Session 448 Glaucoma Imaging II

Transcription

ARVO 2016 Annual Meeting Abstracts
448 Glaucoma Imaging II
Wednesday, May 04, 2016 11:00 AM–12:45 PM
Exhibit/Poster Hall Poster Session
Program #/Board # Range: 5114–5148/C0129–C0163
Organizing Section: Glaucoma
Program Number: 5114 Poster Board Number: C0129
Presentation Time: 11:00 AM–12:45 PM
Quantification of Focal Outflow Enhancement using Differential
Canalograms
Ralitsa Loewen1, Eric N. Brown2, Gordon Scott3, Hardik Parikh1, 4,
Joel S. Schuman1, 5, Nils A. Loewen1. 1Ophthalmology, University of
Pittsburgh, Pittsburgh, PA; 2Ophthalmology, University of Vanderbilt,
Nashville, TN; 3School of Medicine, University of Pittsburgh,
Pittsburgh, PA; 4New Jersey Medical School, Rutgers State
University of New Jersey, Newark, NJ; 5Ophthalmology, New York
University, New York, NY.
Purpose: To quantify focal changes of conventional outflow caused
by ab interno trabeculectomy (AIT).
Methods: Gonioscopic, plasma-mediated ab interno trabeculectomy
(AIT; Trabectome, Neomedix, Tustin, CA) was established in
enucleated pig eyes. We developed a program to automatically
quantify outflow changes (R, package eye-canalogram, github.
com) using a fluorescent tracer reperfusion technique. Trabecular
meshwork (TM) ablation was demonstrated with fluorescent
microspheres in 6 eyes before formal outflow quantification was
performed with two dye reperfusion canalograms (fluorescein
followed by Texas red) in 6 further eyes. Eyes were perfused with a
central, intracameral needle at 15 mmHg. Canalograms and histology
were correlated for each eye.
Results: The pig eye provided a model with high similarity to
AIT in human patients. Histology indicated ablation of TM and
unroofing of most Schlemm’s canal segments. Microspheres
highlighted additional circumferential and radial outflow beyond the
immediate area of ablation. Differential canalograms showed that
AIT caused an increase in outflow of 17±5 fold inferonasally (IN),
14±3 fold superonasally (SN) and also an increase in the opposite
quadrants with a 2±1 fold increase superotemporally (ST) and
3±3 inferotemporally (IT). Perilimbal specific flow image analysis
showed an accelerated nasal filling with additional perilimbal flow
directed into adjacent quadrants.
Conclusions: In this quantitative canalography model,
supraphysiological outflow enhancement by AIT could be measured
in the area of TM ablation and beyond. These new tools are now
available as open source software to aid the investigation of outflow
tract bioengineering and design of new devices.
Commercial Relationships: Ralitsa Loewen, Neomedix (R);
Eric N. Brown, None; Gordon Scott, None; Hardik Parikh, None;
Joel S. Schuman, None; Nils A. Loewen, Neomedix (R)
Support: NEI Grant K08 EY022737 (NAL), American Glaucoma
Society (NAL), P30-EY08099 (JSS), Research to Prevent Blindness
(JSS), CORE P30AEY08098, Alpha Omega Alpha Carolyn L.
Kuckein Student Research Fellowship (HAP)
Automated 360-Degree Gonioscopic Color Photography and its
Current Problems to be Solved for Clinical Use
Masanori Hangai1, Takuhei Shoji1, Yoko Shindo1, Cesare Tanassi2,
Michele Pascolini2. 1Ophthalmology, Saitama Medical University,
Iruma, Japan; 2NIDEK Technologies Srl, Padova, Italy.
Purpose: To determine how successfully 360-degree iridocorneal
angle images were captured by using our prototype digital
gonioscope camera, and to determine the problems to be solved for
routine clinical use.
Methods: Whole circumference iridocorneal angle images were
captured in healthy eyes by using a prototype automated gonioscope
camera (GONIOSCOPE NGS-1), which was developed by NIDEK
Technologies Srl. (Padova, Italy), to test the focusing and image
brightness in the 360-degree. This system circumferentially captures
16 single gonioscopic images of 16 portions illuminated by a
white LED using an automatically-rotating optical gonioprism.
The 16 iridocorneal angle images are overlapping and consecutive.
Iridocorneal angle images on the 4 screens in the superior, nasal,
inferior and temporal portions of the 16 portions were used for the
alignment of capturing position and focusing. Twenty four eyes of
12 Japanese (all Asian) subjects (23-62 years old, mean 37.5) were
examined twice by this protocol. Two Italians (all Caucasian) were
examined as a reference. The frequency of good focus and brightness
on the trabecular meshwork area was evaluated.
Results: Cornea thickness, corneal diameter, and axial length of the
Japanese eyes ranged from 482 to 562 μm (mean ± standard deviation
[SD], 529.1±22.6 μm), from 5.4 to 12.8 mm (11.4±1.9 mm) and from
22.7 to 27.66 mm (24.6±1.4 mm), respectively. The pupil diameter
as measured immediately before examination ranged from 3.5 to
11.9 mm (5.2±2.2 mm). The number of single gonioscopic images
with poor focus per 360-degree imaging ranged from 0 to 8 (44.4%)
(mean±SD, 3.96 [22.0%]±2.5). The number of single gonioscopic
images with dark trabecular meshwork images per 360-degree
imaging ranged from 0 to 6.0 (33.3%) (mean±SD, 0.7 [7.7%]±1.4).
Both the number of single gonioscopic images with poor focus
and with dark trabecular meshwork images were significantly
correlated only with the greater corneal diameter (P=0.025 and 0.020,
rho=-0.446 and -0.461, respectively, in Spearman’s rank correlation
coefficients).
Conclusions: These results suggest that focusing is more
difficult than lightening in the automated 360-degree gonioscopic
photography based on automatically-rotating optical gonioprism
system. Greater corneal diameter appeared to cause poor focusing
and dark trabecular meshwork images.
Commercial Relationships: Masanori Hangai, Nidek (C), Nidek
(F); Takuhei Shoji, None; Yoko Shindo, None; Cesare Tanassi,
NIDEK Technologies Srl; Michele Pascolini, NIDEK Technologies
Srl
A new image based digital gonioscope device for irido-corneal
angle imaging
Maria Cecilia D. Aquino, Victor T. Koh, Vinay Swaroop Balla,
Paul Chew. Ophthalmology, National University Hospital, National
University Health System, Singapore, Singapore.
Purpose: To assess if the new image based digital gonioscope device
is easy to use and applicable in capturing images of the anterior
chamber (AC) iridocorneal angle.
Methods: A stand-alone gonioscopy protoype was used which
comprise of an optical gonioprism and a built-in color high-resolution
camera. A drop of amethocaine 0.5% was instilled on the eye prior
to digital gonioscopy. Before starting the examination, a drop of an
eye gel was put on the tip of the gonioprism. With the joystick, the
instrument was moved towards the apex of the patient’s cornea. A
fixation target in the center of the gonioprism was used to stabilize
the patient’s eye. A semi-automatic alignment algorithm was started
after a good image of the inferior quadrant focusing on the trabecular
meshwork can be captured on the LCD screen. The algorithm
started by showing 4 separate images representing 4 quadrants of
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the iridocorneal angle which was followed by further refinement of
the internal optics. Multi-modal image acquisition was started by
imaging 16 segments (5 images per segments with changing focus
position) to cover all 360 degrees of the iridocorneal angle. When
acquisition was finished, the entire examination was saved internally.
The review button allowed a display and export of the acquired
images.
Results: To date, a total of 37 patients (65 eyes) had photos of
their irido-corneal angles taken with the new device. Each eye took
12 seconds for 360 degree imaging and all the eyes successfully
completed the procedure without any complications. All the images
were taken by a trained ophthalmic technician. Out of 16 images
taken per eye, 13.6 ± 1.5 (mean ± SD) images were focused and clear
enough to identify the angle structures including small iris processes,
faint pigmentation of the trabecular meshwork and peripheral anterior
synechiae. The temporal images of the irido-corneal angles were
consistently found to be suboptimal in image quality.
Conclusions: The new digital gonioscopy imaging device is a
promising semi-automatic tool which is easy to operate and could be
valuable in monitoring and screening for angle closure disease in the
eye. We are planning to conduct clinical trials to compare the device
with conventional slit lamp gonioscopy.
brow, and the other had narrow inter-palpebral fissures, making
prism alignment difficult. Among the 23 eyes that were evaluated,
poor image quality precluded correlation analyses with traditional
gonioscopy and AS-OCT. Modifications to the device are in process
and additional results will be reported.
Conclusions: The preliminary images obtained were largely ungradable, but this might be related to a steep learning curve for
optimal use of the device and some software and hardware issues
with the prototype. Software and hardware updates are in the process
of being developed to improve patient fixation, device alignment
and image quality. Despite issues with the initial data, these updates
combined with increased training makes for a promising tool in
glaucoma diagnosis as it provides objective, repeatable images that
can be documented for monitoring of disease progression.
Digital gonioscope images of the right eye
Commercial Relationships: Maria Cecilia D. Aquino, None;
Victor T. Koh; Vinay Swaroop Balla, None; Paul Chew, None
Auto-gonioscopy: a novel method for imaging the irido-corneal
angle
Christopher Lee1, Varshini Varadaraj1, Sophie LaBarre1,
Lucy I. Mudie1, David S. Friedman1, Michele Pascolini2,
Mattia Minozzi2, Simone Pajaro2, Cesare Tanassi2. 1Wilmer, Johns
Hopkins University, Baltimore, MD; 2Nidek Technologies SRL,
Padova, Italy.
Purpose: Gonioscopy is an integral part of the comprehensive
ophthalmic examination. However, it is subjective with imperfect
intra- and inter-observer reproducibility, and is often not performed
due to physician and patient discomfort. An automated device has
been developed that obtains 360° images of the irido-corneal angle.
This study aims to assess the device’s feasibility, correlation with
parameters measured by traditional gonioscopy, and comparison
with parameters measured by anterior segment optical coherence
tomography (AS-OCT).
Methods: We enrolled 19 patients presenting to the Wilmer Eye
Institute glaucoma service between July and November 2015.
Subjects underwent a slit lamp examination by a glaucoma specialist
including assessment of the limbal anterior chamber depth using
Foster’s modified van Herrick technique, and irido-corneal angle
with Goldmann gonioscopy using Schaffer’s classification. This
was followed by AS-OCT and automated gonioscopy. The Nidek
Technologies NGS-1 auto-gonioscope consists of a 16 mirror faceted
prism that uses a clear, viscous gel interface to make contact with an
anesthetized cornea. Five images at varying focal depths are obtained
for each of the 16 sections over 2 seconds and a stitched 360° image
of the irido-corneal angle is created.
Results: Preliminary analyses of 23 eyes of 17 patients were
performed. We were unable to procure images for two subjects due to
facial anthropometry; one subject had deep-set orbit with a prominent
Example of a good image
Example of a Stitched image
Commercial Relationships: Christopher Lee, None;
Varshini Varadaraj, None; Sophie LaBarre, None;
Lucy I. Mudie, None; David S. Friedman, Nidek Technologies
(C); Michele Pascolini, Nidek Technologies SRL; Mattia Minozzi,
Nidek Technologies SRL; Simone Pajaro, Nidek Technologies SRL;
Cesare Tanassi, Nidek Technologies SRL
Quantification of color information in images obtained by a novel
360-degree gonioscope
Masaki Tanito1, 2, Simone Pajaro3, Andrea De Giusti3. 1Division
of Ophthalmology, Matsue Red Cross Hospital, Matsue, Japan;
2
Department of Ophthalmology, Shimane University Faculty of
Medicine, Izumo, Japan; 3R&D, NIDEK Technologies Srl, Padova,
Italy.
Purpose: Gonioscopy is essential to make a correct diagnosis
of glaucoma, however, requires an examiner’s skill and only
provide subjective information. Assessment of anterior chamber
angle by using currently available modalities including ultrasound
biomicroscopy or anterior segment optical coherence tomography
that enable quantitation of the angle structure are achromatic
technique and therefore don’t provide any chromatic information.
