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Purpose: The optic nerve head (ONH) undergoes complex and deep 3D morphological changes during the development and progression of glaucoma. Optical coherence tomography (OCT) is the current gold standard to visualize and quantify these changes, however the resulting 3D deep-tissue information has not yet been fully exploited for the diagnosis and prognosis of glaucoma. To this end, we aimed: (1) To compare the performance of two relatively recent geometric deep learning techniques in diagnosing glaucoma from a single OCT scan of the ONH; and (2) To identify the 3D structural features of the ONH that are critical for the diagnosis of glaucoma. Methods: In this study, we included a total of 2,247 non-glaucoma and 2,259 glaucoma scans from 1,725 subjects. All subjects had their ONHs imaged in 3D with Spectralis OCT. All OCT scans were automatically segmented using deep learning to identify major neural and connective tissues. Each ONH was then represented as a 3D point cloud. We used PointNet and dynamic graph convolutional neural network (DGCNN) to diagnose glaucoma from such 3D ONH point clouds and to identify the critical 3D structural features of the ONH for glaucoma diagnosis. Results: Both the DGCNN (AUC: 0.97$\pm$0.01) and PointNet (AUC: 0.95$\pm$0.02) were able to accurately detect glaucoma from 3D ONH point clouds. The critical points formed an hourglass pattern with most of them located in the inferior and superior quadrant of the ONH. Discussion: The diagnostic accuracy of both geometric deep learning approaches was excellent. Moreover, we were able to identify the critical 3D structural features of the ONH for glaucoma diagnosis that tremendously improved the transparency and interpretability of our method. Consequently, our approach may have strong potential to be used in clinical applications for the diagnosis and prognosis of a wide range of ophthalmic disorders.

Importance Although the diagnosis of vitreoretinal lymphoma (VRL) can be challenging, early detection is critical for visual prognosis. Objective To analyze the spectrum of optical coherence tomography (OCT) findings in patients with biopsy-proven VRL and correlate these features with clinical parameters. Design Retrospective cross-sectional study Setting Multicenter chart review from 13 retina, uveitis and ocular oncology clinics worldwide over an 11-year period (2008-2019). Participants Patients with a diagnosis of biopsy-proven VRL imaged with OCT at presentation Exposure The ocular information, systemic information and multimodal retinal imaging findings were collected and studied. Main Outcome Measure Characteristics of VRL on OCT Results A total of 182 eyes of 115 patients (63 women, mean age 65 years) were included in this study. The disease was bilateral in 81 (70%) patients, and mean baseline visual acuity (VA) was 0.2±0.89 logMAR (Snellen equivalent of 20/32). At baseline, 38 patients (33%) presented with isolated ocular involvement, 54 (45%) with associated central nervous system (CNS) involvement and 11 (10%) with other systemic lymphomatous involvement and an additional 12 (10%) patients presented with both CNS and other systemic involvement. On OCT, tumor infiltration was identified in various retinal layers including lesions in the sub-retinal pigment epithelium (RPE) compartment (91% of eyes), the subretinal compartment (43% of eyes) and the intraretinal compartment (7% of eyes). Conclusions and Relevance OCT analysis of eyes with vitreoretinal lymphoma identified 3 main regions of retinal infiltration. Sub-RPE location, with or without subretinal infiltration, was the most common pattern of involvement whereas isolated intraretinal infiltration was the least common.

Purpose To investigate the association between the presence of a cilioretinal artery (CRA) and advanced age-related macular degeneration (AMD), including the prevalence of choroidal neovascularization (CNV) and geographic atrophy (GA). Design Retrospective cross-sectional study. Methods Setting: Single center Patient population: A total of 738 patients with AMD who underwent optical coherence tomography angiography (OCTA) were included in the study. Fundus photographs were reviewed to determine the presence of the CRA. Intervention/observation procedures: In patients with a unilateral CRA, paired tests were performed between eyes with and without the CRA to compare AMD severity and prevalence of CNV and GA. Main outcomes: AMD stage, and prevalence of CNV and GA. Macular vasculature, including vessel density, perfusion density, and foveal avascular zone, examined using OCTA. Results A total of 27.8% and 8.1% of patients had a CRA in one and both eyes, respectively. A total of 174 eyes from 87 patients with a unilateral CRA were examined. Eyes with a CRA showed lower AMD stage (4-step AREDS category; P = 0.037) and a lower prevalence of CNV (23.0% vs. 41.4%; P = 0.024) than those without a CRA. The prevalence of GA and macular vessel density, perfusion density, and foveal avascular zone measured by OCTA were similar in both groups. Conclusions In the eyes with a CRA, AMD stage and prevalence of CNV were lower than those in the eyes without a CRA. However, the effect of the CRA on the macular vascular system remains unclear.

