
References
1.
2.
3.
4.
One consistent source of positive feedback that anyone who
works with seniors receives is based on actually talking to the
5.
Editor‐in‐Chief/ [email protected]
Administration on Aging http://www.aoa.gov/aoaroot/press_room/
observances/oam/archive/archive.aspx, last accessed 4/21/2012
Freeman PB, A nagging question, OptometryJAOA 2012;83: 95-96,
Costarella M, Monteleone L, Steindler R, Zuccaro SM, Decline of
physical and cognitive conditions in the elderly measures through
the functional reach a test and the mini-mental state examination,
Arch of Gerentology and Geriatrics 2010;50:332-337
Singh-Manoux A, Kivimaki M, Glymour MM, et al, Timing of onset of
cognitive decline: results from Whitehall II prospective cohort study,
http://www.bmj.com/content/344/bmj.d7622, last accessed
4/21/2012
Bardes CL, Defining “Patient-Centered Medicine,” N Engl J Med
2012;366: 782-3
Marc D. Myers, O.D.
MARC D. MYERS, O.D.
superior vascular
Stein JD, TalwarSignificance
N, Laverne AM,
ophthalmologist(46%).
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overallUnlike typof
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ophthalmologist
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2012;
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saw minor small
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Stephen E. Hess, O.D.
It may be difficult to identify
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Asian, and 53.6% were
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doi:10.1016/j.optm.2011.11.009
of the retina between the macula
The and
authors suggest that if these
The use of VF testing in subjects with
trends of relying on OOI instead of VF
OAG decreased over time, reaching a
continue, the following OOI limitations
44% decrease by 2009. Contrary to
need to be addressed: current
this, there was a significant increase of
normative databases often do not
147% in the use of OOI by 2009. The
include a diverse race and ethnicity
use of FP showed a smaller, more
representation; tilted discs, moderate
stable increase of 8%. Initially in 2001,
to high myopia, small or large optic
optometrists and ophthalmologists
nerve head are challenging to image
were similar in VF testing for OAG
with OOI; software used to detect and
(66% and 65% respectively), but by
quantify progression over time needs
2009 optometrists were less likely to
more research and validation; the
perform VF (44%) compared to
quick turnaround of newer equipment
ophthalmologist (51%).
models must be compatible to older
models so patients can be monitored
For glaucoma suspects, the trend was
over time; and the high cost of OOI
an overall decrease in VF testing for
may limit availability to providers of
1529-1839/$ - see front matter ! 2011 American Optometric Association. All rights reserved.
optometrist (57% in
2001 decreased
lower income, racial minorities, and
to 24%, 2009) and ophthalmologist
other high-risk groups that may not
LIT adequate
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OPTM1152_proof ! 15 December 2011 ! 8:14 am
(50% decreased to 28%, 2001 to
have
2009). For OOI, optometrist’s were
initially less likely to perform them, but
Khadija Shahid, O.D.
by 2009 trends were similar for both
optometrist (47%) and
print & web 4C=FPO
MEDICAL ABSTRACT
OPTOMETRY Clinical Care
Ocular Contusion with Microhyphema and Commotio Retinae
Melissa Misko, O.D.
KEYWORDS
Eye injuries/
complications, anterior
eye segment/injuries,
wounds, nonpenetrating, retina/
injuries, optical
coherence tomography
Abstract
Background: Blunt force trauma can affect all structures in the eye, frequently causing complications
such as hyphema or microhyphema. A hyphema is defined as bleeding in the anterior chamber that
layers and forms a visible clot. A microhyphema occurs when the red blood cells are suspended in the
anterior chamber, and do not form a layered clot. Microhyphema is a rarely reported, visually
significant complication. Ocular trauma is the second most common cause of visual impairment, and
appropriate management must be executed swiftly and efficiently to maximize a patient’s visual
potential.
Case Report: A 21-year-old Indian male presented after ocular contusion to the right eye. His visual
acuity was reduced at initial presentation. Pertinent clinical findings included red blood cells in the
anterior chamber and ecchymosis of the orbital adnexa, with associated conjunctival injection.
Subsequently, the patient developed commotio retinae.
Conclusion: It is important for clinicians to take a detailed case history of the event, perform a
thorough ocular exam, select proper treatment/therapy, monitor the patient closely, and make
appropriate referrals as needed. This case report discusses the clinical findings, treatment, and
management of 1 patient with an ocular contusion resulting in microhyphema and commotio retinae.
Introduction
With approximately 2.4 million eye injuries recorded per year
in the United States, ocular trauma is second only to cataracts
as the most common cause of visual impairment.1 According
to the United States Eye Injury Registry (2000), eye injuries
are the leading cause of monocular visual impairment. Most
injuries occur at home (34-40%), and 13-15% are sports
related,1-3 with the more significant ocular complications
resulting from smaller, faster projectile sports (paintball,
racquetball, hockey, baseball).4,5 Males are affected significantly
more than females, with a reported incidence of 60-80%.1,3,5-8
Age also appears to be a risk factor, with ocular trauma
impacting persons most frequently in late adolescence/early
adulthood (median = 26 years1) and persons over age 70.5.
Acute complications of ocular trauma include hyphema,
commotio retinae, retinal tears/breaks, and vitreous
hemorrhages. While not frequently encountered, hyphemas
occur in up to 33% of blunt trauma cases1,2 and may present as
a macroscopic hyphema or microscopic hyphema. Due to the
self-limiting nature of commotio retinae, frequency of
occurrence is not well reported.
Case Report
A 21-year-old Indian male presented for an emergency ocular
examination following blunt trauma to the eye while playing
racquetball. He reported being hit by the ball in the right eye,
approximately 1 hour prior, with resulting pain, decreased
vision, nausea and dizziness. The patient subsequently vomited
during the exam. No eye protection was being worn at the
time of injury, although he was wearing disposable Biomedics®
toric soft contact lenses. His ocular history was negative for
any other ocular trauma or surgery; however, he did have a
history of physiologic anisocoria OD>OS. His medical history
was unremarkable and he denied any current medications,
ocular or systemic. He did report a positive sulfa drug allergy,
and a family history of diabetes. The patient was a non-smoker
and denied alcohol, recreational or IV drug use. He was
oriented to time, place, and person.
At the time of presentation, the patient’s uncorrected visual
acuity was hand motion at 2 feet OD. Pinhole acuity at
distance was 20/400 OD. The patient reported that his contact
lens was lost during the injury. Corrected visual acuity at
distance OS was 20/20. Pupils were unequal in size (OD>OS)
and unequal in reactivity to light (OS>OD), although no
afferent pupil defect was noted in either eye. The patient
reported confrontation fields were blurry, but he could identify
hand motion in all quadrants OD. The peripheral visual fields
were full to finger count OS. Extraocular muscles were
unrestricted in all gazes with no pain OU. Slit lamp
examination OD revealed 2+ ecchymosis, chemosis, and edema
of the upper lid,1+ ecchymosis, chemosis and edema of the
lower lid, intact conjunctiva with 3+ injection, intact and clear
cornea, dense and diffuse 4+ red and white blood cells in the
anterior chamber (see Figure 1), flat iris with no apparent tear,
and 4/4 anterior chamber angles by Van Herrick estimation.
Lids, lashes, conjunctiva, cornea, anterior chamber, and iris were
clear OS, and anterior chamber angles were 4/4 by Van Herrick
estimation OS. Intraocular pressures were 9 mm Hg OD and
15 mm Hg OS with Goldmann applanation tonometry.
Dilated evaluation OD revealed a clear lens, but fundoscopy
was challenging due to a hazy media. The optic nerve was pink
and distinct with a cup-to-disc ratio of 0.7 round. No pallor or
edema could be appreciated. Retinal vessels appeared normal
with an arterial-venous ratio of 2/3. The macula was positive
for a foveal reflex, with no apparent elevation. No cells or
blood were noted in the vitreous. The peripheral retina was
negative for any apparent hemorrhages, tears, breaks, or holes
360° OD.
nasally (see Figure 3). No cells or blood were observed in the
vitreous. The peripheral retina was negative for any apparent
hemorrhages, tears, breaks, or holes 360° OD; however 2 areas
of commotio retinae were noted inferior temporal (see Figure
4) and superior nasal (see Figure 5). Spectral Domain Optical
Coherence Tomography (OCT) supported a diagnosis of Berlin’s
edema showing areas of hyper-reflectivity in the outer segments
of the photoreceptors (see Figure 6).
Figure 1 Photograph illustrating the author’s hazy view of the
anterior chamber OD. Details of the iris are obscured secondary to
suspended red blood cells in the anterior chamber.
Evaluation of the posterior segment OS was unremarkable for
signs of trauma. The disc was flat, pink and distinct, with a cupto-disc ratio of 0.7 round, macula was clear and flat, with a
positive foveal reflex, retinal vessels were normal with an
arterial-venous ratio of 2/3, lens was clear, and the vitreous and
peripheral retina were clear.
Based on the exam findings, the patient was diagnosed with a
microhyphema OD secondary to a contusion. He was educated
on the self-limiting condition, the long-term complications
associated with ocular trauma (such as cataracts, glaucoma, and
retinal detachment), the importance of follow-up and future eye
care, and the importance of eye protection during sports. The
patient was also strongly advised to limit activity, and to
discontinue vigorous activity to decrease the risk of further
bleeding. Avoiding aspirin and other nonsteroidal antiinflammatory medications was also discussed to decrease the
risk of further bleeding. The patient was educated that a rebleed
can carry serious complications including reduced vision, corneal
staining, increased ocular pressure, and the need for a surgical
intervention. It was recommended that the patient monitor his
vision, as a decrease in vision can indicate a rebleed, and that he
should keep all follow-up appointments.
Further instructions were given to discontinue contact lens
wear until otherwise notified, to keep his head elevated at a
30-45 degree angle while sleeping, and to use cool compresses
OD as needed to minimize ecchymosis and edema. The patient
was given a sample of OmnipredTM 1% (prednisolone acetate,
Alcon) ophthalmic suspension to use one drop every 3 hours
OD and homatropine 5% ophthalmic solution 1 drop 2 times
per day in OD. The patient was advised to follow up the next
day or to contact the doctor on call sooner if vision decreased,
pain increased, or if he experienced flashes or floaters.
The following day, the patient returned for follow up. His visual
acuity had improved to 20/25+ OD. Anterior segment
examination was stable from the previous day, with intraocular
pressures measuring 8 mm Hg OD and 16 mm Hg OS.
Fundoscopy revealed an area of commotio retinae nasal to the
disc (see Figures 2 & 3). The macula was positive for a foveal
reflex and a 1.5 DD area of Berlin’s edema extending inferior
Figure 2 Posterior segment photograph of commotio retinae nasal
to the optic nerve OD.
Figure 3 Posterior segment photograph of commotio retinae nasal
to the optic nerve OD and Berlin’s edema (commotio retinae of the
macula) OD.
A diagnosis of commotio retinae (including Berlin’s edema)
secondary to an ocular contusion OD was added to the
patient’s original diagnosis of microhyphema. The patient was
instructed to continue to keep his head elevated at a 30-45
Figure 4 Posterior segment photograph of commotio retinae in the
inferior temporal quadrant OD.
Figure 5 Posterior segment photograph of commotio retinae in the
superior nasal quadrant OD.
degree angle while sleeping, to use cool compresses OD as
needed, to minimize vigorous activity, to avoid aspirin or other
nonsteroidal anti-inflammatory medications, and to continue
current ophthalmic medications (OmnipredTM 1% ophthalmic
suspension 1 drop every 3 hours OD and homatropine 5%
ophthalmic solution 1 drop 2 times per day OD). The patient was
advised to follow up the next day or sooner if vision decreased,
pain increased, or if he experienced flashes or floaters.
and compression mechanisms including orbital fractures, lid
ecchymosis, conjunctival hemorrhages, corneal abrasions, angle
recession, hyphema, traumatic cataracts, and lens dislocation.1,9
Commotio retinae,10 retinal holes/tears, vitreous hemorrhages,
and orbital fractures are among the posterior complications
caused by the contre-coup mechanism.1-3
The patient was seen every 1-2 days over the course of the next
week. During that time, the commotio retinae resolved; however,
the microhyphema persisted for an additional 2 weeks. The
patient was followed thereafter every 3-4 days. Homatropine was
discontinued after the first week. The patient was slowly tapered
off of the steroid after resolution of the microhyphema. A taper
schedule of qid x 4 days, bid x 2 days, qd x 2 days was utilized. At
2 weeks and 4 days after the initial injury, the patient had
discontinued all topical medications, and all injuries had resolved
without complication. He was approved to resume contact lens
wear. Final visual acuity after complete resolution was 20/20 OD.
Discussion
Ocular trauma can be divided into closed globe injuries and open
globe injuries. Open globe injuries are those with a full thickness
wound in the eye wall (cornea and sclera) such as lacerations, or
ruptures. Closed globe injuries include contusions, superficial
foreign bodies, and partial thickness wounds (for example, a
lamellar laceration), 1,5 with blunt trauma (contusions) accounting
for 40% of ocular traumas.7,9 Damage from blunt trauma is
caused by three mechanisms: coup, contre-coup, and ocular
compression. The coup mechanism is defined as trauma directly
at the site of injury. Contre-coup refers to injury across from the
site of impact or on the opposite side of the eye. For example,
the retina is affected by the contre-coup mechanism after an
object collides with the eye and shock waves carry the impact
posteriorly. Lastly, ocular compression is defined as an initial
globe deformation caused by the impact of an object, and a
rebound, with an overexpansion before returning to its original
shape.5,9 Most anterior segment injuries are a result of the coup
Hyphemas occur in up to 33% of blunt trauma cases1,2 and may
present as a macroscopic hyphema or microscopic hyphema. A
macroscopic hyphema (also known simply as a hyphema) is
present when accumulated blood layers in the anterior chamber.
This layered clot can often be seen without the use of a
microscope, lending to its name as a macroscopic hyphema.
There are two methods commonly used to grade a hyphema.
One method is based on the volume of blood in the anterior
chamber - grade 1 is less than 1/3 of the anterior chamber, grade
2 is between 1/3 and ½ of the anterior chamber, grade 3 is more
than 1/2 but less than the entire anterior chamber, grade 4 is the
entire anterior chamber, also known as a total or “8 ball”
hyphema.1,6 The second grading method uses millimeters to
measure the height of the blood layer.1,6 A microscopic hyphema,
or microhyphema, is defined as blood in the anterior chamber
that will not layer.11 A microscope is used to assess the amount
of circulating erythrocytes in the anterior chamber and graded in
a similar fashion to anterior uveitis: 1+ (5-10 cells/field), 2+
(11-20 cells/field), 3+ (21-30 cells/field), 4+ (>30 cells/field).11 The
source of the erythryocytes suspended in the anterior chamber is
damaged tissue. As the eye is indented by the source of trauma,
the intraocular pressures rises, and the ocular tissues are
stretched equatorially resulting in small tears in the blood vessels
of the iris and ciliary body. 1,6,11
Both macroscopic and microscopic hyphemas may present with
symptoms similar to traumatic uveitis – including pain,
photophobia, and blurry vision.5,6 Minimal literature can be found
on microhyphemas, so treatment and management is rooted in
guidelines for traumatic macroscopic hyphemas.11 Treatment is
designed with 3 goals in mind: to improve patient comfort, to
prevent rebleeding, and to monitor for complications including
increased intraocular pressure and corneal staining.5,11 In most
cases, patients diagnosed with a hyphema do not need to be
hospitalized. Circumstances requiring consideration for
hospitalization include children with hyphema, patients
presenting with total hyphema, patients who may have issues
being compliant with medications and/or guidelines for
recovery, increased or uncontrolled IOP, patients with sickle
cell, and patients with other ocular injuries or severely
decreased vision. It is important to determine whether the
patient’s home environment is safe and conducive to healing and
whether or not the patient is capable of adhering to the
medication and follow-up schedule. Due to the propensity of
bleeding complications, blood work should be discussed for
patients with a spontaneous hyphema or with a personal or
family history of blood dyscrasias (sickle cell disease, leukemia,
Von Willebrand’s disease), bleeding disorders (hemophilia),
thrombotic disorders, etc.12
To improve patient comfort, a topical mydriatic (atropine,
scopolamine) is recommended 1 to 3 times daily to decrease
pain, photophobia, and inflammation secondary to ciliary body
spasm.5,11 A topical corticosteroid (prednisolone acetate 1%) is
also used between 4 times daily to hourly to decrease
inflammation. In addition, research supports the use of a topical
corticosteroid to reduce the risk of a rebleed.12 Along with the
dosage of a mydriatric, bed rest and limited activity (for 3 to 5
days after the initial injury) is recommended to aid healing and
decrease the risk of a rebleed.5,11 A rebleed, or secondary
hemorrhage, has occurred when examination reveals new
blood. For a macrohyphema, this can be observed as a brighter
layer of blood over the older, darker clot, or if new, unsettled
red blood cells can be detected in the anterior chamber above
the settled clot, or simply if the size of the hyphema increases.12
For a microhyphema, an increase in the suspended red blood
cells indicates a rebleed. The risk of rebleed is highest 3 to 5
days after the onset of injury.11 Notably, rebleeds are usually
much larger than the initial bleed.11
Rebleeds have been reported in up to 38% of traumatic
hyphema cases.5 However, the incidence is much lower in
microhyphemas, with only 1.9 to 5% of patients experiencing a
rebleed, which may indicate that microhyphemas are the result
of a less severe injury.11 Regardless of the extent of the initial
hyphema, long-term visual prognosis is worse in cases of
rebleeds.1,13 Along with bed rest and limited activity, topical
and/or oral medications may decrease the risk of a rebleed.
Topical cycloplegics are often used to increase patient comfort.
However, they may also have the benefit of reducing rebleeds,
especially in patients using aspirin, as shown in one study.12 In
other literature, the rate of rebleeds (along with final visual
acuity, and rate of clot absorption) was not statistically different
between groups using a topical mydriatic, miotic, neither, or
both.12 Oral antifibrinolytic medications have been proven to
lower the rate of rebleeds, and possibly delay clearance of the
hyphema.12,13 Most commonly studied antifibrinolytics are
Amicar® (є-aminocaproic acid) and Cyklokapron® (tranexamic
acid), however, both medications are off-label for hyphema use.
12 Although Amicar has been documented to decrease the rate
of rebleeds from 22-33% to 0-4%,12 use of the drug produces
unpleasant systemic side effects including nausea, vomiting and
diarrhea in 25% of patients, and postural hypotension and
dizziness in 6-18%.12,13 Recently, a topical aminocaproic acid
preparation has been developed called Caprogel™. In a study
of 51 patients by Pieramici. et al., rebleeding occurred in 30% of
the untreated group and only 8% of the treated group.13
Patients with microhyphemas or total hyphemas were excluded
from the study. Patients reported less systemic side effects with
the topical preparation as compared to oral antifibrinolytic
agents. Patients also noted minimal ocular irritation. However
further research is needed as the study was terminated due to
recruitment problems.
In the absence of a secondary hemorrhage, light activity can
usually be resumed 2 weeks after the trauma.11 Along with
limiting activity, patients should also be instructed to
discontinue use of aspirin, NSAIDs, and other blood thinners
(e.g. Coumadin®), wear an eye shield while sleeping, and keep
the head elevated approximately 30 degrees above the
horizontal.6,12 The importance of continued follow-up should
be stressed to the patient. A gonioscopy exam and dilated
fundus exam with scleral depression should be performed after
resolution of the microhyphema or hyphema or within 2-6
weeks of injury. To reduce the risk of a rebleed, neither should
be completed within 2 weeks of the original injury, unless
hypotony or elevated IOP necessitates otherwise.1,11,12
The third goal of treatment is to prevent increased intraocular
pressure and corneal staining. Acute intraocular pressure
increases or spikes occur due to fibrin, red blood cells, and/or
platelets that become lodged in the trabecular meshwork.11 In
a patient without sickle cell disease or trait, beta blockers, alpha
agonists, and carbonic anhydrase inhibitors are all adequate
topical therapy options. Since mydriasis has been shown to be
beneficial, miotics should be avoided in all (both non-sickle cell
and sickle cell) patients as a pressure lowering option. The
literature is divided on the use of prostaglandin analogs, which
may increase inflammation and should be used with caution.5,14
Carbonic anhydrase inhibitors are contraindicated in sickle cell
patients as they lower oxygen tension in the anterior chamber
and lead to red blood cell sickling, causing further trabecular
meshwork deposition and decreased aqueous outflow.5
Corneal staining (endothelial toxicity) in combination with
elevated IOP can result in blood breakdown products entering
the stroma. Because corneal staining is more common in
hyphema patients with rebleeds or periods of elevated IOP,
these patients should be monitored closely.5,12 Corneal blood
staining, which causes decreased visual acuity, occurs in
approximately 2-11% of hyphema patients, with the incidence
rising to 33-100% in total hyphema cases.12 A daily slit lamp
examination is needed to detect early corneal staining, seen as a
light yellowing of the deep stroma. Surgical intervention should
be considered at this point to prevent gross blood staining,
which causes decreased vision, and can take 4-6 months to
resolve. This period of decreased vision is an even greater
concern in younger patients as the risk for deprivation
amblyopia increases.12 Surgical intervention (irrigation,
vitrectomy, trabeculectomy) to remove the clot should be
considered when one of the following criteria has been met:
IOP ≥ 60 mm Hg for 48 hours with max medical therapy in a
non-sickle cell patient (due to risk of optic atrophy/central
retinal artery occlusion (CRAO)), IOP ≥ 50 mm Hg for 4 days
with max medical therapy in a non-sickle cell patient (due to
risk of opticatrophy/CRAO), IOP ≥ 24 mm Hg during the first
24 hours or repeated IOP spikes of ≥ 30 mm Hg in a sickle
cell patient (due to risk of optic atrophy/CRAO), total hyphema
with IOP ≥ 25 mm Hg for 5 days (due to risk of corneal
blood staining), or hyphema ≥ 50% with IOP ≥ 25 mm Hg for
≥ 6 days (due to risk of corneal blood staining), hyphema ≥
50% for ≥ 8 days (due to risk of synechia formation).12
OD
OS
OD
OS
Figure 6 Optical Coherence Tomography with arrows indicating the regions of hyper-reflectivity representing disorganization of the
photoreceptors OD; as compared to the well defined layer of photoreceptors, shown by arrows OS.
Commotio retinae, an acute, self-resolving retinal opacification,
horizontal and vertical macular OCT scans taken at follow-up
9,14-19 can occur minutes to hours after a blunt trauma.1,10 Some
#1 (see Figure 6). The arrows OD point to the regions of
literature reports the mid-peripheral retina is the most
hyper-reflectivity as compared to the well defined alternate
commonly affected area, and the macula the least affected.5
layers of coloring, shown by arrows OS.
Others argue that the area surrounding the optic disc and
macula are most susceptible areas secondary to their
After a traumatic event to the eye, patients are at risk for
perpendicular nature to the original insult.9 Regardless of the
several visually devastating delayed complications including
area affected, commotio retinae is the most common retinal
traumatic cataracts, glaucoma, and retinal detachments.
sign of an ocular contusion.5 Commotio retinae of the macula
Traumatic cataracts may develop months to years after the
is called Berlin’s edema. Berlin first described this postblunt insult, slowly compromising vision. Most commonly,
traumatic retinal whitening in 1873,15 hypothesizing that the
ocular contusions produce anterior or posterior subcapsular
retinal whitening was a result of extracellular edema.15
cortex spokes or a ‘sunflower cataract.’5 Treatment (surgical
However, we have since learned that there is no actual
removal) relies largely on the level of visual impairment caused
extracellular or intracellular edema in commotio retinae.3,5,17,19
by the cataract.
In vivo research has shown that the disruption and
disorganization of the outer segments of the photoreceptors,
The 6-month incidence of developing post-traumatic glaucoma,
combined with RPE damage, is the true cause of commotio
as reported by Girkin et al, was 3.39%.7 The report also went
retinae.1,10,14,17-19 Flourescein angiography performed 30
on to associate angle recession with the development of
minutes after trauma has revealed staining of the retinal
glaucoma. Angle recession is thought to occur when the impact
pigmented epithelium corresponding to areas of commotio
of the trauma compresses the eye, pressing the iris against the
retinae. This further confirms the lack of vessel leakage and
lens and consequently forcing trapped aqueous to rupture the
edema.5 Patients presenting for evaluation after an injury may
ciliary body at its scleral spur insertion.9 Additionally, angle
or may not have decreased visual acuity in association with
recession has been found in 70-100% of eyes with a history of
commotio retinae. However, the visual acuity usually recovers
hyphema.1 Glaucoma secondary to angle recession stems from
5,14,19
quickly.
In most cases, the retinal whitening will also
damage sustained by the trabecular meshwork. Over time, scar
Page 1 of
1 develops, thus decreasing the aqueous outflow and
resolve without treatment in 4 to 7 days.1,14,19 Retinal
tissue
pigmented epithelium hyperplasia or atrophy may be left behind. elevating the intraocular pressure. Literature reports up to
3,5,9,19
6-9% of patients with angle recession will develop glaucoma,
with the risk increasing proportionally to a larger area of
New advances with optical coherence tomography have
recession.1,5
illustrated commotio retinae as areas of increased reflectivity in
the area of the photoreceptor outer segment.5,16,18 These areas
Due to the contre-coup mechanism, and the compression and
of hyper-reflectivity represent the photoreceptor
expansion of the ocular tissues upon impact, the vitreous and
disorganization. This was demonstrated in our patient’s
retina can be pulled away from the retinal pigmented epithelium
resulting in retinal dialysis, retinal tears, and posterior vitreous
detachments that evolve to retinal detachments.1,5 These
complications further emphasize the importance of regular
gonioscopy and dilated fundus examinations on patients with a
history of blunt trauma.5,11
Conclusion
Ocular trauma is the second most common cause of visual
impairment and the leading cause of monocular visual
impairment.1,21 The detrimental visual effects of these accidents
could be prevented or minimized with appropriate eye
protection. According to the U.S. Department of Health and
Human Services, only 39.7% of adults (18 years and over) used
eye protection during sports and other potentially harmful
situations in, around, or outside the home in 2008. As primary
eye care providers, it is our responsibility to educate patients
on the vital need for eye protection.20
Ocular contusions may result in a wide array of complications
that can affect both the anterior and posterior segment. This
case report discusses the clinical findings, treatment, and
management of one patient with an ocular contusion resulting
in microhyphema and commotio retinae. Appropriate diagnosis
and treatment is essential in managing these patients to prevent
visually significant sequelae.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Madonna RJ, Nehmad L. Emergency Care in the
Optometric Setting, 1st Ed. McGraw-Hill Companies. 2004.
Kuhn F. Ocular Traumatology. 1st Ed. Springer. 2008.
Shakin JL, Yannuzzi LA. Posterior Segment Manifestations of
Orbital Trauma. Adv Ophthal Plastic and Reconstruct
Surgery 1987;6:115-35.
Baath J, Ells AL, Kherani A, Williams RG. Severe retinal
injuries from paintball projectiles. Can J Ophthalmol
2007;42:620-3.
Banta JT. Ocular Trauma, 1st Ed. Elsevier Saunders. 2007.
Stilger VG, Alt JM, Robinson TW. Traumatic Hyphema in an
Intercollegiate Baseball Player: A Case Report. J Athletic
Training 1999;34(1):25-8.
Girkin CA, McGwin G Jr, Long C, Morris R, Kuhn F.
Glaucoma after ocular contusion: a cohort study of the
United States Eye Injury Registry. J Glaucoma 2005 Dec;
14(6):470-3.
Talley DK. Traumatic anterior uveitis. Optom Clin
1993;3(2):21-6.
Kiel J, Chen S. Contusion injuries and their ocular effects.
Clin Exp Optom 2001;84:1:19-25.
Gregor Z, Ryan SJ. Blood-Retinal Barrier After Blunt
Trauma to the Eye. Graefes Arch Clin Exp Ophthalmol
1982; 219(5):205-8.
Recchia FM, Saluja RK, Hammel K, Jeffers JB. Outpatient
management of Traumatic Microhyphema. Ophthalmology
2002 Aug;10(8):1465-70; discussion 1470-1.
Walton W, Von Hagen S, Grigorian R, Zarbin M.
Management of Traumatic Hyphema. Surv Ophthalmol.
2002 Jul-Aug; 47(4): 297-334.
Pieramici DJ, et al. A phase III, multicenter, randomized,
placebo-controlled clinical trial of topical aminocaproic acid
(Caprogel) in the management of traumatic hyphema.