Recently developed gonioscopic device (Gonioscope NGS-1, NIDEK
Technologies Srl, Italy) was able to automatically acquire true color
images of the irido-corneal angle structures and combine them in a
360-degree picture of the angle (Tanassi C, et al., Abstract Number
4975, ARVO 2015). In this study, image analyses were performed
in the pictures obtained by using NGS-1 to quantify the color
information of the angle.
Methods: The NGS-1 system detects the irido-corneal angle using
a prism with a soft contact to the corneal surface. The prism has
16 mirrored facets, each of them projecting white light to a single
portion of the irido-corneal angle (about 4x4 mm2). A rotating 1.3
megapixel camera element scans all the facets to capture 5 images,
at different focus depth, for each of the 16 sectors in less than
2 seconds. On an each selected image from 16 sectors, a region
of interest (ROI) was manually defined in the area of trabecular
meshwork on the computer screen. From each ROI, pixels’ color
information was extracted in 3 color spaces (e.g., RGB, XYZ, and
Lab), and several indices were calculated.
Results: By image analyses, 9 histograms and 36 single values
(mean, standard deviation, minimum and maximum values for each
color channels) were successfully obtained from a set of 16-images.
Plot of the mean channel values of each portion on the TSNIT graph
showed unique distributions among a, b, and L channels, while 3
channels of RBG or XYZ color spaces largely overlapped each other.
Conclusions: The color information of trabecular meshwork was
analyzed in the 360-degree irido-corneal angle images. By this
initial image analysis, the Lab color space seems to contain the most
information, while the RGB and the XYZ mimic the L channel of the
Lab color space. The established method can be applied to understand
color/pigment variations among specific directions in normal and
glaucomatous eyes.
The graph represents the Mean L values among the 16 images.
Commercial Relationships: Masaki Tanito, NIDEK Co., Ltd. (F);
Simone Pajaro, NIDEK Technologies Srl (C), NIDEK Technologies
Srl; Andrea De Giusti, NIDEK Technologies Srl, NIDEK
Technologies Srl (C)
Three-Dimensional 360 Degrees Imaging of Aqueous Humor
Outflow Structures in the Living Human Eye with SpectralDomain OCT
Anna Dastiridou2, 1, Akram Belghith3, Linda M. Zangwill3,
Robert N. Weinreb3, Alex S. Huang2. 1University Hospital of
Larissa, PASADENA, CA; 2Doheny Eye Institute, Los Angeles,
CA; 3Department of Ophthalmology, Hamilton Glaucoma Center,
University of California, San Diego, La Jolla, CA.
Purpose: To create a three-dimensional model of the circumferential
aqueous humor outflow (AHO) structures in the living human eye
using an automated detection algorithm of Schlemm’s Canal (SC) and
first-order collector channels (CC) applied to non-invasive spectral
domain optical coherence tomography (SD-OCT) images.
Methods: High-resolution SD-OCT images from volume datasets
of angle structures from a living human eye (34 year-old healthy
volunteer) were acquired (Heidelberg Engineering; Spectralis) with
the anterior segment module (scleral mode; ART=9; resolution
axial/lateral/B-to-B; 3.9/11/11 μm). Overlapping volume scans
were manually set circumferentially around the limbus. A Bayesian
Ridge method was used to approximate the location of the SC on
the infrared confocal laser scanning ophthalmoscopic (CSLO)
images with a Cross Multiplication tool developed to initiate SC
and CC detection automated through a Fuzzy Hidden Markov Chain
approach. Individual B-scans were organized 360 degrees around
the limbus anchored to the CSLO image. The guiding principal of
the automated detection method was to set error tolerance such that
missing structures (false negatives) would be prioritized over creating
false structures (false positives).
Automatic segmentation of SC and first-order AHO pathways
were manually confirmed by two masked graders. The following
parameters were graded: complete false negative detection of SC,
complete false positive detection of SC, partial detection of SC
(<50% of the true SC), exaggerated detection of SC (>200% of
the true SC), complete false negative and complete false positive
detection of CC.
Results: 48 out of 5114 (<1%) scans were deemed ungradable.
Overall, the automatic segmentation algorithm performed well,
with 1.5% out of 5066 images showing false negative SC detection,
0.7% false positive SC detection, 3.8% partial SC detection, 0.1%
exaggerated SC detection, 29.5% false negative CC detection and
1.2% false positive CC detection. The agreement between the
two graders in each parameter tested was good (kappa ranging
between 0.63-0.78), with the exception of exaggerated SC detection
(kappa=0.2), where the incidence was extremely low.
Conclusions: 360-degree imaging of AHO structures in the living
human eye is possible and can provide information about the outflow
pathways.
Commercial Relationships: Anna Dastiridou, None;
Akram Belghith, None; Linda M. Zangwill, Topcon Medical
Systems Inc (F), Carl Zeiss Meditec Inc (F), Carl Zeiss Meditec
Inc (R), Optovue Inc (R), Optovue Inc (F), Quark (F), Heidelberg
Engineering GmbH (F); Robert N. Weinreb; Alex S. Huang,
Glaukos (F), Heidelberg Engineering GmbH (F)
Support: NIH/NEI K08EY024674, AGS Mentoring for Physician
Scientists Award 2014, American Glaucoma Society Young Clinician
Scientist Award 2015, Research to Prevent Blindness
Intra-quadrant variability of anterior chamber angle status on
spectral-domain optical coherence tomography
James Leong1, 2, Kent Chow2, Graham Reeves1, Tony Wells1. 1Capital
Eye Specialists, Wellington, New Zealand; 2Ophthalmology,
Christchurch Hospital, Christchurch, New Zealand.
Purpose: To quantify the intra-quadrant variability of anterior
chamber angle (ACA) status in angle closure suspects when using
spectral-domain optical tomography (SD-OCT)
Methods: Retrospective cross-sectional observational study of 16
consecutive patients with suspected angle closure on gonioscopy.
All participants underwent SD-OCT scans consisting of multiple
cross-sectional slices of each ACA quadrant. Angle closure status was
qualitatively graded on these scans by a single observer masked to
gonioscopic findings. The main outcome measures were the intra-
quadrant variability of iridotrabecular contact (ITC) on SD-OCT
scans.
Results: Out of a total 1426 SD-OCT scans, each representing a
single cross-sectional slice of an ACA quadrant, 23% demonstrated
the presence of ITC, while 71% demonstrated the absence of ITC and
6% were inconclusive. Overall, there was fair agreement between
SD-OCT slices in reference to the central slice within each scanned
ACA quadrant (77%, k=0.44). On average, against the reference
central slice, the likelihood of misclassifying an ACA quadrant on the
basis of a single, isolated SD-OCT slice was 23%.
Conclusions: In angle closure suspects, the use of only a single
SD-OCT slice carries a significant risk of misclassification. If clinical
decisions are going to be based on OCT scans of the ACA, multiple
slices in different positions of the same quadrant should be examined.
Commercial Relationships: James Leong; Kent Chow, None;
Graham Reeves, None; Tony Wells, None
Effect of Body Posture on Anterior Chamber Angle in Healthy
Subjects: an Anterior Segment Optical Coherence Tomography
Study
Ji-Hye Park, Chungkwon Yoo, Dong-yun Yeon, Yong Yeon Kim.
Purpose: Previous studies have reported the effect of changing body
posture from the sitting to supine position on intraocular pressure and
anterior chamber angle (ACA) parameters. However, the effect of
lateral decubitus (LD) positioning on ACA parameters is unknown.
This study evaluated how the postural alteration from sitting to LD
position affects the anterior chamber angle in healthy subjects.
Methods: Twenty-three healthy subjects participated in this study.
They underwent anterior segment optical coherence tomography
(AS OCT) imaging in the sitting position. Then, they were asked to
change their body posture to the left LD position. Ten minutes after
assuming the left LD position, they underwent AS OCT imaging
in the same body posture. ACA parameters [1) trabecular-iris angle
(TIA); 2) angle opening distance at 500 μm from the scleral spur
(AOD500), 3) trabecular-iris space area 500 (TISA500), 4) anterior
chamber depth (ACD)] obtained in each posture were compared
between the sitting position and the LD position.
Results: When the participants changed the body posture from the
sitting to the left LD position, ACA parameters of right eyes showed
significant decreases on the temporal side (TIA: 39.53 ± 2.38ο to
38.31 ± 3.47ο; AOD500: 0.72 ± 0.13 to 0.65 ± 0.08; TISA500: 0.25 ±
0.06 to 0.22 ± 0.04; all p<0.05), whereas they showed no significant
changes on the nasal side. Compared between the sitting and left LD
postures, ACA parameters of left eyes showed significant decreases
only on the nasal side (TIA: 39.49 ± 2.24ο to 38.17 ± 2.76ο; AOD500:
0.68 ± 0.09 to 0.64 ± 0.10; TISA500: 0.23 ± 0.04 to 0.21 ± 0.03; all
p<0.05). ACD measured in the sitting position did not differ from that
measured in the left LD posture.
Conclusions: Compared with that measured in the sitting position,
ACD of healthy subjects did not show any significant change in the
left LD position. However, ACA parameters decreased when the site
of measurement was changed from the nasal or temporal side in the
sitting posture to the upper side of the eyeball in the LD posture,
whereas such change was not found when the site of measurement
was changed from the nasal or temporal to the lower side of the
eyeball in the LD posture.
Commercial Relationships: Ji-Hye Park, None; Chungkwon Yoo,
None; Dong-yun Yeon, None; Yong Yeon Kim, None
Corneal Hysteresis and Anterior Segment Optical Coherence
Tomography Parameters in Eyes with Anatomically Narrow
Angles
Kyle D. Kovacs, Syed A. Hussnain, Christopher C. Teng.
Ophthalmology and Visual Science, Yale School of Medicine, New
Haven, CT.
Purpose: The aim of this study is to elucidate the relationship
between corneal hysteresis(CH) and anterior segment structural
parameters in eyes with anatomically narrow angles (ANA).
Methods: This was an IRB-approved retrospective chart review of
eyes with ANA, which were evaluated on initial presentation with
the Ocular Response Analyzer (ORA; Reichert Corp., Buffalo, USA)
and anterior segment OCT (Visante, Carl Zeiss Meditec, Inc, Dublin,
CA). All patients with known ocular pathology other than PAC were
excluded. Anterior segment OCT measurements included: central
corneal thickness (CCTOCT), nasal and temporal peripheral corneal
thicknesses (PCT1 and PCT2), anterior chamber depth (ACD), nasal
angle to temporal angle distance (ATA), and temporal and nasal
angle measurements (angle 0 and 180). Central corneal thickness
via pachymetry (CCTP), and spherical equivalents for each eye were
noted. Means, standard deviations, and Pearson correlations were
performed using Prism®.
Results: This study evaluated 46 eyes of 23 patients (15 female and 8
males). Mean CH, CCTP, IOPg, and spherical equivalent were 10.12
± 2.22 mmHg, 556.8 ± 45.70 um, 13.77 ± 4.24 mmHg, and +0.71
± 2.3D, respectively. Higher CH was more strongly correlated with
increasing CCTOCT (r=0.68; 95% CI 0.49, 0.81, p <0.0001) than with
PCT1 (r=0.55; 95% CI 0.31 to 0.72, p <0.0001) or PCT2 (r=0.46;
95% CI 0.19 to 0.66, p <0.0014). There was no correlation between
CH and any other measured structural parameter in PACS eyes i.e.
ACD, ATA, Angle 0, and Angle 180.
Conclusions: In ANA, higher CH correlates more strongly with
increasing central corneal thickness, rather than peripheral corneal
thickness, and does not correlate with anterior segment structural
parameters such as ACD, ATA, Angle0, and Angle 180. These results
suggest that lower CH observed in ANA may be due to inherent
biomechanical composition of the cornea rather than differences in
angle structure.
Commercial Relationships: Kyle D. Kovacs, None;
Syed A. Hussnain, None; Christopher C. Teng
Support: This research was supported by a department grant from
Research to Prevent Blindness.
