Faculty Bibliography

Purpose:To compare change over time in eye-specific optical coherence tomography (OCT) retinal nerve fiber layer (RNFL)-based region-of-interest (ROI) maps developed using unsupervised deep-learning auto-encoders (DL-AE) to circumpapillary RNFL (cpRNFL) thickness for the detection of glaucomatous progression. Methods:Forty-four progressing glaucoma eyes (by stereophotograph assessment), 189 nonprogressing glaucoma eyes (by stereophotograph assessment), and 109 healthy eyes were followed for ≥3 years with ≥4 visits using OCT. The San Diego Automated Layer Segmentation Algorithm was used to automatically segment the RNFL layer from raw three-dimensional OCT images. For each longitudinal series, DL-AEs were used to generate individualized eye-based ROI maps by identifying RNFL regions of likely progression and no change. Sensitivities and specificities for detecting change over time and rates of change over time were compared for the DL-AE ROI and global cpRNFL thickness measurements derived from a 2.22-mm to 3.45-mm annulus centered on the optic disc. Results:The sensitivity for detecting change in progressing eyes was greater for DL-AE ROIs than for global cpRNFL annulus thicknesses (0.90 and 0.63, respectively). The specificity for detecting not likely progression in nonprogressing eyes was similar (0.92 and 0.93, respectively). The mean rates of change in DL-AE ROI were significantly faster than for cpRNFL annulus thickness in progressing eyes (-1.28 µm/y vs. -0.83 µm/y) and nonprogressing eyes (-1.03 µm/y vs. -0.78 µm/y). Conclusions:Eye-specific ROIs identified using DL-AE analysis of OCT images show promise for improving assessment of glaucomatous progression. Translational Relevance:The detection and monitoring of structural glaucomatous progression can be improved by considering eye-specific regions of likely progression identified using deep learning.

PURPOSE/OBJECTIVE:To investigate the characteristics and rate of central visual field loss after optic disc hemorrhages (DH). DESIGN/METHODS:Prospective cohort study. METHODS:343 eyes of 220 subjects who had at least 3 years of follow-up with minimum of 5 visits with 10-2 and 24-2 visual field (VF) were recruited. Rates of 10-2 mean deviation (MD) loss in each hemifield and pre-defined zones were compared using linear mixed-effects model in DH and non-DH eyes. Clustered pointwise regression analysis was also used to define central VF progressors and compared to 24-2 VF loss using Guided Progression Analysis. RESULTS:39 eyes with DH and 304 eyes without DH had a mean follow-up of 5.2 years. Eyes with DH had rates of 10-2 mean deviation (MD) loss that were 3 times faster than non-DH eyes (mean difference (95% CI): -0.36 dB/year(0.54, 0.18), p<0.001) and were 3.7 times more likely to progress (p=0.002). A larger proportion of glaucomatous eyes showed central VF progression rather than peripheral VF progression in DH group (30.8% vs. 20.5%) compared to non-DH group (10.9% vs. 9.2%). In early glaucoma, the rate of 10-2 MD loss was 5.5 times faster in DH eyes than in non-DH eyes(p<0.001). Superonasal and superotemporal central VF regions progressed more rapidly than other regions, especially in DH eyes. CONCLUSION/CONCLUSIONS:Central visual field loss is accelerated in glaucoma eyes with DH and it corresponds topographically to the DH location. In glaucoma patients with DH, one should consider supplementing 10-2 VFs with 24-2 VFS to monitor the disease.

Purpose : Hypertension (HTN) is a risk factor that may affect glaucoma progression. There is a weak positive correlation between blood pressure (BP) and IOP, and lower ocular perfusion is associated with glaucoma prevalence and progression. Macular damage was once thought to be significant only in late stages of glaucoma, but recent studies have shown it can occur earlier. This study examines glaucomatous structural progression of the global retina nerve fiber layer (RNFL) and the macula ganglion cell layer (GCL+) with optical coherence tomography (OCT) and functional progression with visual fields (VF) and their relationship with hypertension. Methods : 191 eyes of 119 patients enrolled in a prospective, longitudinal study (Structural and Functional Progression of Glaucomatous Damage to the Macula study) were analyzed. These patients were tested with 10-2 and 24-2 VF and spectral-domain OCT obtained at 4-6 month intervals. 72 eyes (37%) had self-reported diagnosis of HTN. Linear mixed effects regression was used to test the relationship between summary statistics from VF and OCT and HTN diagnosis. The goodness-of-fit of relationships was assessed with Bayesian Information Criterion. Results : The average (95% CI) 24-2 and 10-2 MD rate of progression was-0.31 dB/year (-0.43 to-0.19) and-0.36 dB/year (-0.48 to-0.24), respectively. The rate of progression for OCT was-1.14 microns/year (-1.53 to-0.75) for global RNFL and-0.89 microns/year (-1.30 to-0.48) for global macula GCL+. There was no significant difference in rate of progression between HTN and non-HTN patients with any OCT or VF parameter. Yet, models with better goodness-of-fit when testing the relationship between HTN and progression had the following OCT parameters: global macula GCL+, inferior macula GCL+, mean GCL+ of macular vulnerability zone (MVZ), and mean macula GCL+ of less vulnerability zone (LVZ), and VF parameters: 10-2 PSD and 10-2 MD. Conclusions : HTN was not significantly associated with progression using any parameter. However, based on ranked model fits, macular structural and functional parameters had best performance fitting the progression data, suggesting their usefulness as endpoints. Studies defining HTN based on 24-hour BP monitoring and including modalities of treatment may better elucidate whether this prevalent systemic disease is an independent risk factor for glaucoma progression