Ophthalmology 2003 Nov; 100(11):2106-12.
Ehlers JP. Wills Eye Manual, 5th Ed. Lippincott Williams &
Wilkins. 2008.
15. Williams DF, Mieler WF, Williams GA. Posterior Segment
Manifestations of Orbital Trauma. Retina 1990;10(1):S35-44
16. Meyer CH, Rodrigues EB, Mennel S. Acute commotio
retinae determined by cross-sectional optical coherence
tomography. Europen J Ophthal 2003;13(9/10):816-818.
17. Liem AT, Kleunen JE,VanNorren D. Reversible Cone
Photoreceptor Injury in Commotio Retinae of the Macula.
Retina 1995;15(1):58-61.
18. Sony P, et al. Optical coherence tomography findings in
commotio retinae. Clin Experiment Ophthalmol 2006 Aug;
34(6):621-3.
19. Mansour AM, Green R, Hogge C. Histopathology of
Commotio Retinae. Retina 1992;12(1):24-8.
20. U.S. Department of Health and Human Services. Office of
Disease Prevention and Health Promotion. Healthy People
2020. Washington, DC. http://www.healthypeople.gov/
2020/
21. United States Eye Injury Registry. 2000. http://
www.useironline.org/Prevention.htm
Corresponding author: Melissa Misko, O.D., 510 NW 84th
Ave, Apt 617, Plantation, FL 33324. Email:
[email protected].
OPTOMETRY Clinical Research
Central corneal thickness measurements obtained with anterior
segment spectral domain optical coherence tomography compared to
ultrasound pachymetry in healthy subjects
Lori Vollmer, O.D., Joseph Sowka, O.D., Joseph Pizzimenti, O.D., and Xinha Yu, Ph.D.,
M.S.
KEYWORDS
Glaucoma;
risk factors;
central corneal
thickness;
Spectral domain;
optical coherence
tomography;
ultrasound pachymerty
Abstract
Introduction: Central corneal thickness (CCT) imparts information about an individual’s risk of
conversion to glaucoma from ocular hypertension, progression of established glaucoma, and the
likelihood of developing structural and functional abnormalities in patients with ocular hypertension.
Most typically, CCT is measured through ultrasound (US) pachymetry. Currently, optical coherence
tomography (OCT) has the ability to image the anterior segment, cornea, and anterior chamber angle.
With this ability comes the option of determining CCT. The purpose of this study is to ascertain any
significant difference in CCT measurement results as well as quantify the reproducibility of
measurements of the two technologies. In addition, by measuring CCT both with traditional US
pachymetry as well as spectral domain (SD) OCT technology, we sought to determine if CCT
measurement by SD-OCT is an accurate, comparable and viable option.
Methods: Eighty eyes of forty healthy volunteers were used to determine CCT with both SD-OCT
and US pachymetry. Three consecutive measurements were collected with each method on every eye.
Results: CCT measurements made by US pachymetry and SD-OCT were similar and consistent
(r=0.99 for both methods). CCT measurements made by SD-OCT were consistently thinner by
approximately 12 micrometers than measurements made by US pachymetry (p<0.001). Repeated
measurements of CCT obtained by SD-OCT were more reproducible and had less variability than
measurements obtained by US pachymetry. The mean within-subject standard deviation among SDOCT was significantly smaller than that in US pachymetry (1.92 in SD-OCT vs. 2.04 in US
pachymetry, p=0.036).
Conclusions: Measurement of CCT by SD-OCT compares favorably with and is at least as accurate
as measurements made by US pachymetry. Repeat measurements of CCT by SD-OCT have less
variability than those obtained by US pachymetry, are more reproducible, possibly more reliable, and
may better represent actual CCT.
Introduction
A congenitally thin central cornea has been established as a
risk factor for glaucoma. In the Ocular Hypertension
Treatment Study (OHTS), it was seen in multivariate analyses
that baseline factors predicting conversion to primary open
angle glaucoma (POAG) from ocular hypertension included
older age, larger vertical cup-disc ratio (C/D), higher
intraocular pressure (IOP), greater pattern standard deviation,
and thinner central corneal measurement (CCT). Patients in
the OHTS with the thinnest CCT measurement who
additionally had higher IOP and greater vertical C/D ratio
measurement had the greatest conversion to POAG.1,2
Additionally, studies have also associated thin CCT with
increased prevalence of diagnosed glaucoma as well as
glaucomatous structural and functional changes. Henderson
and associates evaluated patients with ocular hypertension in
an attempt to correlate retinal nerve fiber layer thickness as
measured by scanning laser polarimetry with CCT
measurement and found that patients with thin CCT
measurements also had significantly thinner retinal nerve fiber
layer measurements compared to those with thicker CCT
measurements and normal control patients, thus suggesting a
relationship between thin CCT measurements and retinal
nerve fiber layer structural abnormalities.3
Kim and associates examined a case-control patient population
with various forms of open-angle glaucoma and concluded that
visual field progression in these patients was significantly
associated with thinner CCT.4 Hong et al studied patients with
chronic primary angle-closure glaucoma and found that those
with a thinner cornea were at greater risk for visual field
progression even if they maintain a low IOP after treatment.5
Medeiros and associates examined 98 eyes of 98 patients with
pre-perimetric glaucomatous optic neuropathy and saw that
those patients that did eventually develop repeatable visual field
abnormalities during follow-up had a significantly thinner CCT
measurement than those that maintained clear visual fields over
the study period (mean follow-up time of 4.3 +/- 2.7 years).6
The Los Angeles Latino Eye Study surveyed a large population
of Latinos and discovered that persons with thin CCT had a
significantly higher prevalence of open-angle glaucoma than did
those with normal or thick CCT at all levels of IOP.7
Ultrasound (US) pachymetry is the technology most commonly
used in the clinical measurement of CCT and is considered the
gold standard in measuring corneal thickness. It utilizes
acoustic pulses to locate and measure the corneal layers and
interfaces at the location where the speed of sound differs. US
pachymetry requires topical anesthetic. Spectral domain optical
coherence tomography (SD-OCT) is a non-invasive test that
does not require topical anesthetic. It is based on measuring
the delay of infrared light reflected from the tissue to determine
the depth and thickness. SD-OCT produces a cross-sectional
“in vivo” visualization of the tissue for which a caliper can be
used to determine the thickness of the cornea image. The
central cornea can be determined using the reflectivity profile
or by marking the center of the pupil. The corneal cross-section
is used to place the measurement of the calipers, making it
easier to assure that the measurement is located at the central
cornea.
There have been previous studies comparing CCT measurement
obtained with US pachymetry and OCT. Many of these studies
were performed with the time domain (TD) retinal imaging
technology rather than the anterior segment spectral domain
technology.8-11 The difficulties included attempting to image the
anterior segment, namely the cornea, with a device primarily
designed for retinal imaging as well as the lesser tissue
resolution and longer acquisition time associated with time
domain imaging.12 Despite these limitations, it was felt that the
CCT measurements obtained with TD-OCT were accurate,
reliable, and reproducible and results from each technology
were similar, accurate, comparable and reproducible, though not
necessarily interchangeable.
Subsequent studies have compared CCT measurements
obtained by anterior segment SD-OCT in comparison to
measurements obtained by US pachymetry.13-18 Similarly, there
was strong agreement in the measurements by the different
technologies. In some instances, it was found that the CCT as
measured by SD-OCT was thinner than that measured by
ultrasound pachymetry.14,18 It was felt that while CCT
measurements by each technology were accurate and reliable,
they should not be considered interchangeable.
A high degree of reproducibility on subsequent testing is likely
indicative of reliable results being obtained. There are questions
of reproducibility of CCT results obtained by US pachymetry,
even by trained observers. Shildkrot and associates examined
reproducibility of CCT measurements by trained observers
using US pachymetry. In this study CCT was measured by US
pachymetry (mean of 15 measurements for each eye) on 2
separate occasions at least 1 month apart. It was seen that
measured CCT values differed by more than 20 microns in
20.4% of test subjects and 40 microns in 5.1%. The authors felt
that factors affecting CCT measurement by US pachymetry, such
as examiner error or true alterations in corneal thickness by the
technique, required continued investigation.19
Wickham et al evaluated the measurement of CCT by US
pachymetry in a cohort of glaucoma patients over a 3-month
period. They found that measurements by a trained observer
showed fluctuation over the 3-month period, with a mean
difference in corneal thickness of 9.6+/-26.9 microns in the right
eye and 19.0+/-29.2 microns in the left eye, with a bias towards
increased corneal thickness being recorded at the second
reading in both eyes. They concluded that measurements of
CCT taken by US pachymetry within a clinical setting by a
trained observer may show significant variability. They had
suggested that more than 1 measurement of CCT reading may
be required. Failure to do so may result in an inaccurate
assignment of risk.20
Beyond assessment of risk for glaucoma, accuracy and
reproducibility of corneal thickness measurement is especially
important for the ongoing evaluation of corneal thinning
disorders such as keratoconus and conditions of corneal edema
such as disciform keratitis where response to treatment may be
contingent on reduction of tissue thickness.
Methods
Central corneal thickness measurements in 80 eyes of 40
healthy adult volunteers between the ages of 21-45 were
obtained using both US pachymetry (Sonogage Corneo-Gage
Plus™, Cleveland, OH) and SD- OCT (Cirrus 4000™, Carl Zeiss
Meditec, Dublin, California). Exclusion criteria included contact
lens wear within 1 month of testing, history of corneal surgery
(including LASIK or any refractive procedure) and any history or
identification of corneal disease through examination. All
subjects were determined to have normal corneal health by
biomicroscopic examination. The appropriate Institutional
Review Board approved this study and informed consent form
was obtained from each participant before testing.
The sample size was determined based on the average
differences of the two methods. Assuming a difference of 20
micrometers is clinically significant with a standard deviation of
10 micrometers, it was estimated that 80 eyes were needed for
this study. The sample size gives 80% power at the 0.05 level of
significance (2 sided, paired) and also allows the adjustment for
co-variables.
Paired repeated measure design was used in this study. For each
test subject, the CCT of both eyes was measured using the 2
methods (US pachymetry and SD-OCT) on the same day. In
every case SD-OCT was performed first. This was done to
remove any possible induction of artifacts by topical anesthesia
used in the performance of US pachymetry. Each measurement
for each technology was obtained 3 times with the patient
repositioned between each measurement. For consistency, 2
investigators conducted all of the measurements (LV for US
pachymetry and JP for SD-OCT). Each examiner was blind to
the results of the other to eliminate bias. Measurements with
each modality were performed according to written guidelines
from each manufacturer. For US pachymetry, topical anesthetic
was used. For SD-OCT imaging, the corneal center was
determined using the center of the pupil and the corneal crosssection used to mark the central cornea. The device’s internal
caliper-measuring system was used to determine thickness at
this location.
Additionally, as an ancillary test to examine potential interobserver variation in measuring, 6 individuals were tested by the
same investigators with each using both methods. It was seen
that the CCT measurements obtained with SD-OCT and US
pachymetry methods were comparable, despite which examiner
was performing the tests. There were no adverse events noted
during the study.
Statistical Analysis
The main outcome in this study is the difference in measured
CCT results between the 2 methods. Two eyes were measured
for each study subject using each method. A preliminary
examination found that even though the cornea thickness
measurements are highly correlated between 2 eyes for both
methods (r=0.99 for both methods), the average difference
between the 2 methods were not correlated between two eyes
(r=0.25, p=0.12). In addition, when assessing
the 2 methods, we did not consider a person as a cluster
Total (N)
Age (mean, SD)
Race (N, %)
Asian
Black
White
3
1
36
7.5
2.5
90
Sex (N, %)
Female
Male
23
17
57.5
42.5
535.3
34.5
538.2
34.9
523.0
34.5
523.3
34.7
12.2
3.9
14.9
3.4
Pachymetry (Mean, SD)
OCT (Mean SD)
Diﬀerence (Pachy‐OCT) (Mean SD)
OD (micrometers)
OS (micrometers)
OD (micrometers)
OS (micrometers)
OD (micrometers)
OS (micrometers)
Characteris8cs
40
27.5
5.9
1a
Table 1 Characteristics of study subjects.
1b
variable because the focus of the study is the comparison of 2
measurements matched by eyes. Thus, the unit of analysis was
eyes.
The agreement between these 2 methods was assessed using the
Bland-Altman plot.21 That is, the difference between these two
methods for each eye was plotted against the average value of
these 2 methods. Under the null hypothesis that the 2 methods
are equal, the differences should be around zero and no
systematic pattern exists.
The reliability as assessed by reproducibility of each method was
analyzed by comparing the variation of 3 repeated measures for
each method for each eye. The distribution of the within-subject
coefficient of variations (WSCV: standard deviation divided by
mean for each eye) of the 2 methods was plotted. Because the 2
methods are paired by eyes, a Wald test was used to determine
whether the 2 CVs were statistically significantly different.22,23
Furthermore, multivariate analysis was employed to assess the
differences of these 2 methods and adjust for co-variables
including age, race, sex and laterality. To take into account of
matching by eyes, we used a repeated measure model with the
eye as the cluster variable (Generalized Estimate Equation
population average model, GEE). In the multivariate analysis, the
intra-class coefficient in the model for each method is also a
measure of reliability.24 All analyses were done in Stata 11.1 (Stata
Inc., College Station, TX) and SAS 9.2 (Proc Mixed) (SAS Inc.,
Cary, NC).
Figure 1a and 1b Distributions of OCT and pachymetric
measures.
Results
Table 1 presents the basic characteristics of the study subjects
and the univariate analysis of the 2 measurements. The study
subjects are young and predominantly white. The mean CCT for
US pachymetry is 535.3 micrometers for right eyes and 538.2
micrometers for left eyes, which are thicker than mean SD-OCT
measurement of 523.0 micrometers for right eyes and 523.3
micrometers for left eyes, respectively. The unadjusted mean
differences between the 2 measures are 12.2 micrometers for
right eyes and 14.9 for left eyes, respectively.
Given that the difference between the 2 methods was
uncorrelated between 2 eyes, each eye was treated as a separate
unit in the following analysis. The distributions of the 2 measures
are shown in Figure 1a and 1b. Both measures had symmetric
distributions and did not have any outliers.
Figure 2 presents the Bland-Altman plot to examine the
agreement between the 2 methods, matched by eyes. It shows
that regardless of the actual cornea thickness, the US pachymetric
measurements were always thicker than SD-OCT measurements.
Finally, after controlling for race, age, sex, and laterality in the
multivariate GEE analysis results, the average difference between
two methods is 12.3 micrometers (95% Confidence Interval:
11.0-13.7, p<0.001). Race, age, and sex were not related to the
cornea thickness while left eye has slightly higher value than
right eye (mean difference: 2.6 micrometers, p=0.001), possibly
due to operational techniques used by examiners.
Discussion
Figure 2 Bland-Altman plot comparing pachymetric measures
and OCT measures, matched by eyes. Note: the middle line is the
mean difference line at 13.6 micrometers, the shaded area is 2
standard deviation of mean difference (+/- 2*3.9 micrometers).
Figure 3 Within-Subject Coefficient of Variations (WSCV) for OCT
and pachymetric measures. Note: WSCV = (standard deviation
within eye)/mean * 100%. The straight line is a 45 degree line.
On average, the mean difference is 13.9 micrometers (SD: 3.9
micrometers) between US pachymetry and SD-OCT
measurements.
Figure 3 shows the comparisons of within-subject coefficient of
variations (WSCV) within each eye between the 2 methods to
examine the reliability of the 2 measures. The average WSCV
for OCT is 0.49% (SD: 0.56%) and 0.45% (SD: 0.50%) for
ultrasound pachymetry (p=0.35 for comparison). However,
among OCT measures, there are 29 eyes (36%) that had a zero
WSCV value for OCT measures suggesting that OCT may be
more reliable than pachymetry. In fact, the mean within-subject
standard deviation among OCT is significantly smaller than that
in pachymetry (1.92 in OCT vs. 2.04 in Pachymetry, p=0.036).
Since the realization that thin CCT imparts a greater risk of
glaucomatous damage, the determination of CCT has become
commonplace in glaucoma management. While measurement of
CCT typically has been obtained with US pachymetry due to
the ease, accuracy, and low cost of the technology, practitioners
are increasingly using other methods to measure CCT. One
such method is SD-OCT, which has evolved to a level where
anterior segment structures such as the cornea can be easily
and accurately imaged. With this enhanced imaging and caliperbased measuring tools within the SD-OCT software, the
thickness of the cornea can be easily determined. It is
necessary to examine the accuracy and reproducibility of these
alternate forms of CCT measurement in order to determine if
these measurements are correctly assessing glaucomatous risk.
Additionally, conditions that cause corneal thinning, such as
keratoconus, as well as corneal thickening, such as disciform
keratitis, can possibly be followed more objectively if corneal
thickness measurements can be easily obtained with a high
degree of accuracy and reproducibility. Currently, SD-OCT is
used to quantify effects of anti-angiogenic therapy for macular
edema.25 Similarly, SD-OCT can potentially be used to quantify
corneal therapeutic effects in conditions such as disciform
keratitis if it can be determined that the measurements of
corneal thickness by this technology is accurate, reproducible,
and comparable to the current gold standard of US pachymetry.
Leung and associates noted CCT measured by SD-OCT and US
pachymetry to be highly correlated. They felt that SD-OCT is a
reliable alternative for CCT measurement.9 Similar to the study
results presented here, Prospero Ponce et al found that SDOCT CCT measurements were reproducible but always thinner
than US pachymetry in normal and keratoconus-suspect eyes.14
Zhao and colleagues also noted that CCT measurements by
SD-OCT were thinner than that determined by US
pachymetry.18
There are several possible explanations for SD-OCT
consistently measuring CCT thinner than US pachymetry as
well as being more reproducible on repeat measurements. US
pachymetry uses a probe held by hand in space. Thus, it is
incumbent on the examiner to visually localize the cornea
center. Factors such as patient changing fixation, hand
movement, and examiner placement of the probe at slightly offcenter positions on repeat examination can contribute to
higher intra-test variability with US pachymetry. In contrast,
SD-OCT has an internal fixation target. Additionally, once the
anterior segment has been imaged, it is inherently easier to
identify the cornea center for caliper based determination of
thickness.
It is critically important when measuring CCT with US
pachymetry to touch the probe perpendicular (or as close as
possible) to the cornea when obtaining measurements. If the
probe is not perfectly perpendicular, there exists the possibility
that the off axis position allows for the sound waves to
essentially travel through more corneal tissue, thus giving the
false impression of the cornea being thicker than it really is.
SD-OCT, by nature of the head and chin rest, positions the
patient’s cornea perpendicular to the measuring interferometer.
Assuming a normal head position of the patient, the corneal
image should better represent the most orthogonal position for
measurement. This could explain the consistently lower CCT
readings for SD-OCT and that the true CCT is actually better
reflected by the measurements obtained by SD-OCT, as
pachymetry probe-position artifacts can lead to an
overestimation of the true CCT.
true corneal thickness as the corneal center is more accurately
determined and measurements are being made perpendicular
through the minimal amount of corneal tissue.
The strength of this study is its relatively large sample size as
we planned this study based on careful sample size calculation.
In addition, homogeneity of subjects (i.e., all are young, and most
of them are white) allowed us to focus on the measurement
difference. Confounding factors due to age and race were
significantly reduced. Furthermore, we also used multivariate
GEE analysis to take account of subject and eye differences.
References
One weakness of our study is the homogeneous subjects. We
could not examine the difference due to age, race and other eye
conditions. In addition, only 2 investigators were involved in
measurements. This was done to ensure consistency in
measurements. We were unable to explore variations due to
examiners as part of this study, however, a small subset of 6
subjects were tested by the same investigators using both
methods, with the results of SD-OCT and US pachymetry
methods being comparable, despite which examiner was
performing the tests. Future study should specifically address
this issue.
Conclusions
To assess glaucomatous risk, it has become increasingly
important to measure CCT. Traditionally, this has been done
through US pachymetry. However, this technique has been
noted to potentially have significant inter-and-intra-examiner
variation. Such variations could possibly lead to an incorrect
assessment of risk. SD-OCT technology has evolved to the
point where the anterior segment structures can be imaged.
With accurate imaging of the cornea, CCT can be easily
determined, potentially without the artifacts that can be
induced by hand-held US pachymetry. It has been shown that
CCT measurement by SD-OCT is comparable to that
measured by US pachymetry, though the results are not
necessarily interchangeable, mostly due to SD-OCT measuring
thinner.
In our study, the cornea thickness measured by SD-OCT is
about 12 micrometers thinner than that obtained with US
pachymetry. Both methods are considered reliable; however
the reproducibility of repeat measurement is greater with SDOCT than US pachymetry. This may indicate greater reliability
of measurement with SD-OCT. The CCT measurements
obtained by SD-OCT were consistently thinner than that
obtained with US pachymetry. This may reflect probe-position
artifact in US pachymetry leading to an overestimation of CCT.
Based upon our results, it appears that CCT obtained by SDOCT is acceptable to use in glaucoma assessment. The greater
reproducibility of repeat measurements also makes SD-OCT a
better tool by which to follow other corneal disorders
characterized by thinning or thickening, especially when
monitoring therapeutic response. Finally, the consistently
thinner reading obtained with SD-OCT may better reflect the
Disclosure and Acknowledgements
This project was supported in part by the Health Profession
Division Grant from Nova Southeastern University. The
authors have no financial interest in any product discussed in
this manuscript. The authors wish to acknowledge and thank
research assistants Derek Richardson and Doo Kang.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Kass MA, Heurer DK, Higginbotham EJ, et al. The Ocular
Hypertension Treatment Study. A randomized trial determines
that topical ocular hypotensive medication delays or prevents the
onset of primary open angle glaucoma. Arch Ophthalmol
2002;120:701-13.
Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension
Treatment Study: baseline factors that predict the onset of
primary open angle glaucoma. Arch Ophthalmol 2002;
120:714-20.
Henderson PA, Medeiros FA, Zangwill LM, Weinreb RN.
Relationship between central corneal thickness and retinal nerve
fiber layer thickness in ocular hypertensive patients.
Ophthalmology. 2005;112(2):251-6.
Kim JW, Chen PP. Central corneal pachymetry and visual field
progression in patients with open-angle glaucoma.
Ophthalmology. 2004;111(11):2126-32.
Hong S, Kim CY, Seong GJ, Hong YJ. Central corneal thickness and
visual field progression in patients with chronic primary angleclosure glaucoma with low intraocular pressure. Am J
Ophthalmol. 2007;143(2):362-3.
Medeiros FA, Sample PA, Zangwill LM, et al. Corneal thickness as
a risk factor for visual field loss in patients with preperimetric
glaucomatous optic neuropathy. Am J Ophthalmol. 2003;136(5):
805-13.
Francis BA,Varma R, Chopra V, et al. The Los Angeles Latino Eye
Study Group. Intraocular pressure, central corneal thickness, and
prevalence of open-angle glaucoma: the Los Angeles Latino Eye
Study. Am J Ophthalmol. 2008;146(5):741-6.
Bechmann M, Thiel MJ, Neubauer AS, et al. Central corneal
thickness measurement with a retinal optical coherence
tomography device versus standard ultrasonic pachymetry.
Cornea. 2001;20(1):50-4.
Leung DY, Lam DK,Yeung BY, Lam DS. Comparison between
central corneal thickness measurements by ultrasound
pachymetry and optical coherence tomography. Clin Experiment
Ophthalmol. 2006;34 (8):751-4.
Fishman G, Pons ME, Seedor JA, et al. Assessment of central
corneal thickness using optical coherence tomography. J Cataract
Refract Surg. April 2005.Vol 31 (4) 707-11.
Schneider M, Borgulya G, Seres A, et al. Central corneal thickness
measurements with optical coherence tomography and ultrasound
pachymetry in healthy subjects and in patients after
photorefractive keratectomy. Eur J Ophthalmol. 2009;19(2):180-7.
Forte R, Cennamo GL, Finelli ML, de Crecchio G. Comparison of
time domain Stratus OCT and spectral domain SLO/OCT for
assessment of macular thickness and volume. Eye (Lond).
2009;23(11):2071-8.
Kim, H, Budenz DL, Lee PS, et al. Comparison of central corneal
thickness using anterior segment optical coherence tomography
vs ultrasound pachymetry. Am J Ophthalmol. 2008: 145(2)
228-232.
Prospero Ponce CM, Rocha KM, Smith SD, Krueger RR. Central
and peripheral corneal thickness measured with optical coherence
tomography, Scheimpflug imaging, and ultrasound pachymetry in
normal, keratoconus-suspect, and post-laser in situ keratomileusis
eyes. J Cataract Refract Surg. 2009;35(6):1055-62.
15. Li Y, Shekhar R, Huang D. Corneal pachymetry mapping with highspeed optical coherence tomography. Ophthalmology.
2006;113(5):792-9.
16. Swartz T, Marten L, Wang M. Measuring the cornea: the latest
developments in corneal topography. Curr Opin Ophthalmol.
2007;18(4):325-33.
17. Li EY, Mohamed S, Leung CK. Agreement among 3 methods to
measure corneal thickness: ultrasound pachymetry, Orbscan II, and
Visante anterior segment optical coherence tomography.
Ophthalmology. 2007;114(10):1842-7.
18. Zhao PS, Wong TY, Wong WL, et al. Comparison of central
corneal thickness measurements by visante anterior segment
optical coherence tomography with ultrasound pachymetry. Am J
Ophthalmol. 2007;143(6):1047-9.
19. Shildkrot Y, Liebmann JM, Fabijanczyk B, et al. Central corneal
thickness measurement in clinical practice. J Glaucoma.
2005;14(5):331-6.
20. Wickham L, Edmunds B, Murdoch IE. Central corneal thickness:
will one measurement suffice? Ophthalmology. 2005;112(2):225-8.
21. Bland JM, Altman DG. Statistical methods for assessing agreement
between two methods of clinical measurement. Lancet 1986. 1
(8476):307–10.
22. Shoukri MM, Colak D, Kaya N, Donner A. Comparison of two
dependent within subject coefficients of variation to evaluate the
reproducibility of measurement devices. BMC Medical Research
Methodology. 2008;8:24
23. Bland JM, Altman DG. Measurement error proportional to the
mean BMJ 1996; 313:106.
24. Goldstein H. Multilevel Statistical Models. Wiley; 4th edition, 2010.
25. Ding X, Li J, Hu X, et al. Prospective study of intravitreal
triamcinolone versus bevacizumab for macular edema secondary
to central retinal vein occlusion. Retina. 2011 Feb 2. [Epub ahead
of print]
Corresponding author: Lori Vollmer, O.D., Associate Professor
of Optometry, Nova Southeastern University, 3200 S. University
Drive, Fort Lauderdale, FL 33328. Email: [email protected].
Normalization of Retinal Nerve Fiber Layer with Stratus Optical
Coherence Tomography after Bilateral Diabetic Papillopathy
Richard J. Zimbalist, O.D.
KEYWORDS
diabetic papillopathy,
optical coherence
tomography (OCT),
non-arteritic anterior
ischemic optic
neuropathy (NAION),
retinal nerve fiber layer
(RNFL), optic disc
edema (ODE)
Abstract
Background: Diabetic papillopathy is a benign optic neuropathy with a favorable predictable visual
outcome, found in Type 1 and Type 2 patients with diabetes mellitus. The condition manifests with
optic disc edema and minimal optic nerve dyfunction. Previous reports have described several
similarities between diabetic papillopathy and non-arteritic anterior ischemic optic neuropathy; however,
there are clinical differences that make them unique conditions.
Case Report: A 62 year old Caucasian male with Type 2 diabetes manifested bilateral optic disc
edema without visual dysfunction. The patient was diagnosed with diabetic papillopathy after an
extensive systemic evaluation which did not reveal any contributory etiologies. The patient was followed
with serial retinal nerve fiber layer scans using optical coherence tomography over the course of one
year. The optical coherence tomography measurements demonstrate normalization of retinal nerve fiber
layer following optic disc edema resolution.
Conclusions: Presented is a case report demonstrated the normalization of retinal nerve fiber layer
following bilateral diabetic papillopathy. The use of optical coherence tomography is helpful in both
documenting progression and differentiating from similar clinical entities.