Anterior Segment Parameters in Subjects with Asymmetric
Primary Angle Closure Glaucoma
Monisha E. Nongpiur1, 2, Kenric R. Fan3, Jestin W. Chiew3,
Yap S. Cheong3, Shamira Perera1, 2, Tin Aung1, 3. 1Singapore Eye
Research Institute, Singapore National Eye Centre, Singapore,
Singapore; 2Duke-NUS Medical School, Singapore, Singapore; 3Yong
Loo Lin School of Medicine, National University of Singapore,
Singapore, Singapore.
Purpose: To investigate the association between anterior segment
parameters and asymmetric primary angle closure glaucoma (PACG).
Methods: Two hundred and fifty eight subjects with PACG in at
least one eye were recruited from glaucoma clinics. Each subject
underwent anterior-segment optical coherence tomography (AS-OCT,
Visante, Carl Zeiss Meditec, Dublin, CA) imaging, gonioscopy and
visual field (VF) assessment. Visual field asymmetry was defined as a
five point difference between the eyes using the Advanced Glaucoma
Intervention Study (AGIS) scoring system; and unilateral VF defect
was defined as an AGIS score of 0 in the better eye and an interocular
score asymmetry of ≥5.
Results: Based on the study definitions, 53 subjects (20.5%) had
VF asymmetry and 33 (12.8%) had unilateral VF defect. The
mean age of the 53 subjects was 62.1±7.3 years and there were 26
(49.1%) females. Compared to the better eyes, the worse eyes had
significantly higher presenting intraocular pressure (IOP, 32.7±15.7
vs 18.7±8.1; p<0.001), greater vertical-cup-disc ratio (p<0.001) and
use of more glaucoma medications (p<0.001). The worse eyes of
those with VF asymmetry were also characterized by significantly
smaller anterior chamber width (ACW, p=0.02) and smaller posterior
corneal arc length (PCAL, p=0.016). The analysis in subjects with
unilateral VF defect was largely similar, with the affected eye
characterized by significantly narrower gonioscopic angle width
(p=0.004), smaller ACW (p=0.01), smaller PCAL (p=0.006), and
smaller anterior vault (p=0.015).
Conclusions: In our clinic-based study of PACG, we observed that
20% of the subjects had VF asymmetry and about 12% had unilateral
VF defect. Asymmetric PACG was associated with asymmetry in
anterior segment parameters.
Commercial Relationships: Monisha E. Nongpiur, None;
Kenric R. Fan, None; Jestin W. Chiew, None; Yap S. Cheong,
None; Shamira Perera; Tin Aung, None
Support: National Medical Research Council, Singapore (STAR:
NMRC/STAR/0023/2014)
The Relationship Between Intraocular Pressure and Sectoral
Angle Narrowing As Measured With Anterior Segment Optical
Coherence Tomography: The Chinese American Eye Study
Benjamin Xu, Paul Israelsen, Billy X. Pan, Dandan Wang,
Xuejian Jiang, Rohit Varma. Ophthalmology, University of Southern
California, Los Angeles, CA.
Purpose: A detailed description of the biomechanical relationship
between angle narrowing and elevated intraocular pressure has long
eluded clinicians and researchers. Gonioscopy is the current gold
standard in the evaluation of narrow angles although its correlation
with intraocular pressure is poor. Subtle differences in angle
dimensions are also difficult to quantify with gonioscopy. Recent
work has demonstrated a strong correlation between intraocular
pressure and AS-OCT measurements of angle recess area (ARA)
in subjects with elevated intraocular pressure. This relationship
manifests only for ARA values below a certain threshold which
creates a novel OCT-based definition of “narrow.” This study
examines the number of eyes with sub-threshold sectoral ARA
values in subjects with elevated intraocular pressure (IOP) and the
relationship between ARA and IOP as sectoral ARA values decrease.
Methods: We analyzed four AS-OCT images from one eye each of
102 subjects with IOP greater than 21. All subjects were selected
from the Chinese American Eye Study (CHES) – a population based
study of Chinese Americans in Los Angeles, CA. We measured ARA
values 500 micrometers from the scleral spur (ARA500) for each of
eight sections through the angle. We calculated the number of eyes
with a sectoral ARA500 of less than 0.45 mm2, which has previously
been shown to be the mean threshold below which intraocular
pressure begins to rise, as well as intraocular pressure for sectoral
thresholds of 0.9, 0.45, 0.22, and 0.11 mm2.
Results: The eight sectors of the angle had different numbers
of subjects with sub-threshold ARA500 values: superior (44),
superonasal (36), inferonasal (30), superotemporal (26), inferior (25),
inferotemporal (14), and temporal (12). As the mean ARA500 values
decreased, there was asymmetric narrowing of the eight sectors.
Lower sectoral ARA500 thresholds in the inferior, inferotemporal,
and temporal sectors had a more profound impact on IOP compared
to the other sectors.
Conclusions: The results of this study suggest that the narrowest
portions of the angle in an open angle are the most likely to close in
a narrow angle. Additionally, closure of the most open portions of the
angle is correlated with the highest intraocular pressure likely due to
associated closure of other more narrow portions of the angle.
Commercial Relationships: Benjamin Xu; Paul Israelsen, None;
Billy X. Pan, None; Dandan Wang, None; Xuejian Jiang, None;
Rohit Varma, None
Support: NEI Grant EY017337
Study of anterior chamber volume and iris volume provided
by Swept Source-OCT in healthy subjects and angle closure
glaucoma patients
Yuan Zong. Department of Ophthalmology and Visual Science, Eye,
Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan
University, SHANGHAI, China.
Purpose: The aim of this study was to evaluate anterior chamber
volume (ACV), iris volume (IV) provided by Anterior Segment
Swept Source-OCT (SS-OCT) in healthy subjects and angle closure
glaucoma patients.
Methods: A total of 20 eyes from 20 healthy Chinese subjects
with a mean age of 45.5±4.5 years(range:47~65years); and 20 eyes
diagnosed with angle closure glaucoma (ACG) from 20 Chinese
patients with a mean age of 48.5±7.5 years(range:42~70years) were
also enrolled in this study. The anterior chamber volume (ACV) and
iris volume (IV) of these subjects were examined using a SS-OCT.
The independent samples t test was performed to compare the ACV,
IV of the healthy subjects and ACG patients.
Results: Mean ACV, and IV for all healthy subjects were
152.59±29.96 mm*3(range:171.06~56.61 mm*3),and 34.20±4.39mm
*3(range:19.77~44.42 mm*3). Mean ACV, and IV for ACG
patients were 74.70±16.99 mm*3(range:112.89~47.02 mm*3),and
27.47±6.22mm*3(range:12.75~40.22 mm*3). Significant differences
were found between healthy subjects and ACG patients (p<0.05).
Compared with healthy subjects, ACG patients had less ACV and IV.
Conclusions: ACG patients presented a significant decrease in ACV,
it maybe manifested that volume of anterior chamber was a good
indicator for ACG. The results also suggested that iris atrophy widely
existed in ACG patients.
Commercial Relationships: yuan zong, None
Anterior Segment Optical Coherence Tomography (ASOCT) vs.
van Herick Method for Estimating Anterior Chamber Depth in
Teleglaucoma Screenings
David C. Atherton, Pooja A. Padgaonkar, Dan Liu, Bonny Lee,
Bernard C. Szirth, Albert S. Khouri. Institute of Ophthalmology &
Visual Science, Rutgers New Jersey Medical School, MIddletown,
NJ.
Purpose: To determine the agreement between ASOCT and van
Herick method in estimating angle depth.
Methods: Twenty subjects were prospectively enrolled. Average
age was 24.5 yo. All were examined using AS-OCT (Optovue,
i-Vue OCT) and the van Herick method was estimated from images
acquired with slit lamp digital camera (HAAG-STREIT, model 900).
Inclusion: Individuals with anterior segments allowing ASOCT and
slit lamp digital imaging. ASOCT angle was measured in degrees
and the van Herick method was deduced from digital images. Slit
lamp images were acquired as per protocol with a thin slit at 45°
incidence at the temporal limbus. Anterior chamber depth was
compared to corneal thickness (CT). A grade of 0-4 (equivalent to
0°-40° respectively) was assigned based on the depth of the anterior
chamber angle (ACA): 4=ACA>1 CT, 3=ACA ¼ - ½ CT, 2 is ¼ CT,
1 is less than ¼ CT, and 0 is no observable angle. Because the van
Herick is more subjective, 4 readers masked to one another evaluated
van Herick independently. Angle measures were compared using the
Pearson correlation, the significance threshold was set at p < 0.05.
The intraclass correlation (ICC) was determined for the van Herick
method to measure the agreement between four readers.
Results: The mean angle measured by ASOCT was 36.53°. The mean
van Herick grade was 3.59 (Table 1). The Pearson correlation of the
average van Herick grade and the ACA as measured by ASOCT was
weakly positive but did not reach statistical significance (r = 0.318,
p = 0.171, Table 2). The ICC between all van Herick readers was
0.835 (95% CI: 0.678-0.927) indicating good agreement.
Conclusions: The van Herick relies on a slit lamp (heavy, not easily
transported), is a subjective estimation of the angle, and did not
correlate with the actual ACA as measured by ASOCT, an objective
test. This makes ASOCT a better choice for telemedicine screenings
compared to the van Herick. This pilot study indicates the need for
more studies in a more diverse patient population in a teleglaucoma
setting.
A Quantitative Assessment of the Iridocorneal Angle in Asian
Patients with Open-angle Glaucoma or Ocular Hypertension
Using Schwalbe’s Line-based Angle Biometrics
Jeff Penzner5, Quoc Ho1, Xinghuai Sun2, Junyi Chen2, Liang Xu3,
Ya Xing Wang3, Xiaoming Chen4, Ni Li4, Michael R. Robinson5,
Michelle Chen5, Susan S. Lee5. 1University of Colorado, Aurora, CO;
2
Eye & ENT Hospital of Fudan University, Shanghai, China; 3Beijing
Tongren Hospital, Beijing, China; 4West China Hospital, Chengdu,
China; 5Allergan plc, Irvine, CA.
Purpose: To quantitatively describe the iridocorneal angle biometrics
in a cohort of Asian patients with open-angle glaucoma (OAG) or
ocular hypertension (OHT).
Methods: Anterior segment optical coherence tomography (ASOCT) five-line raster scans (Zeiss Cirrus HD-OCT 4000) of the
inferior angle were obtained under dark conditions and images from a
total of 213 eyes of 129 patients were analyzed for iridocorneal angle
biometrics. Images were graded for ability to visualize Schwalbe’s
line (SL), the superior iris surface, and angle recess. ImageJ1
software (1.49v) was used to measure the angle opening distance at
SL (SL-AOD) and trabecular-iris-space-area 500 μm posteriorly from
SL (SL-TISA) in gradable images.
Results: The mean ± SD SL-AOD was 0.70 ± 0.32 mm
(median 0.69, range 0.09 – 1.9), and the mean ± SD SL-TISA was
0.26 ± 0.13 mm2 (median 0.26, range 0.04 – 0.8). The 25th, 50th,
75th, and 95th percentile SL-AODs and SL-TISAs were 0.46,
0.69, 0.88, 1.28 mm, respectively, and 0.17, 0.26, 0.34, 0.49 mm2,
respectively. The Pearson product-moment correlation coefficient for
SL-AOD and SL-TISA was 0.98.
Conclusions: Comparable angle measurements that have been
documented in normal Asian patients are considerably smaller than
the cohort of Asian OAG and OHT patients in this study2. These
findings suggest that further study may be required to understand the
differences in the iridocorneal angle morphology in Asian OAG and
OHT versus normal subjects.
References
1
Rasband, W.S., ImageJ, U. S. National Institutes of Health,
Bethesda, Maryland, USA, http://imagej.nih.gov/ij/, 1997-2015.
2
He Y. et al., Changes in anterior segment dimensions over 4 years in
a cohort of Singaporean subjects with open angles., Br J Ophthalmol.
2015 Aug; 99(8): 1097-102.
Table 1. Average van Herick and OCT.
Table 2. Correlation between AS-OCT and van Herick.
Commercial Relationships: David C. Atherton, None;
Pooja A. Padgaonkar; Dan Liu, None; Bonny Lee, None;
Bernard C. Szirth, None; Albert S. Khouri, None
such as anterior chamber depth (ACD), anterior chamber width
(ACW), angle opening distance at 500-750 μm from the scleral
spur (AOD500/750), trabecular-iris space area at 500-750 μm
(TISA500/750) and angle recess area at 500-750 mm (ARA500/750),
trabecular iris angle (TIA) and anterior chamber volume (ACV).
