ARVO 2016 Annual Meeting Abstracts

360 Glaucoma Imaging I Tuesday, May 03, 2016 3:45 PM 5:30 PM 6A Paper Session Program #/Board # Range: 3759 3765 Organizing Section: Glaucoma Program Number: 3759 Presentation Time: 3:45 PM 4:00 PM Longitudinal reproducibility of spectral domain optical coherence tomography (SD-OCT) in children with stable glaucoma and physiological cupping Limin Xu 2, Mays El-Dairi 1, 4, Evan Silverstein 5, Sharon Freedman 1, 3. 1 Pediatric Ophthalmology, Duke Eye Center, Durham, NC; 2 Duke University School of Medicine, Durham, NC; 3 Glaucoma, Duke Eye Center, Durham, NC; 4 Neuro-Ophthalmology, Duke Eye Center, Durham, NC; 5 Department of Ophthalmology, Virginia Commonwealth University, Richmond, VA. Purpose: Spectralis SD-OCT has previously shown good reproducibility for measurements of both peripapillary retinal nerve fiber layer (RNFL) and macular thickness in eyes of adults with known or suspected glaucoma, as well as in children with healthy eyes. However, few publications consider longitudinal reproducibility of SD-OCT in children. Methods: This retrospective clinical study included 47 eyes of 47 children (age <18yrs) with stable primary congenital glaucoma (PCG), juvenile open-angle glaucoma (JOAG), and physiologic cupping (clinically diagnosed) having had 2 SD-OCT Spectralis (Heidelberg, Germany) studies over >1-year period. Thicknesses of average peripapillary Retinal Nerve Fiber Layer (RNFL) and six individual sectors, as well as volumes of 5 segmented retinal layers and total retina were measured using an 8 8 mm grid centered on the foveal pit. Spectralis review software was used for segmentation. Intraclass correlation coefficients (ICC) and coefficient of variation (COV) were calculated for each of the above OCT parameters. Results: 31 eyes with glaucoma (20 PCG, 11 JOAG) and 16 eyes with physiologic cupping were included. For PCG, JOAG, and physiologic cupping, mean(±sd) ages at initial SD-OCT were 9.7±3.3, 13.3±2.0, and 11.0±3.3 years, respectively; mean times between first and last SD-OCTs were 3.0±1.4, 2.8±1.6, and 2.1±1.1 years, respectively. The intervisit ICCs for the average and sectoral RNFL thicknesses across three visits were 0.887-0.997 for all groups. Intervisit ICCs for segmented retinal layer volumes were 0.806-0.993 for all groups. Intervisit ICCs for total retinal volume for PCG, JOAG, and physiologic cupping across three visits were 0.954, 0.988, and 0.993, respectively. Intervisit COVs for average RNFL thickness were 1.7%, 2.6%, and 1.2% for PCG, JOAG, and physiologic cupping, respectively. For all other parameters, intervisit COV ranged from 0.4-6.7%. Conclusions: The reproducibility of longitudinal SD-OCT measurements was very good (ICC>0.8) for all average and sectoral RNFL thicknesses, as well as for total and segmented retinal volumes. For average RNFL thickness, longitudinal reproducibility of SD-OCT in children with stable glaucoma over ~2 years is comparable to reported short-term reproducibility in children with normal eyes (1.16% COV) and adults with normal eyes and glaucoma (1.62-1.95% COV). Commercial Relationships: Limin Xu, None; Mays El-Dairi; Evan Silverstein, None; Sharon Freedman, Inotek (C), Pfizer (C), FocusROP (P) Program Number: 3760 Presentation Time: 4:00 PM 4:15 PM Reference planes for measuring of lamina cribrosa depth with optical coherence tomography Jayme R. Vianna, Vishva M. Danthurebandara, Glen P. Sharpe, Donna Hutchison, Anne Belliveau, Lesya Shuba, Marcelo T. Nicolela, Balwantray C. Chauhan. Glaucoma, Dalhousie University, Halifax, NS, Canada. Purpose: Anterior lamina cribrosa depth (LCD) is thought to be an important structural parameter of the optic nerve in glaucoma. However, there is no agreement on the optimal technique for its measurement. We performed a reproducibility study to compare two possible reference planes from which to measure LCD: Bruch s membrane (BM) or choroid-sclera interface (CSI). Methods: We included 16 glaucoma patients (mean[sd] age: 65.5[8.7] years) and 16 normal controls (mean[sd] age: 51.0[19.6] years). One randomly selected eye of each subject was examined with enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT, Spectralis, Heidelberg Engineering) 3 times on the same day. The EDI-OCT scan pattern consisted of 24 angularly equidistant radial B-scans centered on Bruch s membrane opening (BMO). In each scan we manually