Introduction
Diabetic papillopathy (DP) was first described in 1971 as the
onset of optic disc edema (ODE) in juvenile Type 1 diabetics
without significant visual acuity or field loss.1 Since its initial
description, multiple reports have also documented DP in
older Type 2 diabetic patients.2-5 There remains discordance
amongst clinicians as to whether DP is a distinct entity or an
extension of non-arteritic anterior ischemic optic neuropathy
(NAION). This report supports DP as a unique and separate
condition from NAION based on both clinical resolution and
serial nerve fiber layer measurement with Optical Coherence
Tomography (Stratus OCT3; Carl Zeiss Meditech, Dublin,
California, USA) through one year of follow up examinations.
Case Report
A 62 year old Caucasian male presented to the clinic with a
chief complaint of gradual decreasing vision at distance and
near, moderate photophobia, and persistent frontal headaches.
Known ocular history included borderline ocular
hypertension, incipient cataracts, and non-exudative macular
degeneration.
Medical history was notable for previous alcohol dependence,
hyperlipidemia, peripheral neuropathy, depression,
hypertension, gout, pyrosis, erectile dysfunction, chronic
headaches, and Type 2 diabetes mellitus. The patient had
known diabetes for five years with a recent reduction in
hemoglobin A1C from 10.0% to 7.4% over a three month
period. Medications at the time of the examination included
amitriptyline, amlodipine besylate, cyanobalamin, HCTZ 25/
Lisinopril 20, insulin aspart, insulin glargine, metformin,
naproxen, omeprazole, pravastatin, quetiapine fumarate,
tramadol, and a daily multivitamin. Examination showed best
corrected visual acuities of 20/25 OD, 20/30 OS with
refractive errors of +2.25-1.25x120 OD and +3.50-0.75x075
OS. Pupils were equal, round and reactive without an afferent
pupillary defect in either eye. Slit lamp examination was
remarkable for trace nuclear sclerotic lenticular changes.
Intraocular pressures were 21 mm Hg OD, 20 mm Hg OS by
applanation. Fundus examination of the right eye revealed
multiple macular hard drusen and a cup-to-disc ratio of 0.1
with few retinal hemorrhages and mild optic disc edema
(ODE). Fundus examination of the left eye revealed multiple
macular hard drusen and a cup-to-disc ratio of 0.1 without
ODE. There was no diabetic retinopathy in either eye. The
mildly decreased visual acuity was consistent with macular
degeneration findings in both eyes. Optical coherence
tomography (OCT) showed a significantly thickened nerve fiber
layer in the right eye with an average thickness of 175.22
microns (Range: 86.0-107.6 µm for age matched Caucasians).
Blood pressure was 150/88 RAS at time of evaluation.
Lab work was obtained to rule out giant cell arteritis (GCA)
given the optic nerve appearance and persistent frontal
headaches. Inflammatory markers were slightly elevated with
an ESR of 33 mm/hr (Range: 0-31 mm/hr) and CRP of 1.5 mg/
dL (Range: 0.01-0.82mg/dL). Complete blood count with
differential showed mild anemia without thrombocytosis. The
patient was started on 40 mg of prednisone with adjustment of
insulin while on oral steroids. A right temporal artery biopsy
was performed within two weeks with a negative finding.
Shortly after the biopsy, the patient self discontinued the
prednisone because there was no symptomatic improvement in
his headaches and he was experiencing polyphagia with weight
gain. A biopsy was not performed on the left temporal artery,
since the patient had minimal systemic symptoms and suspicion
for GCA was rather low. An additional medical workup
including hemoglobin A1C, syphilis serology, lupus panel,
bartonella henselae titer, angiotensin converting enzyme, lyme
titer and MRI of the orbits with and without contrast were all
Figure 1a Photograph of the Right Optic Nerve at Follow Up Visits
Figure 1b Photography of the Left Optic Nerve at Follow Up Visits
within normal limits. Complete blood counts were obtained at
follow up visits, which revealed a consistent mild anemia and
moderate eosinophilia (Ranging from 0.7 -1.6k/cmm with
reference high of 0.6 k/cmm). A lumbar puncture was
performed and revealed an opening pressure of 19 cm with
clear fluid (Range: 5-20 cm). There was no growth of bacterium
or fungus observed over the course of four weeks.
Follow up examinations revealed increased ODE with
peripapillary hemorrhages and cotton wool spots in the right
eye on day 32 (Figure 1a). A similar clinical appearance
developed in the left eye on day 62 (Figure 1b). OCT
measurements were performed on days 4, 32, 62, 251, and 372
after initial presentation. Retinal nerve fiber layer (RNFL)
thickness averages were as high as 236.91 microns OD and
229.95 microns OS (Figure 2). Follow up on day 372 showed
normal appearing optic nerves and nerve fiber layer thicknesses
of 125.02 microns OD and 122.89 microns OS. (It is important
to note there was no evidence of optic atrophy in either eye
consistent with anterior ischemic optic neuropathy.) SITAStandard 24-2 visual field testing (Humphrey-Zeiss Systems,
Dublin, CA, USA) was performed on day 62, and showed a
shallow localized defect supero-nasally in the right eye and
scattered depressed points without clusters in his left. Repeat
testing the following year was similar with the exception of a
slightly enlarged blind spot OD (although high fixation losses on
testing) and an isolated cluster OS. (Figure 3a, 3b) The patient's
visual acuities, pupillary response, and non-contributory retinal
findings remained stable throughout all visits.
Discussion
This case presents several interesting findings associated with a
final diagnosis of diabetic papillopathy. The current diagnosis
criteria for DP includes the presence of Type 1 or Type 2
diabetes mellitus, unilateral or bilateral disc edema, absence of
substantial optic nerve dysfunction, and lack of ocular
inflammation or elevated intracranial pressure.6 DP typically
demonstrates hyperemic edema or dilation of the inner optic
disc microvasculature.5
Diabetic papillopathy presents with ODE that persists for a
period ranging from 3 months to 1 year.2, 5, 6 The optic nerve
returns to its pre-edematous appearance with healthy appearing
rim tissue after resolution. Although many have reported
minimal optic nerve dysfunction following DP, there have been
no reports that discuss the anatomical changes to the RNFL
throughout disease progression. Figures 1a, 1b, and 2 illustrate
the progression of the patient’s ODE and RNFL findings
throughout the course of one year of follow up exams. There is
a notable lack of optic atrophy and RNFL thinning after
resolution of the ODE. The OCT data illustrates the trend
towards normalization of the retinal nerve fiber layer with
resolution of DP.
The pathogenesis of diabetic papillopathy is largely a supposition
despite years of reports and hypotheses. The Diabetes Control
and Complications Trial documented worsening of diabetic
retinopathy with improved metabolic control.7 It has since been
speculated that DP may also be the result of rapid tightening of
blood glucose. A recent report has documented the
development of DP in several patients who had a small cup-to-
Figure 2 RNFL change over follow up visits as measured by Stratus OCT. Note: On 11/24/10 visit, RNFL scan was decentered inferiorly resulting in
suggesting thinning superior right eye.
disc ratio and a large change in Hemoglobin A1C over three
months. The development of diabetic papillopathy was statistically
correlated with a drastic reduction in A1C, averaging
-2.5% amongst the identified cases.8 Studies also show that strict
glycemic control is associated with a significant reduction in
retinal vein volumetric flow rate five days after insulin initiation in
64% of patients. It is postulated that intensive insulin therapy
results in retinal hyperperfusion with subsequent increased
vascular leakage and venous congestion.9 Previous theories of DP
pathogenesis have proposed toxicity and compressive effects of
axonal components as primary etiologies.10-12 Slagle3 proposed
that capillary vasostasis, retention of cellular waste, and
reabsorption in the capillary bed lead to localized edema of the
optic nerve head vasculature. While the above factors may
contribute to the development of DP, additional research is
needed to substantiate these theories.
Several therapies to expedite the resolution of ODE in diabetic
papillopathy have been attempted despite the self-limiting nature
of the condition. There has been no observed benefit after
purposeful elevation of glycemic control, based on the
aforementioned mechanism discussed above.8 Local
corticosteroids have been shown to improve ODE and visual
acuity in case reports of Type 2 diabetics; this suggests the antiinflammatory and anti-angiogenic properties may aid in the
resolution of ODE.13,14 Use of anti-VEGF intravitreal
bevacizumab has also shown improvement of ODE as early as
three weeks after injection.15 Future randomized clinical studies
may be beneficial in determining a definitive treatment modality
for DP.
Reports have attempted to delineate diabetic papillopathy as a
unique and separate identity from NAION. There are notable
differences in the symptoms, natural progression and clinical
outcomes between the two entities. DP is typically asymptomatic
and has healthy nerve tissue after resolution of ODE, whereas
patients with classic NAION experience sudden vision loss and
unilateral ODE followed by optic atrophy within three months.
1,5,16,17 Contreras examined the retinal nerve fiber layer of 27
patients with unilateral NAION for one year with optical
coherence tomography. At the time of presentation, the initial
RNFL thickness was increased in the area of ODE. Normalization
of the RNFL was noted at 6 weeks which corresponded to the
resolution of ODE. The RNFL thickness was decreased and
thinned at months 3, 6, and 12 in atrophic segments of the optic
nerve.17
The development of NAION is believed to be due to acute
ischemia of the short posterior ciliary arteries (PCA) that supply
the anterior optic nerve. Transient non-perfusion or
hypoperfusion of the PCA's is the primary etiology although
embolic lesions have also been demonstrated histopathologically.
Figure 3a Visual field of right eye on Day 62 and Day 372.
Figure 3b Visual field of left eye on Day 62 and Day 372.
18, 19
(i) Marked optic disc edema in one portion of the optic nerve, similar to the pattern of edema with classic
NAION.
(ii) No subjective or objective decrease in vision from classic NAION.
(iii) All other etiologies of optic disc edema are excluded such as hematologic, neurologic, endocrine,
neoplastic, and autoimmune conditions. Patient should be evaluated by primary care physician or
internist for systemic abnormalities.
(iv) The contralateral eye has demonstrated classic NAION in 55% of patients with incipient NAION.
(v) Incipient NAION progressed to classic NAION throughout follow-up in 25% of patients.
(vi) Classic NAION developed in the same eye after complete resolution of incipient NAION in 20% of
patients during a mean follow-up period of 5.8 weeks.
Table 1 Summary of Criteria for Diagnosis and Natural History of Incipient NAION32
Evidence indicates that NAION develops due to localized
ischemia of ganglion cell axons resulting in axoplasmic flow
stasis and optic nerve swelling. The edematous tissue
compresses local capillary beds causing further ischemia and a
cyclical pattern due to the tight orientation of ganglion cell
axons.18 Systemic conditions that have been linked to NAION
include nocturnal hypotension, diabetes mellitus, arterial
hypertension, ischemic heart disease, arteriosclerosis,
hyperlipidemia, sleep apnea, migraine, and carotid dissection.
18,20-26 Ocular risk factors consist of a crowded optic disc, angle
closure glaucoma or any markedly elevated intraocular
pressure, optic nerve drusen, and cataract extraction.27-29
The Ischemic Optic Neuropathy Decompression Trial evaluated
the safety and efficacy of optic nerve sheath decompression
surgery for non-arteritic ischemic optic neuropathy. Patients
who were solely monitored showed greater improvement in
visual acuity when compared to surgical intervention.
Additionally, patients that had undergone decompression had a
significantly greater risk of losing three or more lines of vision
at 6 months.30 High dose oral corticosteroid therapy with
systematic taper has been shown to improve visual acuity and
visual field improvement in NAION. Patients with initial visual
acuity worse than 20/70 and moderate to severe visual field
defects showed the greatest benefit of oral therapy.31 Although
corticosteroid therapy shows promise for the treatment of
classic NAION, the accepted primary therapeutic intervention
continues to be the control of systemic and ocular risk factors.
Hayreh32 reported a new entity regarded as incipient NAION
which may be the mildest form of ischemic optic neuropathy.
The criteria for the diagnosis of incipient NAION are shown in
Table 1. Review of the criteria identifies several shared clinical
characteristics similar to that of diabetic papillopathy. There is a
notable greater incidence of classic NAION development in the
affected or fellow eye when compared to previous reports of
diabetic papillopathy. Our patient exhibited two findings which
support a diagnosis of diabetic papillopathy over incipient
NAION. Criteria (i) was not met as the patient's initial ODE
presentation for each eye revealed diffuse, mild ODE with
thickened RNFL superior and inferior to the optic nerve.
Hayreh also found that the ODE associated with incipient
NAION persists for an average of 9.5 weeks and 8.9 weeks in
diabetics with and without interventional steroid.32 Our patient
demonstrated significant worsening of the ODE bilaterally as
shown on day 62 (8.8 weeks) as seen in Figure 1a,b. It can be
assumed the ODE would have persisted for a significantly
longer duration given the worsening of edema at 8.8 weeks.
Unfortunately, the patient was lost to follow up between day 62
and day 251 which prevented documentation of the true timing
and pattern of resolution. The prolonged duration of ODE is
consistent with DP rather than incipient NAION.2,5,6,32
Conclusion
OCT has been widely used for the evaluation of optic nerve
disorders, however, there are no previous reports documenting
the longitudinal changes to the RNFL in diabetic papillopathy.
The OCT measurements throughout the visits showed
normalization of the RNFL thickness without atrophy following
ODE. Diagnosis of DP must meet the set criteria but clinicians
should also consider using retinal scanning technology to
monitor progression of the RNFL until resolution. This case
report demonstrates how optical coherence tomography is
valuable for monitoring RNFL and can be used to help
differentiate between the similar clinical entities of DP and
incipient NAION.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
Lubow M, Makley TA Jr. Pseudopapilledema of juvenile diabetes
mellitus. Archives of Ophthalmology 1971; 85:417–22.
Bayraktar Z, Alacali N, Bayraktar S. Diabetic papillopathy in Type II
Diabetic Patients. Retina 2002; 22: 752-758
Slagle SS, Musick AN, Eckermann DR. Diabetic papillopathy and its
relation to optic nerve ischemia. Optometry and Vision Science
2009; 86(4), E395–E403
Knight G, Talbot JF, Ward JD. Optic neuropathy associated with
rapid tightening of blood glucose control. Lancet 1984; Mar 24;
1(8378):681.
Regillo CD, Brown GC, Savino PJ, Byrnes GA, Benson WE, Tasman
WS, Sergott RC. Diabetic papillopathy: Patient characteristics and
fundus findings. Archives of Ophthalmology 1995; 113(7), 889-895
Arnold AC. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 6th
ed. Philadelphia: Lippincott Williams & Wilkins; 2005. Chapter 7,
Ischemic Optic Neuropathy; 377-378
Diabetes Control and Complications Trial Research Group. Early
worsening of diabetic retinopathy in the Diabetes Control and
Complications Trial. Archives of Ophthalmology 1998; 116:
874-876
Ostri C, Lund-Andersen H, Sander B, Hvidt-Nielsen D, Larsen M.
Bilateral diabetic papillopathy and metabolic control.
Ophthalmology 2010; 117(11) : 2214-2217.
Grunwald JE, Brucker AJ, Braunstein SN, Schwartz SS, Baker L,
Petrig BL, Riva CE. Strict metabolic control and retinal blood flow
in diabetes mellitus. British Journal of Ophthalmology 1994; 78:
598-604
10. Fruend M, Carmon A, Cohen AM. Papilledema and papillitis in
diabetes: report of two cases. American Journal of Ophthalmology
1965; 60: 18-20.
11. Yanko L, Ticho U, Ivry M. Optic nerve involvement in diabetes.
Acta Ophthalmologica (Copenhagen) 1972; 50: 556-564.
12. Appen RE, Chandra SR, Klein R, Myers FL. Diabetic papillopathy.
American Journal of Ophthalmology 1980; 90: 203-209.
13. Al-Haddad CE, Jurdi FA, Bashshur ZF. Intravitreal triamcinolone
acetonide for the management of diabetic papillopathy. American
Journal of Ophthalmology 2004; 137 (6): 1151-1153
14. Mansour, AM, El-Dairi MA, Shehab MA, Shahin HK, Shaaban JA,
Antonios SR. Periocular corticosteroids in diabetic papillopathy.
Eye 2005; 19(1): 45-51
15. Ornek K, Ogurel T. Intravitreal bevacizumab for diabetic
papillopathy. Journal of Ocular Pharmacology and Therapeutics
2010; 26(2): 217-218
16. Jacobson DM,Vierkant RA, Belongia EA. Nonarteritic anterior
ischemic optic neuropathy. A case-control study of potential risk
factors. Archives of Ophthalmology 1997; 115: 1403-1407.
17. Contreras I, Noval S, Rebodella G, Munoz-Negrete FJ. Follow-up
of nonarteritic anterior ischemic optic neuropathy with optical
coherence tomography. Ophthalmology 2007; 114: 2338-2344
18. Hayreh SS. Acute Ischemic Disorders of the Optic Nerve:
pathogenesis, clinical clinical manifestations and management.
Ophthalmology Clinical North America 1996; 9: 407-442
19. Lieberman MF, Shahi A, Green WR. Embolic ischemic optic
neuropathy. American Journal of Ophthalmology 1978; 86: 206-210
20. Repka MX, Savino PJ, Schatz NJ, Sergott RC. Clinical profile and
long term implications of anterior ischemic optic neuropathy.
American Journal of Ophthalmology 1983; 96:478-483
21. Guyer DR, Miller NR, Auer CL, Fine SL. The risk of
cerebrovascular and cardiovascular disease in patients with
anterior ischemic optic neuropathy. Archives of Ophthalmology
1985; 103: 1136-1142
22. Hayreh SS, Joos KM, Podhajsky P, Long CR. Systemic diseases
associated with nonarteritic anterior ischemic optic neuropathy.
American Journal of Ophthalmology 1994; 118: 766-780.
23. Hayreh SS, Zimmerman MB. Nonarteritic anterior ischemic optic
neuropathy: clinical characteristics in diabetic patients versus
nondiabetic patients. Ophthalmology 2008; 115 (10): 1818-1825
24. Mojon DS, Hedges 3rd TR, Ehrenberg B, Karam EZ, Goldblum D,
Abou-Chebl A, Gugger M, Mathis J. Association between sleep
apnea syndrome and nonarteritic anterior ischemic optic
neuropathy. Archives of Ophthalmology 2002; 120: 601-605.
25. Palombi K, Renard D, Levy P, Chiquet Ch, Deschaux C, Romanet
JP, Pepin JL. Non-arteritic anterior ischaemic optic neuropathy is
nearly systematically associated with obstructive sleep apnea.
British Journal of Ophthalmology 2006; 90:879-882.
26. Li J, McGwin Jr. G,Vaphiades MS, Owsley C. Non-arteritic anterior
ischaemic optic neuropathy and presumed sleep apnoea syndrome
screened be the Sleep Apnea scale of the Sleep Disorders
Questionnaire (SA-SDQ). British Journal of Ophthalmology 2007;
91: 1524-1527
27. Beck RW, Hayreh SS, Podhajsky PA, Tan ES, Moke PS. Aspirin
therapy in nonarteritic anterior ischemic optic neuropathy.
American Journal of Ophthalmology 1997; 123: 212-217
28. Hayreh SS. Non-arteritic anterior ischemic optic neuropathy and
thrombophilia. Graefes Archives for Clinical and Experimental
Ophthalmology 2009; 247: 577-581
29. Hayreh SS. Anterior ischemic optic neuropathy. IV. Occurrence
after cataract extraction. Archives of Ophthalmology 1980; 98:
1410-1416.
30. Ischemic Optic Neuropathy Decompression Trial Research
Group: Optic nerve decompression surgery for nonarteritic
anterior ischemic optic neuropathy (NAION) is not effective and
may be harmful. Journal of the American Medical Association
1995; 273: 625-632
31. Hayreh SS, Zimmerman MB. Non-arteritic anterior ischemic optic
neuropathy: role of systemic corticosteroid therapy. Graefes
Archives for Clinical and Experimental Ophthalmology 2008; 246:
1029-1046
32. Hayreh SS, Zimmerman MB. Incipient nonarteritic anterior
ischemic optic neuropathy. Ophthalmology 2007; 114:1763-1772
Corresponding author: Richard Zimbalist, O.D., Harry S
Truman Memorial Veterans Hospital Eye Clinic, 800 Hospital
Drive, Columbia, MO 65201. Email:
[email protected].
Current Status on the Development and Treatment of Myopia
Jeffrey Cooper M.S., O.D., Erica Schulman, O.D., and Nadine Jamal O.D.
KEYWORDS
atropine, myopia,
myopia control,
cycloplegia,
pirenzepine, contact
lenses, bifocals,
multifocals,
undercorrection, nearsightedness, hyperopic
defocus,
orthokeratology,
corneal refractive
therapy
ABSTRACT
This is a review of the current literature describing the effect of atropine, bifocals, and/or contact lenses
on slowing the progression of myopia. Cumulative data from a number of studies have demonstrated
atropine instilled once a day in myopic eyes resulted in a 90% average reduction of myopia progression,
as compared to untreated eyes, i.e., from 0.50 D/year to 0.05 D/year. Pirenzepine, a muscarinic
pharmacological agent, has a minimal effect on pupil size and accommodation, and it has been shown
to slow myopia by 44%. Bifocals and progressive lenses, which have been used for years to slow the
progression of myopia, have recently been shown to produce, on average, only small, clinically
insignificant treatment effects. However, their effectiveness is increased in children who are esophoric
and have a large lag of accommodation, reducing myopia progression to between 0.25 and 0.40 D/year.
Traditional correcting soft and gas permeable contact lenses, as well as novel spectacle lens designs, have
not been shown to be effective in reducing myopic progression. Under-correction of the refractive error
has been shown not only to be ineffective in slowing myopia, but has also been associated with an
increased rate of myopia progression. Orthokeratology, using reverse geometry designed lenses, has been
shown to be moderately effective in decreasing the progression of myopia by between 30 to 50% in a
number of short-term, well-controlled studies, reducing myopia progression to between -0.25 and -0.35
D/year. Recently, there have been pilot studies using novel peripherally correcting soft contact lenses to
slow the progression of myopia. Two of those lens designs have been shown to be moderately effective in
slowing the progression of myopia, both of which had a 30% efficacy, reducing myopia progression to
0.35 D/year. In summary, myopia control is entering a new era with the use of contact lenses and
pharmaceutical agents to effectively slow its progression with minimal side effects.
Myopia
Myopia is a common refractive condition affecting
approximately 100 million people in the United States.1 Its
prevalence has increased over the past decades, leading to a
growing concern among the public and scientific community.2, 3
The prevalence of myopia varies in different parts of the
world.4-7 Generally speaking, myopia is more prevalent in
industrialized countries and in cities as compared to rural
areas.8-12 In the United States, the prevalence rate has
increased from 25% between 1971 - 1972 to 41.6% between
1999 – 2004.1,2 The prevalence of myopia in Taiwan and
Singapore is 20% to 30% in children 6 to 7 years of age,
increasing to 60% to 80% in young adults.13,14 The rapid
increase in the prevalence of myopia provides strong evidence
that current environmental factors must have a considerable
influence on the development of myopia that can not be
explained by a genetic model.15,16 Understanding how the
environment influences eye growth should be central to
preventing the progression of myopia.
The widespread prevalence and rapidly increasing rates of
myopia make it a significant public health concern. Persons
with higher degrees of myopia have a greater risk of
developing sight-threatening complications i.e., permanent
visual impairment (or “blindness”) from myopic macular
degeneration, cataract, glaucoma, retinal holes and tears, and
retinal detachments.13,14,17,18 Myopia has been implicated as
the sixth leading cause of vision loss.19 Retarding the
progression of myopia in children could ultimately impact the
lives of approximately 42 million adults in the United States.20
Thus, finding an effective method of slowing myopia
progression is important in decreasing the morbidity associated
with this condition.
Myopia has been broadly classified by age of onset as
pathological, school age, or adult onset. Pathologic myopia,
which usually presents before six years of age, is caused by
abnormal and extreme elongation of the axial length of the
eye, generally does not progress, and is usually associated with
retinal changes.21,22 School age myopia occurs between 6 and
18 years of age and is thought to progress and stabilize by the
late teens or early twenties.23 This type of myopia is associated
with higher IQ scores, more time spent reading, and less hours
of exposure to sunlight as compared to non-myopic patients.
24,9,25-28 In Singaporean children, the prevalence and magnitude
of myopia correlates with the time spent in education.29 In
addition, school-age myopia is found more commonly in urban
areas (versus rural areas), and industrialized countries.9,30 Adult
onset myopia occurs between 20 and 40 years of age (early
adult onset) or after 40 years of age (late adult onset). It has
different characteristics as compared to the school age onset
myopia, particularly in that it is associated with accommodative
anomalies and near vision dominated occupations.31 Myopia
progression in all three groups is due to the elongation of the
axial length, which is primarily due to the elongation of the
vitreous chamber depth of the eye.32
If myopia is to be controlled during development, the rate of
eye growth must be slowed. The rate of myopia progression is
highest for young children with an average age for stabilization
of childhood myopia at 16 years of age.33 Once myopia begins
to develop, the mean rate of progression in children 8 to 13
years of age is 0.55 D/year for Caucasian children;33 between
0.63 D/year for Hong Kong Chinese children;34 and 0.82 D/year
determined for Asian children by meta analysis.35 For an average
baseline age of 9 years, estimated annual progression (combined
ethnicities) was 0.80 D/year for females, and a significantly
slower 0.71 D/year for males.35
The etiology, pathogenesis, and treatment of myopia have been
debated for decades, and the exact mechanism of the
development of myopia still remains unclear. Both
environmental and genetic factors have been associated with the
onset and progression of myopia.2,19,22 The strongest evidence
for genetic factors comes from comparing the prevalence of
myopia in uniovular versus binovular twins. Uniovular twins
have a higher prevalence of myopia as compared to binovular
twins, thus supporting the genetic influence on the development
of myopia. In addition, Angle and Wissman36 found that near
work explained only a small part of the variance in teenagers,
and thus concluded that genetics is the most important factor in
determining the development of myopia. Studies have also
shown that having one or two nearsighted parents is a risk
factor for the development of myopia.37-40 However, this does
not completely explain the role of genetics since parents share
both genetic and environmental factors with their offspring.
The concept that myopia evolved from the use and abuse of the
eyes during near vision activities has been credited to Cohn in
1886 and has been traced back to Kepler.41 More recent studies
demonstrate a positive correlation between the presence of
myopia and the following: intelligence,24, 42-43 academic
advancement,44,16,42 avocations requiring near vision use,45,46
after professional school,31,47 caged versus free-ranging animals48
and people confined to restricted spaces such as submarines.49
The implication of most of these studies is that the greater the
time spent performing near work results in an increased
incidence of myopia.50-52 Zylberman,53 while studying children in
religious schools, noted that the incidence of myopia was much
higher in Orthodox Jewish males who spent approximately 16
hours per day studying as compared to Jewish females who did
not study as much. The incidence of myopia in Jewish females
was similar to other Jewish male cohorts who attended nonreligious schools. Zylberman53 suggested that both groups of
males had similar genetic make-ups, but the group that studied
more became more myopic. In both groups, the females who
studied a similar amount developed a similar amount of myopia.
The assumption in most use and abuse theories is that
accommodation is somehow indirectly responsible for axial
length elongation. There is some indirect evidence for this since
myopes exhibit greater lags of accommodation,54,55 higher ACA
ratios,56 57 more esophoria even when they are still emmetropic,
58 reduced accommodative amplitudes,59 worse accommodative
responses,60,61,62 and deficient positive relative accommodation.
63 However, the difference in accommodative function between
emmetropes and myopes is not great enough to explain the
development of myopia. Secondly, it is difficult to determine
which came first, the abnormal accommodative function or the
myopia. Abnormal accommodative findings have lead to a host
of treatment methods including bifocals, progressive addition
lenses (PALs), base-in prism, atropine therapy, and vision therapy.
Mutti and Zadnik64 recently challenged the near vision theories
by noting that recent epidemiological studies suggested that the
amount of time spent outside in sunlight is more closely related
to the development of myopia than the amount of time spent
reading, studying, or working on a computer.65,66,67 In animals
the level and/or amount of illumination during the day can affect
refractive development.68,69,70 A number of studies have
documented a strong negative correlation between the amount
of time children spend outdoors and their refractive error, i.e.
myopia becomes more common in children who spend less time
outdoors.27,65,66 However, this finding has not been observed
universally.71,38,72 Guggenheim et.al73 in a recent study
determined that the amount of time spent outdoors was
predictive of incident myopia independently of physical activity.
They reported that the association of myopia observed for time
outdoors and “sports/outdoor activity” is related to time
outdoors rather than to the level physical activity.