PURPOSE To investigate the safety and efficacy of cultured human corneal endothelial cell (hCEC)-injection therapy with mature differentiated (mature) cell subpopulations (SPs) for corneal endothelial failure (CEF). DESIGN Comparative, interventional case series. METHODS This study involved 18 eyes with CEF that underwent cultured hCEC-injection therapy, categorized into two groups: 1) 11 eyes administered a relatively lower proportion (0.1 to 76.3%) of mature cell SPs [Group 1 (Gr1)], and 2) 7 eyes administered a relatively higher proportion (>90%) of mature cell SPs [Group 2 (Gr2)]. From 1-week to 3-years postoperative, corneal endothelial cell (CEC) density (CECD), central corneal thickness (CCT), and best-corrected visual acuity (BCVA) were recorded, and the CEC parameter's 'spring constant' was calculated. The proportion of mature SPs was evaluated by fluorescence-activated cell sorting analysis based on cell-surface markers. RESULTS At 3-years postoperative, corneal restoration with improved BCVA was attained in 10 of the 11 Gr1 eyes and all Gr2 eyes, the median CECD in Gr2 (3,083 cells/mm2; range, 2,182-4,417 cells/mm2) was higher than that in Gr1 (1,349 cells/mm2; range, 746-2,104 cells/mm2) (P < 0.001), and the spring constant verified the superiority of the mature cultured hCECs. From 24-weeks through 3-years postoperative, the median percentage of CECD decrease was 3.2% in Gr2 and 23.6% in Gr1 (P < 0.005). CCT recovery was prompt and constant in Gr2, while diverse in Gr1. No adverse events were observed. CONCLUSION Our findings showed that mature cell SPs for hCEC-injection therapy provide rapid recovery of CCT, better CECD, and low CECD attrition over 3 years post surgery.

PURPOSE To assess the relationship between best corrected visual acuity (BCVA) and central subfield optical coherence tomography (OCT) features in noninfectious uveitis (NIU)-related macular edema (ME). DESIGN Clinical cohort study from post hoc analysis of two phase 3 clinical trials' data. METHODS Correlation and longitudinal treatment analyses were performed. Of 198 patients with NIU, 134 received suprachoroidally administered CLS-TA (Clearside Biomedical, Inc. proprietary formulation of a triamcinolone acetonide injectable suspension) and 64 received sham, with 12.9% and 72% respectively receiving rescue therapy. RESULTS At baseline, mean BCVA progressively worsened with each ordinal drop in ellipsoid zone (EZ) integrity. Eyes with normal baseline EZ experienced greater 24-week change in BCVA compared to eyes with some degree of baseline EZ disruption (11.9 vs 9.4 letters, P=0.006). In contrast, eyes without central subfield cystoid spaces and/or central subfield SRF at baseline showed less improvement (5.5 letters or 9.5 letters, respectively) at 24 weeks, compared to those eyes with such OCT findings (13.7 letters, P = 0.012 or 17.2 letter, P

International audience; Purpose: To correlate the degree of foveal hypoplasia in congenital aniridia with visual acuity, iris phenotype, and PAX6 mutations.Design: Retrospective case series.Methods: 95 consecutive patients with high quality Spectral-domain optical coherence tomography (SD-OCT) records and available genotype were included in a single referral center. Iris hypoplasia was classified as complete, presence of iris root or remnants and mild atypical aniridia. SD-OCT images were assessed to classify foveal hypoplasia as Grade 1 to 4 and to determine mean thicknesses for retinal layers. For statistical analysis one eye for each patient have been used and one member of the same family has been included (n=76 eyes).Results: Most eyes (93.5%) showed variable degree of foveal hypoplasia. PAX6-positive patients presented higher degree of foveal hypoplasia than patients negative for PAX6 (p