segmented the inner limiting membrane, BM, CSI and the anterior laminar surface. Two independent reference planes were generated, one based on the BM and other based on the CSI, according to their position at a ring centered on the BMO, with inner radius of 1700 µm and outer radius of 1800 µm. From each reference plane, the LCD was measured at all visible locations and combined into a surface, to compute the average LCD and visible laminar area (Figure 1). The optic nerve head neuroretinal rim was quantified by the global BMO-minimum rim width (BMO-MRW). Reproducibility of measurements was assessed by within-subject standard deviations. Factors related to the measurements reproducibility were assessed with Spearman correlation coefficients. Results: The mean (SD) LCD measured with the BM and CSI reference planes was 485 (124) µm and 344 (112) µm, respectively. The respective within-subject standard deviation of LCD was 7.0 µm (95% CI: 5.8-8.2 µm) and 8.0 µm (95%CI: 6.6-9.4 µm). The reproducibility of LCD was not significantly related to its magnitude (Figure 2), the visible laminar area or BMO-MRW (P > 0.15). The mean (SD) visible laminar area corresponded to 84 (26)% of the BMO area. Eyes with larger BMO-MRW had smaller visible laminar areas (P < 0.01). Conclusions: The LCD can be measured with similar reproducibility with either BM or CSI reference planes. However, because the BM reference plane likely depends on choroidal thickness, which can vary with age and other factors, the CSI reference plane is likely more suitable for longitudinal studies.

ARVO 2016 Annual Meeting Abstracts Program Number: 3761 Presentation Time: 4:15 PM 4:30 PM Lamina cribrosa pore tortuosity in healthy and glaucomatous eyes Bo Wang1, 2, Katie Lucy1, Joel S. Schuman1, 2, Ian A. Sigal1, 2, Richard A. Bilonick1, 3, Chen D. Lu4, Hiroshi Ishikawa1, 2, Larry Kagemann1, 2, James G. Fujimoto4, Gadi Wollstein1, 2. 1UPMC Eye Center, Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA; 2 Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA; 3Department of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, PA; 4 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA. Purpose: The lamina cribrosa (LC) is hypothesized to play an important role in the pathogenesis of glaucoma, with impairment to the axoplasmic flow as a leading mechanism for damage. Yet, the path ganglion cell axons take through the LC, which may affect axoplasmic flow, remains poorly characterized. A more tortuous path through the LC may interfere with axoplasmic flow, increasing the risk of glaucoma damage. The purpose of this study was to investigate in vivo the hypothesis that axons of glaucoma eyes take a more tortuous path through the LC compared to healthy eyes. Methods: 10 healthy (H), 23 glaucoma suspect (GS) and 48 glaucoma (GL) eyes from 66 subjects were scanned using a swept source (SS-)OCT system. All subjects underwent a comprehensive ophthalmic exam and diagnosed based on optic nerve appearance and visual field. The LC pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the LC using a custom MATLAB and ImageJ software (Fig A-B). Pore tortuosity, defined in Fig C, was quantified for each eye. A linear mixed effect model was used to identify differences in pore tortuosity between diagnostic categories as well as with VF MD. A Kolmogorov Smirnov test was used to determine difference in variance between diagnostic categories. Results: Pore tortuosity in GL eyes (1.46±0.08) was significantly higher than in H (1.40±0.04, p=0.03) and GS eyes (1.39±0.07, <0.01) (Fig D). GL eyes also had larger variances compared to H and GS (p=0.02, <0.01, respectively) (Fig E). Glaucoma severity, as determined by VF MD, was not associated with pore tortuosity (Fig F). Conclusions: Axons of GL eyes take a more tortuous path through the LC compared to those of H eyes. Furthermore, the tortuosity of GL eyes is more variable than those of H eyes. The causality of the relationship between pore tortuosity and glaucoma damage, as assessed by visual fields, warrants further investigation. Commercial Relationships: Jayme R. Vianna, None; Vishva M. Danthurebandara; Glen P. Sharpe, None; Donna Hutchison, None; Anne Belliveau, None; Lesya Shuba, None; Marcelo T. Nicolela, None; Balwantray C. Chauhan, Heidelberg Engineering (F), Heidelberg Engineering (C) Support: CIHR MOP-11357 (BCC) to access the versions of record.