The mechanism of sunlight has been ascribed to the pinhole
effect causing a reduction of peripheral blur, UV exposure
affecting cross-linking of the sclera, and/or alteration of the
focusing shell when looking from distance to near. The
prevalence of myopia varies minimally across geographical
latitudes, that exhibit a wide range of both the length of day and
the amount of ambient light.74 Thus, Guggenheim et al.73
concluded that it is likely that light levels regulate the eye’s
“gain” response to the visual cues that guide emmetropization
rather than exerting a direct effect on eye growth. Mutti and
Zadnik64 makes a point of stating that the time spent outdoors
is an independent variable, not the inverse of near work. When
looking at epidemiological studies, one must be cognizant of the
cohort being studied. For example, many of the studies involving
amount of sunlight exposure were performed on school-aged
myopes and may not be relevant to adult onset myopia. At the
same time, most of the studies on accommodation used college
aged students versus younger children (between the ages of 8
and 13 years).
The most compelling studies implicating the impact of the
environment on myopia come from animal studies in which the
environment has been manipulated to produce myopia,
hyperopia, or astigmatism in visually immature animals. Wiesal
and Raviola68,75 sutured the lids of monkeys, allowing a minimal
amount of light to penetrate. Form deprivation resulted in the
animals developing myopia secondary to axial elongation of the
vitreous chamber. They concluded that form deprivation
disrupts the feedback mechanism for emmetropization and
resulted in myopia across all species including humans. Similar
myopiagenic effects were observed when translucent diffusers
were placed over an eye rather than suturing the lid closed.
However, myopia did not develop if the animal was patched with
a totally opaque occluder or reared in total darkness, since total
darkness eliminates any signal for visual feedback.76,77
Wallman et al.78 used hemi-retinal sector occluders to create
regional diffusion of light. Hemi-retinal diffusers result in a clear
image on one half of the retina and diffused unfocused light on
the other half. Myopia, with axial elongation, occurred only in
the field in which the occluders diffused the light, i.e.,
asymmetrical elongation of the globe (see Figure 1). Myopia
occurred in the occluded half of the retina, in the presence of
equal illumination in both halves of the retina, and in the absence
of accommodation. Smith and his associates reported similar
results.79 Lastly, these changes occurred in the absence of an
intact optic nerve, demonstrating that changes were local to the
eyeball.80,81 Varying the amount of illumination by the degree of
frosting resulted in varying the degrees of myopia. In a similarly
designed experiment, Diether82 used hemi-regional plus and
minus lenses to induce local retinal blur, which caused a localized
change in axial length in young chicks. Diether suggested that
these results provide further evidence that accommodation is not
responsible for axial elongation. Schaeffel and his associates83,84
used plus and minus contact lenses to create artificial hyperopia
or myopia. When lenses between -10.00 and +15.00 were placed
on primates’ eyes, the growth of their eye(s) compensated for the
focal length created by the lens in an attempt to eliminate blur. (It
should be noted that the eye responded accurately to the
direction of the error.) These studies demonstrate that
emmetropization is driven towards the direction that results in a
clear, higher contrast image. It has been postulated that near visual
activity either disrupts the normal pathway of emmetropization
or results in a change in ocular growth in order to adapt to the
near enviorment.85
Figure 2 Peripheral Blur Drives The Eye to Elongate
If either the macula is ablated, a multifocal lens is placed over an eye (center
plano, peripheral -3.00), or a diffuser placed over the peripheral portion of the
eye while the center is un-obstructed, the eye will elongate in response to the
peripheral blur. This occurs across species (including those with and without
fovea.98,176)
relationship of lag of accommodation in causing myopia is at best
controversial.
Figure 1 Regional Deprivation Causes Localized Axial Elongation
Panel 1 One of the following was placed in front of the nasal field of a
visually immature animal’s eye resulting in a blurred image on the temporal
retina: occluder, translucent lens, or minus lens.
Panel 2 The blurred image on the temporal retina over time causes localized
elongation of the eyeball.205,79 This occurs even when the optic nerve is
severed, demonstrating that cortical feedback is not necessary for localized
elongation.81
Animal studies using positive and negative lenses have
demonstrated that optical defocus can cause directionally
controlled eye growth.84,86-88 Thus, it would not be unreasonable
to presume that hyperopic retinal blur from a larger lag of
accommodation during near viewing could cause
myopia progression in children63, 89, 90 and the larger the amount
of hyperopic defocus, the faster the rate of myopia progression.91
In support of this hypothesis, Gwiazda et al.57 reported an
elevated lag of accommodation two years before the onset of
myopia. Conversely, Mutti et al.92 reported that accommodative
lag in pre-myopic children was not elevated until a year after the
onset of myopia. Rosenfield et al.93 reported that young adults
who became myopic had a smaller lag of accommodation before
and after the onset of myopia. While there is no consensus
regarding lag of accommodation prior to the onset of myopia,
there is a consensus that the lag of accommodation is larger after
the development of myopia.94-96 Recently, Berntsen et al.97
investigated the relationship between accommodative lag and the
rate of myopia progression in a large sample of children; they
reported that foveal hyperopic retinal blur during near viewing
could not explain school-age myopic progression. Thus, the
Previously, the macula (including the fovea), which dominates
cortical vision in primates, was thought to be responsible for the
process of emmetropization. However, recent animal studies have
demonstrated that the peripheral retina has a greater influence
than the macula over emmetropization and ocular growth.98-102
For example, form deprivation causes primate eyes to become
myopic, when only the peripheral retina is deprived. If peripheral
form deprivation is eliminated during the critical period, the
vitreous cavity decreases in size and the eye becomes more
emmetropic.102 This even occurs in the absence of an intact fovea
after ablating the macula with a laser.99 Myopia progression
results in the peripheral posterior pole of myopic eyes to become
relatively hyperopic relative to the central retina due to the round
shape of the globe.103 (See Figure 2.)
It has been suggested that this relative hyperopic defocus may
actually act as a signal for axial elongation.101 Hoogerheide et al.
104 noted that emmetropic or hyperopic airline pilot trainees
were most at risk for becoming myopic when the relative
peripheral refractive error was more hyperopic. In addition,
Schmid105 observed that there was a correlation between
temporal retinal steepness and the development of myopia in
humans. Monkeys reared with centrally unrestricted vision (plano
lens) and -3.00 D in the periphery produced similar myopia as a
full field lenses of -3.00 D of power, demonstrating that peripheral
blur caused axial elongation irrespective of whether central vision
was corrected.98 (See Figure 2) Liu and Wildsoet106 used
peripherally designed lenses in young chicks to create myopia
which resulted in a reduction of axial growth. These findings
support the hypothesis that eye shape, associated with peripheral
defocus, is one of the factors influencing axial eye growth. (See
Figure 3.)
In the Orinda Longitudinal Study of Myopia, which included
predominantly Caucasian subjects, Mutti et al.107 reported that
myopic children had relative peripheral hyperopia, whereas
emmetropic and hyperopic children had relative peripheral
myopia. Relative peripheral hyperopia results in a more prolate
occupation, and amount of light. Currently, genetic make up
cannot be altered, but the environmental factors can be. Thus,
understanding the methodology of emmetropization is
important in developing methods to control myopia.
TREATMENT: SPECTACLE CORRECTION
Bifocals and Multifocal Lenses
Figure 3 Image Shells Of Emmetropic Eyes And Myopic Eyes
With Various Corrections
Panel 1. An emmetropic eye has the image shell congruent with the retina, i.e.,
both the macula and peripheral retina are in focus.
Panel 2. When the eye becomes more myopic, it becomes more elliptical
(prolate), thus the anterior-posterior length increases without a change in the
equator. This results in a more hyperopic periphery. Traditional lenses will
correct the central retina leaving the periphery more hyperopic, i.e., image shell
in the periphery is behind the retina. The amount of hyperopic defocus
increases when looking near during accommodation. A lens that corrects the
peripheral defocus, such as those used in orthokeratology, corrects the macula
(image plane congruent to the macula), while the peripheral image shell is
focused in front of the retina.
ocular shape in myopic eyes, in which the axial length exceeds
the equatorial diameter. Similar findings have been reported in
Chinese subjects with myopia.107-111 Chen et al.109 reported
that relative peripheral refractive errors (RPRE) in Chinese
children and adults with moderate myopia, low myopia,
emmetropia, and low hyperopia were different. They reported
that RPRE for the moderate myopia group had a relative
hyperopic shift while subjects with low hyperopia demonstrated
a relative myopic shift. The RPRE profile for the moderately
myopic group was different for adults as compared to children.
Adult eyes had a greater amount of hyperopic change. Thus, the
periphery of a prolate shaped eye would experience hyperopic
defocus, which might result in the onset and progression of
myopia.98,99
The preceding findings have resulted in a renewed interest in
orthokeratology and novel spectacle and contact lens designs to
correct the hyperopic peripheral defocus in order to eliminate
the local retinal signal for elongation (to be discussed later). In
addition, the neuro-retinal signal for ocular elongation is
thought to have a biochemical basis.19 Thus, if one can block the
signal, then one might slow or stop myopia progression.
Atropine112-138 and pirenzepine139-147 have been shown to slow
the progression of myopia via this presumed mechanism.
In summary, there is ample, solid evidence for both genetic and
environmental factors producing myopia. It may be presumed
that the genetic predisposition for myopia is triggered by
environmental factors such as diet, amount of reading time,
Optometrists first began using bifocal lenses to attempt to slow
myopia progression in the 1940s.148 The rationale was that if
accommodation caused an increase in myopia, then bifocals or
multi-focals would reduce the accommodative response and
thus slow myopia progression. A more recent alternate theory
suggested that myopic children do not accommodate as well as
emmetropic children.57 This inaccurate accommodation
somehow creates a retinal blur that acts as a signal for myopia
progression, similar to the blur-induced myopia that can be
experimentally produced in animals.54,55,60 Gwiazda et al.
reported that myopic children with esophoria have a greater lag
of accommodation than other myopic children and that myopic
children have a greater lag of accommodation than emmetropic
children.54,55,60 A greater accommodative lag would cause
retinal blur and possibly a stronger stimulus for myopia
progression. Thus, the elimination of a lag of accommodation is
thought to slow the progression of myopia.
Goss149 performed a retrospective analysis of children between
6 and 15 years of age from three optometry practices to assess
the effect of bifocal lenses on the rate of myopia progression.
Sixty children wore bifocal lenses with an add power that varied
between +0.75 D to +1.25 D, and 52 children wore single vision
lenses. Children in the bifocal group displayed either esophoria
at near, a low amplitude of accommodation, negative relative
accommodation (NRA) and positive relative accommodation
(PRA) which were more plus and/or less minus than normal
values, a subjective refraction showing more minus than static
retinoscopy, or a reported symptom of intermittent distance
blur. As a group there was no statistically significant difference in
progression between the bifocal group (0.37 D/year) and the
single vision group (0.44 D/year). However, when Goss looked
only at the esophoric children, there was a statistically
significant decrease in myopia progression for children wearing
bifocal lenses as compared to single vision lenses, 0.32 D/year
versus 0.54 D/year, respectively. Myopia progression was also
analyzed based on lens type and near cross cylinder findings. For
children with a near cross cylinder finding greater than or equal
to +0.50 D, there was also a statistically significant difference in
myopia progression for children wearing bifocal glasses as
compared to single vision glasses; 0.25 D/year versus 0.48 D/
year, respectively.
Grosvenor et al.150,151 randomly placed 207 children between
the ages of 6 and 15 years into three treatment groups; single
vision glasses, +1.00 D bifocals, and +2.00 D bifocals. At the end
of the three year study, Grosvenor et al.151 reported that for
the 124 children who completed the study, there was no
significant difference in myopia progression in children wearing
single vision glasses or bifocal lenses. Goss149 re-analyzed
Grosvenor’s data, looking only at the esophoric children, and
reported that for this group, there was 0.20 D/year less myopia
progression for the bifocal wearers compared to single vision
lens wearers.
Fulk et al.152,,153 conducted a prospective, randomized study of
82 esophoric children, (age 6 to 13), to evaluate whether
bifocals (+1.50 D add) were effective in slowing myopic
progression over 30 months. The authors noted that during at
least one of five follow-up examinations, 33% of the bifocal
wearers were observed to read over the top of their bifocals.
Fulk reported that there was a 20% reduction in myopia
progression for esophoric children wearing bifocal lenses as
compared to single vision, a difference of 0.25D over 30
months. Fulk observed that if the outliers were excluded, which
consisted of the five children who progressed more than 2.00 D
over 30 months, then there was a 44% reduction in myopia
progression for esophoric patients wearing bifocals. Myopia
progression was 1.25 D or more in 25% of the bifocal group as
compared to 44% of the single vision group, a 0.49 D difference
over 30 months. The number of patients who demonstrated
more than 2.00 D of myopia progression was similar in both
groups. The authors concluded that improper bifocal use was
associated with faster myopic progression; 67% of the children
who progressed by more than -1.25 D were observed to look
over the top of their bifocal on at least one of five follow-up
visits.
Bifocal lenses, as compared to progressive addition lenses, are
not as cosmetically appealing, and do not vary in power for
different working distances. Both progressive lens and bifocals
fit high should improve the proper use of the reading addition.
Leung and Brown154 conducted a clinical trial to evaluate the
efficacy of progressive lenses on slowing myopia progression.
Sixty-eight children between the ages of 9 and 12, who had
myopia between 1.00 D and 5.00 D with less than 1.50 D of
astigmatism, were fit with either progressive lenses or single
vision lenses. The mean myopic progression over the 2-year
study was 0.76 D for the +1.50 D add group, 0.66 D for the
+2.00 D add group, and 1.23 D for single vision group. The
progressive lens groups exhibited a statistically significant
decrease in the amount of myopic progression associated with
axial length changes as compared to the single vision lens group.
There was no statistical difference between the two progressive
lens groups. The axial lengths of the children in all groups
increased with increasing degrees of myopia, and the majority of
change occurred in the vitreous chamber. Leung and Brown
noted that esophoric subjects wearing progressive lenses
progressed 46% less than non-esophoric subjects wearing single
vision lenses. The difference in myopic progression over 2 years
between children with esophoria wearing single vision lenses as
compared to progressive lenses was 0.71 D.
The Correction of Myopia Evaluation Trial (COMET), a 3 year
prospective, randomized, double-masked clinical trial, evaluated
the effect of progressive lenses (with a +2.00 D add) in 469
myopic children 6 to 11 years of age (spherical equivalent
between -1.25 D and -4.50 D).155 After 3 years, there was a
statistically significant, but clinically insignificant, 0.20 D
reduction in myopia progression over 3 years for children
wearing progressive lenses as compared to single vision lenses.
Children with larger accommodative lags (greater than 0.43 for
a 33cm target) wearing single vision lenses had the most
progression at the end of the 3 years. For children with both
larger lags of accommodation and near esophoria, there was a
statistically significant decrease in myopia progression in
children wearing progressive lenses as compared to single vision
lenses: 1.08 D verses 1.72 D, respectively. However the 3 year
treatment effect decreased after 5 years to 0.49 D/year.156
(Though, progressive lenses are more effective when one or
both of the parents are myopic, there are no long-term data for
this sub-group.)
A more novel use of multifocal glasses involves the use of
specially designed glasses to correct for the central myopic
error while, at the same time eliminating the peripheral
hyperopic refractive error induced by traditional glasses.109 This
residual error results in a blur which is believed to be the
stimulus for increased myopic progression. Sankaridurg et al.157
reported on the effect of correcting peripheral hyperopic
defocus on myopia progression in 210 Chinese children after 12
months of wear of one of three novel spectacle lens designs.
The myopic children were randomized into one of four groups:
wearing either one of three peripheral correcting spectacle lens
designs or a conventional, single-vision spectacle lens. Both
central and peripheral cycloplegic auto-refractions, and axial
length were measured at 6 and 12 months. Myopic progression
in eyes wearing special peripherally correcting lenses and
traditional spectacle lenses at 6 and 12 months was 0.55 D ±
0.35 D and 0.78 ± 0.50 D, respectively. There was no
statistically significant difference in the rates of progression with
the peripherally correcting lenses as compared to traditional
spectacle lenses. However, in one sub-group, the authors
reported that the younger children (6 to 12 years) with
parental history of myopia, had significantly less progression
(0.68 D ± 0.47 D vs. -0.97 D ± 0.48 D) with one type of lens
compared to traditional spectacles (mean difference of 0.29 D).
One of the major problems with spectacle glasses is the
inability to control where the patient looks through the lens,
thus inducing variability in correcting the optics of the eye.
Cheng D, Schmid KL, et al.158 measured myopic progression in a
group of Chinese Canadian children, who were progressing
more than 0.50 D/year as determined with cycloplegic
refraction and ultrasonography. In this unmasked study subjects
were placed in one of three lens treatment groups: myopic
progression averaged 0.77 D/year in the single-vision lenses
group, 0.48 D/year in the +1.50 executive bifocal group, and
0.35 D/year for prismatic bifocal group (+1.50 add with 3 prism
base in prism in each eye): axial length increased proportionally
to the refractive changes. Cheng et al.159 concluded that bifocal
lenses with and without BI prism can slow myopic progression
in children with high rates of progression after 2 years of wear
by approximately 45%. They reported that the effect of the
bifocals was not related to any of the other concurrent
variables measured: myopic duration before trial, lag of
accommodation, hours of close work conducted per week,
hours of outdoor activities per week, near phoria, and /or
parental myopia.
Cheng, Woo, and Schmid159 argue that the difference between
their positive results and other studies, which did not show
such a large effect, might be related to the lack of consideration
for the proper add based on lag of accommodation, the lack of
correction of the exophoria induced by relaxing
accommodation with a near add, and/or the use of high fitting
executive bifocals to ensure the use of the near reading add. A
+1.50 add was chosen since it was close to the average lag of
accommodation, and the BI prism prescribed was the average
required to correct the exophoria measured at near. Cheng et
al.159 suggested that previous studies using multifocal
progressive lenses suffered from the problem in not knowing
what part of the lens the children viewed through. They felt
that the prescription of a high fitting bifocal would eliminate this
problem. (The practitioner needs to be aware of the cosmetic
problem that executive bifocals impose.) One must be careful
in the interpretation of this data in light of the COMET study,
which demonstrated a 5 year loss of the early effect of
treatment with progressive lenses. Lastly, the most effective
treatment with bifocals occurred in a very specific group of
subjects who were children of Chinese origin, who progressed
rapidly, and wore bifocals.154,158,159
The major benefit of any progressive lenses, bifocals, or novel
peripheral correcting lenses, is the low risk of complications or
adverse effects and their effectiveness in esophoric myopic
children, which constitute about 30% of myopic children.152 The
major disadvantages of progressive lenses are cost, lack of
strong scientific support of efficacy in the majority of nonesophoric myopic patients, and poor long-term data.
Under correction
Under-correction has been a popular method advocated by
professionals to slow down the progression of myopia. In two
separate studies, under-correction was associated with either an
increase in the progression of myopia or no change as
compared to fully corrected controls.160,161 Thus, undercorrection is associated with a faster progression of myopia, and
should no longer be advocated.
CONTACT LENSES
Single vision contact lenses
Randomized clinical trials comparing soft contact lenses to
spectacle lenses to slow the progression of myopia found no
significant difference in myopia progression.162 Walline et al., in
the Contact Lens and Myopia Progression (CLAMP) Study,
performed a randomized trial to determine if rigid contact
lenses (RGPs) would affect myopia progression.163 They found
that children wearing RGP lenses had less myopia progression
as measured by refraction than children wearing soft contact
lenses. However, it was found that only the corneal curvature
of RGP wearers was flatter than that of soft contact lens
subjects; there was no significant difference in axial length in
either cohort. Thus, refractive changes were most likely due to
a temporary flattening of the cornea and did not represent a
true slowing of myopia. In another randomized clinical trial by
Katz et al.,164 there was no significant difference in refractive
error between RGP lens wearers and spectacle wearers. These
studies suggest that RGPs do not reduce the progression of
myopia as previously thought.
Orthokeratology
Orthokeratology (also called OK, ortho-k, corneal reshaping,
corneal refractive therapy or CRT, and vision shaping treatment
or VST), first described by Jessen in the 1960s, uses reverse
geometry rigid gas-permeable contact lenses to reshape the
cornea resulting in a temporary elimination of refractive error.
There has been a resurgence in prescribing this treatment over
the past decade due to better oxygen permeability of lens
materials and improvement in the fit of the lenses.165,166 The
reverse geometry design flattens the central cornea while
creating mid peripheral steeping which theoretically corrects
hyperopic peripheral defocus, and in turn is thought to slow
myopic progression. In 2003, Reim and his associates167
performed a retrospective chart review of myopia progression
in children between the ages of 6 and 18 with myopia between
0.50 D and 5.25 D. These subjects were fit with the DreimLens
orthokeratolgy lens. In his cohort, 253 eyes were examined
after one year of wearing the DreimLens, and 164 eyes were
examined after 3 years of wearing the DreimLens. They
reported a mean increase in myopia of 0.39 D over the 3 years,
or 0.13 D/year. This was significantly less than the average
reported progression of myopia, -0.50 D/year with single vision
spectacle lenses.
Walline and associates,166 in the Children’s Overnight
Orthokeratology Investigation (COOKI) pilot study, evaluated
refractive error, visual changes, and biomicroscopy findings
before and after 6 months of overnight orthokeratology in 29
subjects who were between 8 and 11 years of age, with 0.75 D
to 5.00 D of myopia and less than 1.50 D of corneal
astigmatism. Subjects were fit with Paragon corneal refractive
therapy contact lenses. At the 6-month visit, the mean
uncorrected visual acuity was 20/25, and the mean spherical
equivalent refraction was -0.16 ± 0.66 D in each eye. During
the morning visits, 58.8% of the children showed mild corneal
staining, and only 35.3% of children showed mild corneal
staining at the afternoon visit. No lasting adverse visual effects
from corneal-reshaping contact lens wear were reported; thus
Walline et al. concluded “overnight corneal reshaping contact
lenses was efficacious for young myopic patients.”
Cho and associates,168 in the Longitudinal Orthokeratology
Research in Children (LORIC) study, compared the axial length
of the eye measured with A-scan ultrasound in subjects
between the ages of 7 and 12 with myopia between 0.25 D and
4.50 D, with less than 2.00 D of astigmatism. The children were
fit with either corneal reshaping contact lenses (N=35) or
prescribed single vision spectacles. The single vision spectacle
control group was selected from another study. Eighty one
percent of the children completed the study. There was a
significant slowing of eye growth in the ortho-k group, reflected
in less of an increase in axial length (AL) and vitreous chamber
depth (VCD) measurements; i.e., AL increased in the ortho-k
group by mean 0.29 ± 0.27 mm, and by 0.54 ± 0.27 mm in the
spectacle group. Similar results were found for VCD; i.e., 0.23 ±
0.25 mm increase for the ortho-k and 0.48 ± 0.26 mm increase
for the control groups. The average myopic reduction was 46%,
however, there was substantial variability in the amount of eye
elongation for any subject, suggesting that there is no way to
predict the effect of orthokeratology on myopia progression for
any individual.
Walline and associates169 performed a study to determine
whether corneal reshaping contact lenses slow eye growth in
the Corneal Reshaping and Yearly Observation of
Nearsightedness (CRAYON) Study. Forty children, 8 to 11
years of age, who had between 0.75 D and 4.00 D of myopia
with less than 1.00 D astigmatism, were fit with Corneal
Refractive Therapy (Paragon Vision Sciences) contact lenses
which they wore for 2 years. Seventy percent of the children
completed the study; none of the dropouts were due to
complications as most were due to lack of interest in wearing
contact lenses. The control group subjects were selected from
the Contact Lens and Myopia Progression (CLAMP) Study.170
Axial length was measured using A-scan ultrasound for both
children fit in corneal reshaping contact lenses and a matching
control group of children wearing soft contact lenses. In
children wearing corneal reshaping contact lenses, as compared
to soft contact lens wearers, the rate of change in axial length
was on average 0.16 mm per year less and vitreous chamber
depth was 0.10 mm per year less. This represents a 38%
reduction in myopic progression.
Kakita et al.171 recently conducted a study to assess the
influence of overnight orthokeratology on axial elongation in
children using spectacle lens wearers as a control group. Axial
length was measured at the baseline exam, and repeated after 2
years using the IOL Master. After 2 years the axial length
increased 0.39 ± 0.27 mm for the orthokeratology group and
0.61 ± 0.24 mm for the spectacle group; the difference was
statistically significant. These findings demonstrated that
orthokeratology slows axial elongation in myopic children by
approximately 36%, and thereby slows the progression of
myopia as compared to spectacle lens correction. In a similar
study, Santodomingo-Rubido et al.172 compared axial length
growth in white children myopia wearing OK lenses and
distance single vision spectacles (SV) for a 2-year period. They
reported that the axial length increased significantly over time
for both the OK group (0.47mm) and SV group (0.69mm). The
difference represented a reduction of myopia.
Swarbrick et al.173 compared changes in axial length and
refractive error during overnight orthokeratology with daily
wear rigid gas-permeable contact lens wear in myopic children.
Twenty-six myopic children wore an overnight orthokeratology
lens in one eye and a gas permeable lens for daily wear in the
other eye for 6 months. After 6 months the lenses were
reversed. Axial length was measured using the IOL Master and
refraction was measured with an auto-refractor. Swarbrick et
al.173 found that overnight orthokeratology lens wear inhibited
axial length increase and myopia progression over a 12-month
period. After 12 months, the orthokertology eyes showed no
change in axial length and a slight decrease in myopia, whereas
the gas permeable eye showed increased axial length and
myopic progression. Crossover of the orthokeratology lens
with the gas permeable contact lens produced similar results
and conclusions.
Kwok-Hei Mok and Sin-Ting Chung174 measured refractive
error and central corneal curvature for 34 children wearing
Ortho-K lenses and for 36 children who wore spectacles 6
years or a longer. All the Ortho-K patients had a washout
period that was determined to occur when the keratometry
findings at the end of the study matched the findings prior to
beginning the study. Myopic progression was calculated as a
change of myopia from the baseline to the final visit. Average
myopic progression of the overnight Ortho-K contact lens was
0.37 ± 0.49 D (0.05 D/year) while average myopic progression
of the single-vision spectacle group was 2.06 ± 0.81 D (0.29 D/
year) after 7 years. Lastly, there was no incidence of microbial
keratitis in their patients. It is of interest to note the reduced
rate of progression of both the Ortho-K group and the
spectacle group, as compared to other studies. There were no
A scans nor cycloplegic refractions. However, this preliminary
study does provide good pilot data demonstrating the longterm effect of Ortho-K.
Recently Hiraoka et al. published a 5 year, long term study to
compare axial length changes in myopic children receiving either
overnight orthokeratology (OK) or spectacles as controls.
There were 59 subjects who had axial length measured with an
IOL Master. The increase in axial length during the 5-year study
period was 0.99 mm ± 0.47 for the OK group and 1.41 ±
0.68mm for the control groups,. The difference was statistically
significant for the first 3 years, but not for the fourth and fifth
year. These findings are similar to the COMET bifocal study in
which the treatment effect seems to diminish after 3 years.
Thus, one needs to be careful to generalize short-term data to
long-term conclusions. Like other OK studies the effectivity
was approximately 30%.
It has been suggested that the peripheral retina plays a role in
emmetropization, specifically that hyperopic peripheral defocus
may stimulate axial myopia.102,109,176 In animal studies, peripheral
form deprivation produces axial myopia. In both humans and
animals, myopic eyes are relatively hyperopic in the periphery
since the radius of the peripheral retina is shorter than that of
the central retina. When traditional glasses or contact lenses
correct the error at the posterior pole, relative peripheral
retinal hyperopic defocus is created which has been implicated
as a signal for local axial elongation. Orthokeratology flattens
the central cornea, which results in a steepening of the midperipheral cornea.177 This mid-peripheral corneal steepening
creates less peripheral defocus than single plane correction,
which is the suggested mechanism for the effect on the
progression of myopia. In support of this theory, Kang and
Swarbrick,178 noted in a recent study that myopic children have
relative peripheral hyperopia as compared to their central
refraction. After 3 months of wearing orthokeratology lenses in
one eye, hyperopic shifts in refraction were measured between
30 degrees in the temporal visual field and 20 degrees in the
nasal visual field. Peripheral refraction was similar to center at
all positions in the temporal visual field while remaining
significantly myopic at all locations in the nasal visual field. On
the other hand, there was no change in either central or
peripheral refraction in the control eye, which wore a
traditional gas perm contact lens. Kang and Swarbrick178
concluded that orthokeratology changes the relative peripheral
hyperopia found at baseline to relative peripheral myopia after
orthokeratology. They suggested that the induced myopic
defocus in the periphery is thought to provide a mechanism for
myopia control.