Purpose To validate the performance of postnatal growth and retinopathy of prematurity (G-ROP) screening criteria in a Taiwanese cohort. Design Screening evaluation with retrospective data Method Premature infants who underwent retinopathy of prematurity (ROP) screening between January 2015 and April 2019 at a tertiary hospital were examined. Infants with known final ROP results and complete longitudinal weight records were included. G-ROP screening criteria, both original and simplified (G-ROP 180 g), were applied as the prediction model for type 1 ROP; sensitivity and specificity were analyzed. The reduction in the number of infants requiring ROP screening and the number of funduscopic examinations were calculated. Result A total of 303 infants with documented ROP outcomes and complete weight gain records were examined; 103 infants developed ROP, of whom 29 developed type 1 ROP, while the other 200 did not develop ROP. For the detection of type 1 ROP, the sensitivity and specificity of the original G-ROP screening criteria were 96.6% and 42.3%, and 100% and 31% for the simplified G-ROP 180 g model, respectively. The reduction in the number of infants requiring screening and funduscopic examinations was 32.6% and 33.5% for the original G-ROP criteria, and 28.1% and 23.2% for the G-ROP 180 g model, respectively. Conclusion Both the original G-ROP and G-ROP 180 g criteria attained high sensitivities in detecting type 1 ROP in the current Taiwanese cohort, with the G-ROP 180 g model outperforming the original one. Validation and modification may be required before applying G-ROP screening criteria to different populations.

To evaluate the correlation between structural parameters and visual acuity (VA) in advanced glaucoma.Prospective, cross-sectional study.A total of 238 eyes from 238 patients (82 were men and mean ± SD age was 59.9 ± 13.8 years) from a tertiary center were divided into an advanced (mean deviation of 24-2 visual field tests from -12.01 to -20.0 dB) and severe (-20 dB) glaucoma group. Structural parameters were obtained by RTVue (Optovue Inc) optical coherence tomography and angiography. Pearson correlation, partial correlation adjusted for age and axial length, and receiver operating characteristic curves to detect decreased VA (20/25) were performed.In the advanced glaucoma group (133 eyes), superficial (Pearson correlation coefficient, r = -0.46, P.001; partial correlation coefficient, r' = -0.30, P.001) and deep macular vessel densities (VDs) (r = -0.47, P.001; r' = -0.30, P.001) showed highest correlation with VA. The area under the receiver operating characteristic curves of the superficial parafoveal/macular VDs were 0.816 (95% CI, 0.735-0.897) and 0.808 (95% CI, 0.725-0.891), respectively. In the severe glaucoma group (105 eyes), deep nasal grid VD (r = -0.31, P = 0.002; r' = -0.35, P.001) showed highest correlation with VA. Deep macular VD showed better correlation with VA than other structural parameters. The area under the receiver operating characteristic curves of deep macular VD and deep nasal grid VD were 0.740 (95% CI, 0.632-0.849) and 0.748 (95% CI, 0.640-0.857), respectively.Macular VD showed better correlation with VA in advanced glaucoma. Deep macular VD, especially nasal grid, may be a promising structural parameter in severe glaucoma.

Purpose To identify risk factors for surgical failure after gonioscopy-assisted transluminal trabeculotomy (GATT) in juvenile open angle glaucoma (JOAG). Design Prospective, interventional case series. Methods Seventy eyes of 70 patients with JOAG underwent GATT as the initial surgery. Surgical success was defined as a post-operative intraocular pressure (IOP) of ≤21 mmHg with at least a 20% reduction from pre-operative IOP with or without the use of anti-glaucoma medication (qualified and complete success, respectively) at each post-operative visit. IOP spike was defined as IOP >30 mmHg and an increase of at least 10 mmHg from IOP prior to the spike, and then reduced to ≤21 mmHg. Results The median age at the time of surgery was 19.3 (range: 4.9-37.5) years with a visual field mean deviation (MD) -17.4±10.6 dB. Mean IOP decreased from 31.3±9.5 mmHg pre-operatively to 15.8±2.7 at 12 months post-operatively. The complete and qualified success rates were 74.3% and 91.4%, respectively. Fifty-two (74%) eyes had an IOP spike with a median spike duration of 3.5 days (range 1-21). Longer duration of IOP spike (P=0.009) and older age at the time of surgery (P=0.025) were both associated with worse surgical outcomes. Advanced disease was associated with prolonged IOP spike (P=0.007). Conclusions GATT provided excellent outcomes in patients with severe JOAG. Older age and longer duration of post-operative IOP spike are risk factors for failure. Severe cases are more likely to have longer durations of IOP spike. Frequent IOP monitoring during the early post-operative period is needed to detect IOP spikes in these patients.

