Anterior Juxtascleral Delivery of Anecortave Acetate in Eyes with

Anterior Juxtascleral Delivery of Anecortave Acetate
in Eyes with Primary Open-Angle Glaucoma:
A Pilot Investigation
ALAN L. ROBIN, ABBOT F. CLARK, DAVID W. COVERT, SCOTT KRUEGER, MICHAEL V. W. BERGAMINI,
THERESA A. LANDRY, JAIME E. DICKERSON, JR, SALLY A. SCHEIB, TONY REALINI, JOSEPH M. DEFALLER,†
AND GERALD D. CAGLE
● PURPOSE:
To describe the intraocular pressure (IOP)lowering effects in eyes with open-angle glaucoma (OAG)
after treatment with an anterior juxtascleral depot of
anecortave acetate.
● DESIGN: Prospective, interventional case series.
● METHODS: Seven eyes of six subjects with OAG, with
uncontrolled IOP while being administered one or more
topical medications, received 24 mg anecortave acetate
delivered by anterior juxtascleral depot. IOP was assessed
at baseline and regularly after treatment for up to 24
months.
● RESULTS: Mean IOP before anecortave acetate treatment was 31.3 ⴞ 11.3 mm Hg and dropped by 9.5 ⴞ 4.5
mm Hg (32.7% ⴞ 16.8%) within one week after
treatment. This IOP reduction was sustained through six
months (8.4 ⴞ 5.4 mm Hg [29.6% ⴞ 12.4%]) and 12
months (9.5 ⴞ 5.7 mm Hg [34.0% ⴞ 15.9%]) after a
single anecortave acetate treatment. The injection process was well tolerated, and no eyes experienced any
injection-related or drug-related serious adverse events.
● CONCLUSIONS: Both the anterior juxtascleral depot of
a drug and anecortave acetate may be promising candidates for IOP reduction in eyes with OAG. Additional
studies are required to establish better their efficacy and
safety, optimal dosing frequency, mechanism of action,
and potential additivity to other IOP-lowering therapies.
(Am J Ophthalmol 2009;147:45–50. © 2009 by
Elsevier Inc. All rights reserved.)
O
PEN-ANGLE GLAUCOMA IS ASSOCIATED WITH AL-
most no symptoms until it reaches the advanced
stages. As such, the clinical management of
glaucoma frequently is compromised by patient nonadherence to therapy. Numerous studies have documented the
†
Deceased.
Accepted for publication Jul 25, 2008.
From the Wilmer Institute and Bloomberg School of Public Health,
Johns Hopkins University (A.L.R.); and the University of Maryland,
Baltimore, Maryland (A.L.R.); Alcon Research Ltd, Fort Worth, Texas
(A.F.C., D.W.C., S.K., M.V.W.B., T.A.L., J.E.D., S.A.S., J.M.D., G.D.C.);
and West Virginia University, Morgantown, West Virginia (T.R.).
Inquiries to Alan L. Robin, Johns Hopkins University, School of Public
Health and Wilmer Institute, 6115 Falls Road, Suite 333, Baltimore, MD
21209; e-mail: [email protected]
0002-9394/09/$36.00
doi:10.1016/j.ajo.2008.07.039
©
2009 BY
prevalent issue of lack of adherence, persistence with
intraocular pressure (IOP)-lowering therapy, or both.1–3
One reason frequently cited by glaucoma patients is the
complexity of a multidrug regimen.4 Even in the prostaglandin era, 40% of subjects with ocular hypertension still
require multiple medications to achieve a modest 20%
reduction in IOP.5 The percentage of patients requiring
adjunctive therapy in established glaucoma is even higher
because current guidelines recommend a minimum initial
IOP reduction of 25%.6
Prostaglandin analogs have become the initial therapy
for ocular hypertension and glaucoma for most patients. In
a sizable number, this medication alone is insufficient to
control IOP adequately. Topical ␤-adrenergic therapy
usually is considered as a first-line adjunctive therapy.
Despite its advantage as being once daily with complimentary mechanisms of action, there is minimal additive effect
of a ␤-blocker to a prostaglandin analog.7–9 Even with the
addition of a topical carbonic anhydrase inhibitor or
␣-agonist three times daily, not much more than 2 mm Hg
of IOP lowering is achieved.10 The addition of more drugs
increases the costs to the patient and society and also
increases the risk of side effects and preservative-related
ocular surface inflammation.11 Further complicating the
situation, most glaucoma patients already are using other
medications for systemic diseases, adding to the overall
medication burden of the patient.12 The need exists for a
safe and highly effective IOP-lowering agent with an
extended duration of action that reduces or eliminates
patient involvement in dosing.