PRCIS/UNASSIGNED:The Manhattan Vision Screening and Follow-up Study in Vulnerable Populations is a 5-year prospective, cluster-randomized study to improve detection and management of glaucoma and other eye diseases in vulnerable populations living in affordable housing developments. PURPOSE/OBJECTIVE:To describe the study design and methodology of the Manhattan Vision Screening and Follow-up Study in Vulnerable Populations, which aims to investigate whether community-based vision screenings can improve detection and management of glaucoma, vision impairment, cataract, and other eye diseases among vulnerable populations living in affordable housing developments in upper Manhattan. METHODS:This 5-year prospective, cluster-randomized, controlled trial consists of vision screening and referral for follow-up eye care among eligible residents aged 40 and older. Visual acuity, intraocular pressure (IOP), and fundus photography are measured. Participants with visual worse than 20/40, or IOP 23-29▒mmHg, or unreadable fundus images fail the screening and are scheduled with the on-site optometrist. If IOP is ≥30▒mmHg, participants are assigned as "fast-track" and referred to ophthalmology. Participants living in seven developments randomized to the Enhanced Intervention Group who fail the screening and need vision correction receive complimentary eyeglasses. Those referred to ophthalmology receive enhanced support with patient navigators to assist with follow-up eye care. Participants living in three developments randomized to the Usual Care Group who fail the screening and need vision correction are given an eyeglasses prescription only and a list of optical shops. No enhanced support is given to the Usual Care Group. All participants referred to ophthalmology are assisted in making their initial eye exam appointment. CONCLUSION/CONCLUSIONS:This study targets vulnerable populations where they live to ensure improved access to and utilization of eye-care services in those who are least likely to seek eye care.

PURPOSE/OBJECTIVE:To compare spectral-domain optical coherence tomography (SDOCT) measured circumpapillary retinal nerve fiber layer (cpRNFL) among four glaucomatous optic disc phenotypes in early glaucoma. DESIGN/METHODS:Clinical cohort study METHODS: In this study, 218 early glaucoma eyes that had at least 3 years of follow-up and a minimum of 4 SDOCT scans were recruited. The optic discs were classified into four types based on appearance: 76 generalized cup enlargement (GE), 53 focal ischemic (FI), 22 myopic glaucomatous (MY), and 67 senile sclerotic (SS). A linear mixed-effect model was used to compare the rates of global and regional cpRNFL thinning among optic disc phenotypes. RESULTS:After adjusting for confounders, the SS group (mean (95% CI): -1.01 (-1.30, -0.73) µm/year) had the fastest mean rate of global cpRNFL thinning followed by FI (-0.77 (-0.97, -0.57) µm/year), MY (0.59 (-0.81, -0.36) µm/year) and GE (-0.58 (-0.75, -0.40) µm/year) at p<0.001. The inferior temporal sector had the fastest rate of cpRNFL thinning among the regional measurements except for the MY group (-0.68 (-1.10, -0.26) µm/year), p=0.002). In the multivariable analysis, GE (p=0.002) and MY (p=0.010) phenotypes were associated with significantly slower global rates of cpRNFL thinning when compared to the SS phenotype. CONCLUSIONS:Rates of cpRNFL thinning were different among the four glaucomatous optic disc phenotypes. Those patients with early glaucoma with SS phenotype have the fastest cpRNFL thinning. These patients may benefit from more frequent monitoring and the need to advance therapy if cpRNFL thinning is detected.