PURPOSE: Prior studies on compressive optic neuropathy (CON) have come from large tertiary centers, which may contain referral bias toward more severe or atypical disease. To our knowledge, there are no studies to determine the population-based etiologies and clinical outcomes of compressive optic neuropathy (CON). This study aims to bridge that gap using the Rochester Epidemiology Project database. DESIGN: Retrospective, population-based cohort METHODS: Medical records of all residents living in Olmsted County, Minnesota from January 1, 2000 through December 31, 2018 were screened for CON. Demographic and clinical information were collected before and after treatment. RESULTS: 23 patients had a confirmed diagnosis of CON during our study period, which provided an overall incidence of 1.14 per 100,000 per year. Average age at onset of CON was 51 years (SD 24), and 39% were male. The most common etiologies were pituitary adenoma and meningioma. There was significant improvement in visual fields (p < 0.003) but not in visual acuity (p = 0.08) after patients underwent treatment for CON. There was also a significant relationship between the time until treatment and the degree of visual field improvement at follow-up (Pearson correlation rho = −0.58, p < 0.047). CONCLUSION: To our knowledge, this study provides the first population-based incidence of CON. The finding that earlier treatment leads to better visual outcomes stresses the importance of having CON on the differential diagnosis of patients with optic neuropathy.

PURPOSE: To estimate and compare cross-sectional scotopic versus mesopic macular sensitivity losses measured by microperimetry, and to report and compare the longitudinal rates of scotopic and mesopic macular sensitivity losses in ABCA4 gene associated Stargardt Disease (STGD1). DESIGN: Multicenter prospective cohort study. METHODS: PARTICIPANTS: 127 molecular confirmed STGD1 patients enrolled from 6 centers in the USA and Europe and followed every 6 months for up to 2 years. OBSERVATION PROCEDURES: The Nidek MP-1S device was used to measure macular sensitivities of the central 20° under mesopic and scotopic conditions. The mean deviations (MD) from normal for mesopic macular sensitivity for the fovea (within 2° eccentricity) and extrafovea (4°−10° eccentricity), and the MD for scotopic sensitivity for the extrafovea were calculated. Linear mixed effects models were used to estimate mesopic and scotopic changes. MAIN OUTCOME MEASURES: Baseline mesopic mean deviation (mMD) and scotopic MD (sMD) and rates of longitudinal changes in the mMDs and sMD. RESULTS: At baseline, all eyes had larger sMD, and the difference between extrafoveal sMD and mMD was 10.7 dB (p

Purpose Suboptimal functional outcomes following rhegmatogenous retinal detachment (RRD) repair may be related to photoreceptor abnormalities including alterations of the ellipsoid zone (EZ) which may not be apparent on cross-sectional optical coherence tomography (OCT). This study assessed EZ recovery using en face OCT following RRD repair and its association with visual acuity. Design Post hoc analysis of a randomized controlled trial. Methods Patients with macula-off RRD were followed at 3, 6, 12 and 24 months post-operatively and annually thereafter. En face OCT of the EZ slab were analyzed. Hyporeflective areas were co-localized with EZ abnormalities on cross-sectional OCT B-Scans and measured by two masked graders. Primary outcome was change in area of EZ hyporeflectivity from 3 to 24 months and its association with ETDRS visual acuity recovery was also assessed. Results 271 images of 61 patients were assessed. Mean area of hyporeflectivity significantly decreased from 3 to 24 months (-2.98 (95%CI,1.82-4.13) mm2, P Conclusions En face OCT provides a novel biomarker for visualizing and quantifying EZ recovery following RRD repair that is associated with ETDRS visual acuity recovery. A steady decline in the area of EZ hyporeflectivity was observed over many years with delayed recovery in patients with longer duration of macula-off.

To find predictive factors of neovascular glaucoma (NVG) development in eyes with anterior segment neovascularization without glaucoma (ASNVWG), and poor visual outcomes in eyes that have already developed NVG.Retrospective, clinical cohort studies.A retrospective chart review was performed on 106 eyes of 94 patients with ASNVWG and 245 eyes of 225 patients with NVG. Measured outcomes included the development of NVG at any time point of the disease for the ASNVWG arm, and a visual acuity of ≤20/200 at 6 months after initial presentation for the NVG arm.Overall, 25% of ASNVWG eyes progressed to NVG. Progression was associated with retinal vein occlusion (RVO) (P.01), lower median presenting BCVA (P.01), and concurrent traction retinal detachments (TRDs) (P = .025). Sixty-eight percent of NVG eyes had a BCVA of ≤20/200 by 6-month follow-up, which was associated with RVO (P = .005), vitreous hemorrhage on presentation (P = .001), and no panretinal photocoagulation (PRP) treatments (P.001). BCVA20/200 at 6 months was associated with ≥1 PRP or intravitreal bevacizumab (IVB) treatment within 1 week of presentation or ≥3 PRP or IVB treatments overall (P.001).RVO, presenting visual acuity, and concurrent TRD are risk factors for NVG in eyes with ASNVWG. In eyes with NVG, RVO and concurrent vitreous hemorrhage are risk factors for ≤20/200 vision at 6 months, whereas treatment with ≥1 PRP or IVB within 1 week of presentation, or ≥3 treatments of PRP or IVB within 6 months are protective.