Parameters were compared to evaluate whether the outcome of the
surgery differed among the patients by cluster analysis. Statistical
analyses were completed using MedCalc v.13.1.2.0 (MedCalc
Software bvba, Ostend, Belgium).
Results: All angle parameters obtained from the 20 eyes showed
good measurement reproducibility (intraclass correlation coefficient
0.82–0.979). As expected, the IOP and number of medications
decreased significantly (p<0.05) after the procedure. There was
a statistically significant difference between preoperative and
postoperative measurements for AOD 500, TISA 500, AOD 750 and
TISA 750 (p<0.05). The mean differences of ACD and ACV were
0.26 and 26.6 respectively (p=0.06 and p=0.02) (Table 1) (Figure 1).
Conclusions: Imaging the anterior chamber angle with swept source
OCT provides an efficient approach to visualize the surgical site
before and after combine Trabectome catarct surgery. Given that
these angle metrics can be measured reliably, they may be useful
parameters to track longitudinally in glaucoma patients before and
after various interventions, in order to evaluate their relationship to
other metrics of glaucoma progression.
Figure 1. Frequency distributions of [a] Schwalbe’s Line-based angle
opening distance (SL-AOD) and [b] trabecular-iris-space-area (SLTISA)
Commercial Relationships: Jeff Penzner, Allergan plc; Quoc Ho,
None; Xinghuai Sun, None; Junyi Chen, None; Liang Xu, None;
Ya Xing Wang, None; Xiaoming Chen, None; Ni Li, None;
Michael R. Robinson, Allergan plc; Michelle Chen, Allergan plc;
Susan S. Lee, Allergan plc
Clinical Trial: NCT01781962
Assessment of Anterior Segment Measurements with Swept
Source Anterior Segment Optical Coherence Tomography Before
and After Combined Trabectome Cataract Surgery
Handan AKIL1, Mayss Al-Sheikh1, Brian Francis1, 2,
Srinivas R. Sadda1, 2, Vikas Chopra1, 2. 1Doheny Imaging Reading
Center, Doheny Eye Institute, Los Angeles, CA; 2Ophtalmology,
David Geffen School of Medicine, Los Angeles, CA.
Purpose: To investigate the changes in anterior segment parameters,
as assessed by swept source anterior segment optical coherence
tomography (AS-OCT) after combined Trabectome cataract surgery
in open angle glaucoma patients.
Methods: Twenty eyes of 19 patients with open angles were
scanned with AS-OCT (SS-1000 CASIA; Tomey Co. Ltd. Nagoya,
Japan) before and 4 weeks after combined Trabectome cataract
(phacoemulsification) surgery. A hierarchical cluster analysis was
performed using AS-OCT parameters obtained before Trabectome,
Table1. Comparision of the anterior chamber parameters before and
after the combined Trabectome surgery
Figure 1. Anterior segment swept source OCT imaging before and
after the combined Trabectome surgery.
Commercial Relationships: Handan AKIL, None;
Mayss Al-Sheikh, None; Brian Francis, Lumenis (F), Innfocus (F),
allergan (F), BVI endooptiks (C), aquesys (F); Srinivas R. Sadda,
Optos (F), Carl Zeiss (F), Novartis (C), Thrombogenics (C),
Allergan (F), Bayer (C), Avalanche (C), Iconic (C), Stem cells
Inc (C), Genentech (F), Optos (C), Genentech (C), Allergan (C);
Vikas Chopra
Support: Allergan grant
Evaluation of filtration bleb by multi-contrast anterior-segment
optical coherence tomography
Deepa Kasaragod1, Shuichi Makita1, Yuta Ueno2, Sujin Hoshi2,
Shinichi Fukuda2, Tetsuro Oshika2, Yoshiaki Yasuno1. 1COG,
University of Tsukuba, Tsukuba, Japan; 2Department of
Ophthalmology, Faculty of Medicine, University of Tsukuba,
Tsukuba, Japan.
Purpose: Blebs are evaluated by multi-contrast Jones matrix optical
coherence tomography (JM-OCT). Scattering OCT, birefringence
tomography and OCT angiography (OCT-A) are simultaneously
obtained by JM-OCT. The features in the tomographies are discussed
in a descriptive manner.
Methods: Six eyes of 4 patients who had undergone glaucoma
filtration surgery were imaged by a custom-built multi-contrast JMOCT. Multi-contrast volumetric images listed above were obtained
on 6 mm x 6 mm area using a protocol of 256 A-lines × 256 B-scans
× 2 repeats at the same location. Intraocular pressure (IOP) was
measured using a Goldmann’s applanation tonometer. Multi-contrast
cross-sectional images are created as follows: The birefringence
tomography is displayed in a pseudo color image in which the
color and brightness represent the birefringence and scattering,
respectively. Cross-sectional OCT-A signal (red) is overlaid on
scattering OCT (green).
Results: Figure 1 shows the case of a 65-year-old male patient
imaged 6-day after trabeculectomy (IOP = 6 mmHg). In the
birefringence images (a, c, e), high birefringence of sclera is visible
beneath the fluid pool (white arrow heads). In OCT-A images (b, d,
f), nearly no or only a very small vessels exist above the fluid pool in
the ischemic region (b, white arrow), while large vessels are visible
beneath the fluid pool (red arrow). In non-ischemic region, large
vessels are visible in the superior tissue to the fluid pool (f, yellow
arrow heads).
In 5 out of 6 cases, superior tissues do not show high birefringence
in both ischemic and non-ischemic regions. In 3 of 6 cases, ischemic
region is appeared with large flow regions in deep layers or below
fluid pool. 2 cases show no presence of larger vessels in ischemic
region at any depth. In 3 of 6 cases, large vessels are seen above fluid
pool at non-ischemic region.
Conclusions: Late bleb leakage has often been associated with the
presence of large avascular bleb. Hence OCT-A would be useful for
its prediction. The birefringence tomography specifically visualizes
the collagenous tissue. So, it can be utilized for the detection of
subconjunctival fibrosis and scarring. In addition, scattering OCT is
known to be useful for morphological bleb analysis. JM-OCT, which
provides all these images simultaneously, could contribute to further
optimize the filtration surgery.
Commercial Relationships: Deepa Kasaragod, Tomey Corporation
(F); Shuichi Makita, Tomey Corporation (P), Tomey Corporation
(F); Yuta Ueno, None; Sujin Hoshi, None; Shinichi Fukuda, None;
Tetsuro Oshika; Yoshiaki Yasuno, Tomey Corporation (F), Tomey
Corporation (P)
Anterior Segment Parameters As Predictors of Intraocular
Pressure Reduction After Phacoemulsification in Eyes with Open
Angle Glaucoma
Yen C. Hsia, Sasan Moghimi, Paul Coh, Rebecca I. Chen,
Marisse Masis, Shan C. Lin. Ophthalmology, UCSF, San Francisco,
CA.
Purpose: To evaluate intraocular pressure (IOP) change after cataract
surgery in eyes with open angle glaucoma (OAG) and its relation to
angle and anterior segment parameters measured by anterior segment
optical coherence tomography (AS-OCT).
Methods: In this prospective study, 81 eyes of 69 OAG patients
underwent phacoemulsification and lens implantation. IOP and
biometric parameters were measured by AS-OCT preoperatively
and 4 months after surgery. The glaucoma medication regimen was
kept the same after cataract surgery. Percentage of IOP change and
its relation to biometric parameters, including anterior chamber
depth (ACD), anterior chamber volume (ACV), iris thickness (IT),
iris curvature, lens vault (LV), anterior chamber width (ACW), and
angle parameters including angle opening distance (AOD 500 and
AOD750) and trabecular iris space area (TISA500 and TISA750)
were evaluated. The main outcome measure was percentage IOP
change after phacoemulsification.
Results: There were 71 patients with 81 eyes (21 male and 50
female) in our study with an overall mean age of 76.8±7.4 years.
The average IOP reduction was −2.1±2.9 mmHg (12.8 %), from a
preoperative mean of 15.0±3.4 mmHg, at 4 months after cataract
surgery. In univariate linear regression, preoperative IOP (B=-2.755,
p<001), AOD500 (B=45.177,p=0.03), AOD750 (B=35.701, p=0.01),
and TISA500 (B=62.755, p=0.05) were significantly associated with
percentage IOP decrease. Iris parameters, ACW, ACV, and ACD
were not correlated with IOP drop. In multivariate analysis, higher
preoperative IOP (B=-2.625, p<0.001) and AOD750 (B=42.752,
p=0.001) were significantly associated with percentage IOP change
(r2=0.40). Although preoperative IOP (p< 0.001, r2= 29 %) was a
better predictor of percentage of IOP change, AOD750 can predict
14% of IOP change (p=0.003) after adjusting for age and gender.
Conclusions: The percentage of IOP reduction after cataract surgery
in eyes with open angle glaucoma is significantly greater in eyes with
narrower angle and higher preoperative pressure. Combining angle
parameters and preoperaive IOP can be helpful in predicting the
amount of IOP drop in OAG patients.
Commercial Relationships: Yen C. Hsia; Sasan Moghimi, None;
Paul Coh, None; Rebecca I. Chen, None; Marisse Masis, None;
Shan C. Lin, None
Angle configuration changes and Intraocular pressure reduction
in normotensive glaucoma(NTG) after cataract operation
WONSEOK LEE, Hyoung Won Bae, Samin Hong, Chan Yun Kim,
Gong Je Seong. Yonsei University, college of medicine, Seoul, Korea
(the Republic of).
Purpose: To investigate the change of anterior angle morphology
after phacoemulsification with intraocular lens implantation
in eyes with cataract using Swept-Source optical coherence
tomography(SS-OCT) in normotensive glaucoma(NTG) patients.
Methods: Group 1 is the “Normal group” including normal subjects
except cataract. Group 2 is the “Normotensive glaucoma group (NTG
group)” diagnosed as normotensive glaucoma with cataract. 33 eyes
of 27 patients (Group 1) and 22 eyes of 18 patients (Group 2) were
performed phacoemulsification with intraocular lens implantation.
Before and after the operation, postop 1 day, 1 week and 1 month,
the anterior chamber angles were evaluated by SS-OCT(CASIA®,
Tomey) under dark conditions using three-dimensional angle analysis
scan protocol. In order not to indent eyes, we obtained SS-OCT
scans and analyzed with nasal, temporal, superior and inferior
quadrant of eyes in naturally eye opening status. AOD, TISA, and
TIA were calculated automatically by SS-OCT after the observer
marked the scleral spurs. IOP and species of glaucoma medications
were also checked before and after cataract surgery. These repeated,
longitudinal data were analyzed by SPSS®(IBM®, SPSS® Statistics
20) based on longitudinal-parametric, paired t-test. All patients were
included and all the results were meaningful with P<0.05.
Results: Enrolled 45 patients were 23 men and 22 women. The mean
age was 68.71±9.82 years. Preoperative means of AOD, TISA, and
TIA were 0.51±0.27(mm), 0.21±0.11(mm2), and 28.83±11.51(°).
Postop 1day, 1 week and 1month, the means of AOD, TISA,
TIA were 0.63±0.19(mm), 0.24±0.08(mm2), 32.05±7.54(°), and
0.67±0.24(mm), 0.26±0.1(mm2), 36.78±8.4(°) and 0.67±0.24(mm),
0.26±0.1(mm2), 36.78±8.4(°). Therefore, angle parameters were
increased meaningfully after cataract surgery. Preoperative
intraocular pressure was 13.50±2.59(mmHg), and postoperative IOP
was 11.42±2.97(mmHg) in NTG group. After the cataract surgery,
IOP reduction was obtained in NTG group meaningfully (p=0.003).
NTG patients used 1.55±0.61 species of anti-glaucoma eyedrops
before surgery, but 0.82±0.73 species after surgery (p=0.005).
Conclusions: The eyes that were performed cataract operation have
improved anterior chamber angle parameters and decreased IOP. It
could be predicted that cataract surgery can improve aqueous humor
dynamic in normotensive glaucoma patients.