In summary, Ortho-K results in an approximately 40% reduction
in the progression of myopia. Its advantages are that it both
eliminates the need for daytime contact lens wear and reduces
the progression of myopia. Its disadvantages include cost, risk
of infection, discomfort, problems with insertion and removal,
and reduced visual acuity as compared to glasses or daily wear
contact lenses. In addition, it is difficult to determine which
subjects will demonstrate slowing of their myopia and by how
much. Lastly, there are no good controlled long-term studies
demonstrating that the reduction continues after year one.
Multifocal Soft Contact Lenses
There have been two types of multifocal contact lens treatment
strategies. The first involves the use of multifocal contact
lenses, which are similar to progressive lenses to slow the
progression of myopia. The second, more novel use, is that of
multifocal lenses that are designed to eliminate the peripheral
hyperopia induced with spherically correcting contact lenses.
179,180,181
The success of orthokeratology has led both researchers and
the major soft contact lens companies to design soft contact
lenses that might slow the advancement of myopia. Woods et
al.182 performed an experiment to determine whether lens
induced myopia in chickens can be inhibited when the central
minus power is combined with a hyperopic peripheral lens
design. Chicks were fit unilaterally with peripheral correcting
lenses, with the central power being a -10.00 D, or a
conventional -10.00 D control lens of the same physical
parameters as the test lens. Refractive error was measured by
retinoscopy. This study showed that lens-induced myopia in
chicks wearing conventional lenses can be reduced by using
multifocal, peripherally correcting lenses. The difference in the
induced myopia provides further evidence of the influence of
peripheral retinal hyperopic defocus on eye growth.
Antstice and Phillips179 tested the ability of an experimental
Dual-Focus (DF) soft contact lens to reduce myopic
progression. The experimental group wore a Dual-Focus lens
that had a central zone that corrected refractive error and
concentric treatment zones that created 2.00 D of
simultaneous peripheral myopic retinal defocus during distance
and near viewing. The control group wore single vision distance
lenses with the same parameters but without treatment zones.
Children wore the Dual-Focus lens in a randomly assigned eye
(period 1) and the control lens in the other eye for 10 months.
The lenses were then switched between eyes, and worn for
another 10 months (period 2). Cycloplegic auto-refraction,
axial length measured by partial coherence interferometry, and
accommodation using an open-field auto-refractor, were
measured at the end of each 10 month period. The mean
change in spherical equivalent refraction with dual-focus lenses
(-0.44 ± 0.33 D) was less than with the control lenses (-0.69 ±
0.38 D); mean increase in axial length was also less with DualFocus lenses (0.11 ± 0.09 mm) than with the control lenses
(0.22 ± 0.10 mm). In 70% of the children, myopia progression
was reduced by 30% or more in the eye wearing the DualFocus lens compared to that wearing the control lens. Visual
acuity and contrast sensitivity with Dual-Focus lenses were
similar to the control lenses. Dual-Focus lenses provided
normal visual acuity and contrast sensitivity and allowed for
normal accommodative responses to near targets.
Holden and The Vision CRC Myopia Control Study Group
evaluated a soft contact lens designed to correct central vision
but reduce relative peripheral hyperopia, which would slow the
rate of myopia progression.181 Cycloplegic auto-refraction and
axial length were measured after 6 months of wear of the
experimental lens group and spherical lens control group.
Progression of myopia with the experimental lens was
significantly less than with the control, -0.26 ± 0.25 D versus
0.60 ± 0.29 D. Similarly, axial length increase was less with the
experimental lens as compared to the control lens, 0.08 ± 0.11
mm versus 0.25 ± 0.12 mm. Holden et al. concluded that after
6 months of wear, progression of myopia with the experimental
contact lens designed to maintain clear central vision but
reduce relative peripheral hyperopia, was 56% less than that
with standard sphero-cylindrical spectacles. They also
concluded that “longer experience with wear of such contact
lenses is needed, however the data are promising with regard to
a new generation of contact lenses aimed at myopia control.”
In a subsequent study, Holden et al.180 measured central high
and low contrast visual acuity with a log MAR chart (VA) and
contrast sensitivity (CS) in subjects wearing peripherally
correcting lenses and conventional lenses. Peripheral VA & CS
were measured at 30° nasal and temporal eccentricity. There
were no differences for high and low contrast VA and central
CS between groups. However, there was a significant
improvement in measurements of peripheral VA at both 30°
nasal and temporal eccentricity equivalent to a 3 line
improvement in the experimental lens design group. Also, CS
improved at 30° temporal eccentricity.
Holden et al.169 reported that peripheral visual acuity was
better with these lenses and that the improvement in peripheral
vision was most likely due to a reduction in peripheral defocus.
The authors concluded that these experimental lenses, designed
to maintain clear central vision but reduce relative peripheral
hyperopia, “have the capability of correcting central vision
without blur, slowing the progression, and enhancing peripheral
vision - a relatively unique and beneficial combination of
effects.”
More recently, Chinese children, aged 7 to 14 years, with
baseline myopia between sphere -0.75 to -3.50 D, were fitted
with the novel contact lens designed to reduce relative
peripheral hyperopia (n=45) and were followed for 12 months.
183 Their findings were compared to a matched control group
(n=40). The estimated progression at 12 months was 34% less,
at -0.57 D, with the novel contact lenses as compared with
-0.86 D for spectacle lenses. The baseline axial length was
24.6mm and after a year, the estimated increase in axial length
(AL) was 33% less at 0.27 mm versus 0.40 mm for the contact
lens and spectacle lens groups, respectively. The effectiveness
was less in the second 6 months than the first six months.
Most surprising was that almost 30% of the children dropped
out of the study, due to discomfort of the lens. The 12 month
data support the hypothesis that reducing peripheral hyperopia
can alter central refractive development and reduce the rate of
progression of myopia.
Yet, one needs to be careful in evaluating these results. In
previous PAL studies, efficacy in the first year was 28%; however
it decreased significantly in the second year to 17%.155 By the
end of the study there was only a small difference between the
PAL lenses and the single vision lenses over the longer duration
of the study.156 The PAL study points to the importance of long
term data before drawing broad general conclusions about a
particular method of intervention. Lastly, none of these novel
multi-focal contact lenses have been approved for wear.
Currently approved contact lenses, that might conceptually
correct both central myopia and relative peripheral hyperopia,
include lenses designed to correct the distance centrally with a
peripheral near add. The Biofinity multifocal D lens has a
central optic zone that is fully corrected for distance. Beyond
this central zone is an aspheric periphery that decreases myopic
correction or increases hyperopic correction from the center
moving outward in any direction. This design results in a clearer
image focusing on the peripheral retina thus decreasing the
amount of peripheral retinal blur. Although this specific lens has
not been evaluated for its effect on slowing myopic
progression, the hypothesis still applies. These lenses may
ultimately be combined with atropine to compound their effect
on myopia.
ATROPINE
Atropine is an alkaloid extracted from a variety of plants
(Atropa belladonna, Datura stramonium, and Mandragora
Author
Gimbel106
1973
# of children
completed
study
594
Treatment
Length of
study
Control Group
(mean progression)
Atropine Group
(mean progression)
1gtt 1% atropine
OU
3 years
-1.22D
(over 3 years)
-0.41D
(over 3 years)
Kelly et al175
1975
282
1 gtt 1% atropine
OU q.d. or b.i.d.
1 year
-0.52D
(over 6 months)
+0.58D decrease in myopia
(over 1 year)
Dyer110
1979
168
1 gtt 1% atropine
OU qhs
2-8 years
(avg. 4.2
years)
Change in myopia:
No change or improved: 2%
-0.75D: 14%
1.00-1.75D: 35%
2.00-2.75D: 22%
3.00D: 27%
Change in myopia:
No change or improved: 47%
-0.75D: 34%
1.00-1.75D: 8%
2.00-2.75D:7%
3.00D:1%
Sampson107
1979
100
1gtt 1% atropine
OU qhs
+2.25D bifocal
1 year
NO CONTROL
Change in myopia:
-0.25 to +0.50D: 79%
+0.75D to +1.00D: 15%
>+1.00D: 6%
1% atropine in 1
eye qhs x 1 year,
next year
atropine qhs in
other eye
1gtt 1% atropine
OU qhs
4 years
Bedrossian10 90 children on
8
atropine
1979
(62 followed
for 2 yrs, 28
followed for 4)
Gruber111
200
1985
-0.82 D/Y
+0.21 D decrease in myopia
(over first year, similar results (over first year, similar results during
during 4 years)
4 years)
1-7.5 years
(mean
treatment 1-2
years)
1 gtt 1% atropine 1-9 years
OU qhs
(median
+2.25D bifocal treatment 3
years)
-0.28D/Y
-0.11D/Y
-0.34D/Y
-0.12D/Y
Brodstein109
1984
399
Brenner113
1985
79
1 gtt 1% atropine
OU qhs
1-9 years
(mean
treatment 2.9
years)
NO CONTROL
Yen et al115
1985
96
1 gtt1% atropine
OU qhs
bifocals
1 year
-0.91D/Y
Average refractive error at initial
exam was
-0.87D and increased over the nine
years of maximum follow-up to an
avg of -2.73D
-0.22D/Y
Change in myopia:
No change: 6.25%
< or = -0.50D: 31.25%
-0.51 to -1.0D: 31.25%
>-1.0D: 31.25%
Change in myopia:
No change: 56%
< or = -0.50D: 22%
-0.51 to -1.0D: 19%
>-1.0D: 3%
TABLE 1 Historical atropine studies are presented. It is apparent that in all of these studies, atropine is effective in slowing the progression of myopia.
Though nearly all of these studies are retrospective, most do have some form of control. In these studies the researchers were not blind, and they were
performed before sophisticated A-scan measurements. In spite of their limitations, the number of positive studies with minimal side effects is impressive.
Also, there is some strong long-term data.
officinarum). The name comes from the original use of dilating a
woman’s pupils during the 16th century to make them appear
more attractive. Atropine is a non-selective muscarinic
antagonist which causes maximum mydriasis within 40 minutes
of the initial drop and cycloplegia within 5-48 hours after the
first drop. The residual effects on accommodation last 10-14
days.184
The first report describing the use of atropine to slow myopia
progression was by Wells in the 19th century, 185 during which
time atropine was used extensively to slow myopia progression.
The use of atropine declined after the turn of the 20th
century due to paralysis of accommodation and photophobia.129
22
During the First International Myopia Conference in 1964,
Bedrossian and Gostin reported on the beneficial effect of
atropine on slowing myopia progression. This report provided a
renewed interest in the treatment of myopia progression with
atropine.,33 Seventy-five patients in an A-B cross over design
between the ages of 7 and 13 were prescribed one drop of 1%
atropine in one eye for the first year and then the other eye for
following year. After 1 year of treatment, the eyes treated with
atropine had an average decrease of 0.21 D of myopia, as
compared to the control eyes that had an average increase of
0.82 D of myopia. After the second year, the eye that received
atropine had an average decrease of 0.17 D of myopia. The
control eyes (which one year before were treated with
atropine) had an increase in myopia on average of 1.05 D. Of
the 150 treated eyes, 112 showed either a decrease in myopia
or no change, whereas only 4 eyes that were used as the
control had a decrease or no change in myopia.114,117
Recent studies using topical atropine have demonstrated both
statistically and clinically significant reductions in myopia
progression (See table 2). Chiang et al.187 performed a
retrospective, non-comparative case series to evaluate the
treatment of childhood myopia with the use of atropine and
bifocal spectacle correction. Seven hundred and six Caucasian
children from 6 to 16 years of age were treated with one drop
of 1% atropine once weekly in both eyes for 1 month to 10
years (median 3.62 years). Seventy percent of the children were
completely compliant with the regimen and 30% were only
partially compliant. The most common reasons stated for the
partial compliance were photophobia, inconvenience, or
headache. The mean rate of myopia progression in the
completely compliant group was -0.08 D/year, as compared to
-0.23 D/year in the partially compliant group.
Kennedy et al.129 reported on 214 children aged 6 to 15 years
old who were treated with one drop of 1% atropine once daily
in both eyes for 18 weeks to 11.5 years (median 3.35 years).
The mean myopia progression during atropine treatment was
Table 2 presents the best estimate of the effectively in reducing the progression of myopia for each treatment. First, we determined the mean myopic
progression rate per year for spectacle lenses from each study, then, we determined the mean myopic progression for all the other treatment modalities (D/year).
We then corrected each treatment, i.e., if the mean rate of progression of the control was different than our calculated. Column 3 depicts the findings after 1
year. We then assumed a linear progression and calculated the amount of increased myopia after 8 years (column 4). Columns 5 and 6 present pros and cons
of each treatment. 1= Not effective, 2=Expensive, 3=Blur, 4=Redness, 5=Allergy, 6=Infection, 8=Mydriasis, 9=Minimal scientific data, 10=Not
available, 21=Inexpensive, 22= Moderately effective, 23=Very effective, 24=Strong scientific data, 25= Long term studies, 26= Minimal side effects
Subsequently, Gimbel,115 Kelly et al.,186 Dyer,119 Sampson,116
Bedrossian,114,117,121 Gruber,111 Brodstein,118 Brennar,122 and Yen,
124 from 1973 to 1989, reported in a number of studies that
children using atropine had a reduction in the rate of myopia
progression. These children demonstrated a range of
progression, which varied from an increase of 0.22 D/year to a
decrease of 0.58 D/year as compared to the control groups,
which demonstrated an increase from 0.28 D/year to 0.91 D/
year. Table 1 summarizes these studies. Most of the patients in
these studies were between 6 and 13 years old, which is when
the greatest progression of myopia occurs.
0.05 D/year, which was significantly less than the control
subjects (0.36 D/year). Myopia progression after atropine was
discontinued was calculated for 158 patients. Upon
discontinuing atropine, children progressed 0.22 D/year, as
compared to 0.13 D/year in the control group. However, this
increase in myopia progression was not enough to offset the
decrease in myopia progression during atropine treatment. The
final refraction was still much lower in the atropine treated
group.
Chua et al.133 performed a prospective, randomized, doublemasked, placebo-controlled study on 400 children, ages 6 to 13
years, evaluating the use of atropine as a method for myopia
control. This study, known as the Atropine for the Treatment of
Childhood Myopia study (ATOM), evaluated the efficacy and
safety of topical atropine in slowing both the progression of
myopia and axial elongation in Asian children. One eye of each
subject was randomly chosen for treatment(one drop of 1%
atropine), while the other eye received an eye drop placebo
once nightly for 2 years. All children were prescribed
progressive, photochromic lenses. Three hundred forty-six
children completed the study. After 2 years, the mean
progression of myopia in the placebo-treated eyes was 1.20 ±
0.69 D and only 0.28 ± 0.92 D in the atropine-treated eyes.
Over a 2 year period, there was a 77% reduction in the amount
of myopia progression for children using atropine as compared
to the control. The mean change in axial elongation in the
placebo treated eyes was 0.38 ± 0.38 mm, whereas in the
atropine-treated eyes the axial length was essentially unchanged
(decreased by 0.02 ± 0.35 mm). After 2 years, 65.7% of the
atropine treated eyes progressed less than -0.50D, whereas only
16.1% of the placebo treated eyes progressed less than -0.50D. Only 13.9% of atropine treated eyes progressed more than
-1.00D whereas 63.9% of placebo treated eyes progressed
more than -1.00D.
!
Figure 4 –Progression of Myopia in Eyes Treated or Not
Treated with Atropine
This bar graph depicts the difference in percentage of children progressing less
than -0.25 D in a year with either atropine 1% or a control, and those
progressing more than -a diopter with atropine or a control. It is readily
apparent that atropine is effective at slowing the progression of myopia over a
2 year period of time.133
Figure 4 compares the percentage of children who progressed
less than -0.50 D and more than -2.00 D over the 2 years. The
authors concluded topical 1% atropine was effective in slowing
myopia progression.
Shih et al.188 evaluated the effectiveness of 0.5% atropine to
slow the progression of myopia. The randomized clinical trial
included 227 children, 6 to 13 years of age, placed into one of
three groups: group one received 0.5% atropine daily with
multifocal glasses, group two received a placebo drop daily with
multifocal glasses, and group three received a placebo drop daily
while wearing single vision glasses. One hundred and eighty
eight children completed the study. At the end of 18 months,
the mean myopic progression was 0.42 ± 0.07 D in children
using 0.5% atropine with multi-focal glasses, which was
significantly less than the 1.19 ± 0.07 D and 1.40 ± 0.09 D for
children using placebo drops with multifocal glasses and single
vision glasses, respectively. There was no significant difference
between the last two groups, thus the authors concluded that
the reduction of myopia progression was due solely to the use
of atropine and not the multifocal spectacle correction.
Approximately 50% of the children using atropine with multifocal glasses progressed less than 0.25 D/year and only 10%
progressed greater than 0.75 D/year. Ten percent of the
children using placebo drops with multi-focal glasses progressed
less than 0.25 D/year, while approximately 60% progressed
greater than 0.75 D/year. Approximately 5% of children using
placebo drops with single-vision lenses progressed less than
0.25 D/year and 70% progressed greater than -0.75 D/year. The
progression of myopia in all the groups was highly correlated
with an increase in axial length.
!
Figure 5 –Effect of Various Concentrations of Atropine in
Slowing Myopia
This bar graph depicts the difference in percentage of children progressing
less than -0.25 D in a year with various concentration atropine (0.1%,
0.25%, 0.5%) or the control, and those progressing more than -a diopter
with atropine (0.1%, 0.25%, 0.5%) or the control. It is readily apparent
that atropine is effective at slowing the progression of myopia over a 2 year
period of time in Shih’s study, and the effect on progression varies with the
concentration, though the results may have been affected by the different lenses
worn by each group.128 A recent study suggests that the effectivity is not
significantly dependent on the concentration.190
Shih et al.128 evaluated the efficacy of various concentrations of
atropine in slowing myopia progression. Two hundred children,
6 to 13 years of age, were randomly prescribed one drop of
0.5%, 0.25%, or 0.1% atropine, or 0.5% tropicamide (control
treatment) in both eyes nightly. Children prescribed 0.5%
atropine were given a bifocal (+2.00 add), children prescribed
0.25% atropine were under corrected by 0.75 D, and children
using 0.1% atropine were given their full distance prescription.
Ninety three percent of children completed the study. The
mean progression of myopia was 0.04 ± 0.63 D/year in the 0.5%
atropine group, 0.45 ± 0.55 D/year in the 0.25% atropine group,
and 0.47 ± 0.91 D/year in the 0.1% atropine group, as compared
to 1.06 ± 0.61 D/year in the control group. The authors defined
myopic progression to be greater than -0.25 D/year. At the end
of the 2-year treatment, 61% of children in the 0.5% atropine
group, 49% in the 0.25% atropine group, and 42% in the 0.1%
atropine group had no myopic progression, whereas only 8% in
the control group had no myopic progression. The authors
defined fast myopic progression to be greater than 1.00 D/year.
Four percent of children in the 0.5% atropine group, 17% in the
0.25% atropine group, and 33% in the 0.1% atropine group
demonstrated fast myopic progression, whereas 44% in the
control group showed fast myopic progression. The authors
concluded that all three concentrations of atropine were
effective in slowing myopia progression, with 0.5% being the
most effective, although their results may have been confounded
by the differences in lenses that each group used. (See Figure 5.)
Lu et al.189 investigated the effect of seasonal modifications in
the concentration of atropine used on slowing the progression
of myopia (n=120). The concentration was modified based
upon season, sunlight intensity, and severity of myopia: 0.1% for
summer, 0.25% for spring and fall, and 0.5% for winter for 63
children, while 57 children received no drops (control). For
children less than 7 years of age with less than 0.50 D of
myopia, 0.5% atropine was not used. The use of atropine was
reduced to twice weekly for very low myopes (less than 0.75
D). Sunglasses with ultra-violet (UV) protection were
prescribed for children to be used when outdoors, and
progressive lenses were given for children who reported
difficulty in the classroom. After one year, mean myopia
progression was 0.28 ± 0.75 D for children using atropine and
1.23 ± 0.44 D for children in the control group. There was a
77% reduction in myopia progression for children using atropine
as compared to the control group.
Lee et al.134 conducted a retrospective chart review of 57
Taiwanese children 6 to 12 years of age to evaluate the efficacy
of 0.05% atropine in slowing myopia progression. Twenty-one
children received one drop of 0.05% atropine in both eyes
every night while 36 children were not treated (control). Mean
progression of myopia was 0.28 ± 0.26 D/year in the 0.05%
atropine group, as compared to 0.75 ± 0.35 D/year in the
control group. The authors considered myopia progression less
than -0.50 D/year to be relatively stationary, whereas greater
than 0.50 D of myopia progression/year to be poorly
controlled. Eighty three percent of children in the treatment
group had relatively stationary myopia progression, as compared
to only 22.2% in the control group. In the 0.05% atropine
group, 16.7% of children progressed greater than 0.50 D/year,
whereas 77.8% of the control group progressed greater than
-0.50 D/year. The authors concluded, “0.05% atropine regimen
is a good starting point as medical treatment for the control of
myopia progression.”
Fang et al.137 conducted a retrospective chart review of 50
Taiwanese children aged 6 to 12 years to evaluate the efficacy of
0.025% atropine for prevention of myopia onset in pre-myopic
children (spherical equivalent refraction of less than +1.00 D,
with cylindrical refraction of less than -1.00 D). Twenty four
children received one drop of 0.025% atropine in both eyes
every night and 26 children were untreated (control). Mean
myopic shift was -0.14 ± 0.24 D/year in the 0.025% group, as
compared to -0.58 ± 0.34 D/year in the control group. The
authors considered a myopic shift greater than -0.50 D/year to
be a fast myopic shift. Eight percent of children using atropine
had a fast myopic shift, compared to 58% of the control group.
The authors defined the onset of myopia as a change equal to
or greater than 1.00 D in the myopic direction. Twenty one
percent of children using atropine became myopic, as compared
to 54% of children in the control group. The authors
concluded, “topical administration of 0.025% atropine can
prevent myopia onset and myopic shift in pre-myopic
schoolchildren for a 1-year period.”
Recently the ATOM2 studies were performed to evaluate lower
concentrations of atropine. The mean myopia progression at 2
years was 0.15 D/year for atropine 0.5%; 0.19 D/year for
atropine 0.1%; and 0.24 D/year for atropine 0.01% groups.179 In
comparison, myopia progression in ATOM1 at 2 years was -0.60
D/year in the placebo group and -0.14 D/year in the atropine
1% group. The authors found that differences in myopia
progression (0.19 D) and axial length change (0.14 mm)
between groups were small and clinically insignificant. Atropine
0.01% had a negligible effect on accommodation and pupil size,
and no effect on near visual acuity. They concluded that
atropine 0.01% had minimal side effects when compared with
atropine at 0.1% and 0.5%, and retained comparable efficacy in
controlling myopia progression. (See Table 2 for a comparison
of each method of treatment over time.)
Prior to this paper, there had been two other reviews of various
treatments for myopia. In each review the authors
acknowledged the efficacy of atropine in slowing myopia
progression. However, each author independently, without any
supporting data from trial subjects, concluded that the benefit
of atropine use for myopia control is outweighed by the
possible systemic and ocular side effects.191,192
These conclusions warrant a review of the side effects
associated with atropine. Systemic side effects associated with
topical atropine use can be divided into three types: fatal,
serious, and mild. There have been 8 deaths associated with
atropine, and only one since 1950.1184,193,194 All the deaths,
except one, were in children 3 years of age or younger suffering
from congenital health conditions and who were ill at the time
of presentation. The one child without congenital defects
received a fatal dose of 18.1 mg of atropine within a 24-hour
period.184,193 Thus, there have been no fatal occurrences in
children over 3 years of age with appropriate atropine dosing.
Pupillary dilation and cycloplegia from atropine result in glare,
photophobia, and near vision blur which are the most
commonly reported side effects to atropine. These symptoms
can be minimized with the use of photochromic progressive
lenses, or the use of atropine in concentrations less than .025%.
Serious systemic and central nervous system side effects occur
at 20 times the minimum dose and include the following: hot
and dry skin, facial flushing, dryness of the nose, loss of taste,
constipation, difficulty swallowing, difficulty sleeping, drowsiness,
excitement, changes in heartbeat, hallucinations, fever, headache,
dizziness, nervousness, nausea, vomiting, and allergic reactions
(rash, hives, itching, difficult breathing, tightness in the chest,
swelling of the mouth, face, lips, or tongue). Decreased
salivation and drying of the mouth are usually the first signs of
toxicity.193 The side effects of atropine are serious, but are
fortunately short-lived, and have never been fatal, in healthy
children over 2 years of age.193
During the 2 year ATOM study133 that included 400 children, no
serious adverse events were reported. Reasons for withdrawal
were: allergic or hypersensitivity reactions or discomfort
(4.5%), glare (1.5%), blurred near vision (1%), logistical difficulties
(3.5%) and others (0.5%). There was no decrease in bestcorrected visual acuity. Glare and photophobia were minimized
with the use of photochromic lenses.
Shih et al.128 reported the incidence of adverse effects due to
the use of topical atropine in their study of 200 children (186
children completed the study). Seventy eight percent of the
children using 0.5% atropine had no complaints of light
sensitivity after 3 months. Fifteen percent of the children who
used 0.5% atropine dropped out of the study: two children
complained of severe light sensitivity, two children were fearful
of long-term side effects, one child had recurrent allergic
blepharitis, and four children were unable to consistently put
drops in every night. Children who used 0.25% or 0.1%
atropine reported no systemic or ocular complications. One
hundred percent of the children who used 0.1% atropine, and
93% of children who used 0.25% atropine, did not complain of
photophobia or blurred near vision after 4 weeks of using
atropine.
In Kennedy’s study,129 of the 214 patients who were using 1%
atropine, 40% reported photophobia, 10.7% reported blurred
vision, 3.7% reported ocular discomfort, 3.7% reported ocular
allergic reaction, 2.3% reported headaches, 2.3% reported bad
taste in their mouth, 1.9% reported dry mouth, 1.4% reported
dry eyes, 0.5% reported psychological problems, and 0.5%
reported dizziness. Though the percentage of patients with side
effects appears high, they did not result in a significant dropout
rate. (The high percentage of photophobia reported by
Kennedy was prior to today’s fast acting improved
photochromic lenses which have eliminated most of the
subjective complaints of photophobia.133)
In a study of 21 children who used atropine 0.05%, seven
complained of photophobia in the morning, but only one had
photophobia that continued into the afternoon, and only two
children reported blurred near vision.134 No child reported
irritation or an allergic reaction. In another study using 0.025%
atropine,137 only four children in the treatment group and two
children in the control group reported photophobia (24 and 26
children completed the study, respectively). None of the
children reported blurred near vision nor had any systemic side
effects.
In the Amblyopia Treatment Studies (ATS),195-197 1% atropine
was dosed unilaterally in a group of subjects being treated for
amblyopia. In ATS1,195 which included 204 patients less than 7
years of age, at least one ocular side effect was reported for
26% of children, most commonly light sensitivity (18%), lid or
conjunctival irritation (4%), and eye pain or headache (2%). Two
patients reported facial flushing, one of who remained on
atropine with no further problems and one was switched to
homatropine. Atropine was not discontinued due to its side
effects in any other patients. No other systemic side effects of
atropine were reported. In ATS3,196 among 201 patients aged 7
to 13 years old, atropine was generally well tolerated. Four
percent of patients discontinued treatment due to symptoms
related to cycloplegia. Ocular side effects noted in ATS4,197
(most commonly light sensitivity), were reported by 13 (16%) of
the children receiving daily atropine and 25 (29%) of the
children receiving weekend atropine. However, these symptoms
did not result in a change in compliance with the treatment
regimen.
The ATOM study133 found that the paralysis of accommodation
and the associated near vision blur secondary to atropine
treatment was temporary and was reversible upon cessation of
treatment. Six months after cessation of atropine, the
measured amplitude of accommodation was larger than the
pre-treatment level. In addition, at 6 months after terminating
atropine, there was no significant difference in near visual acuity
in the atropine-treated eyes as compared to placebo-treated
eyes.133
In summary, atropine has been used in both myopia control and
amblyopia treatment studies with a minimal number of local
side effects and no serious side effects. In none of the studies
were the local side effects serious enough to cause a large
number of patients to discontinue atropine treatment.