PURPOSE/AIM/UNASSIGNED:In the United States, high rates of vision impairment and eye disease disproportionately impact those who lack access to eye care, specifically vulnerable populations. The objective of our study was to test instruments, implement protocols, and collect preliminary data for a larger 5-year study, which aims to improve detection of eye diseases and follow-up eye care in vulnerable populations using community health workers (CHW) and patient navigators. In the study, trained CHWs conducted vision screening and patient navigators scheduled on-site eye exams and arranged appointments for those referred to ophthalmology to improve adherence to follow-up eye care. MATERIALS AND METHODS/UNASSIGNED:Eligible individuals age 40-and-older were recruited from the Riverstone Senior Center in upper Manhattan, New York City. Participants underwent on-site vision screening (visual acuity with correction, intraocular pressure measurements, and fundus photography). Individuals who failed the vision screening were scheduled with an on-site optometrist for an eye exam; those with ocular pathologies were referred to an ophthalmologist. Participants were also administered the National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ-8) and Stopping Elderly Accidents, Deaths, and Injuries (STEADI) test by community health workers. RESULTS/UNASSIGNED:Participants (n=42) were predominantly older adults, with a mean age of 70.0 ± 9.8, female (61.9%), and Hispanic (78.6%). Most individuals (78.6%, n=33) failed vision screening. Of those who failed, 84.8% (n=28) attended the on-site eye exam with the optometrist. Ocular diagnoses: refractive error 13/28 (46.4%), glaucoma/glaucoma suspect 9/28 (32.1%), cataract 7/28 (25.0%), retina abnormalities 6/28 (21.4%); 13 people required eyeglasses. CONCLUSION/UNASSIGNED:This study demonstrates the feasibility of using CHWs and patient navigators for reducing barriers to vision screening and optometrist-based eye exams in vulnerable populations, ultimately improving early detection of eye disease and linking individuals to additional eye care appointments. The full five-year study aims to further examine these outcomes.

Identifying progression is of fundamental importance to the management of glaucoma. It is also a challenge. The most sophisticated, and probably the most useful, commercially available clinical tool for identifying progression is the Guided Progression Analysis (GPA), which was initially developed to identify progression using 24-2 visual field tests. More recently it has been extended to retinal nerve fiber layer (RNFL) and ganglion cell + inner plexiform layer (GCIPL) thicknesses measured with optical coherence tomography (OCT). However, the OCT GPA requires a minimum of 3 tests to determine "possible loss (progression)" and a minimum of 4 tests to determine if the patient shows "likely loss (progression)." Thus, it is not designed to answer a fundamental question asked by both clinician and patient, namely: Did damage progress since the last visit? Some clinicians use changes in summary statistics, such as global/ average circumpapillary RNFL thickness. However, these statistics have poor sensitivity and specificity due to segmentation and alignment errors. Instead of relying on the GPA analysis or summary statistics, one needs to evaluate RNFL and GCIPL probability maps and circumpapillary OCT b-scan images. In addition, we argue that the clinician can make a better decision about suspected progression between two test days by topographically comparing the changes in the different OCT maps and images, as well as topographically comparing the changes in the visual field to the changes in the OCT probability maps.

Purpose/UNASSIGNED:The purpose of this study was to determine if the rate of change in the depth of the surface of the lamina cribrosa due to glaucomatous remodeling differs between glaucoma patients of African descent (AD) and European descent (ED). Methods/UNASSIGNED:There were 1122 images taken longitudinally over an average of 3 years (range = 0.9-4.1 years) from 122 patients with glaucoma followed in the African Descent and Glaucoma Evaluation Study (ADAGES) and Diagnostic Intervention and Glaucoma Study (DIGS) were automatically segmented to compute anterior lamina cribrosa surface depth (ALCSD). The rate of ALCSD change was compared across racial groups after adjusting for baseline characteristics known to be associated with ALCSD or disease progression (visual field, ALCSD, corneal thickness, optic disk size, and age). Results/UNASSIGNED:After adjusting for all other covariates, the ED group had significantly greater ALCSD posterior migration (deepening) than the AD group (difference = 2.57 µm/year, P = 0.035). There was a wider range of ALCSD change in the ED compared with the AD group, and more individuals had greater magnitude of both deepening and shallowing. No other covariates measured at baseline had independent effects on the longitudinal changes in ALCSD (baseline visual field severity, baseline ALCSD, corneal thickness, Bruch's membrane opening [BMO] area, or age). Conclusions/UNASSIGNED:Glaucomatous remodeling of the lamina cribrosa differs between AD and ED patients with glaucoma. Unlike the cross-sectional associations seen with aging, in which a deeper ALCSD was seen with age in the ED group, glaucomatous remodeling in this longitudinal study resulted in more posterior migration of ALCSD in ED compared to AD patients.