Commercial Relationships: WONSEOK LEE, None; Hyoung
Won Bae, None; Samin Hong, None; Chan Yun Kim, None; Gong
Je Seong, None
Clinical Trial: http://gseirb.yuhs.ac, 2015-0228-001
A New Definition of Narrow Angles Based on Anterior Segment
Optical Coherence Tomography Measurements: The Chinese
American Eye Study
Natasha Naik, Benjamin Xu, Paul Israelsen, Billy X. Pan,
Dandan Wang, Xuejian Jiang, Rohit Varma. Ophthalmology, USC
Eye Institute, Los Angeles, CA.
Purpose: Gonioscopy is the current gold standard in the evaluation
of narrow angles although it is a poor predictor of which patients
will develop elevated intraocular pressure (IOP) and primary angle
closure glaucoma. Previous studies comparing gonioscopy and
anterior segment optical coherence tomography (AS-OCT) found
varying degrees of agreement between the two methods leading
researchers to question the clinical role of AS-OCT. Recent work has
demonstrated a strong correlation between intraocular pressure and
AS-OCT measurements of angle recess area (ARA) in subjects with
elevated intraocular pressure. This relationship manifests only for
ARA values below a certain threshold which creates a novel OCTbased definition of “narrow.” This study examines the relationship
between this threshold value and ARA values from angles that are
“narrow” on gonioscopy but do not exhibit elevated IOP.
Methods: We analyzed four OCT images from one eye each of 28
subjects selected from the Chinese American Eye Study (CHES), a
population based study of Chinese Americans in Los Angeles, CA.
These subjects had IOP less than 21 and gonioscopic grade of 0 or
1 in all four quadrants based on the modified Shaffer grading scale.
We calculated ARA values measured 500 micrometers from the
sclera spur (ARA500) and compared these values to 0.45 mm2, which
has previously been shown to be the mean threshold below which
intraocular pressure begins to rise. We also plotted ARA value against
gonioscopic grade for each eye to assess their relationship in these
“narrow” angle subjects.
Results: Among the 28 subjects with angle grade of 0 or 1 in all four
quadrants, the majority had ARA500 values greater than 0.45 mm2
(range 0.047 to 0.124, median = 0.70, STD = 0.021). Only 7 subjects
had ARA500 values of 0.45 mm2 or less (range 0.015 to 0.034,
median = 0.030, STD = 0.007). The linear regression line of ARA500
values plotted against angle grade revealed a weak correlation
between the two (slope = 0.004, R2 = 0.003).
Conclusions: Our results show that in subjects with normal IOP, the
majority of angles “narrow” on gonioscopy do not fit the AS-OCT
definition of “narrow.” These results coupled with previous results
demonstrating a strong correlation between low ARA values and high
IOP suggest that AS-OCT might be more effective than gonioscopy
in assessing patient risk for elevated IOP.
Commercial Relationships: Natasha Naik, None; Benjamin Xu,
None; Paul Israelsen; Billy X. Pan, None; Dandan Wang, None;
Xuejian Jiang, None; Rohit Varma, None
Support: Grant EY-017337 from National Eye Institute, Bethesda,
MD, and Research to Prevent Blindness, New York, NY.
Longitudinal changes of anterior chamber changes after
physiologic pupil dilation in South Chinese population
Wei Wang1, Lanhua Wang1, Xingxing Guo1, Mingguang He2.
1
Zhongshan ophthalmic center, Sun Yat-sen University, Guangzhou,
China; 2Centre for Eye Research Australia, Melbourne, VIC,
Australia.
Purpose: Primary angle closure glaucoma (PACG) is a leading cause
of irreversible blindness. Although longitudinal changes in static
and dynamic anterior segment structure with age was important for
predicting future risk of PACG, data on this topic is limited. Our
hypothesis is that static and dynamic parameters of the anterior
segment would change over time.
Methods: A population-based, cohort study was conducted among
subjects aged 50 and older residing in Liwan District, Guangzhou,
China. In November 2008 and November in 2013, a systematically
selected subjects underwent complete ocular examinations and
anterior segment optical coherence tomography (AS-OCT) imaging
under dark and light conditions. Customized Zhongshan Angle
Assessment Program (ZAAP) software was used to AS-OCT
parameters. Baseline and 5-year change in AS-OCT parameters in
dark and light-to-dark changes were determined.
Results: A total of 160 (66.4%) subjects underwent AS-OCT
examinations in 2008 and 2013 were eligible for analyses. The
mean age of analysed subjects was 64.8 ±7.1 years, and 65.6%
were female. Overall, there was an trend of narrowing of angle in
dark, with decreasing significantly in angle parameters (AOD500,
TISA500), anterior chamber parameter (ACD, ACW, ACA, ACV),
increases in iris parameters (IT750, IT2000, Iarea, Icurve, Ivolume),
and LV at 5 years (all P<0.05). Similar trend of parameter of lightto-dark changes were observed. After adjusting age and sex, the
following baseline parameters were associated with a greater decrease
in TISA500 at 5 years: height, AOD250, TISA500, TISA750, ARA,
ΔAOD500, ΔTISA500, ΔTISA750, ΔARA, ΔACW, and ΔACA (all
P<0.05).
Conclusions: Angle width decreased, iris and lens vault increased,
and light-to-dark changes declined during the 5-year follow-up.
Subjects with greater baseline height, wider angle width, more
pronounced dark-to-light changes experienced greater angle
narrowing at follow-up.
Commercial Relationships: Wei Wang, None; Lanhua Wang,
None; Xingxing Guo; Mingguang He, None
Laser Peripheral Iridotomy changes Anterior Chamber
Architecture significantly in Acute Angle Closure
Jan D. Unterlauft, Peter M. Wiedemann. Ophthalmology,
Universitaets-Augenklinik Leipzig, Leipzig, Germany.
Purpose: The pressure gradient between anterior and posterior
chamber in acute angle closure (AAC) and primary angle closure
suspects (PACS) can be balanced by a sufficient laser peripheral
iridotomy (LPI). The changes induced by LPI in patients suffering
from unilateral AAC were examined using Scheimpflug-photography
techniques and were compared to healthy eyes to define threshold
values which may help to discriminate between healthy and diseased
eyes.
Methods: Using Scheimpflug photography anterior chamber
depth (ACD), anterior chamber volume (ACV), anterior chamber
angle (ACA) and central corneal thickness (CCT) were measured
before and after LPI in both eyes of unilateral AAC cases. These
measurements were compared to a group of healthy control eyes
using receiver operating characteristic (ROC) analysis to determine
threshold values for ACD, ACV and ACA.
Results: ACD, ACV and ACA increased significantly after LPI in
the 25 eyes suffering from unilateral AAC. ACD, ACV, ACA and
CCT values in the AAC eyes obtained before LPI were compared to
a control group of 59 healthy eyes with wide open chamber angles.
The cut-off values revealed by ROC analysis were 2.1 mm for ACD,
90.5mm2 for ACV and 27.25° for ACA.
Conclusions: The results confirm the significant changes of anterior
segment architecture induced by LPI in AAC eyes. The found
threshold values for ACD, ACV and ACA may help in daily clinical
routine to discriminate between healthy eyes and those in need for a
prophylactic LPI.
Commercial Relationships: Jan D. Unterlauft, None;
Peter M. Wiedemann, None
Quantitative analysis of the lens position and the curvature of the
anterior lens surface in normal Japanese subjects
Kazuhiko Mori1, Junta Kubo1, 2, Rie Oda1, 2, Yoko Ikeda1, 3,
Morio Ueno1, Kojiro Imai1, 4, Haruna Yoshikawa1, Yuji Yamamoto1,
Noriko Koizumi2, Shigeru Kinoshita5, Chie Sotozono1.
1
Ophthalmology, Kyoto Prefectural Univ of Med, Kyoto, Japan;
2
Biomedical Engineering, Doshisha University, Kyotanabe, Japan;
3
Oike Ikeda Eye Clinic, Kyoto, Japan; 4Medical Innovation and
Translational Medical Science, Kyoto Prefectural Univ of Med,
Kyoto, Japan; 5Frontier Medical Science and Technology for
Ophthalmology, Kyoto Prefectural Univ of Med, Kyoto, Japan.
Purpose: Various factors, including lens position and shape, jointly
involve acute angle closure. Lens vault (LV) is one of the indicators
to quantify the lens position, while others which quantify the
curvature of the anterior lens surface have yet to be fully elucidated.
The purpose of this study was to develop a new indicator to quantify
the lens surface shape, and to reveal its association with other ocular
features.
Methods: This study involved 188 eyes of 94 normal Japanese
subjects (26 males and 68 females; mean age: 67.2±5.9 years).
Inclusion criteria included subjects who 1) visited the outpatient
clinic of Kyoto Prefectural University of Medicine, Kyoto, Japan
between June 2014 and April 2015, 2) were diagnosed by glaucoma
specialists as normal based on several ophthalmic examinations,
and 3) in whom reliable horizontal images could be obtained using
anterior segment optical coherence tomography (AS-OCT) (SS-1000
CASIA; Tomey Corp.). In all eyes, AS-OCT images were imported to
image processing software (Image J 1.48q; NIH). The line connecting
the scleral spur (SS) was regarded as the SS-baseline, and anterior
chamber depth (ACD), width (ACW), and LV were defined as
described (Nongpiur ME, 2011). The perpendicular distance at the
point of 2mm apart from visual axis, from the anterior lens surface to
the horizontal line at the anterior pole parallel to the SS-baseline were
defined as nasal and temporal lens protrusion distance (LPDn and
LPDt, respectively). When the pupillary diameter was less than 4mm,
those cases in which the anterior capsular position beneath the iris
could not be clearly detected were excluded. The clinical features of
age, sex, refractive error (RE), corneal radius (CR), and axial length
(AL) were also measured. Step-wise multiple regression analysis was
performed, regarding LPD or LV as an objective value, and age, sex,
RE, CR, AL, ACD, and ACW as explanatory variables.
Results: Statistical differences were found between LPDn and LPDt
on either eye (Wilcoxon signed-rank test, p<0.05). LPD and LV
were found to be independent, and LV was correlated with age,
ACD, ACW, and CR. Step-wise multiple regression analysis showed
that ACD (p<0.001) and CR (p=0.02) were significant explanatory
variables for LPD.
Conclusions: LPD in the normal Japanese subjects was not
completely symmetrical, but was related to CR and ACD.
clarified as useful in plateau iris patients, lens characteristics may
contribute in some degree to pupil block. In our sample, LL/LV
ratio seems to be a helpful predictor of iridotomy effectiveness in
the presence of a clinical plateau iris. This work may trigger further
studies about this potential quantitative and easily measurable clinical
index in PIC/PIS field.
Commercial Relationships: Ines Leal; David C. Sousa, None;
Helena P. Filipe, None; Luis Abegao Pinto, None
Commercial Relationships: Kazuhiko Mori, Ocular Instruments
(P), Santen (P); Junta Kubo, None; Rie Oda, None; Yoko Ikeda,
Santen (P); Morio Ueno, Santen (P), Senju (P); Kojiro Imai,
None; Haruna Yoshikawa, None; Yuji Yamamoto, None;
Noriko Koizumi, None; Shigeru Kinoshita, Santen (P), Senju (P);
Chie Sotozono, None
Can ultrasound biomicroscopy predict angle opening after
iridotomy in clinical plateau iris? A prospective study reporting a
new clinical index
Ines Leal1, David C. Sousa1, Helena P. Filipe2, 3, Luis Abegao Pinto1.
1
Ophthalmology, Centro Académico de Medicina de Lisboa, Lisbon,
Portugal; 2Ophthalmology, Hospital of Armed Forces, Lisbon,
Portugal; 3Clinical and Surgical Ophthalmology, ALM Oftalmolaser,
Lisbon, Portugal.
Purpose: Plateau iris syndrome (PIS) and plateau iris configuration
(PIC) are classically defined by a narrow angle and a double-hump
configuration on gonioscopic examination. In PIC, a relative pupil
block mechanism may be present and iridotomy is sometimes
effective. Ultrasound biomicroscopy (UBM) is a helpful ancillary
exam in PIC/PIS workup. Our aim was to investigate if we can
predict, using UBM, the response of a PIC/PIS to an iridotomy.