(Anecdotally, the first author of this paper has used atropine for
the last ten years on over 100 patients without any incident of a
serious side effect, and notes that most children surprisingly
tolerate atropine with minimal complaints.)
There is always concern of long-term effects when using any
medication. Luu et al.198 assessed retinal function in children on
atropine treatment, by performing multifocal electroretinograms (mfERGs) on 48 children who received 1%
atropine eye drops once daily for 2 years and 57 children who
received placebo eye drops. Recordings were performed during
the second and third month after the cessation of treatment.
Both the response amplitude and implicit time of N1 and P1
and k21 were measured. The difference between the N1 and P1
amplitudes and implicit times between atropine-treated and
placebo-treated eyes were not statistically significant. There
was also no significant difference between k21 amplitude and
implicit time between atropine-treated and placebo-treated
eyes. The authors of this study concluded that since retinal
function was not significantly affected soon after stopping
atropine (when the concentration of atropine in the retina
would be highest), that it is highly unlikely that there would be
retinal impairment years later when the concentration of
atropine would be less.
To assess whether the slower rate of myopia progression and
axial length elongation would be maintained after stopping
atropine, or if there would be a rebound effect that would
eliminate the initial treatment effect, the patients from the
ATOM study were evaluated up to 1 year after stopping
treatment.136 Only a small number of children dropped out
after the two years of treatment, i.e., 3% of the placebo group
and 5% of the atropine group. After atropine was discontinued
for 2 years, the mean myopic progression in the atropinetreated group was 1.14 ± 0.80 D over 1 year, whereas the
progression in placebo-treated eyes was 0.38 ± 0.39 D. In the
first half of the third year, the mean rate of myopia progression
in the atropine-treated eyes was 1.51 ± 1.40 D/year, as
compared to 0.40 ± 0.65 D/year in the placebo-treated eyes.
Over the second half of the third year, the mean rate of myopia
progression in the atropine-treated eyes was -0.76 ± 0.70 D/
year, as compared to -0.38 ± 0.58 D/year in the placebo-treated
eyes. For the atropine treated eyes, the rate of myopia
progression was significantly less in the second half of the third
year as compared to the preceding 6 months. Over the entire
3 year period, the eyes treated with atropine still showed much
less myopia than the placebo-treated eyes. Although the effect
of atropine on the final refractive status was reduced after
cessation of atropine for 1 year, the change in axial length of the
atropine-treated eyes was significantly smaller than of the
placebo-treated eyes, and did not change as much as the
refractive error. Over the 3 years, the increase in axial length of
the atropine-treated eyes was 0.29 ± 0.37 mm, as compared to
0.52 ± 0.45 mm in the placebo-treated eyes. The authors
suggested that most of the increase in refractive status was not
due to a rebound effect but due to the more powerful
cycloplegic effect obtained with atropine 1% as compared to
cyclogel 1% which was used for measurements after
termination of atropine.
In conclusion, since discontinuation of atropine had a small
regression in refractive error but no effect on axial length, most
of the change appears to be due to the difference in cycloplegic
refraction achieved with cyclogel as compared to atropine.
Atropine causes a greater cycloplegic effect than Cyclogel 1%,
thus, the initial baseline for refractive error demonstrates more
myopia with Cyclogel 1% than the amount measured
immediately after beginning treatment with atropine 1%. This
results in a greater perceived improvement of myopia control
during the first year treatment and a falsely perceived rebound
effect at the end of treatment. It is more important to note
that axial length data did not change when atropine treatment
was terminated. The study also showed that over the course of
three years only 23% of atropine-treated eyes progressed more
than 2.00 D as compared to 30% of placebo-treated eyes. Only
44% of atropine-treated eyes progressed more than 1.50 D as
compared to 56% of placebo-treated eyes.
Atropine is a non-specific, muscarinic antagonist, which binds to
muscarinic receptors on the ciliary muscle and thus blocks
accommodation. Initially, atropine was suggested as a method
for myopia control based on the thought that the act of
accommodation influenced myopia progression; this presumed
mechanism for control has since been disproven. McBrien et al.
125 were the first to demonstrate that atropine reduces
experimental myopia and axial elongation via a nonaccommodative mechanism. McBrien et al.125 monocularly
deprived (MD) chicks of pattern vision by placing a translucent
occluder over the left eye, which has been found to cause an
increase in axial elongation and myopia in human infants,199
chicks,125 tree shrews,201 cats,202 gray squirrels,125 marmosets,203
and monkeys.204 Since the muscles of chicks contain only
nicotinic receptors, atropine should not have had an effect on
accommodation or pupil size. Chicks were treated with intravitreal injections of atropine or saline; after eight days of MD
there was 20.9 D of experimentally induced myopia in salineinjected chicks, as opposed to only 2.8 D of myopia in atropineinjected chicks. This significant reduction in experimentally
induced myopia in atropine-injected MD chicks was associated
with a significant reduction in axial length elongation (0.21mm
versus 1.04 mm). Corneal iontophoresis of 10% carbachol,
which binds to nicotinic receptors, induced the same degree of
accommodation in both atropine-injected and saline-injected
eyes, demonstrating that accommodation was not affected by
atropine. Thus, the authors concluded that, “chronic atropine
administration prevents experimentally induced myopia in
chick(s) via a non-accommodative mechanism.”
Applying translucent lenses designed to deprive only part of the
visual field in chicks results in local areas of axial elongation.205
Atropine blocks the effects of local elongation. Since it is not
possible to accommodate different amounts in the same eye,
some other mechanism besides accommodation, must be
responsible for localized elongation. Emmetropization can still
occur even when the optic nerve is severed, disrupting the
feedback mechanism necessary for accommodation,83,81 which
suggests that local retinal mechanisms may be sufficient for
gross regulation of refractive error.101 It has also been
demonstrated that experimental myopia can be induced in a
species that does not possess a functional accommodative
system.125 Lastly, experimental myopia can be produced in a
species where the accommodative feed back loop has been
blocked by bilateral destruction of the Edinger-Westphal
nucleus.83 Since accommodation does not play a major role in
myopia development, the obvious question then is how does
atropine prevent myopia progression? Muscarinic receptors
located in the retinal pigment epithelium are believed to be
involved in the development of refractive error.206 However,
the biochemical basis of how atropine inhibits axial elongation
remains obscure, and there are doubts whether muscarinic
receptors are involved at all. These findings have led to the
search for other muscarinic drugs that do not affect
accommodation or pupillary dilation.
Pirenzepine, an M1-selective muscarinic antagonist, has those
attributes and has been used to retard the progression of
myopia in animals without significantly affecting accommodation
or pupillary size.137 In experimental studies on humans, Bartlett
et al.134,207 demonstrated that pirenzepine caused minimal
mydriasis or effect on accommodative amplitude. They
concluded that the adverse events reported were mild or
moderate (redness and irritation) in severity but resolved
rapidly. Siatkowski et al.146 evaluated the safety and efficacy of
2% pirenzepine ophthalmic gel in school-aged children with
myopia. The children, aged 8 to 12 years, had spherical
equivalents from -0.75 to -4.00 D, and astigmatism of 1.00 D or
less. At 1 year, there was a mean increase in myopia of -0.26 D
in the pirenzepine group versus -0.53 D in the placebo group.
Eleven percent of the patients in the pirenzepine group
discontinued participation in the study because of adverse
effects while none of the placebo group did. Pirenzepine was
effective (50%) and relatively safe in slowing the progression of
myopia during a one-year treatment period. In the 2 year
follow-up study, Siatkowski et al.147 reported that the mean
increase in myopia was -0.58 D in the pirenzepine group and
-0.99 D in the placebo group. Only one more patient dropped
out in the second year. They concluded that pirenzepine
ophthalmic gel 2% was effective in slowing the progression of
myopia over a 2 year period without significant side effects. It is
of interest to note that axial length did not have a significant
change in the treatment group. Pirenzepine unfortunately is not
currently commercially available in the US.
Tan et al.144 evaluated the safety and efficacy of pirenzepine 2%
ophthalmic gel in slowing the progression of myopia in schoolaged children using a parallel-group, placebo-controlled,
randomized, double-masked study. Subjects received 2% gel
twice daily (gel/gel), 2% gel once daily (placebo/gel), or placebo
twice daily (placebo/placebo) for one year. At 12 months, there
was a mean increase in myopia in the gel/gel group by -0.47 D,
placebo/gel group by -0.70 D, and placebo/placebo group -0.84
D. Eleven percent of the pirenzepine group discontinued
participation in the study due to adverse events. Tan et al.
concluded that pirenzepine gel 2% twice daily resulted in
approximately 45% efficacy in slowing the progression of
myopia over a 1 year treatment period and was a relatively safe
treatment.
DISCUSSION
The purpose of this literature review is to provide an updated
review of the current research in regard to slowing myopia
progression and to provide the reader with unbiased
information to help make appropriate clinical decisions.
Atropine used once a day in both eyes is clearly the most
successful treatment to slow the progression of childhood
myopia. Cumulative data from a number of studies employing
atropine 1% demonstrated up to a tenfold reduction in the rate
of myopia progression as compared to untreated eyes, 0.05 D/
year verses 0.50 D/year. Concentrations of less than 0.5%
result in a decreased efficacy but still demonstrate a stronger
effect on reducing myopia than other treatment regimens.
Recent studies demonstrate that lower concentrations, i.e., .
025% or .01% are more effective than Ortho-K or other soft
lens designs.
The most common side effects of atropine include pupillary
dilation, which leads to an increased sensitivity to light and UV
radiation, and cycloplegia resulting in near vision blur. These
problems have been minimized with the use of progressive
lenses which incorporate photochromic properties, and UV
filtration. The risk of other ocular and systemic side effects is
minimal. In the studies included in this paper, more than 85% of
children were able to tolerate the side effects, and continued
with their assigned treatment protocol. The minimal local
effects in most patients were not serious enough to cause
discontinuation of atropine treatment. Previous reviews that
state that atropine is not used or should not be because it is
not tolerated by patients have no scientific basis. (Anecdotally,
the first author, who has used atropine, progressive lenses, and
contact lenses in the treatment of myopia, has had minimal
problems with patient tolerance of atropine.) Only one of the
long-term studies provided any evidence of rebound, while all of
the others did not. However, this rebound effect was explained
by the initial cycloplegic effect of atropine being greater than
cyclogel. The exact mechanism of atropine in slowing myopia
progression does not involve accommodation; it is presumed to
block the signal stimulating the elongation of the globe via
receptors at the retina.
Figure 6 –Effect of Treatment Over Time Of Myopic Patient
This graph depicts the progression of myopia of a patient of one of the
authors (JC). Progressive lenses initially slowed the progression of myopia
in the first year but not in subsequent years. Once the patient was placed on
atropine, the progression stopped. The patient, now 16 years old, was
recently seen by (JC) without progression of his myopia. He has elected to
stop using the atropine, and was recently fit with orthokeratology contact
lenses without sequel. His unaided visual acuity in each eye is 20/20.
The studies reviewed using atropine in children vary in
methodology, inclusion criteria, number of subjects, duration
and completeness of follow-up, and data analysis. Despite this,
they all show that the progression rate of myopia with atropine
use is significantly lower than in the control group and the
ability to control myopia is far superior to any other treatment.
No study to date has determined how long a child needs to be
on atropine to slow myopia progression, or how fast the myopia
will progress after cessation of treatment for longer than 2
years. Parents may be concerned that although atropine has
been used for over 100 years for long durations in patients with
uveitis and in multiple studies for 1 to 4 years, the long term
effects on a large population of children is unknown. Clinicians
may be concerned by the possibility of long term-increased
toxicity due to light exposure; however, current lenses that
incorporate UV filters and photochromic lenses mitigate the
risk.
Children with a strong family history of myopia who are rapidly
progressing in myopia should be given the option of atropine
use. Figure 6 depicts the long-term history of a patient treated
with progressive addition lenses and atropine 1% at night. The
atropine stopped the progression with a paucity of symptoms. If
symptoms do develop while using 1% atropine, then 0.5% can
be used. Currently, 0.5% atropine is not commercially available,
but can be formulated at compounding pharmacies upon
request. Seasonal variation can be used to titrate the
appropriate concentration for symptoms, i.e., lower
concentration during the summer when children are not
reading as much and the sun is stronger. More recent studies
have shown that even lower dosages such as atropine .01% may
be used alone or to supplement orthokeratology or any other
method of myopia control if initial reduction is not adequate.
Clinically, the biggest problem with the higher concentrations of
atropine is that the social desire to eliminate glasses cannot be
met due to loss of accommodative ability and need for
compensatory lenses.
For those children in whom myopia is progressing more slowly,
or there is a need to eliminate glasses for either cosmetic or
functional reasons, the second choice might be
orthokeratology. Orthokeratology has a high acceptance rate
with children and provides a “wow” phenomenon, often seen
with LASIK. Patients are appreciative of it’s ability to eliminate
the need for glasses during the day and decreased the
progression of myopia. It should be acknowledged that
orthokeratology comes with its own risks of discomfort,
keratitis, and potential corneal ulceration. Patients are often
concerned about the risk of overnight wear of contact lenses.
Even though the risk of complications with overnight wear of
orthokeratology is appreciably less than with soft lenses, it still
exists. The decreased risk is probably related to improved
oxygen permeability of the lenses and reduced adhesion of
either proteins or bacteria. Though not currently available,
myopia-controlling soft multifocal contact lenses, which will
attempt to correct for hyperopic peripheral retinal defocus, may
have an exciting future. Since there are no currently FDA
approved lens designs, the closest commercially manufactured
lens today is either the Vistakon Oasis Presbyopic lens or the
Cooper vision Biofinity Multifocal “D” lens. (See figure 7 for a
comparison of each treatment.)
The last treatment recommended is progressive addition lenses
for esophoric patients. Utilization of progressive lenses in other
non-esophoric myopic patients provides minimal benefits, but
lenses. If the child is esophoric , the use of progressive addition
spectacle lenses can be recommended. Patients with myopia
that want to slow the process but who require or desire
traditional contact lenses should be prescribed UV filtering daily
wear contact lenses. Ultimately, the decision of which
treatment or combination of treatments to be used should be
based upon the wants and needs of the patient.
CONCLUSION
Figure 7 –Progression of Myopia Over Time By Treatment
This is a cumulative graph, based on the results of numerous studies, of the
projected treatment effects of each treatment to control myopia over time. It
is assumed that yearly progression with traditional glasses is 0.60 D/year
(mean rate), and that the progression rate is linear (which may not be true).
We recognize that the studies varied in findings and with ethnicity, thus, we
used mean number. Each treatment result was corrected using a correction
based upon the control group to maintain uniformity of treatment results in
regard to the rate of progression of the control. For example, if the control
progressed by 0.80 D/year then the treatment progression was decreased by .
60/.80 or 75%. Atropine has been collapsed into two groups Atropine 1%
and .5%, and low concentration of atropine, which include atropine .01%
to .25%. It is readily apparent that atropine is the most effective treatment
of myopic progression, followed by orthokeratology, and lastly, progressive
lenses. According to the graph, under-correction is not an appropriate
treatment of myopia. Lastly, when interpreting these results, one must be
cognizant that the progression of an individual may be very differently than
the mean.
In considering myopia treatment, remember what the 19thcentury philosopher Arthur Schopenhauer208 said: “All truth
passes through three stages. First, it is ridiculed. Second, it is
violently opposed. And third, it is accepted as being selfevident.”208 Treatment of myopia with atropine is in the second
stage, and orthokeratology is ending the second stage. Either
atropine or orthokeratology will pass to the third stage or a
better “atropine/orthokeratology” will come in to use.
Atropine and orthokeratology are effective methods to slow
the progression of myopia and should be in optometry’s
armamentarium to fight the effects of this growing pandemic.
REFERENCES
1.
2.
3.
4.
5.
6.
also minimal risk. In the end, patients should be informed of the
current status of myopia treatment with either an explanation
or literature to explain the options. Caregivers and patients
should be provided unbiased risks and benefits of each
treatment strategy to help make informed decisions. It is the
obligation of both optometrists and ophthalmologists to
properly educate patients. There is a true risk of not slowing
myopia progression; both patient and doctor have to make
appropriate, scientifically and clinically valid assessments
regarding appropriate treatment. (See Figure 7 for a comparison
of effectivity of each treatment over time.)
As a general rule, the more sedentary the patient, the earlier
the onset, the greater the risk factors (i.e., parents having
myopia or family history of retinal holes or tears) the more
likely that atropine will be suggested. Atropine dosage can be
seasonally varied to reduce photophobia and blur complaints.
On the other hand, patients who develop myopia later,
associated with less progression, and/or are more athletic, the
more likely that orthokeratology should be recommended.
When parents have concerns about their children sleeping with
contact lenses or using medications, a non-proven treatment
using a Coopervision Biofinity Multifocal “D” +2.50 add, or
Vistakon Oasys Multifocal lens is suggested. Lastly, there are
those parents who are against the use of drops or contact
7.
8.
9.
10.
11.
12.
13.
Vitale S, Sperduto RD, Ferris FL, 3rd. Increased prevalence of
myopia in the United States between 1971-1972 and 1999-2004.
Arch Ophthalmol 2009;127(12):1632-9.
Saw SM, Katz J, Schein OD, Chew SJ, Chan TK. Epidemiology of
myopia. Epidemiol Rev 1996;18(2):175-87.
Matsumura H, Hirai H. Prevalence of myopia and refractive
changes in students from 3 to 17 years of age. Surv Ophthalmol
1999;44 Suppl 1:S109-15.
Fotouhi A, Hashemi H, Khabazkhoob M, Mohammad K. The
prevalence of refractive errors among schoolchildren in Dezful,
Iran. Br J Ophthalmol 2007;91(3):287-92.
Rudnicka AR, Owen CG, Nightingale CM, Cook DG, Whincup PH.
Ethnic differences in the prevalence of myopia and ocular
biometry in 10- and 11-year-old children: the Child Heart and
Health Study in England (CHASE). Invest Ophthalmol Vis Sci
2010;51(12):6270-6.
Naidoo KS, Raghunandan A, Mashige KP, Govender P, Holden BA,
Pokharel GP, et al. Refractive error and visual impairment in
African children in South Africa. Invest Ophthalmol Vis Sci
2003;44(9):3764-70.
Saw SM, Goh PP, Cheng A, Shankar A, Tan DT, Ellwein LB. Ethnicityspecific prevalences of refractive errors vary in Asian children in
neighbouring Malaysia and Singapore. Br J Ophthalmol
2006;90(10):1230-5.
Uzma N, Kumar BS, Khaja Mohinuddin Salar BM, Zafar MA, Reddy
VD. A comparative clinical survey of the prevalence of refractive
errors and eye diseases in urban and rural school children. Can J
Ophthalmol 2009;44(3):328-33.
Saw SM, Hong RZ, Zhang MZ, Fu ZF,Ye M, Tan D, et al. Near-work
activity and myopia in rural and urban schoolchildren in China. J
Pediatr Ophthalmol Strabismus 2001;38(3):149-55.
Garner LF, Owens H, Kinnear RF, Frith MJ. Prevalence of myopia in
Sherpa and Tibetan children in Nepal. Optom Vis Sci 1999;76(5):
282-5.
Sapkota YD, Adhikari BN, Pokharel GP, Poudyal BK, Ellwein LB. The
prevalence of visual impairment in school children of upper-middle
socioeconomic status in Kathmandu. Ophthalmic Epidemiol
2008;15(1):17-23.
Nangia V, Jonas JB, Sinha A, Matin A, Kulkarni M. Refractive error in
central India: the Central India Eye and Medical Study.
Ophthalmology 2010;117(4):693-9.
Lin LL, Shih YF, Hsiao CK, Chen CJ, Lee LA, Hung PT. Epidemiologic
study of the prevalence and severity of myopia among
schoolchildren in Taiwan in 2000. J Formos Med Assoc
2001;100(10):684-91.
14. Saw SM, Carkeet A, Chia KS, Stone RA, Tan DT. Component
dependent risk factors for ocular parameters in Singapore
Chinese children. Ophthalmology 2002;109(11):2065-71.
15. Smith EL, 3rd. Prentice Award Lecture 2010: A Case for Peripheral
Optical Treatment Strategies for Myopia. Optom Vis Sci
2011;88(9):1029-44.
16. Bar Dayan Y, Levin A, Morad Y, Grotto I, Ben-David R, Goldberg A,
et al. The changing prevalence of myopia in young adults: a 13-year
series of population-based prevalence surveys. Invest Ophthalmol
Vis Sci 2005;46(8):2760-5.
17. Fong DS, Epstein DL, Allingham RR. Glaucoma and myopia: are
they related? Int Ophthalmol Clin 1990;30(3):215-8.
18. Haug SJ, Bhisitkul RB. Risk factors for retinal detachment following
cataract surgery. Curr Opin Ophthalmol 2012;23(1):7-11.
19. Saw SM. A synopsis of the prevalence rates and environmental risk
factors for myopia. Clin Exp Optom 2003;86(5):289-94.
20. Vitale S, Ellwein L, Cotch MF, Ferris FL, 3rd, Sperduto R. Prevalence
of refractive error in the United States, 1999-2004. Arch
Ophthalmol 2008;126(8):1111-9.
21. Curtin BJ, Iwamoto T, Renaldo DP. Normal and staphylomatous
sclera of high myopia. An electron microscopic study. Arch
Ophthalmol 1979;97(5):912-5.
22. Curtin BJ. Physiologic vs pathologic myopia: genetics vs
environment. Ophthalmology 1979;86(5):681-91.
23. Morgan I, Rose K. How genetic is school myopia? Prog Retin Eye
Res 2005;24(1):1-38.
24. Saw SM, Tan SB, Fung D, Chia KS, Koh D, Tan DT, et al. IQ and the
association with myopia in children. Invest Ophthalmol Vis Sci
2004;45(9):2943-8.
25. Peckham CS, Gardiner PA, Goldstein H. Acquired myopia in 11year-old children. Br Med J 1977;1(6060):542-5.
26. Xiang F, Morgan IG, He MG. New perspectives on the prevention
of myopia. Yan Ke Xue Bao 2011;26(1):3-8.
27. Jones LA, Sinnott LT, Mutti DO, Mitchell GL, Moeschberger ML,
Zadnik K. Parental history of myopia, sports and outdoor
activities, and future myopia. Invest Ophthalmol Vis Sci 2007;48(8):
3524-32.
28. Wu PC, Tsai CL, Hu CH, Yang YH. Effects of outdoor activities on
myopia among rural school children in Taiwan. Ophthalmic
Epidemiol 2010;17(5):338-42.
29. Au Eong KG, Tay TH, Lim MK. Education and myopia in 110,236
young Singaporean males. Singapore Med J 1993;34(6):489-92.
30. Ip JM, Rose KA, Morgan IG, Burlutsky G, Mitchell P. Myopia and the
urban environment: findings in a sample of 12-year-old Australian
school children. Invest Ophthalmol Vis Sci 2008;49(9):3858-63.
31. Simensen B, Thorud LO. Adult-onset myopia and occupation. Acta
Ophthalmol (Copenh) 1994;72(4):469-71.
32. Hosaka A. The growth of the eye and its components. Japanese
studies. Acta Ophthalmol Suppl 1988;185:65-8.
33. Tan NW, Saw SM, Lam DS, Cheng HM, Rajan U, Chew SJ. Temporal
variations in myopia progression in Singaporean children within an
academic year. Optom Vis Sci 2000;77(9):465-72.
34. Fan DS, Lam DS, Lam RF, Lau JT, Chong KS, Cheung EY, et al.
Prevalence, incidence, and progression of myopia of school
children in Hong Kong. Invest Ophthalmol Vis Sci 2004;45(4):
1071-5.
35. Donovan L, Sankaridurg P, Ho A, Naduvilath T, Smith EL, 3rd,
Holden BA. Myopia Progression Rates in Urban Children Wearing
Single-Vision Spectacles. Optom Vis Sci 2011:89(1): 27-32
36. Angle J, Wissmann DA. The epidemiology of myopia. Am J
Epidemiol 1980;111(2):220-8.
37. Gwiazda J, Deng L, Dias L, Marsh-Tootle W. Association of
Education and Occupation with Myopia in COMET Parents.
Optom Vis Sci 2011.
38. Low W, Dirani M, Gazzard G, Chan YH, Zhou HJ, Selvaraj P, et al.
Family history, near work, outdoor activity, and myopia in
Singapore Chinese preschool children. Br J Ophthalmol
2010;94(8):1012-6.
39. Mutti DO, Mitchell GL, Moeschberger ML, Jones LA, Zadnik K.
Parental myopia, near work, school achievement, and children's
refractive error. Invest Ophthalmol Vis Sci 2002;43(12):3633-40.
40. Kurtz D, Hyman L, Gwiazda JE, Manny R, Dong LM, Wang Y, et al.
Role of parental myopia in the progression of myopia and its
interaction with treatment in COMET children. Invest Ophthalmol
Vis Sci 2007;48(2):562-70.
41. Rosenfield M. In: Rosenfield M, Gilmartin B, editors. Myopia and
Nearwork. Boston: Butterworth Heinemann, 1998:91.
42. Teasdale TW, Fuchs J, Goldschmidt E. Degree of myopia in relation
to intelligence and educational level. Lancet 1988;2(8624):1351-4.
43. Cohn SJ, Cohn CM, Jensen AR. Myopia and intelligence: a
pleiotropic relationship? Hum Genet 1988;80(1):53-8.
44. Saw SM, Wu HM, Seet B, Wong TY,Yap E, Chia KS, et al. Academic
achievement, close up work parameters, and myopia in Singapore
military conscripts. Br J Ophthalmol 2001;85(7):855-60.
45. Iribarren R, Cerrella MR, Armesto A, Iribarren G, Fornaciari A. Age
of lens use onset in a myopic sample of office-workers. Curr Eye
Res 2004;28(3):175-80.
46. Cortinez MF, Chiappe JP, Iribarren R. Prevalence of refractive
errors in a population of office-workers in Buenos Aires,
Argentina. Ophthalmic Epidemiol 2008;15(1):10-6.
47. Chow YC, Dhillon B, Chew PT, Chew SJ. Refractive errors in
Singapore medical students. Singapore Med J 1990;31(5):472-3.
48. Young FA, Leary GA.Visual-optical characteristics of caged and
semifree-ranging monkeys. Am J Phys Anthropol 1973;38(2):
377-82.
49. Kinney JA, Luria SM, McKay CL, Ryan AP.Vision of submariners.
Undersea Biomed Res 1979;6 Suppl:S163-73.
50. Parssinen O, Lyyra AL. Myopia and myopic progression amoung
schoolchildren: a three-year follow-up study. Invest Ophthalmol
1993; 34(9): 2794-802.
51. Hepsen IF, Evereklioglu C, Bayramlar H. The effect of reading and
near-work on the development of myopia in emmetropic boys: a
prospective, controlled, three-year follow-up study. Vision Res
2001; 41(19): 2511-20.
52. Klein AP, Suktitipat B, Duggal P, Lee KE, Klein R, Bailey-Wilson JE,
et al. Heritability analysis of spherical equivalent axial length,
corneal curvature, and anterior chamber depth in the Beaver Dam
Eye Study. Arch Ophthalmol 2009; 127(5): 649-55.
53. Zylbermann R, Landau D, Berson D. The influence of study habits
on myopia in Jewish teenagers. J Pediatr Ophthalmol Strabismus
1993;30(5):319-22.
54. Rosenfield M, Gilmartin B. Accommodative error, adaptation and
myopia. Ophthalmic Physiol Opt 1999;19(2):159-64.
55. Gwiazda JE, Hyman L, Norton TT, Hussein ME, Marsh-Tootle W,
Manny R, et al. Accommodation and related risk factors associated
with myopia progression and their interaction with treatment in
COMET children. Invest Ophthalmol Vis Sci 2004;45(7):2143-51.
56. Mutti DO, Jones LA, Moeschberger ML, Zadnik K. AC/A ratio, age,
and refractive error in children. Invest Ophthalmol Vis Sci
2000;41(9):2469-78.
57. Gwiazda J, Thorn F, Held R. Accommodation, accommodative
convergence, and response AC/A ratios before and at the onset of
myopia in children. Optom Vis Sci 2005;82(4):273-8.
58. Goss DA, Jackson TW. Clinical findings before the onset of myopia
in youth: 3. Heterophoria. Optom Vis Sci 1996;73(4):269-78.