(A) SS-OCT en face of the LC with (B) a subset of pore paths traced shown in 3D. (C) Method of assessing pore tortuosity divide the path length through pore centroids (red) by the distance between the top and bottom pore (purple). (D) Boxplot and (E) density distribution of pore tortuosity grouped by diagnostic category (H green, GS blue, GL red). (F) Scatter plot of tortuosity according to VF MD. Commercial Relationships: Bo Wang, None; Katie Lucy, None; Joel S. Schuman, Zeiss (P); Ian A. Sigal, None; Richard A. Bilonick, None; Chen D. Lu, None; Hiroshi Ishikawa, None; Larry Kagemann, None; James G. Fujimoto, Optovue (I), Optovue (P), Zeiss (P); Gadi Wollstein Support: NIH: R01-EY013178, R01-EY025011, R01-EY011289, P30-EY008098, T32-EY017271; Eye and Ear Foundation (Pittsburgh, PA); Research to Prevent Blindness (New York, NY). Program Number: 3762 Presentation Time: 4:30 PM 4:45 PM Diagnostic Innovations in Glaucoma Study (DIGS): OCT Angiography Vessel Density in Glaucomatous Eyes with Focal Lamina Cribrosa Defects Min Hee Suh 1, 2, Linda M. Zangwill 1, Akram Belghith 1, Adeleh Yarmohammadi 1, Patricia Isabel C. Manalastas 1, Alberto Diniz-Filho 1, Naeem Fatehee 1, Siamak Yousefi 1, Robert N. Weinreb 1. 1 Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, San Diego, CA; 2 Ophthalmology, Inje University Haeundae Paik Hospital, Busan, Korea (the Republic of). Purpose: Influence of anatomical differences of the lamina cribrosa (LC) on the vascular hemodynamics of the optic nerve head remains unknown. Optical coherence tomography angiography (OCTA) provides in vivo images of the vessel density located within the peripapillary retinal nerve fiber layer (RNFL). The present study investigated whether peripapillary RNFL vessel density assessed by OCTA is reduced in glaucomatous eyes with a focal LC defect by swept-source OCT (SS-OCT). Methods: Among 130 eyes with open angle glaucoma, 58 (44.6 %) eyes had focal LC defects and 72 (55.4 %) did not have a defect based on the serial horizontal B-scan images of the SS-OCT. For the measurement of the circumpapillary vessel density and RNFL thickness, the optic disc region was imaged with spectral-domain OCT. Only good quality OCTA images identified according to the Shiley Eye Institute Imaging Data Evaluation and Analysis (IDEA) Reading Center protocol were included. Circumpapillary vessel density was calculated as the percentage area occupied by actively flowing vessels in the measured region by the OCTA. Circumpapillary vessel densities and RNFL thicknesses were compared in global area and in 8 45 -sized sectors between eyes with and without LC defects. Results: Mean circumpapillary vessel densities of eyes with LC defects were significantly lower than those without defects in global area, and in superotemporal (ST), superonasal (SN), inferotemporal (IT), and inferonasal (IN) sectors (P < 0.05). Sector differences were highest in the IT (54.2 ± 1.5 vs. 59.3 ± 1.4 %, respectively) followed by ST (56.9 ± 1.1 vs. 60.8 ± 1.0 %, respectively), IN (54.9 ± 1.1 vs. 57.9 ± 1.0 %, respectively), and SN (54.3 ± 1.0 vs. 56.8 ± 0.8 %, respectively) sectors. Age, circumpapillary RNFL thicknesses in all areas, visual field MD and pattern standard deviation, presence of the optic disc hemorrhage, mean ocular perfusion pressure and intraocular pressure were not different between the two groups (P > 0.05). Conclusions: Circumpapillary