Methods: Prospective observational study. A double-hump on
gonioscopy was identified in all eyes and the patients were scheduled
for an iridotomy. UBM was performed before and after iridotomy by
the same masked observer. Further analysis of stored UBM images
was performed by a second masked observed and included evaluation
of qualitative and quantitative data concerning iridocorneal angle
anatomy, anterior chamber parameters and lens characteristics. Only
high-quality images were accepted and STATA v13.0 was used for
statistics.
Results: From Feb-Set/15, 22 eyes of 13 Caucasian patients (8
women) were enrolled. In 7 (31.8%) eyes, a patent iridotomy resulted
in angle opening. Mean anterior chamber depth before and after
iridotomy was 2.58±0.4mm and 2.54±0.3mm (p=0.30), respectively.
Lens vault (LV) was 0.54±0.1mm and lens lenght (LL) 4.10±0.3mm.
Mean LL/LV ration was 8.17±2.1. In a logistic regression model,
LL/LV ratio was significantly associated with angle opening after
iridotomy (odds ratio, 1.86; 95% confidence interval 1.03 to 3.30).
Iridotomy was not effective in eyes with a LL/LV ratio below 6,9.
Conclusions: To conclude about a definitive PIS diagnosis it is
mandatory to analyze the angle after an iridotomy. Although not yet
Evaluation of angle closure as a risk factor for reduced corneal
endothelial cell density
Varshini Varadaraj1, Sabyasachi S. Sengupta2,
Krishnamurthy Palaniswamy2, Kavitha Srinivasan2,
Mohideen A. Kader3, Ganesh Raman4, Sharmila Reddy5,
Pradeep Y. Ramulu1, Rengaraj Venkatesh2. 1Wilmer Eye Institute,
Baltimore, MD; 2Aravind Eye Hospital, Pondicherry, India; 3Aravind
Eye Hospital, Tirunelveli, India; 4Aravind Eye Hospital, Coimbatore,
India; 5Aravind Eye Hospital, Madurai, India.
Purpose: Acute angle closure attacks are frequently accompanied by
corneal edema. However, little is known about the status of corneal
endothelial cells at early stages of angle closure in eyes naïve to
prior surgery, iridotomy, or severe IOP elevation. Here, we compare
endothelial cell density (ECD) in unoperated eyes with open angles
and eyes at various stages of angle closure disease.
Methods: This cross sectional study evaluated both eyes of sibling
pairs recruited from one of 4 Aravind Eye Hospitals in Tamil Nadu,
India, between September 2012 and May 2014. Masked examiners
completed gonioscopic evaluation and eyes were classified as 1)
open angle (OA), 2) primary angle closure suspect (PACS), or
3) primary angle closure/primary angle closure glaucoma (PAC/
PACG). Specular microscopy was performed in both eyes and group
differences in endothelial cell density were analyzed using a nested
multilevel model with mixed effects to account for clustering at
familial and individual levels.
Results: Analyses included 814 eyes of 407 patients, including 127
eyes (15.6%) with PAC/PACG, 466 (57.3%) with PACS, and 221
(27.1%) with OA. Participants were predominantly female (69.8%)
and mean age was 49.2 (SD: 8.6) years. Lower ECD was observed
with increasing age (β =-6.3 cells/mm2 [95% CI: -9.3 to -3.3] per
year, p<0.001), greater irido-trabecular contact (β =-15.6 cells/
mm2 [95% CI: -28.3 to -2.9] per quadrant of contact, p=0.016), and
shallow (<2.5mm) anterior chamber (AC) depth (β =-40 cells/mm2
[95%CI: 78.9 to 1.1] vs. deeper [>2.5 mm] AC depth, p=0.044). In
age-adjusted analyses, PACS eyes had a lower ECD than OA eyes
(β=-54.7 cells/mm2 [95% CI=-47.8 to -85.3], p=0.018) though PAC/
PACG eyes were not significantly different than OA eyes (β=-18.6
cells/mm2 [95% CI=-85.9 to 2.5], p=0.058).
Conclusions: Lower ECD may be present in eyes with angle closure,
particularly those with a shallower AC and/or greater iridotrabecular
contact, even prior to initiation of treatment. Additional longitudinal
studies are needed to further establish whether these factors are
associated with higher rates of endothelial cell loss.
Commercial Relationships: Varshini Varadaraj;
Sabyasachi S. Sengupta, None; Krishnamurthy Palaniswamy,
None; Kavitha Srinivasan, None; Mohideen A. Kader,
None; Ganesh Raman, None; Sharmila Reddy, None;
Pradeep Y. Ramulu, None; Rengaraj Venkatesh, None
Support: Research to Prevent Blindness and Morton F. Goldberg
Director's Discovery Fund
Evaluation of anterior chamber imaging parameters in
pseudoexfoliation patients
Jibran Mohamed-Noriega, Karim Mohamed-Noriega,
Jesus Alberto Ruiz-Gonzalez, Alejandro Martínez-LópezPortillo, Jesus Mohamed-Hamsho, Humberto Cavazos,
JESUS H. GONZALEZ, Edgar Eliezer Cuervo-Lozano. Universidad
Autónoma de Nuevo León, Monterrey, Mexico.
Purpose: Pseudoexfoliation syndrome (PEX) was historically
described as responsible for an open angle type of glaucoma,
recently, different frequencies of angle closure have been described
in PEX. Angle closure prevalence varies a lot between ethnic groups.
We hypothesized that if the difference in prevalence in angle closure
between PEX populations is explained by the different prevalence of
angle closure, the biometric characteristics will be similar between
control and cases. We performed a prospective, cross-sectional,
comparative, case-control study to compare anterior segment
parameters of angle closure.
Methods: We included 144 eyes of 72 patients; PEX with glaucoma
(n=36): PEX with no glaucoma, PEG (n=23) and control (n=85).
Male gender cases were 42%, 57% and 22% in PEX, PEG and
controls respectably (p=0.002). Age (mean ± standard deviation,
SD) was 76±7, 75±6 and 73±8 in PEX, PEG and control groups
respectably (p=0.147). All eyes were evaluated with Pentacam HR
(Oculus, Wetzlar, Germany), IOL Master version 4.08 (Carl Zeiss
Meditec, Jena, Germany) and Visante AS-OCT (Visante, Carl Zeiss
Meditec, Dublin, CA). Independent Student’s t-test, Pearson Chi2,
ANOVA and Bonferroni tests were used for statistical analysis.
Results: The anterior chamber depth ACD (mean±SD) of control/
PEX showed no differences in Pentacam (2.55±0.39mm)/
(2.37±0.22mm), IOL master (2.89±0.38mm)/(2.833±__mm) or
Visante (2.65±0.33mm)/ (2.606±__mm). The iridocorneal angle
ICA (mean±SD) of control/PEX was smaller in PEX by Pentacam
(34.78±9.23)/(30.44±5.58) and Visante (30.48±10.4)/(25.58±5.25),
with a statistically significant of p 0.016 and p 0.070 respectively.
With Pentacam the anterior chamber volume ACV (mean±SD)
for control/PEX was similar between groups (109.6 ±25.6mm3)/
(113.363±24.79mm3).
Conclusions: We found a narrower ICA in PXF patients compare to
healthy controls. However other biometric measures of the anterior
chamber are similar between both groups. We hypothesized that the
reason of conflicting findings between PXF biometry in different
studies may be because angle closure in PXF patients is cause by
different mechanism in different populations. In our study of northern
Mexico we may have a mechanism that rely more in the forward
movement of the iris in the periphery rather than in the central
anterior chamber. One limitation of our study is the use patients with
cataract as controls.
Commercial Relationships: Jibran Mohamed-Noriega,
None; Karim Mohamed-Noriega, None; Jesus Alberto RuizGonzalez, None; Alejandro Martínez-López-Portillo;
Jesus Mohamed-Hamsho, None; Humberto Cavazos, None;
JESUS H. GONZALEZ, None; Edgar Eliezer Cuervo-Lozano,
None
Support: Paicyt
Iris crypts Influence the Dynamic Changes of Iris
Jacqueline Chua1, 2, Sri Gowtham Thakku1, Tin Tun1, Monisha
E Nongpiur1, 2, Michael J. Girard1, 3, Tien Yin Wong1, 2, Tin Aung1, 2,
Ching-Yu Cheng1, 2. 1Singapore National Eye Centre, Singapore Eye
Research Institute, Singapore, Singapore; 2Duke-National University
of Singapore Graduate Medical School, Singapore, Singapore;
3
Department of Biomedical Engineering, National University of
Singapore, Singapore, Singapore.
Purpose: There is increasing evidence that the dynamic response of
the iris during pupil dilation plays a crucial role in angle closure. Iris
surface features (crypts, furrows and color) were previously reported
to be correlated with the anatomical characteristics of the iris.
However, the dynamic correlations to these surface features remain
unclear. We hypothesized that variation within the surface features
may underlie the differential response of the iris during pupil dilation.
Methods: This is a retrospective observational clinical study of 76
Chinese adults aged 50 years and over without ocular diseases. Study
participants received eye examination where digital iris photographs
were taken and graded for iris crypts and iris furrows following
a grading scheme. Iris color was measured objectively, using the
Commission Internationale de l’Eclairage (CIE) L* color parameter.
Anterior segment was imaged by swept-source optical coherence
tomography (Casia SS-1000 OCT, Tomey, Nagoya, Japan) under
bright light and dark room conditions. Iris volumes in light and dark
conditions were measured with custom semi-automated software and
the change in iris volume was quantified. Angle opening distance
(AOD) at 750 μm was measured using the built-in SS-OCT software.
Associations of the change in iris volume after pupil dilation with
underlying iris surface features in right eyes were assessed using
linear regression analysis.
Results: In light condition, higher iris crypt grade was associated
independently with smaller iris volume (β [change in iris volume
in millimeters per crypt grade increment] = -1.10, 95% confidence
interval (CI): -1.90 to -0.30; P = 0.008) and greater reduction of iris
volume on pupil dilation (β [change in iris volume in millimeters
per crypt grade increment] = 0.30, 95%CI: 0.10 to 0.50; P = 0.004),
adjusted for age, gender, presence of corneal arcus, pupil size, and
AOD. Iris furrows and color were not associated with iris volume in
light condition or change in iris volume (all P > 0.05).
Conclusions: Our results are consistent with our hypothesis that
eyes with smaller and less iris crypts lose less iris volume on pupil
dilation. However, the dynamic responses were not related to either
iris furrows or color. These findings highlight the potential role of iris
crypts in the reduction of iris volume on pupil dilation, especially in
angle closure.
Commercial Relationships: Jacqueline Chua, None; Sri
Gowtham Thakku; Tin Tun, None; Monisha E Nongpiur, None;
Michael J. Girard, None; Tien Yin Wong, None; Tin Aung, None;
Ching-Yu Cheng, None
Iris Crypts are Protective for Acute Primary Angle Closure
Ching-Yu Cheng1, 2, Victor T. Koh4, Jacqueline Chua1, 2, Yuan Shi5,
Monisha E. Nongpiur3, 2, Baskaran Mani3, 2, Rajesh Sasikumar3,
Shamira Perera3, 2, Tin Aung3, 2. 1Ocular Epidemiology Research
Group, Singapore Eye Research Institute, Singapore National Eye
Centre, Singapore, Singapore; 2Eye ACP, Duke-NUS Graduate
Medical School, Singapore, Singapore; 3Glaucoma Research Group,
Singapore Eye Research Institute, Singapore National Eye Centre,
Singapore, Singapore; 4Department of Ophthalmology, National
University Health Systems, National University of Singapore,
Singapore, Singapore; 5Statistics Unit, Singapore Eye Research
Institute, Singapore National Eye Centre, Singapore, Singapore.
Purpose: We aimed to determine the relationship between iris surface
features and past attack of acute primary angle closure (APAC) in
eyes with angle closure.