Anecortave acetate, an angiostatic cortisene recently
evaluated as a therapy for neovascular age-related macular
degeneration (AMD), may be such a candidate therapy for
long-term IOP reduction. Anecortave acetate is a cortisol
derivative, formed by replacing the hydroxyl group at
carbon 11 with a double bond between carbons 9 and 11,
and the addition of an acetate group at carbon 21.13 The
resulting molecule lacks glucocorticoid activity.14,15
Anecortave acetate has been shown to possess angiostatic
activity via inhibition of proteases that degrade the extracellular matrix, thus blocking migration of vascular endothelial cells,16,17 and has been studied in phase III clinical
trials as a potential treatment for neovascular AMD.13,18
ELSEVIER INC. ALL
RIGHTS RESERVED.
45
TABLE 1. Baseline Demographics and Pertinent Ocular Histories of Participating Subjects in Anecortave-Treated Eyes with
Open-Angle Glaucoma
Subject
Eye
Eye color
Age (yrs)
Gender
Race
Diagnosis
Cup-to-disc ratio
No. of medications
Baseline IOP (mm Hg)
1
2
3
4
5
6
6
Right
Blue
63
Female
White
POAG
0.9
1
23
Right
Blue
52
Male
White
PDS
0.9
1
29
Right
Blue
65
Female
White
POAG
0.9
4
36
Left
Blue
48
Female
White
POAG
0.9
1
25
Right
Hazel
70
Male
White
PXF
0.6
3
52
Right
Hazel
56
Male
White
POAG
0.5
1
23
Left
Hazel
56
Male
White
POAG
0.5
1
23
IOP ⫽ intraocular pressure; PDS ⫽ Pigmentary Glaucoma syndrome; POAG ⫽ primary open-angle glaucoma; PXF ⫽ pseudoexfoliation
glaucoma; yrs ⫽ years.
Unlike corticosteroids such as prednisone, dexamethasone,
or triamcinolone, anecortave acetate does not reduce
inflammation or cause cataracts.14
Anecortave is relatively insoluble and has been found to
exert its effect near where it is delivered. To this end, a
novel approach was investigated and is reported herein.
This involved the use of a 30-gauge needle, under modified
topical anesthesia, delivering the medication as a depot in
a circumferential manner surrounding the limbus, over the
trabecular meshwork (anterior juxtascleral delivery [AJD]
system). This article describes a case series of seven eyes of
six subjects with open-angle glaucoma (OAG), uncontrolled with at least a prostaglandin analog, who were
treated with anecortave acetate using an AJD. We describe
the procedure, the IOP-lowering, the duration of IOPlowering, and adverse events.
let therapy, any known contraindications to therapy with
steroid-related compounds, or any unstable medical condition that would preclude compliance with study visits.
Subjects were not washed out of prior prostaglandin
analogs or other topical or systemic glaucoma medications,
but were discontinued from all prior glaucoma therapy
with the exception of a prostaglandin analog (which was
continued during this study) at the time of treatment with
anecortave acetate.
After a comprehensive ophthalmologic evaluation, consenting subjects received an AJD of anecortave acetate.
Approximately 20 minutes before the AJD, the ocular
surface was pretreated with both 0.5% apraclonidine and
2.5% phenylephrine to vasoconstrict conjunctival vessels.
Topical proparacaine was administered, followed by topical 0.5% moxifloxacin and topical 2.5% povidone iodine
to minimize the risk of infection. A cotton-tipped applicator was saturated with topical proparacaine and was
applied to the inferior conjunctiva for approximately one
minute. Subjects then were instructed to look upward. A
30-gauge needle was introduced into the subconjunctival
space bevel down until the investigator was sure it was in
the sub-Tenon space. Its position was monitored throughout the procedure. Through this 30-gauge needle, 0.8 ml
3% anecortave acetate solution (24 mg) was injected into
the anterior sub-Tenon space slowly over one to two
minutes. The injections were all video recorded. Subjects
were questioned after the AJD regarding comfort. They
were asked to return in one hour to insure that there was
no IOP elevation. They then were evaluated weekly for
the first month, and then monthly thereafter for up to two
years. All IOP measurements were obtained at approximately the same time of day. Baseline IOP measurement
was a mean of two separate IOP measurements. The
investigator was not masked to either the treatment or the
treated eye. Assessments included changes in medical and
ocular history and solicitation of adverse events; photo-
METHODS
THIS WAS A PROSPECTIVE, UNCONTROLLED CASE SERIES,
conducted under an Investigational New Drug application
(IND no. 60219) obtained from the Food and Drug
Administration (FDA) by the investigator, which limited
the number of subjects included in the study. The six
subjects included in this report were recruited consecutively from the investigator’s referral glaucoma practice.