vessel density was significantly lower in glaucomatous eyes with focal LC defects than those without defects, while glaucoma severity did not differ between the two groups. These differences were highest in superotemporal and inferotemporal sectors. Commercial Relationships: Min Hee Suh, None; Linda M. Zangwill, Quark (F), Nidek Inc (F), Heidelberg Engineering GmbH (F), Carl Zeiss Meditec Inc. (P), Topcon Medical Systems Inc. (F), Carl Zeiss Meditec Inc. (F), Optovue Inc. (F); Akram Belghith, None; Adeleh Yarmohammadi, None; Patricia Isabel C. Manalastas, None; Alberto Diniz-Filho, None; Naeem Fatehee, None; Siamak Yousefi; Robert N. Weinreb, Alcon (C), Carl Zeiss Meditec (F), Amatek (C), Heidelberg Engineering GmbH (F), Optovue (F), Topcon (C), Genentech (F), Nidek (F), Carl Zeiss Meditec (C), Aquesys (C), Novartis (F), Topcon (F), Bausch&Lomb (C), Aerie (F), Allergan (C), Valeant (C) Support: NIH Grants P30EY022589, EY11008, EY019869, EY021818 Clinical Trial: NCT00221897 Program Number: 3763 Presentation Time: 4:45 PM 5:00 PM Swept-Source OCT Optic Nerve Head Structural Features of Primary Open Angle Glaucoma and Disc Hemorrhage Sophie Cai 1, Marissa K. Shoji 1, Elise Taniguchi 1, Dejiao Li 1, Leonardo A. Pereira 1, 2, Stacey C. Brauner 1, Scott H. Greenstein 1, Angela Turalba 1, Louis R. Pasquale 1, 3, Lucy Shen 1. 1 Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA; 2 Ministry of Education of Brazil, CAPES Foundation, Brasilia, Brazil; 3 Channing Division of Network Medicine, Brigham and Women s Hospital, Boston, MA. Purpose: To identify localized differences in optic nerve head (ONH) structure imaged by swept-source optical coherence tomography (SS- OCT) in eyes with primary open angle glaucoma (POAG) and history of disc hemorrhage (DH), eyes with POAG but no DH history, and control eyes with no major non-cataract pathology. Methods: POAG patients with history of inferotemporal DH, POAG patients with no DH history, and controls were recruited for this prospective, cross-sectional study. SS-OCT (Topcon) radial and 5-line cross ONH scans were performed. One eye per patient was included. Bruch s membrane opening-minimum rim width (BMO- MRW) was measured from inferotemporal radial scans and compared across groups by ANOVA. Percentage frequencies of inferotemporal prelaminar and lamina cribrosa (LC) defects (Figure) identified by two masked observers were compared across groups by Fisher s exact test. Multiple comparison post hoc tests were used to identify significant pairwise differences (P<0.05). Results: 14 POAG patients with DH, 13 POAG patients without DH, and 12 controls were included. Patient groups were well matched by age, sex, and ethnicity (mean age 66.0±13.0 years, 35.9% male, and 100.0% Caucasian overall). Eyes with POAG with and without DH had similar Humphrey Visual Field mean deviations (mean -3.6±3.0

db overall). Mean inferotemporal BMO-MRW differed significantly across groups (P<0.001), being thinner in eyes with POAG and DH (127.3±49.3 µm) and eyes with POAG but no DH (122.5±49.3 µm) than in controls (198.2±37.7 µm) (P=0.001; P<0.001) (Table). Prelaminar defect frequency differed significantly across groups (P=0.014). In subgroup analysis, specifically prelaminar hyporeflectivity frequency differed across groups (P=0.004), being higher in eyes with POAG and DH (57.1%) than in controls (0.0%; P=0.002). LC defect frequency