59. Maddock RJ, Millodot M, Leat S, Johnson CA. Accommodation
responses and refractive error. Invest Ophthalmol Vis Sci
1981;20(3):387-91.
60. Harb E, Thorn F, Troilo D. Characteristics of accommodative
behavior during sustained reading in emmetropes and myopes.
Vision Res 2006;46(16):2581-92.
61. Nakatsuka C, Hasebe S, Nonaka F, Ohtsuki H. Accommodative lag
under habitual seeing conditions: comparison between adult
myopes and emmetropes. Jpn J Ophthalmol 2003;47(3):291-8.
62. Langaas T, Riddell PM, Svarverud E,Ystenaes AE, Langeggen I,
Bruenech JR.Variability of the accommodation response in early
onset myopia. Optom Vis Sci 2008;85(1):37-48.
63. Goss DA, Rainey BB. Relationship of accommodative response and
nearpoint phoria in a sample of myopic children. Optom Vis Sci
1999;76(5):292-4.
64. Mutti DO, Zadnik K. Has near work's star fallen? Optom Vis Sci
2009;86(2):76-8.
65. Dirani M, Tong L, Gazzard G, Zhang X, Chia A, Young TL, et al.
Outdoor activity and myopia in Singapore teenage children. Br J
Ophthalmol 2009;93(8):997-1000.
66. Rose KA, Morgan IG, Ip J, Kifley A, Huynh S, Smith W, et al.
Outdoor activity reduces the prevalence of myopia in children.
Ophthalmology 2008;115(8):1279-85.
67. Zhang M, Li L, Chen L, Lee J, Wu J, Yang A, et al. Population density
and refractive error among Chinese children. Invest Ophthalmol
Vis Sci 2010.
68. Raviola E, Wiesel TN. Effect of dark-rearing on experimental
myopia in monkeys. Invest Ophthalmol Vis Sci 1978;17(6):485-8.
69. Napper GA, Brennan NA, Barrington M, Squires MA, Vessey GA,
Vingrys AJ. The duration of normal visual exposure necessary to
prevent form deprivation myopia in chicks. Vision Res 1995;
35(9): 1337-44.
70. Ashby R, Ohlendorf A, Schaeffel F. The effect of ambient
illuminance on the development of deprivation myopia in chicks.
Invest Ophthalmol Vis Sci 2009; 50(11): 5348-54.
71. Saw SM, Nieto FJ, Katz J, Schein OD, Levy B, Chew SJ. Factors
related to the progression of myopia in Singaporean children.
Optom Vis Sci 2000; 77(10): 549-54.
72. Lu B, Congdon N, Liu X, Choi K, Lam DS, Zhang M, et al.
Associations between near work, outdoor activity, and myopia
among adolescent student in rural China: the Xichang Pediatric
Refractive Error Study Report No 2. Arch Ophthalmol 2009;
127(6): 769-75.
73. Guggenheim JA, Northstone K, McMahon G, Ness AR, Deere K,
Mattocks C, et al. Time outdoors and physical activity as
predictors of incident myopia in childhood: a prospective cohort
study. Invest Ophthalmol Vis Sci 2012; 53(6): 2856-65.
74. Vannas AE, Ying GS, Stone RA, Maguire MG, Jormananinen V, Tervo
T. Myopia and natural lighting extremes: risk factors in Finnish
army conscripts. Acta Ophthalmol Scand 2003; 81(6): 588-95.
75. Wiesel TN, Raviola E. Myopia and eye enlargement after
neonatoal lid fusion in monkeys. Nature 1977; 266(5597); 66-8.
76. Raviola E, Wiesel TN. An animal model of myopia. N Engl J Med
1985;312(25):1609-15.
77. Guyton DL, Greene PR, Scholz RT. Dark-rearing interference with
emmetropization in the rhesus monkey. Invest Ophthalmol Vis Sci
1989;30(4):761-4.
78. Wallman J, Gottlieb MD, Rajaram V, Fugate-Wentzek LA. Local
retinal regions control local eye growth and myopia. Science
1987;237(4810):73-7.
79. Smith EL, Hung LF, Huang J, Blasdel TL, Humbird TL, Bockhorst
KH. Optical Defocus Influences Refractive Development in
Monkeys via Local, Regionally Selective Mechanisms. Invest
Ophthalmol Vis Sci 2010.
80. Troilo D, Wallman J. The regulation of eye growth and refractive
state: an experimental study of emmetropization. Vision Res
1991;31(7-8):1237-50.
81. Wildsoet C, Pettigrew J. Experimental myopia and anomalous eye
growth patterns unaffected by optic nerve section in chickens:
Evidence for local control of eye growth. Clinical Vision Science
1988;3:99-107.
82. Diether S, Schaeffel F. Local changes in eye growth induced by
imposed local refractive error despite active accommodation.
Vision Res 1997;37(6):659-68.
83. Schaeffel F, Troilo D, Wallman J, Howland HC. Developing eyes that
lack accommodation grow to compensate for imposed defocus.
Vis Neurosci 1990;4(2):177-83.
84. Schaeffel F, Glasser A, Howland HC. Accommodation, refractive
error and eye growth in chickens. Vision Res 1988;28(5):639-57.
85. Flitcroft DI. Ophthalmologists should consider the causes of
myopia and not simply treat its consequences. Br J Ophthalmol
1998;82(3):210-1.
86. Norton TT, Siegwart JT, Jr., Amedo AO. Effectiveness of hyperopic
defocus, minimal defocus, or myopic defocus in competition with a
myopiagenic stimulus in tree shrew eyes. Invest Ophthalmol Vis Sci
2006;47(11):4687-99.
87. Smith EL, 3rd, Hung LF. The role of optical defocus in regulating
refractive development in infant monkeys.Vision Res 1999;39(8):
1415-35.
88. Wildsoet C, Wallman J. Choroidal and scleral mechanisms of
compensation for spectacle lenses in chicks.Vision Res
1995;35(9):1175-94.
89. Charman WN. Near vision, lags of accommodation and myopia.
Ophthalmic Physiol Opt 1999;19(2):126-33.
90. Goss DA, Hampton MJ, Wickham MG. Selected review on genetic
factors in myopia. J Am Optom Assoc 1988;59(11):875-84.
91. Irving EL, Callender MG, Sivak JG. Inducing myopia, hyperopia, and
astigmatism in chicks. Optom Vis Sci 1991;68(5):364-8.
92. Mutti DO, Mitchell GL, Hayes JR, Jones LA, Moeschberger ML,
Cotter SA, et al. Accommodative lag before and after the onset of
myopia. Invest Ophthalmol Vis Sci 2006;47(3):837-46.
93. Rosenfield M, Desai R, Portello JK. Do progressing myopes show
reduced accommodative responses? Optom Vis Sci 2002;79(4):
268-73.
94. Abbott ML, Schmid KL, Strang NC. Differences in the
accommodation stimulus response curves of adult myopes and
emmetropes. Ophthalmic Physiol Opt 1998;18(1):13-20.
95. Bullimore MA, Gilmartin B, Royston JM. Steady-state
accommodation and ocular biometry in late-onset myopia. Doc
Ophthalmol 1992;80(2):143-55.
96. Gwiazda J, Thorn F, Bauer J, Held R. Myopic children show
insufficient accommodative response to blur. Invest Ophthalmol
Vis Sci 1993;34(3):690-4.
97. Berntsen DA, Sinnott LT, Mutti DO, Zadnik K. Accommodative lag
and juvenile-onset myopia progression in children wearing
refractive correction.Vision Res 2011;51(9):1039-46.
98. Smith EL, 3rd, Hung LF, Huang J. Relative peripheral hyperopic
defocus alters central refractive development in infant monkeys.
Vision Res 2009;49(19):2386-92.
99. Smith EL, 3rd, Ramamirtham R, Qiao-Grider Y, Hung LF, Huang J,
Kee CS, et al. Effects of foveal ablation on emmetropization and
form-deprivation myopia. Invest Ophthalmol Vis Sci 2007;48(9):
3914-22.
100. Huang J, Hung LF, Ramamirtham R, Blasdel TL, Humbird TL,
Bockhorst KH, et al. Effects of form deprivation on peripheral
refractions and ocular shape in infant rhesus monkeys (Macaca
mulatta). Invest Ophthalmol Vis Sci 2009;50(9):4033-44.
101. Charman WN, Radhakrishnan H. Peripheral refraction and the
development of refractive error: a review. Ophthalmic Physiol Opt
2010;30(4):321-38.
102. Smith EL, 3rd, Kee CS, Ramamirtham R, Qiao-Grider Y, Hung LF.
Peripheral vision can influence eye growth and refractive
development in infant monkeys. Invest Ophthalmol Vis Sci
2005;46(11):3965-72.
103. Mutti DO, Hayes JR, Mitchell GL, Jones LA, Moeschberger ML,
Cotter SA, et al. Refractive error, axial length, and relative
peripheral refractive error before and after the onset of myopia.
Invest Ophthalmol Vis Sci 2007;48(6):2510-9.
104. Hoogerheide J, Rempt F, Hoogenboom WP. Acquired myopia in
young pilots. Ophthalmologica 1971;163(4):209-15.
105. Schmid GF. Association between retinal steepness and central
myopic shift in children. Optom Vis Sci 2011;88(6):684-90.
106. Liu Y, Wildsoet C. The effect of two-zone concentric bifocal
spectacle lenses on refractive error development and eye growth
in young chicks. Invest Ophthalmol Vis Sci 2011;52(2):1078-86.
107. Mutti DO, Sholtz RI, Friedman NE, Zadnik K. Peripheral refraction
and ocular shape in children. Invest Ophthalmol Vis Sci 2000;41(5):
1022-30.
108. Atchison DA, Pritchard N, Schmid KL. Peripheral refraction along
the horizontal and vertical visual fields in myopia.Vision Res
2006;46(8-9):1450-8.
109. Chen X, Sankaridurg P, Donovan L, Lin Z, Li L, Martinez A, et al.
Characteristics of peripheral refractive errors of myopic and nonmyopic Chinese eyes.Vision Res 2010;50(1):31-5.
110. Sng CC, Lin XY, Gazzard G, Chang B, Dirani M, Chia A, et al.
Peripheral refraction and refractive error in singapore chinese
children. Invest Ophthalmol Vis Sci 2011;52(2):1181-90.
111. Lim LS,Yang X, Gazzard G, Lin X, Sng C, Saw SM, et al. Variations in
eye volume, surface area, and shape with refractive error in young
children by magnetic resonance imaging analysis. Invest
Ophthalmol Vis Sci 2011;52(12):8878-83.
112. Oyama N, Sato T. A series of investigations into myopia. Report I.
The refractive state of primary pupils before and after the
instillation of atropine.Yokohama Med Bull 1952;3(2):72-6.
113. oung FA. The Effect of Atropine on the Development of Myopia in
Monkeys. Am J Optom Arch Am Acad Optom 1965;42:439-49.
114. Bedrossian RH. The effect of atropine on myopia. Ann Ophthalmol
1971;3(8):891-7.
115. Gimbel HV. The control of myopia with atropine. Can J
Ophthalmol 1973;8(4):527-32.
116. Sampson WG. Role of cycloplegia in the management of functional
myopia. Ophthalmology 1979;86(5):695-7.
117. Bedrossian RH. The effect of atropine on myopia. Ophthalmology
1979;86(5):713-9.
118. Brodstein RS, Brodstein DE, Olson RJ, Hunt SC, Williams RR. The
treatment of myopia with atropine and bifocals. A long-term
prospective study. Ophthalmology 1984;91(11):1373-9.
119. Dyer JA. Role of cyclopegics in progressive myopia.
Ophthalmology 1979;86(5):692-4.
120. Gruber E. Treatment of myopia with atropine and bifocals.
Ophthalmology 1985;92(7):985.
121. Bedrossian RH. The treatment of myopia with atropine and
bifocals: a long-term prospective study. Ophthalmology
1985;92(5):716.
122. Brenner RL. Further observations on use of atropine in the
treatment of myopia. Ann Ophthalmol 1985;17(2):137-40.
123. Kao SC, Lu HY, Liu JH. Atropine effect on school myopia. A
preliminary report. Acta Ophthalmol Suppl 1988;185:132-3.
124. Yen MY, Liu JH, Kao SC, Shiao CH. Comparison of the effect of
atropine and cyclopentolate on myopia. Ann Ophthalmol
1989;21(5):180-2, 87.
125. McBrien NA, Moghaddam HO, Reeder AP. Atropine reduces
experimental myopia and eye enlargement via a
nonaccommodative mechanism. Invest Ophthalmol Vis Sci
1993;34(1):205-15.
126. Kennedy RH. Progression of myopia. Trans Am Ophthalmol Soc
1995;93:755-800.
127. Chou AC, Shih YF, Ho TC, Lin LL. The effectiveness of 0.5%
atropine in controlling high myopia in children. J Ocul Pharmacol
Ther 1997;13(1):61-7.
128. Shih YF, Chen CH, Chou AC, Ho TC, Lin LL, Hung PT. Effects of
different concentrations of atropine on controlling myopia in
myopic children. J Ocul Pharmacol Ther 1999;15(1):85-90.
129. Kennedy RH, Dyer JA, Kennedy MA, Parulkar S, Kurland LT,
Herman DC, et al. Reducing the progression of myopia with
atropine: a long term cohort study of Olmsted County students.
Binocul Vis Strabismus Q 2000;15(3 Suppl):281-304.
130. Romano PE, Donovan JP. Management of progressive school
myopia with topical atropine eyedrops and photochromic bifocal
spectacles. Binocul Vis Strabismus Q 2000;15(3):257-60.
131. Pointer RW. Atropine and photochromic bifocals for 800 cases of
school myopia. Binocul Vis Strabismus Q 2000;15(3):256.
132. Romano PE. There's no longer any need for randomized control
groups; it's time to regularly offer atropine and bifocals for school
myopia; comments on evidence-based medicine. Binocul Vis
Strabismus Q 2001;16(1):12.
133. Chua WH, Balakrishnan V, Chan YH, Tong L, Ling Y, Quah BL, et al.
Atropine for the treatment of childhood myopia. Ophthalmology
2006;113(12):2285-91.
134. Lee JJ, Fang PC,Yang IH, Chen CH, Lin PW, Lin SA, et al. Prevention
of myopia progression with 0.05% atropine solution. J Ocul
Pharmacol Ther 2006;22(1):41-6.
135. Fan DS, Lam DS, Chan CK, Fan AH, Cheung EY, Rao SK. Topical
atropine in retarding myopic progression and axial length growth
in children with moderate to severe myopia: a pilot study. Jpn J
Ophthalmol 2007;51(1):27-33.
136. Tong L, Huang XL, Koh AL, Zhang X, Tan DT, Chua WH. Atropine
for the treatment of childhood myopia: effect on myopia
progression after cessation of atropine. Ophthalmology
2009;116(3):572-9.
137. Fang PC, Chung MY,Yu HJ, Wu PC. Prevention of myopia onset
with 0.025% atropine in premyopic children. J Ocul Pharmacol
Ther 2010;26(4):341-5.
138. Song YY, Wang H, Wang BS, Qi H, Rong ZX, Chen HZ. Atropine in
Ameliorating the Progression of Myopia in Children with Mild to
Moderate Myopia: A Meta-Analysis of Controlled Clinical Trials. J
Ocul Pharmacol Ther 2011:27(4): 361-368.
139. Stone RA, Lin T, Laties AM. Muscarinic antagonist effects on
experimental chick myopia. Exp Eye Res 1991;52(6):755-8.
140. Leech EM, Cottriall CL, McBrien NA. Pirenzepine prevents form
deprivation myopia in a dose dependent manner. Ophthalmic
Physiol Opt 1995;15(5):351-6.
141. Cottriall CL, McBrien NA. The M1 muscarinic antagonist
pirenzepine reduces myopia and eye enlargement in the tree
shrew. Invest Ophthalmol Vis Sci 1996;37(7):1368-79.
142. Luft WA, Ming Y, Stell WK.Variable effects of previously untested
muscarinic receptor antagonists on experimental myopia. Invest
143. Bartlett JD, Niemann K, Houde B, Allred T, Edmondson MJ,
Crockett RS. A tolerability study of pirenzepine ophthalmic gel in
myopic children. J Ocul Pharmacol Ther 2003;19(3):271-9.
144. Tan DT, Lam DS, Chua WH, Shu-Ping DF, Crockett RS. One-year
multicenter, double-masked, placebo-controlled, parallel safety and
efficacy study of 2% pirenzepine ophthalmic gel in children with
myopia. Ophthalmology 2005;112(1):84-91.
145. Le QH, Cheng NN, Wu W, Chu RY. Effect of pirenzepine
ophthalmic solution on form-deprivation myopia in the guinea
pigs. Chin Med J (Engl) 2005;118(7):561-6.
146. Siatkowski RM, Cotter S, Miller JM, Scher CA, Crockett RS,
Novack GD. Safety and efficacy of 2% pirenzepine ophthalmic gel
in children with myopia: a 1-year, multicenter, double-masked,
placebo-controlled parallel study. Arch Ophthalmol 2004;122(11):
1667-74.
147. Siatkowski RM, Cotter SA, Crockett RS, Miller JM, Novack GD,
Zadnik K. Two-year multicenter, randomized, double-masked,
placebo-controlled, parallel safety and efficacy study of 2%
pirenzepine ophthalmic gel in children with myopia. J AAPOS
2008;12(4):332-9.
148. Saw SM, Gazzard G, Au Eong KG, Tan DT. Myopia: attempts to
arrest progression. Br J Ophthalmol 2002;86(11):1306-11.
149. Goss DA, Grosvenor T. Rates of childhood myopia progression
with bifocals as a function of nearpoint phoria: consistency of
three studies. Optom Vis Sci 1990;67(8):637-40.
150. Young FA, Leary GA, Grosvenor T, Maslovitz B, Perrigin DM,
Perrigin J, et al. Houston Myopia Control Study: a randomized
clinical trial. Part I. Background and design of the study. Am J
Optom Physiol Opt 1985;62(9):605-13.
151. Grosvenor T, Perrigin DM, Perrigin J, Maslovitz B. Houston Myopia
Control Study: a randomized clinical trial. Part II. Final report by
the patient care team. Am J Optom Physiol Opt 1987;64(7):
482-98.
152. Fulk GW, Cyert LA, Parker DE. A randomized trial of the effect of
single-vision vs. bifocal lenses on myopia progression in children
with esophoria. Optom Vis Sci 2000;77(8):395-401.
153. Fulk GW, Cyert LA, Parker DE. A randomized clinical trial of
bifocal glasses for myopic children with esophoria: results after 54
months. Optometry 2002;73(8):470-6.
154. Leung JT, Brown B. Progression of myopia in Hong Kong Chinese
schoolchildren is slowed by wearing progressive lenses. Optom Vis
Sci 1999;76(6):346-54.
155. Gwiazda J, Hyman L, Hussein M, Everett D, Norton TT, Kurtz D, et
al. A randomized clinical trial of progressive addition lenses versus
single vision lenses on the progression of myopia in children.
156. Gwiazda JE, Hyman L, Everett D, Norton T, Kurtz D, Manny R. Fiveyear results from the correction of myopia evaluation trial
(COMET). Investigative Ophthalmology and Visual Science
2006;47: E–abstract 1166.
157. Sankaridurg P, Donovan L,Varnas S, Ho A, Chen X, Martinez A, et
al. Spectacle lenses designed to reduce progression of myopia: 12month results. Optom Vis Sci 2010;87(9):631-41.
158. Cheng D, Schmid KL, Woo GC, Drobe B. Randomized trial of
effect of bifocal and prismatic bifocal spectacles on myopic
progression: two-year results. Arch Ophthalmol 2010;128(1):12-9.
159. Cheng D, Woo GC, Schmid KL. Bifocal lens control of myopic
progression in children. Clin Exp Optom 2011;94(1):24-32.
160. Adler D, Millodot M. The possible effect of undercorrection on
myopic progression in children. Clin Exp Optom 2006;89(5):
315-21.
161. Chung K, Mohidin N, O'Leary DJ. Undercorrection of myopia
enhances rather than inhibits myopia progression. Vision Res
2002;42(22):2555-9.
162. Walline JJ, Jones LA, Sinnott L, Manny RE, Gaume A, Rah MJ, et al. A
randomized trial of the effect of soft contact lenses on myopia
progression in children. Invest Ophthalmol Vis Sci 2008;49(11):
4702-6.
163. Walline JJ, Jones LA, Mutti DO, Zadnik K. A randomized trial of the
effects of rigid contact lenses on myopia progression. Arch
Ophthalmol 2004;122(12):1760-6.
164. Katz J, Schein OD, Levy B, Cruiscullo T, Saw SM, Rajan U, et al. A
randomized trial of rigid gas permeable contact lenses to reduce
progression of children's myopia. Am J Ophthalmol 2003;136(1):
82-90.
165. Lui WO, Edwards MH. Orthokeratology in low myopia. Part 1:
efficacy and predictability. Cont Lens Anterior Eye 2000;23(3):
77-89.
166. Walline JJ, Rah MJ, Jones LA. The Children's Overnight
Orthokeratology Investigation (COOKI) pilot study. Optom Vis
Sci 2004;81(6):407-13.
167. Reim T, Lund M, Wu R. Orthokeratology and adolescent myopia
control. Contact Lens Spectrum 2003;18:40–2.
168. Cho P, Cheung SW, Edwards M. The longitudinal orthokeratology
research in children (LORIC) in Hong Kong: a pilot study on
refractive changes and myopic control. Curr Eye Res 2005;30(1):
71-80.
169. Walline JJ, Jones LA, Sinnott LT. Corneal reshaping and myopia
progression. Br J Ophthalmol 2009;93(9):1181-5.
170. Walline JJ, Jones LA, Mutti DO, Zadnik K. Use of a run-in period to
decrease loss to follow-up in the Contact Lens and Myopia
Progression (CLAMP) study. Control Clin Trials 2003;24(6):711-8.
171. Kakita T, Hiraoka T, Oshika T. Influence of overnight
orthokeratology on axial elongation in childhood myopia. Invest
172. Santodomingo-Rubido J,Villa-Collar C, Gilmartin B, GutierrezOrtega R. Myopia Control with Orthokeratology Contact Lenses
in Spain (MCOS): Refractive and Biometric Changes. Invest
Ophthalmol Vis Sci 2012.
173. Swarbrick H, Alharbi A, Lum E, Watt K. Changes in Axial Length
and Refractive Error During Overnight Orthokeratology for
Myopia Control. Invest Ophthalmol Vis Sci 2011;52: E-Abstract
2837. 2011.
174. Kwok-Hei Mok A, Sin-Ting Chung C. Seven-year retrospective
analysis of the myopic control effect of orthokeratology in
children: a pilot study. Clinical Optometry 2011.
175. Hiraoka T, Kakita T, Okamotot F, Takahashi H, Oshika T. Long-term
effect of overnight orthokeratology on axial length elongation in
childhood myopia: a 5-year follow-up study. Invest Ophthalmol
Vis Sci 2012;53(7): 3919-9.
176. Smith EL, 3rd, Hung LF, Huang J, Blasdel TL, Humbird TL, Bockhorst
KH. Effects of optical defocus on refractive development in
monkeys: evidence for local, regionally selective mechanisms.
177. Lui WO, Edwards MH. Orthokeratology in low myopia. Part 2:
corneal topographic changes and safety over 100 days. Cont Lens
Anterior Eye 2000;23(3):90-9.
178. Kang P, Swarbrick H. Peripheral refraction in myopic children
wearing orthokeratology and gas-permeable lenses. Optom Vis Sci
2011;88(4):476-82.
179. Anstice NS, Phillips JR. Effect of dual-focus soft contact lens wear
on axial myopia progression in children. Ophthalmology
2011;118(6):1152-61.
180. Holden B, Sankaridurg P, Lazon P, Ho A, Xiang C, Lin J, et al.
Central And Peripheral Visual Performance Of A Novel Contact
Lens Designed To Control Progression Of Myopia. Invest
Ophthalmol Vis Sci 2011;52: E-Abstract 6518 2011.
181. Holden BA, Sankaridurg P, Lazon de la Jara P, Smith EL, Chen X,
Kwan J, et al. Reduction in the Rate of Progress of Myopia With a
Contact Lens Designed to Reduce Relative Peripheral Hyperopia.
Invest Ophthalmol Vis Sci 2010;51: E-Abstract 2220 2010.
182. Woods j, Guthrie S, Keir N, Dillehay S, Tyson M, Griffin R, et al. The
Effect Of A Unique Lens Designed For Myopia Progression
Control (MPC) On The Level Of Induced Myopia In Chicks. Invest
Ophthalmol Vis Sci 2011;52: E-Abstract 6651 2011.
183. Sankaridurg P, Holden B, Smith E, 3rd, Naduvilath T, Chen X, Jara
PL, et al. Decrease in Rate of Myopia Progression with a Contact
Lens Designed to Reduce Relative Peripheral Hyperopia: OneYear Results. Invest Ophthalmol Vis Sci 2011.
184. North RV, Kelly ME. A review of the uses and adverse effects of
topical administration of atropine. Ophthalmic Physiol Opt
1987;7(2):109-14.
185. Curtin B. The Myopias. Philadelphia: Harper & Row Publishers;
1985.
186. Kelly TS, Chatfield C, Tustin G. Clinical assessment of the arrest of
myopia. Br J Ophthalmol 1975;59(10):529-38.
187. Chiang MF, Kouzis A, Pointer RW, Repka MX. Treatment of
childhood myopia with atropine eyedrops and bifocal spectacles.
Binocul Vis Strabismus Q 2001;16(3):209-15.
188. Shih YF, Hsiao CK, Chen CJ, Chang CW, Hung PT, Lin LL. An
intervention trial on efficacy of atropine and multi-focal glasses in
controlling myopic progression. Acta Ophthalmol Scand
2001;79(3):233-6.
189. Lu P, Chen J. Retarding progression of myopia with seasonal
modification of topical atropine. Journal of Ophthalmic and Vision
Research 2010;5:75-81.
190. Chia A, Chua WH, Cheung YB, Wong WL, Lingham A, Fong A, et al.
Atropine for the Treatment of Childhood Myopia: Safety and
Efficacy of 0.5%, 0.1%, and 0.01% Doses (Atropine for the
Treatment of Myopia 2). Ophthalmology 2011.
191. Saw SM, Shih-Yen EC, Koh A, Tan D. Interventions to retard myopia
progression in children: an evidence-based update. Ophthalmology
2002;109(3):415-21.
192. Gwiazda J. Treatment options for myopia. Optom Vis Sci
2009;86(6):624-8.
193. Hiett J, Carlson D. Ocular Cholinergic Agents. In: Onofrey, editor.
Clinical Optometric Pharmacology and Therapeutics. Philadelphia:
Lippincott, 1991:1-21.
194. Jimenez-Jimenez FJ, Alonso-Navarro H, Fernandez-Diaz A, AdevaBartolome MT, Ruiz-Ezquerro JJ, Martin-Prieto M. [Neurotoxic
effects induced by the topical administration of cycloplegics. A
case report and review of the literature]. Rev Neurol 2006;43(10):
603-9.
195. Group PEDI. A randomized trial of atropine vs. patching for
treatment of moderate amblyopia in children. Arch Ophthalmol
2002;120:268-78.
196. Group PEDI. Randomized trial of treatment of amblyopia in
children aged 7 to 17 years. Arch Ophthalmol 2005;123:437-47.
197. Group PEDI. A randomized trial of atropine regimens for
treatment of moderate amblyopia in children. Ophthalmology
2004(111):2076-85.
198. Luu CD, Lau AM, Koh AH, Tan D. Multifocal electroretinogram in
children on atropine treatment for myopia. Br J Ophthalmol
2005;89(2):151-3.
199. Sminia ML, de Faber JT, Doelwijt DJ, Wubbels RJ, Tjon-Fo-Sang M.
Axial eye length growth and final refractive outcome after
unilateral paediatric cataract surgery. Br J Ophthalmol 2010;94(5):
547-50.
200. Zhang Z, Li S. The visual deprivation and increase in axial length in
patients with cataracts.Yan Ke Xue Bao 1996;12(3):135-7.
201. Sherman SM, Norton TT, Casagrande VA. Myopia in the lid-sutured
tree shrew (Tupaia glis). Brain Res 1977;124(1):154-7.
202. Ni J, Smith EL, 3rd. Effects of chronic optical defocus on the
kitten's refractive status.Vision Res 1989;29(8):929-38.