To compare visual outcome and recurrence rates of eyes with noninfectious inflammatory choroidal neovascularization (CNV) treated with or without anti-vascular endothelial growth factor (VEGF) injections and immunosuppression.Retrospective, nonrandomized clinical study.Participants: Patients with CNV secondary to noninfectious inflammatory causes who attended uveitis clinics at Moorfields Eye Hospital between January 2000 and April 2016. Data were gathered from the clinical notes of all subjects examined in clinic.change in best-corrected visual acuity (BCVA), mean time to CNV recurrence, moderate vision loss (≤20/50), and severe vision loss (≤20/200).A total of 166 patients (204 eyes) with noninfectious inflammatory CNV were included in this study with a median follow-up of 6.9 years (interquartile range: 2.9-11.7; 1652 eye-years). The mean BCVA at the time of CNV diagnosis was 0.38 ± 0.05 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent 20/47) in the eyes that received the first-line anti-VEGF treatment and 0.44 ± 0.03 logMAR (Snellen equivalent 20/55) in the eyes on other treatment modalities (P = .39). Eyes treated first with anti-VEGF (n = 55) received the mean of 4.35 ± 0.53 injections and showed a statistically significant improvement in vision at all time points (P.001) except for a 5-year visit (P = .25). The rest of the eyes demonstrated no significant change in vision throughout follow-up (all P.05). At the final visit, the mean BCVA was 0.26 ± 0.11 logMAR (Snellen equivalent 20/36) in the former and 0.35 ± 0.06 logMAR (Snellen equivalent 20/44) in the latter. The mean time to CNV recurrence was 186 ± 15.1 months, and the risk was significantly reduced by treatment with oral corticosteroids (adjusted hazard ratio = 0.32, confidence interval: 0.17-0.59, P.001) or anti-VEGF injections (adjusted hazard ratio = 0.31, confidence interval: 0.18-0.52, P.001).Eyes that developed inflammatory CNV were at risk of vision loss. Those receiving early anti-VEGF injections achieved a better visual outcome and had a reduced risk of CNV recurrence. Oral corticosteroids also had an effect that reduces the risk of recurrence in eyes previously treated.

PURPOSE: To assess test-retest repeatability of the accommodative response (AR) in children with and without amblyopia and adults using the Grand Seiko autorefractor. DESIGN: Prospective reliability assessment. METHODS: Test-retest of accommodation was obtained while participants viewed 20/150 sized letters at 33 cm using the Grand Seiko autorefractor in children 5 to

To investigate the diagnostic value of elevated retinal pigment epithelium (RPE) and double-layer sign (DLS) in identifying macular neovascularization (MNV) secondary to central serous chorioretinopathy (CSCR).Retrospective, cross-sectional study.Patients with CSCR underwent optical coherence tomography (OCT) and OCT angiography (OCT-A) scanning at Moorfields Eye Hospital. OCT scans were reviewed to identify the presence/absence of an RPE elevation. The maximum length and maximum height of the elevated RPE were measured. A minimum length of 1000 µm and a maximum height of 150 µm were used to define the "double-layer sign." Other qualitative anatomical features were also graded from OCT scans. OCT-A was examined to confirm the presence/absence of MNV. Binary logistic regression analyses were used to assess the association between OCT features and the detection of MNV on OCT-A. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the diagnostic accuracy.One hundred sixty-three eyes from 132 patients were included. Elevated RPE was detected in 148 eyes (91%). OCT-A-confirmed MNV was detected in 54 eyes (33%). The sensitivity and specificity of RPE elevation were 100% and 13.8%, respectively. DLS was identified in 95 eyes (58%). The sensitivity and specificity of DLS for detecting MNV were 87% and 56%, respectively. Hyperreflectivity and nonhomogeneity of the sub-RPE space were independently associated with MNV within the DLS (odds ratio, 17.7 and 14.8, P.001 and P = .02, respectively). None of the other demographic or anatomical features were associated with MNV. The presence of nonhomogeneous hyperreflective RPE elevation had a sensitivity and specificity of 98% and 67%, with PPV and NPV of 60% and 99%, respectively.Nonhomogeneous and hyperreflective space under an elevated RPE of any length or height indicates an eye with higher risk of MNV than DLS. OCT-A should at least be performed for these eyes to confirm the presence of MNV and treat accordingly.