differed across groups (P<0.001), being higher in eyes with POAG and DH (50.0%) than in eyes with POAG but no DH (0.0%) and also than in controls (0.0%) (P=0.006 for both). Conclusions: SS-OCT enables identification of ONH structural features associated with POAG and specifically with DH. Compared to BMO-MRW and prelaminar defects, LC defects were specifically associated with DH. A longitudinal study is underway to further elucidate potential structural causes and consequences of DH. Figure. Representative SS-OCT optic nerve head prelaminar and lamina cribrosa defects Commercial Relationships: Sophie Cai, None; Marissa K. Shoji; Elise Taniguchi, None; Dejiao Li, None; Leonardo A. Pereira, None; Stacey C. Brauner, None; Scott H. Greenstein, None; Angela Turalba, None; Louis R. Pasquale, None; Lucy Shen, None Support: Harvard Glaucoma Center of Excellence and Miller Research Funds Program Number: 3764 Presentation Time: 5:00 PM 5:15 PM Impact of lamina cribrosa (LC) and optic nerve head (ONH) surface deformation on visual field (VF) progression in glaucoma: A 5-year prospective study Christopher K. Leung, Zhonghen Wu, Lin Chen. School of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong. Purpose: While progressive ONH deformation and VF loss define glaucoma, their temporal relationship is poorly understood. It remains obscure what levels of IOP would impact ONH deformation and whether ONH deformation predicts VF change. We investigate the effect of IOP on the rates of change of anterior LC surface depth (ALCSD) and ONH surface depth (ONHSD) and examine if these rates of change are predictive of VF progression in glaucoma. Methods: 146 eyes of 95 glaucoma patients (age: 50.3±14.5 years) were followed for OCT measurements of ALCSD and ONHSD (with reference to BMO in 6 evenly spaced radial scans for each eye in each visit) and perimetry every 4 months for 5 years (range: 5.0-7.4 years). The influence of IOP and other covariates on the rates of change of ALCSD/ONHSD was evaluated with linear mixed models with adjustment of correlation between fellow eyes. A joint longitudinal survival model was applied to determine the impact of the rates of change of ALCSD/ONHSD on prediction of VF progression (defined as likely progression by the EMGT criteria). Results: 2519 follow-up visit measurements were analyzed (each eye had ~17 visits). 43 and 41 eyes showed progressive posterior deformation whereas 34 and 35 eyes showed progressive anterior deformation of the LC surface and ONH surface, respectively (as determined by linear regression analyses between ALCSD/ONHSD and time for individual eyes). The mean rates of change of ALCSD/ ONHSD were 5.3µm/year/4.2µm/year (posterior deformation); and -5.9µm/year/-4.4µm/year (anterior deformation), respectively. IOP (p 0.044) was positively whereas age (p<0.001) and baseline ALCSD/ ONHSD (p 0.002) were negatively associated with the rates of change of ALCSD/ONHSD. Each 5µm/year increase in the rate of change of ALCSD/ONSHD (i.e. posterior deformation) was associated with a 3.19-fold (95% CI: 1.28-9.92)/8.46-fold (95% CI: 1.37-52.5) increase in risk of VF progression after controlling for IOP, age and baseline ALCSD/ONHSD. An example is shown in Figure. Conclusions: The rates of change of LC and ONH surface deformation, which are subject to the influence of IOP, age and baseline ALCSD/ONHSD, are predictive of VF progression.