Methods: This was a case-control study involving Asian patients
diagnosed with previous APAC, primary angle closure suspect
(PACS), and primary angle closure (PAC) at a tertiary eye centre in
Singapore between August 2012 and January 2015. All participants
underwent a standardized ophthalmic examination and digital slitlamp iris photography. Iris surface features were graded based on
crypts (by number and size), furrows (by number and circumferential
extent) and color. The fellow eyes of APAC were used as proxies for
APAC eyes to compared with PACS/PAC eyes with regards to their
iris surface features, as the post-attack APAC eye frequently had
structural iris changes and altered iris surface architecture.
Results: A total of 71 patients with APAC and 186 with PACS or
PAC were included in the analysis (mean age: 68.0 ± 7.2 years and
32.7% male). Higher grade of iris crypts were significantly associated
with lower risk of APAC occurrence (OR = 0.54 for one grade higher
in crypt grade; P = 0.013, adjusted for age, gender, ethnicity and
pupil size). That is, having one grade more in the iris crypt reduced
the likelihood of having APAC by almost 50%. We did not observe
significant associations between iris furrows or iris color with
presence of APAC (both P > 0.05).
Conclusions: Our study comprising Asian eyes with angle closure
suggests that the presence of numerous and larger crypts may be
protective for APAC. As such, assessing iris surface architecture for
iris crypts grade could be a new measure for risk stratification of
developing APAC in eyes with angle closure.
Commercial Relationships: Ching-Yu Cheng, None;
Victor T. Koh, None; Jacqueline Chua, None; Yuan Shi,
None; Monisha E. Nongpiur, None; Baskaran Mani, None;
Rajesh Sasikumar, None; Shamira Perera, None; Tin Aung, None
Support: NMRC NIG/1069/2012 and CSA/033/2012
Hydrodynamic and Morphological Changes along the Trabecular
Outflow Pathway in POAG Eyes
Lihua Gong1, 2, Elliot D. Cha1, Haiyan Gong1. 1Ophthalmology,
Boston University, Boston, MA; 2Ophthalmology, Qingpu Branch of
Zhongshan Hospital Affiliated to Fudan Universtiy, Shanghai, China.
Purpose: This study aimed to determine outflow patterns and
morphological changes responsible for decreased outflow facility
(C) in eyes with primary open angle glaucoma (POAG) compared to
normal eyes.
Methods: Five POAG and six normal enucleated human eyes were
perfused for 30 minutes at 15mmHg to establish a baseline C. The
anterior chamber of each eye was exchanged (5ml) and perfused
with a fixed volume (200µl) of fluorescent tracer to label outflow
patterns. The anterior segment of each eye was obtained, globally
imaged and dissected radially into 16 wedges, from which the frontal
sections were cut and imaged with confocal microscopy. Percent
effective filtration area (EFA) was calculated from the measured
lengths of tracer distribution in the trabecular meshwork (TM),
episcleral veins (ESV), and along the inner wall (IW) of Schlemm’s
canal. TM thickness was measured. Numbers of CCs and percentage
of herniation into CC ostia were analyzed. The same sections were
further processed for light and electron microscopy. Student’s t-test
and correlation analysis were performed.
Results: C was significantly lower in POAG eyes than normal eyes
(p<0.01), which was associated with a significant decrease in EFA
(p<0.01) in all three regions (TM, IW and ESV). In both POAG and
normal eyes, significantly higher EFA was found in the TM than IW
and ESV (p<0.01); EFA in the latter two were similar. EFA in ESV
was positively correlated with C in all eyes (R=0.629, p<0.05). Mean
TM thickness significantly decreased in POAG compared to normal
eyes (p<0.01). Nasal quadrants showed preferential outflow in both
normal and POAG eyes compared to the other quadrants, which
was associated with a greater regional TM thickness. However, the
difference in TM thickness reached statistical significance only in
normal eyes. Greater percent herniation into CC ostia was found in
POAG compared to normal eyes (p<0.05). More TM endothelium
loss, extracellular matrix accumulation in the trabecular beams, and
beam fusion were observed in POAG eyes.
Conclusions: Preferential outflow found in the nasal quadrants of
normal and POAG eyes is associated with increased regional TM
thickness. Significant reduction in EFA contributes to decreased C in
POAG eyes, which is a result of morphologic changes including more
compact TM, more herniation-blocked CCs, and TM beam fusion due
to loss of endothelial covering.
Commercial Relationships: Lihua Gong; Elliot D. Cha, None;
Haiyan Gong, None
Support: NIH EY022634 and The Massachusetts Lions Eye
Research Fund
A weakened blood-aqueous barrier at the pupillary capillaries – a
qualitative immunohistochemical study
Hongfang Yang1, Paula Yu2, Xinghuai Sun1, Dao-Yi Yu2.
1
Ophthalmology, Fudan University affiliated EENT Hospital,
Shanghai, China; 2University of Western Australia, Perth, WA,
Australia.
Purpose: Inflammatory exudation is commonly observed around
pupil in clinic. We hypothesize that high permeability exists in iridal
pupil region. This study is to investigate the distribution of junctional
proteins in blood vessels in conjunction with their barrier function at
the iris pupillary region.
Methods: Twenty-one freshly enucleated porcine eyes were divided
into two groups. Group one with 12 eyes were used to test barrier
function by perfusion of FITC-albumin through the temporal long
posterior ciliary arteries at 200µm/min for 0 min (2 eyes), 2 min
(5 eyes) and 8 min (5 eyes). The irises were cryosectioned for
confocal microscopy to detect diffusion / leakage of FITC-albumin,
followed by stained using H & E and Van Gieson. Group two with
9 eyes were used for perfusion labelling for a combination of VEcadherin, claudin-5 and αSMA. Iris sectors were flat-mounted for all
experimented eyes. Confocal images were collected using the same
laser intensity and gain setting. Signal intensities were compared
for FITC-albumin and for junctional proteins by three independent
observers.
Results: FITC-albumin signal was detectable in the iris vasculature
at 2 mins time point and with increased intensity at 8 mins time point.
Variation in FITC intensity was noted for different parts of the iris
vasculature, with the superficial and deep capillary network in the
pupillary region showing a greater intensity than other parts of the
iris. Labelling of junctional proteins found the iris capillary networks
to have relatively weak, uneven and discontinuous Claudin-5
labelling compared to the larger iris vessels. Iris capillary networks
also showed partial and scarce coverage by αSMA positive cells in
contrast to the abundant presence of αSMA in the iris arteriole and
venous smooth muscle cells.
Conclusions: The iris pupillary capillaries may present a weaker
blood-aqueous barrier based on the discontinuous and uneven
presence of Claudin-5 and a greater prominence of FITC-albumin
than other immediate surrounding vasculatures in the iris. The
scarcity of αSMA positive cells in the pupillary capillaries may have
a role in the relatively weaker barrier function in this region. Further
study will be needed to confirm whether volume change of iris is
remarkably obvious in this region than others.
Fig1. FITC-albumin signal at different time points.
Commercial Relationships: Hongfang Yang, None; Paula Yu,
None; Xinghuai Sun, None; Dao-Yi Yu
DBA 2J mouse model for experimental glaucoma – pitfalls and
problems
Anita J. Turner, Roshana Vanderwall, Vivek Gupta,
Alexander Klistorner, Stuart L. Graham. Faculty of Medicine and
Health Sciences, Macquarie University, Sydney, NSW, Australia.
Purpose: Purpose: The DBA2J mouse has been described as a
model for congenital experimental glaucoma. This inbred strain
develops anterior segment anomalies, iris atrophy, peripheral anterior
synechiae and pigment dispersion leading to raised intraocular
pressure (IOP) and glaucomatous damage as well as corneal, heart
and major vessel calcification. We used this model to determine the
effects of a neuroprotective agent during development of glaucoma
and found that it was difficult to assess the progression of the disease
due to the abovementioned abnormalities.
Methods: Methods: We followed 52 mice from 12 weeks to 12
months of age and evaluated iris changes, corneal calcification,
intraocular pressure – iCare tonometer, retinal electrophysiology,
and retinal structure with optical coherence tomography (OCT) and
correlated findings with histology.
Results: Results: Iris changes became apparent from 6m whereby
pupil dilation was limited or deformed. Corneal calcification
developed as early as 12 weeks, all mice displayed significant
calcification by 6m. In controls, mean IOP was 8.4 ± 0.2mmHg at
3m and did not begin to increase until 9m (mean 13.8 ± 0.9mmHg;
range 8.3 – 27.0). By 12m some mice showed little IOP elevation
(mean 19.0 ± 1.4 mmHg; range 8.0 – 27.3) despite substantial iris
changes. We believe that the IOP measurements may be inaccurate
due to extensive corneal calcification. Longitudinal OCT imaging
indicated progressive thinning of the RGC layer, cupping at the optic
nerve head and INL damage in many eyes however several mice
exhibiting these changes did not have elevated IOP. It was often
difficult to obtain OCT images due to corneal calcifications and pupil
abnormalities. Mean STR was decreased (90uV at 3m; 35uV at 12m)
with a minor change in ERG (472uV at 3m; 448uV at 12m) possibly
due to the lack of pupil dilation. During the study a total of 20 mice
died due to cardiac calcification (13), thoracic cavity malformation
(2), bladder obstruction (2), aortic aneurysm (1), other causes (2).
Conclusions: Conclusions: This model presents serious problems
with corneal calcification affecting the ability to accurately assess
IOP and to obtain OCT images. Due to the variable time to onset and
degree of IOP elevation, planning interventional trials of therapeutic
agents is difficult. In addition, the high rate of systemic complications
leading to cardiovascular dysfunction and death is a complicating
factor.
Commercial Relationships: Anita J. Turner, None;
Roshana Vanderwall, None; Vivek Gupta, None;
Alexander Klistorner, None; Stuart L. Graham, None
Support: Supported by Novartis
Fig2.Claudin-5 and alpha-SMA labelling echo vascular permeability
Age-related changes in anterograde transport, axonal integrity
and visuomotor function in DBA/2J and C57BL/6J mice
Xiaoling Yang1, 2, Yolandi van der Merwe1, 4, Leon C. Ho1, 3,
Ian P. Conner2, 4, Kira L. Lathrop2, Gadi Wollstein2, 4,
Joel S. Schuman2, 4, Kevin C. Chan1, 2. 1NeuroImaging Laboratory,
University of Pittsburgh, Pittsburgh, PA; 2UPMC Eye Center, Eye and
Ear Institute, Ophthalmology and Visual Science Research Center,
Department of Ophthalmology, University of Pittsburgh, Pittsburgh,
PA; 3Department of Electrical and Electronic Engineering, University
of Hong Kong, Hong Kong, China; 4Department of Bioengineering,
Swanson School of Engineering, University of Pittsburgh,
Pittsburgh, PA.
Purpose: Although elevated intraocular pressure (IOP) and age
are major risk factors for glaucoma, their effects on glaucoma
pathogenesis are incompletely understood. This study evaluated
the IOP, visuomotor function, anterograde transport and axonal
integrity of the visual system at different ages in the DBA/2J (D2)
mouse model of chronic glaucoma, with an aim to probe the onset of
glaucomatous changes and their progression. Age-matched C57BL/6J
(B6) mice were assessed as a control.
Methods: Four separate groups of D2 and B6 female mice
underwent IOP and optokinetic assessments at the age of 5 (D2/
B6, n=6/5), 7 (n=6/5), 9 (n=6/5) and 12 (n=13/4) months old
(mos) using the TonoLab tonometer and OptoMotry system.
Manganese(Mn)-enhanced MRI (MEMRI) of anterograde transport
was then performed to a subset of mice (n=2-6 per age per D2/B6
group) in a 9.4-Tesla scanner at 8 hours after binocular intravitreal
MnCl2 injection, and the remaining mice were sacrificed for
immunohistochemistry of prechiasmatic optic nerve (ON) integrity.
Results: The IOP of D2 mice increased significantly at 9 mos and
progressed further at 12 mos, whereas no apparent IOP difference
was found in B6 mice across age (Fig. 1a). Visual acuity of D2
mice continued to worsen from 5 to 9 mos, whereas B6 mice
performed better in optokinetics than D2 mice at each age (Fig.