203. Troilo D, Judge SJ. Ocular development and visual deprivation
myopia in the common marmoset (Callithrix jacchus). Vision Res
1993;33(10):1311-24.
204. Smith EL, 3rd, Harwerth RS, Crawford ML, von Noorden GK.
Observations on the effects of form deprivation on the refractive
status of the monkey. Invest Ophthalmol Vis Sci 1987;28(8):
1236-45.
205. Smith EL, 3rd, Huang J, Hung LF, Blasdel TL, Humbird TL, Bockhorst
KH. Hemiretinal form deprivation: evidence for local control of
eye growth and refractive development in infant monkeys. Invest
206. Fischer AJ, McKinnon LA, Nathanson NM, Stell WK. Identification
and localization of muscarinic acetylcholine receptors in the
ocular tissues of the chick. J Comp Neurol 1998;392(3):273-84.
207. Cottriall CL, McBrien NA, Annies R, Leech EM. Prevention of
form-deprivation myopia with pirenzepine: a study of drug
delivery and distribution. Ophthalmic Physiol Opt 1999;19(4):
327-35.
208. Schopenhauer A. BrainyQuote.com. Retrieved October 10, 2011,
from BrainyQuote.com Web site::Web site: http://
www.brainyquote.com/quotes/quotes/a/arthurscho103608.html
Corresponding author: Erica Schulman, O.D., 40 Park Ave Apt
3F, New York, NY 10016. Email: [email protected].
New trends in early diagnosis of hydroxychloroquine toxic retinopathy
Gary L. Vanderzee, O.D, and Douglas Tassi, O.D.
KEYWORDS
Toxic maculopathy,
hydroxychloroquine,
bull’s eye maculopathy,
spectral domain
optical coherence
tomography (OCT)
ABSTRACT
Background: Toxic retinopathy is an uncommon sequella in the treatment of certain autoimmune
diseases with hydroxychloroquine (HCQ). We present two cases of HCQ toxic retinopathy, as well as a
discussion on how to diagnose and manage early toxicity findings.
Case Reports: Two cases are presented of patients who experienced toxic effects of HCQ therapy.
The first patient had bull’s eye maculopathy confirmed with visual field testing and optical coherence
tomography (OCT). The second patient had early signs of toxic maculopathy validated by repeat visual
field and OCT testing.
Conclusion: Management of toxic maculopathy includes the cessation of hydroxychloroquine,
continued monitoring of the toxic effects and optimizing the remaining vision. The irreversible and
potential devastating effect of HCQ toxic maculopathy underscores the importance of early diagnosis
and working with the patient’s rheumatologist.
Introduction
In the US, the chronic use of hydroxychloroquine sulfate is for
the treatment of autoimmune disorders, such as systemic
lupus erythromatosus and rheumatoid arthritis. Its more
toxic predecessor, chloroquine, is currently not used very
much in the US. The incidence of toxic maculopathy is low,
but these patients are, nonetheless, at risk for the
development of toxic maculopathy. Permanent visual damage
happens with advanced toxic maculopathy often characterized
by “bull’s eye” maculopathy. Visual morbidity may be avoided
in these patients if early diagnosis is made and drug therapy is
discontinued. Therefore, the key is early detection through
appropriate screening methods.
Case 1
An 85-year-old white man presented to the eye clinic for
consultation. He was referred by a rheumatologist for routine
hydroxychloroquine monitoring. This was his first time to our
eye clinic. He had been followed every six months but had
been delinquent the past couple of years. He reported that he
had been on hydroxychloroquine for approximately 11 years
but not sure of the exact duration. His initial complaint was
that his right eye had been watering lately. The patient’s ocular
history was positive for cataract surgery OU.
A review of his medical history showed he was taking: 200 mg
hydroxychloroquine b.i.d. p.o. and methotrexate 25 mg/ml
(inject .8ml subcutaneously) every seven days for rheumatoid
arthritis, diltiazem 240 mg daily for hypertension, 2 cap
terazosin hcl 2 mg q.h.s. daily for benign prostatic
hypertrophy, albuterol 90 mcg 200D oral inhaler 2 puffs q.i.d.,
Fluticasone HFA 220 mcg 120D oral inhaler, inhaling albuterol/
ipratropium nebulizer solution daily for asthma, nystatin oral
suspension 2 tsp. q.i.d. p.r.n. for recurrent oral yeast infections,
½ tab tramadol hcl 50 mg tab b.i.d. for pain, and ½ tab
furosemide 40 mg p.o. daily for fluid retention. He was also
taking multivitamins, glucosamine, calcium, and folic acid. He
reported no known drug allergies. His family history was noncontributory. He did not smoke or drink alcohol.
The patient’s best corrected distance visual acuities were 20/30
OD and 20/25- OS with a mixed hyperopic astigmatic
correction. His pupils, extraocular motility, and color vision by
Ishihara color plates were normal. Intraocular pressures were
15 mm Hg in each eye by Goldmann applanation tonometry.
Biomicroscopy showed centered and clear posterior chamber
intraocular lenses in each eye. Results of visual field testing
with the Humphrey 10-2 (Carl Zeiss Meditec Inc. Dublin, CA)
macular threshold showed bilateral paracentral scotomas with
central 30 sparing (see Figure 1). Macular evaluation was
performed with the Cirrus HD optical coherence tomographer
(HD-OCT) (Carl Zeiss Meditec Inc. Dublin, CA) which
revealed paracentral thinning of the retina, loss of the inner
segment/outer segment (IS/OS) junction line in the macula with
central sparring of both eyes (see Figures 2, 3). Also of note, a
large retinal pigment epithelium (RPE)detachment was found
between the macula and optic nerve OD. Dilated fundus
evaluation was remarkable for macular RPE irregularity of both
eyes that looked like a “bull’s eye.” (A fundus camera was not
available, so retinal photos could not be taken.) The patient
was counseled on hydroxychloroquine retinopathy and its
permanent and sometimes progressive nature and the need for
close follow-up. His rheumatologist promptly discontinued the
hydroxychloroquine when notified of the findings.
He was scheduled and returned for a three-month follow-up
appointment. His entering visual acuities were unchanged. All
other findings appeared to be stable, with the exception of his
macular threshold visual field test. It showed some slight
progression in visual field loss OU. Photo documentation was
done with the Canon CX-1 digital retinal camera (Canon USA,
Lake Success, NY). The annular perifoveal hypopigmentation
can be seen on the fundus images (see Figures 4, 5). Spectral
domain optical coherence tomography (SDOCT) was repeated
and found to be relatively unchanged with the exception of an
improving pigment epithelial detachment OD.
Case 2
A 65-year-old man presented to the eye clinic for his 6-month
hydroxychloroquine follow-up. He had been followed every
6-9 months for the past nine years. He reported being on
!
!
Figure 1 Baseline Humphrey macular threshold visual field tests for left and right eyes of case 1. Significant paracentral scotoma
noted in both eyes from hydroxychloroquine toxic retinopathy.
hydroxychloroquine for the past 10-11 years. He had no
entering complaints and reported that his vision seemed to be
stable. His ocular history was positive for cataract surgery OD.
A review of his medical history revealed hypertension and
rheumatoid arthritis. He smoked cigarettes and had an
occasional drink.
His medications included 1 ½ tab atenolol 50 mg p.o. for blood
pressure, 1 tab hydrochlorothiazide 25 mg q.a.m. p.o. for blood
pressure, 1 tab hydroxychloroquine 200 mg b.i.d. p.o. for
rheumatoid arthritis, ½ tab lisinopril 20 mg q.a.m. p.o. for blood
pressure, 1 cap terazosin hcl 5 mg q.h.s. p.o. for blood pressure,
and benign prostatic hypertrophy. Family history was positive
for a sister and brother with diabetes.
His best corrected visual acuities were 20/20 OD and 20/20 OS
with a low hyperopic astigmatic correction. Pupils and ocular
motility were unremarkable, but color vision testing by Ishihara
color plates showed only one out of seven plates seen by the
right eye and left eye with no previous defect noted. Goldmann
applanation pressures were 16 mm Hg in both the right and left
eyes. Biomicroscopy disclosed a posterior chamber intraocular
lens in the right eye and a 1-2+ nuclear sclerotic cataract OS. A
Humphrey SITA-standard 10-2 central threshold visual field test
revealed early paracentral annular scotoma of both eyes (see
Figure 6). Confirmation of the visual field defect was attempted
by performing SDOCT macular scan and the 5 line raster scan.
The 5 line raster on the Cirrus HD-OCT found a moth-eaten
appearance to the IS/OS junction line in the paracentral retina
OU (see Figure 7), and the macular scan found paracentral
thinning in three quadrants OD and one quadrant OS (see
Figure 8). Dilated fundus evaluation noteworthy findings were
mild retinal pigmented epithelial irregularities and drusen noted
in the macula OU (see Figure 9). The patient was informed of
the findings which most likely pointed to early
hydroxychloroquine retinopathy. His rheumatologist was
informed of the findings and subsequently withdrew the
hydroxychloroquine. The patient was informed of the
importance of close follow-up to see if the retinopathy will
progress. He was scheduled for another appointment for repeat
10-2 threshold visual fields and HD-OCT in 3 months. Testing
done at the 3 month follow-up evaluation substantiated the
visual field and OCT findings with no further evidence of
progression.
Discussion
The incidence of hydroxychloroquine maculopathy in the
literature is variable. In one study of 526 patients, the overall
incidence was reported at 0.5%. The reported incidence
increased to 3.4% of the patients if they were on the
recommended dosage of hydroxychloroquine for more than six
years.1 In one of the largest studies of 1207 patients, 5 patients
developed toxic maculopathy. This is a rate of 0.4% of patients
who were on the recommended dosage of 6.5 mg/kg.2 Marmor
MF, et al., reported that the risk of toxicity increases toward 1%
after five to seven years of use or a cumulative dose of 1000 g of
hydroxychloroquine.3
!
!
Figure 2 Baseline Zeiss HDOCT macular cube tests for right and left eyes of case 1. Note the parafoveal thinning of the retina,
greater in the left eye as compared to the right eye. There is a loss of the parafoveal hump that is visible with the cross section and the
three dimensional views of normal patients. There is an asymptomatic retinal pigment epithelial detachment between the macula and
optic nerve of the right eye.
Early hydroxychloroquine toxic retinopathy is often defined by
two methods. One is the development of a persistent paracentral
scotoma to threshold white stimulus. The other is a repeatable
bilateral visual field defect on two separate visits. Early
hydroxychloroquine retinopathy is considered when there is an
acquired paracentral scotoma without corresponding fundus
changes. Advanced retinopathy consists of scotomas in the
presence of parafoveal RPE atrophy. This is what we would
classically call bull’s eye maculopathy.4
Corneal changes in hydroxychloroquine treatment consist of the
development of a vortex keratopathy. This drug-induced
keratopathy is usually visually innocuous. In some cases, if the
corneal verticillata are dense, this could cause halos and glare. The
keratopathy develops in less than 10% of patients treated with
hydroxychloroquine. Corneal deposits were found in 95% of
patients treated with chloroquine.5 The vortex keratopathy is not
related to dosage. This keratopathy is not associated with the
level of risk of retinal toxicity and will resolve without
complication if the medication is discontinued. This vortex
keratopathy also appears with amiodarone treatment,
chlorpromazine treatment, and Fabry’s disease. Other side effects
may include decreased visual acuity, night vision problems, and
color vision defects, especially in the blue-yellow spectrum.
Rarely, vascular attenuation and optic atrophy may result.4
The exact mechanism of retinal toxicity is unknown. Previous
studies have implicated outer retinal structures such as the
photoreceptors and the retinal pigmented epithelium. The
hydroxychloroquine molecule binds to the pigmented epithelium
which disrupts lysosomal function and consequently there is
lipofuscin accumulation. Therefore, photoreceptor loss may be
attributed to this alteration in RPE metabolism. A recent study by
Stepien, et al., using a prototype research ultra-high resolution
optical coherence tomograph, found a diminished cone
photoreceptor density in the affected perifoveal retina. This
corresponded to the “moth-eaten” appearance of the IS/OS layer
found by the OCT.6,7 Others suspected ganglion cells, the inner
plexiform layer, or the nerve fiber layer.6,7,8,9 Some of the earlier
animal studies pointed to inner ganglion cells or nerve fiber layer
thinning as to the target for retinal toxicity. Korah and Kuriakose
have OCT evidence pointing to loss of ganglion cell layers
attributing to the thinning of the macula and parafoveal region.10
Pasadhika, et al., performed a study showing that chronic use of
hydroxychloroquine is associated with thinning of the inner
perifoveal retinal layers. This can be detected or found even in
the absence of functional or structural clinical changes involving
the photoreceptor or retinal pigmented cell layers. They feel this
is the contributing factor in paracentral scotomas that can be
observed as a first clinical sign.11 What is known is that there is
loss of parafoveal retinal function which is due to associated
retinal morphological or structural changes.
Currently, the greatest risk factor in hydroxychloroquine
maculopathy is an accumulative dosage of the medication at or
greater than 1000 grams. The recommended daily dosage of
!
Figure 3 Zeiss HDOCT 5 line raster scans of the right and left eyes that were obtained on 3 month follow up to the eye clinic for
case 1 with advanced HCQ toxic retinopathy. Note the loss of the inner segment/outer segment junction line in the parafoveal
region (blue arrow)resulting in a drop of inner retinal tissue or “sink holes” (green arrow). This gives the appearance of “flying
saucers” (red arrow) under the fovea of both eyes.
hydroxychloroquine is 200 mg twice a day. Therefore, the
highest risk for these patients presents at 6.8 years. Other risk
factors include: duration of treatment greater than 5 years,
dosage greater than 400 mg per day or exceeding 6.5 mg/kg/day
based on lean body weight, age greater than 60 years,
concomitant liver or kidney disease, and other retinal disease.3,4
One must also note that many patients on hydroxychloroquine
for rheumatoid arthritis may also be taking methotrexate which
!
!
Figure 4 Canon color photographs of the right and left eye of
case 1. There is a small pink central spot surrounded by a
slightly darker ring and ultimately a lighter ring giving the
appearance of a bull’s eye. Bull’s eye maculopathy is a sign of
advanced HCQ retinopathy.
can cause renal and liver failure. Our patient in Case 1 was
recently diagnosed with kidney failure and is taking
subcutaneous methotrexate. Is it possible that the
methotrexate caused the renal failure which contributed to the
toxic retinopathy?
When it comes to retinal screening protocol there have been
some changes recently due to some of the new technology that
has come available. SDOCT has been noted to find
abnormalities in the presence of normal
ophthalmoscopy findings. There have been
some patients reported with profound
abnormalities with visual field testing and
multifocal electroretinogram (mfERG) in
the presence of normal macular
appearance.12 In February 2011, the
American Academy of Ophthalmology
released new guidelines for the
recommended examination schedule of
patients on antimalarial medication. Those
guidelines are as follows: A baseline
examination is advised for patients starting
these drugs to serve as a reference point and to rule out
maculopathy, which might be a contraindication to their use.
Annual screenings should begin after 5 years (or sooner if there
are unusual risk factors).3 The American Academy of
Ophthalmology released new testing guidelines for patients on
antimalarial medication. The recommendations are as follows:
BCVA (best corrected visual acuity), dilated fundus exam at
!
!
Figure 5 Canon red free photographs of the right eye and left
eye respectively of case 1. Note the darker fovea surrounded by
slightly lighter circle and then the eventually lighter ring.
least within the first year of antimalarial drug use, 10-2 central
threshold automated visual fields with a white target. Subtle,
repeatable visual field defects are an indication to do objective
testing. At least one of the following objective tests should be
performed for routine screening if available: SDOCT, fundus
autofluorescence (FAF), and mfERG. Newer testing, such as
mfERG, SDOCT, and FAF can be more sensitive than visual
fields.3 How often the patient should be evaluated in the first
five years of treatment is up to the managing doctor based on
individual patient risks and the doctor’s judgment. (The
occurrence of toxic retinopathy in the first 5 years of treatment
is not zero. There are documented cases of toxic retinopathy
!
with cumulative doses of 760g and as
little as 86g.13) Annual screening is
recommended after five to six years
and more frequent examination with
patients who have higher risk.
There is a lack of consensus for
which test is the most diagnostically
useful for toxic retinopathy secondary
to hydroxychloroquine use. When
determining which techniques or
tests to perform on patients, one
would ideally want instrumentation
that is inexpensive, objective, quick,
and non-invasive, as well as sensitive and specific for detecting
early toxicity.7
Visual field testing for hydroxychloroquine patients should
consist of a threshold macular visual field test to detect
reductions in retinal sensitivity. Macular toxicity will produce
partial to total ring scotomas. These ring scotomas form in the
parafoveal zone of the visual field from 4 to 9 degrees. Of
interest is the foveal sparing which occurs frequently in
hydroxychloroquine retinopathy. The central 10-2 threshold
visual field test is recommended by the American Academy of
Ophthalmology for screening for HCQ maculopathy. Macular
threshold visual fields may be the best way for the average
clinician to determine early toxicity in patients without the
availability of instruments like the SDOCT or mfERG. Amsler
grid testing should not take the place of macular threshold
Figure 6 Humphrey 10-2 Central threshold visual field test of the! left and right eye for case 2 shows paracentral relative scotoma
3-50 from fixation as noted by the pattern deviation.
!
!
Figure 7 5 line raster on the Cirrus HDOCT of the right and left eye respectively of case 2. Note the area of discontinuity or
“moth-eaten appearance” (red arrow) of the inner segment/outer segment junction line greater temporally in comparison to a more
normal IS/OS junction line (green arrow) of both the right and left eye scans. Also of note is loss of parafoveal heaping of tissue,
especially the right eye.
visual fields in the evaluation of these patients.3 A disadvantage
with threshold visual field testing is that there is a steep learning
curve for the patients. Repeatable paracentral scotomas with
white light are an indication to perform another more objective
test such as mfERG, SDOCT, or FAF.
The mfERG is an objective but more difficult test to administer.
There is also the issue of clinical availability, patient
cooperation, and cost when it comes to the mfERG.7,14
However, the mfERG recently has shown promise in detecting
early stages of retinal toxicity in hydroxychloroquine
retinopathy.7 Kellner, et al., reports that mfERG can reliably
detect retinal functional loss associated with CQ/HCQ
retinopathy. In some patients, the mfERG showed reduced
response amplitudes when other functional tests were normal
(color vision, central visual field, and visual acuity) and
morphological examinations were normal (FA,
ophthalmoscopy).12,14
Spectral domain optical coherent tomography is positioned to
become a very valuable technology in the management of
patients on antimalarial medication. With recent advances in
SDOCT, it is possible to obtain cross-sectional images of the
retina with resolutions of 3-5 um.7 In the future, with the use
of adaptive optics, eliminating optical aberrations, HD-OCT may
achieve resolution of an impressive 1 μm. The instrument
potentially allows for an earlier diagnosis in an objective fashion
with quick acquisition time. OCT functions as a type of optical
biopsy in situ with resolution approaching that of excisional
biopsy and histopathology.15 OCT findings in early
hydroxychloroquine maculopathy include a distinctive
discontinuity or “moth eaten” area of the IS/OS junction line
(see Figure 7). The “moth-eaten” appearance of the IS/OS
junction may be due to diminished cone photoreceptors in this
area. The greatest area affected was the perifoveal retina where
the cone density is the highest. This moth-eaten IS/OS junction
can sometimes be detected before abnormalities appear with
10-2 central visual field testing.7 More advanced cases of
maculopathy may have a complete loss of the IS/OS junction
line. “Sink holes” form where displacement effects of the inner
retinal layers fill space previously occupied by atrophic outer
retinal layers (see Figure 3). This shift toward the RPE results in
flattening of the perifoveal hump of tissue and loss of foveal
depression. As “sink holes” form in the parafoveal area, the
fovea takes on the appearance of a “mushroom cap.” Others
have referred to this as producing the “flying saucer” sign.6
Irregularity of the retinal pigment epithelium layer can also be
present and observed with the OCT (see Figure 3). These
pathological signs or changes in morphological structure will be
best visualized using the highest definition mode. With the
Cirrus HD-OCT, this would be a 5 line or 1 line raster scan
viewed in black and white. Chen, et al., found the SDOCT
particularly useful in that they were able to diagnose early toxic
retinopathy in the presence of normal ophthalmoscopy,
autoflourescence, fluorescein angiography, and time domain
OCT. The SDOCT showed thinning of the outer nuclear layer
in the perifoveal region.6 Rodriguez-Patilla, et al., found that a
!
!
Figure 8 Macular thickness cube on the Cirrus HDOCT of both the right and left eyes for case 2. Note the paracentral annular
thinning of the retina, greater in the right eye as compared to the left eye. There is a distinct loss of the macular hump temporally
in the right eye.
!
!
research SDOCT correlated well with an
mfERG.16
!
Fundus autofluorescence (FAF) is a recent
technique that uses photography or
scanning laser microscopy to detect and
quantify the stimulated emission of light
from naturally occurring fluorophores. An
intense light flash (300-600 nm) excites the
lipofuscin molecule and a weak light is reemitted. The weak signal needs to be
processed digitally for “noise” reduction and
enhancement. The longer the wavelength of light, the deeper
the penetration into ocular tissues. Lipofuscin, known as the
aging pigment, is the most significant of these. It accumulates in
post-mitotic neurons due to age, long-term phototoxicity, and
from ocular disease. The RPE phagocytizes the cellular
byproducts of the photoreceptors which contribute to the
accumulation of lipofuscin. The toxic effects of
hydroxychloroquine cause lipofuscin to accumulate in the RPE.17
Early on there is increased FAF in a pericentral ring around the
Figure 9 Canon photographs of the right eye of case 2. Color photograph displaying mild retinal pigmented epithelium
irregularities and drusen of the macula consistent with early macular degeneration. (top right picture) red free photograph of the
right eye showing only signs of early age-related macular degeneration. (Bottom left picture) FAF picture of the right eye. Note
increased intensity of fluorescence in parafoveal retina consistent with early lipofuscin accumulation indicating increased retinal
damage.
fovea and, as the toxicity advances, the ring of fluorescence will
continue to broaden and intensify. Individuals with increased
FAF often demonstrate decreased retinal sensitivity with
microperimetry. Kelmenson, et al., found correlation of
increased FAF and retinal thinning on the OCT in the area of
RPE dropout in more advanced toxic retinopathy cases.19 In
later stages, there is an absence of FAF and a “bull’s eye”
appearance becomes evident. Therefore, FAF is a technique that
is capable of finding abnormalities in the RPE. In fact, FAF is
more sensitive when screening for early RPE alterations in
HCQ retinopathy as compared to ophthalmoscopy and
fluorescein angiography. It therefore can be used as a reliable
instrument to detect hydroxychloroquine retinal toxicity.14
Progression of hydroxychloroquine retinopathy is variable and
unpredictable after discontinuation of medication. There is a
common misconception that once hydroxychloroquine has
been discontinued the retinal disease process will not progress.
This unfortunately is not the case. The binding of
hydroxychloroquine to the pigment cells of the retinal pigment
epithelium has a very long half life, which is the reason for
progression. If the retinal toxicity has been diagnosed early on,
the chance of future progress is less severe. If the retinal
toxicity is more advanced, there is a significant chance the
retinal disease will progress despite discontinuation of the
medication. The continued progression of the retinal disease
has been reported up to three years after medication cessation.
18 In one study consisting of eight years of long-term follow up
after cessation of medication, it was determined that 63% of
patients went on to have one or more lines of visual acuity loss
and progression of visual field damage.5
It is important to make an earlier diagnosis of macular toxicity
before permanent functional vision damage occurs.
Hydroxychloroquine toxic maculopathy is more likely to
progress when diagnosed at later stages than when detected
earlier in the disease process. Since the appearance of “bull’s
eye” maculopathy is a late stage disease finding, diligent followup, appropriate testing, and assessing the patient’s risk is
imperative for prevention. With no known treatment for toxic
maculopathy, the key to management is early diagnosis. A timely
diagnosis can be made with the advent of new technologies,
thus reducing the risk of visual morbidity from antimalarial
medication.
Acknowledgements
The authors would like to thank Tara Siemonsma for her
assistance with photography and Cindy Tassi for editing the
manuscript.
References
1.
2.
3.
Mavrikakis I, Sifikakis PP, Mavrikakis E, Rougas K,
Kostopoulos C, Mavrikakis M. The incidence of irreversible
retinal toxicity in patients treated with
hydroxychloroquine: a reappraisal. Ophthalmology 2003 Jul;
110(7):1321-1326
Lew GD, Munz SJ, Paschal J, Cohen HB, Prince KJ, Peterson
T. Incidence of hydroxychloroquine retinopathy in 1.207
patients in large multicenter outpatient practice. Arthritis
Rheum. 1997 Aug; 40(8):1482-6.
Marmor MF, Kellner U, Lai T, et al. Revised
recommendations on screening for chloroquine and
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
hydroxychloroquine retinopathy. Ophthalmology. 2011;
118(2):415-22.
Hanna B, Holdeman N, Tang R, Schiffman J. Retinal toxicity
secondary to plaquenil therapy. Optometry.2008;79(2):
90-94.
Easterbrook M. Long term course of anti-malarial
maculopathy after cessation of treatment. Canadian Journal
of Ophthalmology 1990 Aug; 25(5):249-251.
Chen E, Brown DM, Benz MS, Fish RH, et al. Spectral
domain optical coherence tomography as an effective
screening test for hydroxychloroquine retinopathy (the”
flying saucer” sign). Clin Ophthalmol.2010;4:1151-1158.
Stepien KE, Han DP, Schell J, et al. Spectral domain optical
coherence tomography and adaptive optics may detect
Hydroxychloroquine retinal toxicity before symptomatic
vision loss. Trans Am Ophthalmol Soc. 2009; 12:107:28-33.
Pasadhika S, Fishman GA. The effects of chronic exposure
to hydroxychloroquine or chloroquine on inner retinal
structures. Eye. 2010; 24(2):340-6.
Pasadhika S, Fishman GA, Choi D, Shahidi M. Selective
thinning of the perifoveal inner retina as an early sign of
hydroxychloroquine retinal toxicity. Eye. 2010;24(5):
756-762.
Korah S and Kuriakose T. Optical coherence tomography in
a patient with chloroquine-induced maculopathy. Indian J
Ophthalmol. 2008;56(6): 511-13.
Pasadhika S, Fishman GA, Choi D, Shahidi M. Selective
thinning of the perifoveal inner retina as an early sign of
hydroxychloroquine retinal toxicity. Eye. 2010;24(5):756-62.
Chang WH, Katz BJ, Warner JE,Vitale AT, Creel D, Digre KB.
A novel method for screening the multifocal
electroretonogram in patients using hydroxychloroquine.
Retina. 2008;28(10)1478-86.
Douche C, Bechetoille A, Ebran JM. Routine monitoring of
patients treated with synthetic antimalarials. J Fr
Ophthalmol. 1983;6(8-9):689-95.
Kellner U, Renner AB, Tillack H. Fundus autofluorescence
and mfERG for early detection of retinal alterations in
patients using chloroquine/hydroxychloroquine. Invest
Ophthalmol Vis Sci. 2006;47:3531-3538.
Drexler W, Fujimoto JG. State-of-the-art retinal optical
coherence tomography. Prog Retin Res. 2008; 27(1):45-88.
Rodriguez-Padilla JA, Hedges III TR, Monson B, et al. Highspeed ultra-high-resolution optical coherence tomography
findings in hydroxychloroquine retinopathy. Arch
Ophthalmol. 2007; 125(6):775-780.
Gunduz K, Pulido J, Bakri S, et al. Fundus autofluorescence
of choroidal melanocytic lesions and the effects of
treatment. Trans Am Ophthalmol Soc. 2007;105:172-179.
Brinkley J.R., Dubois E.L., Ryan S.J. Long term course of
chloroquine retinopathy after cessation of medication.
American Journal of Ophthalmology 1979; 88(1):1-11
Kelmenson AT, Brar VS, Murthy RK, Chalam KV. Fundus
autofluorescence and spectral domain optical coherence
tomography in early detection of Plaquenil maculopathy. Eur
J Ophthalmol. 2010.; 20(4)785-8.
Corresponding author: Gary L. Vanderzee, O.D., Sioux Falls
Veterans Affairs Health Care System, 2501 W. 22nd Street,
Sioux Falls, SD, 57017. Email: [email protected].

Freeman May 2012 - American Optometric Association

Transcription

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