PurposeTo compare convolutional neural network (CNN) analysis of en face vessel density images to gradient boosting classifier (GBC) analysis of instrument-provided, feature-based optical coherence tomography angiography (OCTA) vessel density measurements and OCT retinal nerve fiber layer (RNFL) thickness measurements for classifying healthy and glaucomatous eyes.DesignComparison of diagnostic approaches.MethodsA total of 130 eyes of 80 healthy individuals and 275 eyes of 185 glaucoma patients with optic nerve head (ONH) OCTA and OCT imaging were included. Classification performance of a VGG16 CNN trained and tested on entire en face 4.5×4.5-mm radial peripapillary capillary OCTA ONH images was compared to the performance of separate GBC models trained and tested on standard OCTA and OCT measurements. Five-fold cross-validation was used to test predictions for CNNs and GBCs. Areas under the precision recall curves (AUPRC) were calculated to control for training/test set size imbalance and were compared.ResultsAdjusted AUPRCs for GBC models were 0.89 (95% CI=0.82, 0.92) for whole image vessel density GBC, 0.89 (0.83, 0.92) for whole image capillary density GBC, 0.91 (0.88, 0.93) for combined whole image vessel and whole image capillary density GBC, and 0.93 (0.91, 095) for RNFL thickness GBC. The adjusted AUPRC using CNN analysis of en face vessel density images was 0.97 (0.95, 0.99) resulting in significantly improved classification compared to GBC OCTA-based results and GBC OCT-based results (P ≤ 0.01 for all comparisons).ConclusionDeep learning en face image analysis improves on feature-based GBC models for classifying healthy and glaucoma eyes.

Purpose To develop a novel deep-learning approach that can describe the structural phenotype of the glaucomatous ONH and can be used as a robust glaucoma diagnosis tool. Design Retrospective, deep-learning approach diagnosis study. Method We trained a deep learning network to segment three neural-tissue and four connective-tissue layers of the ONH. The segmented OCT images were then processed by a customized autoencoder network with an additional parallel branch for binary classification. The encoder part of the autoencoder reduced the segmented OCT images into a low-dimensional latent space (LS); whereas the decoder and the classification branches reconstructed the images and classified them as glaucoma or non-glaucoma, respectively. We performed principal component analysis on the latent parameters and identified the principal components (PCs). Subsequently, the magnitude of each PC was altered in steps and reported how it impacted the morphology of the ONH. Results The image reconstruction quality and diagnostic accuracy increased with the size of the LS. With 54 parameters in the LS, the diagnostic accuracy was 92.0±2.3% with a sensitivity of 90.0±2.4% (at 95% specificity), and the corresponding Dice coefficient for the reconstructed images was 0.86±0.04. By changing the magnitudes of PC in steps, we were able to reveal how the morphology of the ONH changes as one transitions from a ‘non-glaucoma’ to a ‘glaucoma’ condition. Conclusions Our network was able to identify novel biomarkers of the ONH for glaucoma diagnosis. Specifically, the structural features identified by our algorithm were found to be related to clinical observations of glaucoma.

PURPOSE: To determine the change in intraocular pressure (IOP), ocular hypotensive medication use after cataract extraction in the Medication Group of the Ocular Hypertension Treatment Study (OHTS). DESIGN: Secondary analysis of randomized clinical trial data METHODS: We included 92 participants (n=149 eyes) of the OHTS Medication Group who underwent cataract surgery in at least one eye during the study, and 531 participants (n=1004 eyes) of the Medication Group who did not undergo cataract surgery. We defined the “split date” as the first study visit that cataract surgery was reported for the cataract surgery group, and the 15(th) visit in the control group to equalize the median number of visits. We then compared the two groups at visits relative to this split date. • MAIN OUTCOME MEASURES: Difference in preoperative and postoperative IOP, and number of classes of ocular hypotensive medications between the cataract and control group over a 72 month period. RESULTS: Cataract surgery significantly decreased the number of ocular hypotensive medications at all postoperative visits (mean −0.4 medications, p