To be eligible for participation, subjects were 18 years of
age or older and were diagnosed with OAG that was poorly
controlled in the investigator’s opinion despite the use of
either a single topical prostaglandin analog or both a
prostaglandin analog and the addition of at least one more
topical medication. Subjects were excluded from participating if any of the following criteria were met: intraocular
surgery within 60 days, myopic retinopathy or refractive
error of more than ⫺8.00 diopters (D), a history of scleral
buckling surgery, clinical evidence of scleral thinning, use
of anticoagulation therapy other than aspirin or antiplate46
AMERICAN JOURNAL
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JANUARY 2009
TABLE 2. Mean Intraocular Pressure, Intraocular Pressure Reduction from Baseline, and Percent Intraocular Pressure Reduction
from Baseline Through 12 Months in Anecortave-Treated Eyes with Primary-Open Angle Glaucoma
Baseline
Individual data
Subject 1
Subject 2
Subject 3
Subject 4
Subject 5
Subject 6, left eye
Subject 6, right eye
Summary IOP data
No. (eyes)
Mean IOP
Mean IOP reduction
Percent IOP reduction
Mean no. of medications
23
29
36
25
52
23
23
7
30.1
1.7
Week 1
12
26
20
13
44
16
18
7
21.3
⫺8.9
⫺31.2
1.7
Week 2
Week 3
11
27
21.5
13
32
16
15
12
27
20
12.5
28
14
7
19.4
⫺10.8
⫺35.9
1.7
6
18.9
⫺12.4
⫺39.1
1.8
Week 4
Month 2
Month 3
Month 4
12
27
18
12
27
16
17
13
27
15
12
14
27
13
13
14
28
15
18
15
16
15
20
7
18.4
⫺11.7
⫺37.3
1.7
6
16.3
⫺10.2
⫺37.7
1.5
6
17.0
⫺9.5
⫺34.3
1.5
Month 5
Month 6
Month 12
16
18
15.5
17
16
24
18
19
16
16
23
16
16
17
21
20
25
6
19.0
⫺7.5
⫺26.6
1.2
6
16.4
⫺10.1
⫺36.4
1.5
6
19.2
⫺7.3
⫺26.1
1.5
5
18.8
⫺8.0
⫺28.7
1.4
20
13
IOP ⫽ intraocular pressure.
graphs of the eye and sclera for the first three months;
best-corrected Snellen visual acuity evaluation; external
examination of the eye and its adnexae; extraocular
motility, restriction of gaze, or both; pupil responsiveness
including the presence of afferent pupillary defect; slitlamp examination of the anterior segment and lens;
gonioscopy; dilated fundus examination at six-month intervals; IOP measurement using Goldmann tonometry;
and standard automated perimetry annually.
The primary statistical endpoint for this small pilot
study was mean IOP change from baseline at each follow-up visit. A one-tailed t test (null hypothesis, mean
IOPtreated ⱖ mean IOPbaseline vs alternative hypothesis,
mean IOPtreated ⬍ mean IOPbaseline) was performed for
each time point. A maximum of one eye from each subject
was included in the analysis. Because both eyes for Subject
6 were treated, a separate t test was carried out at each time
point including either the right or left eye for Subject 6.
FIGURE 1. Line graph demonstrating individual eye intraocular
pressure (IOP) response to a single anterior juxtascleral depot of
anecortave in eyes treated with anecortave acetate and having
open-angle glaucoma (OAG). Note that Subject 6 was treated in
both eyes, one month apart. LE ⴝ left eye; RE ⴝ right eye.
RESULTS
WE ENROLLED A TOTAL OF SEVEN EYES OF SIX SUBJECTS.
The baseline characteristics and pertinent ocular histories
of these seven eyes are given in Table 1. All summary
statistics and analyses were calculated using only one eye
from each patient (including only the right eye from
Subject 6). These were repeated using the left eye, which
yielded similar results.