Longitudinal OCT images (vertical meridian) (A), VFs (B) and IOP readings (C) of a 23-year-old POAG patient with posterior LC and ONH deformation (D) evident before VF progression. Commercial Relationships: Christopher K. Leung, Tomey (C), Tomey (F), Santen (R), Carl Zeiss Meditec (F), Allergan (R), Optovue (F), Global Vision (R), Allergan (C); Zhonghen Wu, None; Lin Chen, None Support: Hong Kong GRF 2015 Program Number: 3765 Presentation Time: 5:15 PM 5:30 PM Mitochondrial Flavoprotein Fluorescence in Glaucoma Suspects, Primary Open-Angle Glaucoma, and Healthy Controls Lawrence Geyman 1, 2, Alexander Pinhas 3, 1, Brian Krawitz 1, 2, Shelley Mo 1, 2, Matthew Field 4, Richard B. Rosen 1. 1 New York Eye and Ear Infirmary of Mount Sinai, New York, NY; 2 Icahn School of Medicine at Mount Sinai, New York, NY; 3 North Shore-LIJ Health System, Manhasset, NY; 4 University of Michigan, Ann Arbor, MI. Purpose: Oxidative stress and mitochondrial dysfunction have been linked to the development of glaucoma by several authors. Previously, we reported increased flavoprotein fluorescence (FPF) in patients with moderate to advanced primary open-angle glaucoma (POAG) as compared to age-matched controls. In this study, we measured the level of FPF in eyes classified as glaucoma suspects

(GS) and compared them to healthy controls and to patients receiving treatment for POAG. Methods: 7 GS patients (7 eyes, mean age 56, range 48-68 years), 14 POAG patients (14 eyes, mean age 57, range 44-68 years), and 12 age-matched controls (12 eyes, mean age 52, range 42-65 years) were imaged with the OcuMet Beacon retinal metabolic analyzer (OcuSciences, Ann Arbor, MI). Images were obtained over 13-degree circular fields centered at the macula and optic disc. A histogram curve of pixel intensities for each image was generated. Average FPF intensity was calculated from all pixels within the circular field. FPF heterogeneity was determined from the width of the histogram curve at one-half the maximum FPF frequency (Fig. A). Unpaired Student s t-tests were used to assess statistical significance. Results: Average FPF intensity was significantly higher in GS eyes compared to control eyes at both the macula (383±74 vs 290±77, p=0.021) and optic disc (407±58 vs 309±74, p=0.0093). FPF heterogeneity was significantly higher in GS eyes compared to control eyes at the optic disc (197±31 vs 134±31, p<0.001), but not at the macula (159±34 vs 126±44, p=0.10). Average FPF intensity and FPF heterogeneity of POAG eyes at the macula (374±114 and 151±39, respectively) and optic disc (390±110 and 176±44, respectively) were similar to glaucoma suspects (Fig. B). Conclusions: FPF appears sensitive to underlying mitochondrial dysfunction in GS eyes at both the macula and the optic disc and may prove a useful metric for identifying the earliest evidence of glaucoma. Lack of difference between GS and POAG patients may be due to effects of treatment on the POAG group. Longitudinal studies to correlate clinical variables to changes in FPF will help to define potential roles for the RMA in the detection and management of glaucomatous change. Fig. B: Histograms of the average FPF intensity and FPF heterogeneity (error bars indicate standard error of the mean). Commercial Relationships: Lawrence Geyman, None; Alexander Pinhas, None; Brian Krawitz, None; Shelley Mo, None; Matthew Field, OcuSciences; Richard B. Rosen, NanoRetina (C), Carl Zeiss Meditech (C), OD-OS (C), Opticology (I), Genetech (F), Advanced Cellular Technologies (C), Clarity (C), Regeneron (C), Optovue (C), Allergan (C) Fig. A: FPF heterogeneity indicated by the horizontal solid line.