Purpose To provide an update on the hemodynamic model of age-related macular degeneration (AMD). Design Evidence-based perspective. Methods Review of literature and experience of authors. Results Choroidal hemodynamics are not the primary cause of AMD as proposed by Ephraim Friedman in 1997. However, evidence is accumulating to suggest that choroidal perfusion is an important environmental influence that contributes to our understanding disease progression in this complex genetic disease. While early and intermediate AMD appear to be influenced to a large extent by the underlying genetics, the asymmetry of disease progression to the later stages of AMD cannot be explained by genetics alone. The progression of disease and the asymmetry of this progression appear to correlate with abnormalities in choroidal perfusion that can be documented by optical coherence tomography. These perfusion abnormalities in the setting of a thickened Bruch's membrane are thought to exacerbate the impaired nutritional exchange between the retinal pigment epithelium and the choriocapillaris. We propose that the genetic susceptibility to develop AMD combined with age-related changes in macular choroidal hemodynamics, such as increasing choriocapillaris perfusion deficits and decreasing choroidal vascular densities, play an important role in disease progression and may help explain the asymmetry between eyes, particularly in the later stages of AMD. Conclusions This updated hemodynamic model of AMD focuses on disease progression and highlights the importance of age-related changes in the choroidal circulation as a major environmental influence on disease severity in eyes that are genetically susceptible to develop AMD.

PURPOSE To elucidate clinical factors related to the presence of loculation of fluid (LOF) in the posterior choroid in central serous chorioretinopathy (CSC). DESIGN Retrospective, cross-sectional study. METHODS This single-center study included 158 eyes from 158 patients with CSC who were classified into LOF and non-LOF groups. The groups were compared for age, sex, spherical equivalent, axial length, subfoveal choroidal thickness (SCT), and scleral thickness. Using swept-source optical coherence tomography (OCT), we determined the presence of LOF based on B-scan and en face images. Scleral thickness was measured 6 mm posterior to the scleral spur in four directions using anterior segment OCT. RESULTS The 158 eyes were classified into 98 eyes in the LOF group and 60 eyes in the non-LOF group. In univariable analyses, the LOF group was younger (P = .01) and had a higher male ratio (P = .03) and greater SCT (P < .001) than the non-LOF group. All scleral thicknesses at the superior, temporal, inferior, and nasal points were greater in the LOF group than in the non-LOF group (426.2 μm vs. 395.1 μm, 445.7 μm vs. 414.9 μm, 459.2 μm vs. 428.8 μm, 445.4 μm vs. 414.3 μm, all P < .05). Multivariable analyses found that SCT (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.02, P < .001) and mean scleral thickness (OR: 1.02, 95% CI: 1.02-1.03, P = .002) were significantly associated with the presence of LOF. CONCLUSION A thick choroid and thick sclera appeared to be related to the presence of LOF in CSC.

Purpose To determine the role and optimal timing of glaucoma surgery in relation to Boston keratoprosthesis type 1 (KPro) implantation. Design Retrospective, comparative, non-randomized clinical study. Methods Single-center study of a total of 100 eyes (100 patients) implanted with a KPro between 2008-2017 and diagnosed with glaucoma before or after KPro. Patients were separated into 2 groups: those with preexisting glaucoma and those who developed glaucoma de novo after KPro. Groups were then divided based on whether patients were medically or surgically managed. Glaucoma surgery included glaucoma drainage device (GDD) implantation, trabeculectomy, and cyclophotocoagulation (CPC). Primary outcomes included best-corrected visual acuity (BCVA), glaucoma progression, and complications. Differences in outcomes were compared using parametric and non-parametric tests, as well as log-rank test to compare time-to-outcome events. Results Among 72 eyes with preexisting glaucoma, 27 (38%) had glaucoma surgery before KPro (18 GDD), while 45 (62%) were medically managed only. Among the latter, 19 (42%) needed glaucoma surgery post-KPro (16 GDD). Among 28 eyes with de novo glaucoma, 12 (43%) had glaucoma surgery post-KPro (9 GDD). For eyes with preexisting glaucoma, glaucoma progression was greater with glaucoma surgery performed post-KPro (100%) compared to pre-KPro (74%, P=0.016) and to medical management (54%, P=0.002). No increase in complications were observed with glaucoma surgery compared to medications only (P>0.05), while fewer eyes maintained BCVA of 20/200 or better over time with medical management (P=0.013). Eyes with de novo glaucoma had similar progression, BCVA and complications between medical and surgical care (P>0.05). Conclusions Glaucoma surgery should be performed prior or with KPro in eyes with preexisting glaucoma. Complication rates are not increased when glaucoma surgery is performed in KPro eyes with preexisting or de novo glaucoma. To ensure optimal glaucoma control, glaucoma surgery should be performed as early as possible in KPro eyes with good visual potential.