The mean IOP before treatment with anecortave acetate was 31.3 ⫾ 11.3 mm Hg. The seven treated eyes were
using a mean of 1.7 ⫾ 1.5 medications (range, one to four
medications) at baseline. Anecortave acetate therapy produced a rapid and substantial reduction in IOP (Table 2;
VOL. 147, NO. 1
Figure 1). Within one week of treatment, mean IOP dropped
by 9.5 ⫾ 4.5 mm Hg (32.7% ⫾ 16.8%). By four weeks after
treatment, the mean IOP dropped by 12.7 ⫾ 8.1 mm Hg
(39.23% ⫾ 17.6%). These IOP reductions were sustained
through six months (8.4 ⫾ 5.4 mm Hg [29.6% ⫾ 12.4%])
and 12 months (9.5 ⫾ 5.7 mm Hg [34.0% ⫾ 15.9%]) after a
single anecortave acetate treatment.
Most eyes demonstrated a substantial reduction in IOP
after anecortave acetate therapy, but not all achieved
adequate IOP control, despite large IOP reductions. The
IOP in Subject 5’s right eye dropped from 52 to 27 mm Hg
(a 25 mm Hg [48.1%] reduction) within four weeks of
ANECORTAVE ACETATE
IN
GLAUCOMA
47
24 mg anecortave acetate for 12 months (Subject 6’s right eye
included), or 50% of subjects if Subject 6’s left eye was used.
This difference is because the right eye for Subject 6 had an
IOP of 20 mm Hg at month 3 (13% reduction from baseline),
returning to 16 mm Hg at month 5. In contrast, the left eye
had IOPs in the teens until the 12-month visit. These results
are depicted in a Kaplan-Meier plot in Figure 2. All injections were well tolerated without injection-related complications. One subject had a vasovagal episode, but later
reported having similar events when having blood drawn.
All reported a pressure sensation associated with the
injection that lasted at most for a few hours. No serious
adverse events were noted by any subject at any visit.
DISCUSSION
FIGURE 2. Kaplan-Meier survival analysis in eyes treated with
anecortave acetate and having OAG with IOP control, with an
IOP of less than 21 mm Hg, being considered successful therapy.
Note that Subject 6 is considered separately for the right eye
included (dashed line) and left eye included (solid line).
FOR THOSE PATIENTS WHO REACH GLAUCOMA END-STAGE
disease and eventually blindness, it is estimated that the costs
for benefits, healthcare, and reduced tax revenues total $1.5
billion per year.19 Many other costs can be associated with
increasing visual impairment. These include the costs associated with decreased ability to complete daily activities,
increased falls, increased risk of car accidents and increased
mortality.20 Therefore, the use of an anterior juxtascleral
administration of anecortave acetate may have the potential
to preclude or delay the progression of this chronic disease
process and may have a significant positive impact on the
economic and psychological burden of glaucoma.
Intraocular pressure reduction is the only treatment that
has been established to lower the risk of glaucomatous
progression. Numerous highly effective methods of IOP
reduction are available, including medications, laser therapy, and surgical interventions. Medications typically are
used as first-line therapy, with a wide variety of medications and combinations from which to choose.21 Successful
medical therapy, however, is dependent on patient adherence to prescribed treatment regimens, and there exist
many important barriers limiting such adherence.4 The
consequence of inadequate treatment arising from patient
nonadherence is disease progression, characterized by permanent and irreversible loss of visual function. Although
there is no direct consistent evidence linking nonadherence with progression of disease,22 there are suggestions
that nonadherence can affect outcomes in subjects with
glaucoma.23 There is also evidence in other medical fields
that adherence to therapy can affect outcomes.24
Glaucoma drug discovery and development peaked in
the mid 1990s with the introduction of three new classes of
topical IOP-lowering medications: the topical carbonic
anhydrase inhibitors, adrenergic agonists, and prostaglandins, all within two years. Since then, several same-class
drugs and one combination of existing drugs have been
introduced, but no new innovation in drug class for
IOP-lowering has emerged in more than a decade. IOPlowering drug delivery, still limited to daily topical instil-
anecortave acetate treatment, but still was higher than target
with three topical medications; this eye underwent trabeculectomy without any complications and with good IOP
control two years after surgery. Subject 2’s right eye demonstrated no appreciable response to anecortave acetate therapy;
IOP remained within 2 to 3 mm Hg of its 29 mm Hg baseline,
and ultimately required two additional topical medications at
month 4 to achieve adequate control.