1b). For MEMRI, Mn enhanced to similar extents along D2 and B6
visual pathways at 5 and 7 mos (white arrows in Fig. 1c). Reduced
Mn enhancement began in the superior colliculus of D2 mice at
9 mos, and progressed further together with the ON and lateral
geniculate nucleus at 12 mos (Fig. 1d); Neurofilament expression
gradually decreased in ON of D2 mice from 5 to 12 mos, whereas
pan-microglia and Tau expressions gradually increased in ON of D2
mice (Fig. 2). The axonal integrity in B6 mice appeared relatively
comparable across age (Fig. 2).
Conclusions: Anterograde Mn transport along the visual pathway in
D2 mice began to be disrupted at the onset of IOP increase at 9 mos
and progressed further at 12 mos together with further IOP increase,
neurofilament loss and elevated pan-microglia and Tau protein levels.
Visual acuity in D2 mice appeared to deteriorate earlier than IOP
increase and Mn transport disruption and was worse than B6 mice
at every age, which suggested additional factors, such as gliosis, are
contributing to the visuomotor deficits in D2 mice.
Commercial Relationships: Xiaoling Yang, None; Yolandi van
der Merwe, None; Leon C. Ho, None; Ian P. Conner, None;
Kira L. Lathrop, None; Gadi Wollstein, None; Joel S. Schuman,
Zeiss Inc. (P); Kevin C. Chan, None
Support: National Institutes of Health P30-EY008098 and UL1TR000005 (Bethesda, Maryland); BrightFocus Foundation G2013077
(Clarksburg, Maryland), Alcon Research Institute Young Investigator
Grant (Fort Worth, Texas); Eye and Ear Foundation (Pittsburgh,
Pennsylvania); and Research to Prevent Blindness (New York, New
York).
Assessment of age-related eye morphology and aqueous humor
flow dynamics in the DBA/2J mouse model of pigmentary
glaucoma using ocular MRI and anterior chamber iPerfusion
systems
Darragh Crosbie1, James Keaney1, 2, Joseph M. Sherwood3,
Darryl R. Overby3, W D. Stamer4, Lawrence Tam1, Peter Humphries1.
1
Genetics Department, Trinity College Dublin, Dublin, Ireland; 2Ross
University School of Veterinary Medicine, Basseterre, Saint Kitts and
Nevis; 3Imperial College London, London, United Kingdom; 4Duke
University, Durham, NC.
Purpose: Using contrast enhanced Gadolinium(Gd)-MRI and a novel
anterior chamber perfusion system (iPerfusion) age related changes
in the morphology and flow dynamics of aqueous humor (AqH) were
compared between wild-type C57BL/6 and glaucomatous DBA/2J
mouse eyes.
Methods: WT and DBA mouse eyes were compared at 3 and 9
months using a rodent-specific 7T MRI. Pre-scan images without
contrast agent were used to assess eye anatomy: anterior chamber
(AC) and vitreous body (VB) morphology, and eye and lens size.
Gd-DTPA (Magnevist) was injected intravenously at time 0 and the
eyes were scanned each minute for the subsequent hour to measure
AqH flow. In order to reliably assess differences in AqH outflow, a
novel AC perfusion system (iPerfusion) was used to measure outflow
facility.
Results: We treated WT mice with topical latanoprost eyedrops
to demonstrate the ability of MRI to assess AqH flow dynamics in
the AC. Latanoprost-treated eyes showed a decreased rate of Gd
accumulation (Diff = -1.274 ± 0.3973(%/min), p = 0.0184) and peak
Gd intensity in the AC in comparison to saline treated contralateral
eyes. Furthermore, MRI images showed an age-related increase in
AC area, AC depth and eye size in DBA mice as compared to WT
mice from 3 to 9 mo (p<0.0001, N = 6). In addition, no significant
changes were observed in either rate of AC Gd accumulation or Gd
peak intensity in the AC of WT mice, and no difference was found
between 3-mo wt and DBA mice. However, 9-mo DBA animals
showed a decrease in Gd accumulation (Diff 10.33 ± 2.779, p<0.01)
and peak Gd intensity. Facility in DBA2J shows an average of 46%
reduction from 9 to 6 mo (N=4). Similarly, leakage of gadolinium
from the ciliary body posteriorly into the VB was observed in 9-mo
DBA mice and not in WT mice.
Conclusions: MRI is a useful tool for in vivo analysis of the eye,
as demonstrated for a common mouse model of glaucoma. It allows
for morphological measurements of mouse eye structures and can
be used to assess AqH dynamics. The DBA model shows age related
changes in AC morphology and outflow facility that is not seen in
WT mice; although more animals need to be tested to determine
whether facility is significantly different. Gd-MRI analysis with
iPerfusion data indicates that aged DBA mice also have a lower and
dysregulated AqH inflow in comparison to aged WT mice.
Commercial Relationships: Darragh Crosbie, None;
James Keaney, None; Joseph M. Sherwood; Darryl R. Overby,
None; W D. Stamer, None; Lawrence Tam, None;
Peter Humphries, None
Spatial and temporal dissection of pathogenesis in a mouse model
of anterior segment dysgenesis and glaucoma caused by a Col4a1
mutation
Mao Mao, Yvonne Ou, Marton Kiss, Douglas B. Gould.
Ophthalmology, Univ of California, SF Sch of Med, San Francisco,
CA.
Purpose: Mutations in collagen type IV alpha 1 (COL4A1) cause
anterior segment dysgenesis (ASD) that can lead to glaucoma.
Because of the widespread distribution of COL4A1 in ocular
basement membranes and the complex crosstalk between tissues
of different embryological origin during development, dissecting
the primary insults of pathogenesis can be difficult. Here, we use
conditional expression of mutant COL4A1 to determine the primary
location and timing of insults in ASD and glaucoma.
Methods: We developed a conditional allele with LoxP sites flanking
exon 41 of Col4a1 (Col4a1flex41) that recreates the Col4a1Δex41
allele known to cause severe ASD in mice. We used Actb-Cre mice
(ubiquitous CRE expression) to validate the Col4a1 flex41 allele for
CRE-mediated excision. Next, we crossed Col4a1+/flex41 mice to three
different tissue-specific CRE recombinase strains: MLR10-Cre (lens),
Wnt1-Cre (neural crest derived periocular mesenchyme), and Tie2Cre (vascular endothelial cells), to generate corresponding tissuespecific mutants. Finally, we used Rose26-CreERT mice (tamoxifen
inducible CRE) to study the timing of pathogenesis. We tested the
extent of ASD by performing slit-lamp examination, measuring
intraocular pressure (IOP), and analyzing histological sections of
anterior segment structures and optic nerves.
Results: Ubiquitous expression of mutant COL4A1 recapitulated the
complete spectrum of ASD observed in Col4a1+/Δex41 mice, validating
the conditional mutation. Using induction with tamoxifen we found
that expressing the mutation after E12.5 did not cause ASD. Lensspecific mutants developed cataracts, mild ASD, IOP elevation, and
optic nerve degeneration; however, other cell-type-specific mutants
did not.
Conclusions: Our results suggest that early developmental events
underlie ASD and that the lens is a primary site of pathogenesis.
While lens-specific conditional mutants had cell-autonomous
pathology, other mutant lines appeared to be normal. However,
absence of ASD in those lines might due to compensation from
other cell types and therefore their roles in the full manifestation of
the phenotype cannot be ruled out – especially since lens-specific
mutants did not fully phenocopy Col4a1+/Δex41 mice.
Commercial Relationships: Mao Mao, None; Yvonne Ou;
Marton Kiss, None; Douglas B. Gould, None
Support: NIH Grant EY019887 EY002162
Wound healing after Trabeculectomy in rabbits: Ultrasound
Biomicroscopy (UBM) correlation with clinical findings
Edward Yung1, Jonathan P. Wright1, Alan G. Fong1, 2,
Kevin Kaplowitz1, Robert A. Honkanen1. 1Ophthalmology, SUNY
Stony Brook, Smithtown, NY; 2Ophthalmology, Bascom Palmer Eye
Institute, Miami, FL.
Purpose: Evaluation of wound healing in rabbits after
trabeculectomy has previously been based on serial clinical
examinations and IOP monitoring. We hypothesize that anterior
segment ultrasound biomicroscopy can be used to demonstrate
objective findings of wound healing and bleb failure correlating to
clinical findings in an experimental rabbit model.
Methods: Four eyes of four male New Zealand white rabbits
underwent limbal-based trabeculectomy ab externo by the same
surgeon (RH) without the use of antifibrotic agents. Each eye
underwent serial evaluation after surgical intervention with the
current standard of Moorefield clinical bleb grading. Ultrasound
biomicroscopy was carried out using the Vevo 770 Ultrasound
Imaging System (ViewSonic, Toronto, CA) with a RMV704 probe
to evaluate the criteria of bleb height, size of cystic spaces, the
presence of hypoechoic areas, and visibility of scleral tract. Clinical
bleb failure was defined as a Moorfield bleb grading height of 1 or
maximal area grading of less than 2. Statistical significance was
evaluated with the Student’s t-test.
Results: Average follow up time was 40.5 days post-operatively
after trabeculectomy. Mean peak Moorfield bleb height grading was
2.75 ± 0.96, and was demonstrated 2 days post-operatively. Average
time to clinical bleb failure was between 11 and 14 days by bleb
grading. Ultrasound biomicroscopy evaluation demonstrated baseline
conjunctival/bleb thickness of 0.3 ± 0.07 mm. Peak bleb height was
2.95 ± 1.97 mm 2 days after trabeculectomy (p=0.054), followed by
a rapid decline in bleb height by post-operative day 9 (1.27 ±0.29
mm, p=0.14). Complete loss of cystic bleb spaces was found by
post-operative day 14 in all 4 cases. Loss of hypoechoic regions was
demonstrated after an average of 10.75 ± 2.36 days post-operatively
and occurred in all four eyes by post-operative day 14.
Conclusions: Our results demonstrate that UBM yields objective
indicators of bleb failure that correlate well with clinical findings.
Thus, this imaging modality can be a valuable adjunct to clinical
examination for evaluating bleb survival in experimental rabbit
models of glaucoma filtering surgery. Further studies with a larger
population size will be needed to determine statistical significance.
Commercial Relationships: Edward Yung, None;
Jonathan P. Wright; Alan G. Fong; Kevin Kaplowitz, None;
Robert A. Honkanen, Endo Pharmaceuticals (F)
Support: Endo Pharmaceuticals
Conclusions: Four-dimensional imaging using two-photon
microscope indicated MCP-1 affected the cellular dynamics in
the subconjunctival tissue. The evaluation of cellular dynamics
in the subconjunctival tissue using this technique may lead to the
understanding of the wound healing process after filtration surgery.
Commercial Relationships: Sachi Kojima, None; Toshihiro Inoue,
None; Tomokazu Fujimoto, None; Hidenobu Tanihara, None
Support: JSPS KAKENHI 15K15636
Four-dimensional imaging revealed influences of monocyte
chemoattractant protein-1 on immune cell dynamics in the
subconjunctival tissue
Sachi Kojima, Toshihiro Inoue, Tomokazu Fujimoto,
Hidenobu Tanihara. Ophthalmology, Kumamoto University,
Kumamoto, Japan.
Purpose: To visualize influences of monocyte chemoattractant
protein-1 (MCP-1) on the immune cells in the subconjunctival tissue
using two-photon laser scanning microscope.
Methods: LysM-eGFP mice (gene-targeted mice expressing
enhanced green fluorescent protein under the control of the
endogenous lysozyme M promoter) were anesthetized by isoflurane.
Vessels were visualized by intravenous injection of 70 kDa of
Texas red–conjugated dextran. Using two-photon laser scanning
microscope, three-dimensional images of the subconjunctival tissue
were acquired every 1 minute for 30 minutes through phosphatebuffered saline with or without 10µg/ml MCP-1 in custom-made
eyecup. Raw imaging data were processed and analyzed with Imaris
software.
Results: Intravital green-labeled LysM-eGFP-positive cells and
red-labeled vessels were successfully visualized using two-photon
laser scanning microscope. Compared with the control, the number of
LysM-eGFP-positive cells in the subconjunctival tissue increased in
the presence of MCP-1. Moreover, the motility LysM-eGFP-positive
cells was enhanced under the influence of MCP-1.

Session 448 Glaucoma Imaging II

Transcription

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