Table 2 and Figure 1 provide data through 12 months
after a single injection of anecortave acetate. Five eyes
(four patients) were observed through up to 24 months of
follow-up. Subject 1, who was able to discontinue her
single topical medication four months after treatment,
remained controlled, with IOPs of 20 mm Hg or less with
no medications at all visits through 24 months. Subject 3,
who began the study with an IOP of 36 mm Hg with four
medications, maintained an IOP of 20 mm Hg or less with
no further IOP-lowering interventions through 19 months
of follow-up after anecortave acetate therapy. Subject 4
was able to discontinue prostaglandin monotherapy three
months after anecortave acetate therapy, required that it
be restarted 11 months after therapy, and remained controlled with IOP of 15 mm Hg or less for a total of 19
months after anecortave acetate treatment. Subject 6
received anecortave acetate therapy to both eyes, with
adequate IOP control until 13 months after treatment,
when IOP in each eye rose to 28 mm Hg. Both eyes were
retreated with anecortave acetate 24 mg, after which IOP
in both eyes remained at 20 mm Hg or below through 11
more months of follow-up (24 months total).
Using 21 mm Hg and a 20% reduction from baseline as an
arbitrary threshold for adequate IOP control, two-thirds of
the subjects were controlled by a single administration of
48
AMERICAN JOURNAL
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JANUARY 2009
lation by patients, has not kept pace with ophthalmic drug
delivery for other conditions, in which slow-release, sustained-delivery devices can be inserted into the eye to treat
chronic conditions such as cytomegalovirus retinitis,
chronic uveitis, and diabetic macular edema.25–27
Anecortave acetate represents a potential innovation in
both drug class and drug delivery for glaucoma management.
In this small pilot case series, anecortave acetate demonstrated substantial IOP-lowering ability. Its periocular safety
when injected as a posterior juxtascleral depot already has
been established in United States FDA phase III trials for
AMD,13,18 and it was well tolerated when injected as an
anterior juxtascleral depot by all eyes in this and our steroidrelated ocular hypertension series. The mechanism by which
anecortave acetate lowers IOP is unknown, but the magnitude, rapidity, and duration of IOP reduction after a single
anterior juxtascleral depot injection are remarkable.
In this series, we demonstrated that anecortave acetate
significantly lowered IOP in six of seven eyes with OAG
and that its effect lasted for at least three months and up
to 19 months. Notably, the percent IOP reduction was
comparable throughout the IOP spectrum, lowering IOP
by a consistent 40% to 50% at four weeks in eyes with
baseline IOP ranging from 23 to 52 mm Hg. Retreatment
was successful in both eyes of Subject 6, dropping IOP by
8 to 9 mm Hg within two weeks and maintaining this
reduction at seven months after retreatment. All injections were well tolerated and cosmetically acceptable by
one hour after injection. These favorable observations
support a potential role for anecortave acetate in the
management of chronic glaucoma.
The mechanism of anecortave acetate’s IOP-lowering
ability currently is not fully understood. Glucocorticoids
and the growth factor transforming growth factor
(TGF)-␤2 have been implicated in glaucoma pathogenesis. Glucocorticoid treatment can cause elevated IOP in
humans, animals, and in an ex vivo perfusion-cultured
anterior segment model.28,29 Likewise, elevated TGF-␤2
also can elevate IOP in perfusion-cultured anterior segments30,31 as well as in mice transduced with a TGF-␤2
expression vector (Shepard AR, et al, unpublished data,
2008). We have been examining the effects of treating
cultured human trabecular meshwork (TM) cells with the
glucocorticoid dexamethasone as well as TGF-␤2 to understand better how these insults alter TM cell gene expression.
Both of these agents increase the messenger ribonucleic acid
(mRNA) and protein expression of plasminogen activator
inhibitor-1 (PAI-1) in TM cells. PAI-1 plays a major role in
extracellular matrix metabolism because it directly inhibits
the activation of plasminogen and indirectly inhibits the
activation of pro–matrix metalloproteinases. Inhibition of
these extracellular proteinases increases deposition of extracellular matrix in the TM, which are features of both
glucocorticoid-induced and TGF-␤2–induced ocular hypertension as well as primary open-angle glaucoma (POAG).
Transduction of mouse eyes with an adenovirus PAI-1 expression vector elevates IOP (Pang I-H, unpublished observation, 2007), demonstrating that increased expression of
PAI-1 in the anterior segment can be pathogenic. The
elevated PAI-1 expression induced by either dexamethasone
or TGF-␤2 in cultured TM cells can be inhibited in a
dose-dependent manner by concomitant addition of anecortave desacetate in the culture medium, which at least in part
may be responsible for this agent’s ability to lower IOP in
glaucoma- and steroid-induced ocular hypertensive patients.
The EC50 for this inhibition of PAI-1 expression is approximately 100 to 500 ␮m (Clark AF, unpublished observation,
2007).
Limitations of this series include its very small number of
eyes and the lack of any control data. As such, general
statements regarding the efficacy and safety of this novel
treatment for IOP reduction are not possible. It may be that
the IOP reduction in part was the result of regression to the
mean, observer bias, or increased adherence to IOP-lowering
medications after the AJD. It also may be that the actual act
of the injection caused the IOP to be diminished.
The possible safety of this method also can not be
appreciated fully by this limited number of subjects. Complications such as scleral perforation with secondary hemorrhage, cataract formation, or endophthalmitis certainly
are not likely, but are possible.
In summary, anecortave acetate may be a promising candidate for IOP reduction in eyes with POAG. The drug offers
the potential for substantial IOP reductions, and its mode of
delivery—via an anterior juxtascleral depot— offers the potential for longer-term IOP control without the requirement
of daily therapeutic adherence by patients. Future studies are
required to establish better the efficacy and safety of anecortave acetate administered as an anterior juxtascleral depot
injection for the reduction of IOP. The focus is on eyes with
OAG to determine the optimal dosing and duration of action
and to establish its mechanism of action and potential
additivity to other available IOP-lowering treatments.
THE AUTHORS INDICATE NO FINANCIAL SUPPORT. DR ROBIN IS A PAID CONSULTANT TO ALCON RESEARCH LTD AND HAS
a patent pending. Dr Clark has a patent for anecortave acetate. Dr Realini is a paid consultant to Alcon Research Ltd. Mr Covert and Drs Clark, Krueger,
Bergamini, Landry, Dickerson, DeFaller, and Cagle are employees of Alcon Research Ltd. Involved in design of study (A.L.R., A.F.C., J.M.D., G.D.C.);
conduct of study (A.L.R.); data management and analysis (A.L.R., S.A.S., S.K., M.V.W.B., J.E.D., T.A.L., T.R.); and manuscript preparation and review
(A.L.R., A.F.C., S.K., M.V.W.B., T.A.L., J.E.D., S.A.S., G.D.C., T.R., D.W.C.). This study was performed under an investigator Investigational New
Drug application from the Food and Drug Administration (IND no. 60219) and was approved by the Sterling Institutional Review Board. All subjects
provided both oral and written informed consent. The study was conducted consistent with Health Insurance Portability and Accountability Act
regulations. It was not necessary to register this with clinicaltrials.gov.
The anecortave acetate was supplied by Alcon Research Ltd.
VOL. 147, NO. 1
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Biosketch
Alan L. Robin earned his bachelor’s degree at Yale University, New Haven, Connecticut, and his MD at Tufts University,
School of Medicine, Boston, Massachusetts. He trained in ophthalmology at the Greater Baltimore Medical Center, and
in glaucoma with both Harry A. Quigley, MD, and Irvin Pollack, MD at the Wilmer Institute, Johns Hopkins University
School of Medicine, Baltimore, Maryland. Dr Robin was awarded the 2005 American Academy of Ophthalmology
Outstanding Humanitarian Service Award. His current interests are clinical glaucoma, adherence and execution of
glaucoma therapies, novel treatments for glaucoma, and international ophthalmology.
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Biosketch
Abbot F. Clark received his PhD in cellular and molecular biology at Case Western Reserve University in Cleveland,
Ohio and did his post-doctoral training in immunology and physiology at the University of Texas Southwestern Medical
Center in Dallas, Texas. He worked for more that 20 years in Ophthalmic Discovery Research at Alcon Laboratories in
Fort Worth, Texas and just recently joined the University of North Texas Health Science Center in Fort Worth, where
he is Professor of Cell Biology & Genetics and Director of the Visual Sciences Program. Dr Clark continues to explore
the cellular and molecular pathogenic mechanisms for glaucoma and other ocular diseases.
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