Purpose To compare the effect of duration of fluorometholone 0.1% treatment on corneal haze after photorefractive keratectomy (PRK) with mitomycin C (MMC) 0.02%. Design Prospective, randomized, double-blind, clinical trial. Methods Setting: Single center clinical trial. Study Population: A total of 252 myopic PRK candidates (252 eyes) aged 21 to 40 years with a mean spherical equivalent (SE) of ≤ 6 diopters (D) were randomized to receive one of the three corticosteroid regimens after PRK (group A = 1 month followed by 2-month placebo, group B = 2 months followed by 1-month placebo and group C = 3 months). Main Outcome Measures: Corneal haze incidence, subjective SE, uncorrected distance visual acuity (UDVA), and corneal densitometry. Results The corneal haze incidence (grade ≥ 1) at 12 months was 1.35% (1/74 eyes) in group A and 0% in the other two groups. The mean anterior corneal densitometry (grayscale unit) was 21.19 ± 2.07, 21.09 ± 2.19, and 21.31 ± 2.21 in group A, B and C, respectively. The mean SE was 0 ± 0.09, 0 ± 0.11, and 0 ± 0.10 and UDVA (decimal) was 1 ± 0, 1 ± 0.01, and 1 ± 0 in group A, B and C, respectively. During 1-year follow-up, no statistically significant difference was observed in mean SE (p = 0.158), UDVA (p = 0.343) and anterior corneal densitometry (p = 0.109) at any stage between the study groups. Conclusions Long-term topical corticosteroids are not necessary following PRK with MMC for moderate myopia.

Purpose To describe the effectiveness and side effect profile of difluprednate therapy in a series of patients with anterior scleritis. Design Retrospective, interventional case series. Methods Data collected from all patients with anterior scleritis who used difluprednate as a single treatment agent from 1/1/2018 to 1/1/2020 included: demographics, scleritis type, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, best-corrected visual acuity (BCVA), and lens status. The primary outcome was clinical resolution of scleritis. Secondary outcomes included BCVA loss ≥ 2 lines, change in lens status or cataract surgery, and IOP ≥24 mm Hg. Results Twenty-five patients (35 eyes) were analyzed. The median age was 60 years (range 13-78); 60% were female; 64% were Caucasian. Forty percent had bilateral disease; 44% of patients had an associated systemic disease. The majority of eyes (66%) had diffuse anterior scleritis. Eighty-three percent of eyes achieved resolution of scleritis, with a median time of resolution of 6 weeks. Eyes treated with an initial dose of ≥4 times daily were more likely to achieve disease resolution (hazard ratio [HR] = 3.43, 95% confidence interval [CI] 1.19, 9.88, p=0.02). Nine eyes had IOP elevation. Four eyes lost two lines or more of BCVA, one due to cataract progression. One eye underwent cataract surgery. Conclusions Difluprednate alone may effectively treat non-infectious anterior scleritis with a tolerable side effect profile.

Purpose To compare the outcomes of using an internal limiting membrane (ILM) flap and the conventional ILM peel technique for small- or medium-sized full-thickness macular hole (FTMH) repair. Design Retrospective, interventional case series. Methods Eyes with an FTMH ≤ 400 µm that underwent vitrectomy with either a single-layer inverted ILM flap (flap group, 55 eyes) or an ILM peel (peel group, 62 eyes) were enrolled. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Results Primary hole closure was achieved in 54 (98%) and 60 (97%) eyes in the flap and peel groups, respectively. The preoperative and postoperative 12-month BCVA were comparable between the groups but were significantly better in the flap than in the peel groups at 1 month (logMAR, mean ± SD, 0.83 ± 0.43 vs. 1.14 ± 0.50, P = 0.001), 3 months (0.58 ± 0.33 vs. 0.82 ± 0.43; P = 0.002), and 6 months (0.56 ± 0.32 vs. 0.72 ± 0.48; P = 0.028). In the flap group, foveal gliosis was less common than the peel group at 1 month (P = 0.030) and restored external limiting membrane and interdigitation zone was more common at 3 months (P = 0.046 and Conclusions Both the single-layer ILM flap and conventional ILM peel techniques closed FTMHs and improved vision. ILM flaps were associated with better visual outcomes up to 6 months postoperatively and should be considered in FTMHs ≤ 400 µm.

To assess changes in intraocular pressure (IOP) 1 hour after pharmacological dilation in eyes treated with laser peripheral iridotomy (LPI) and untreated fellow eyes of primary angle closure suspects (PACS).A prospective randomized, fellow-eye controlled trial.A total of 889 participants with PACS aged 50 to 70 years with LPI in 1 randomly selected eye and a fellow untreated eye were included. All participants underwent comprehensive examinations before and at 2 weeks, 6 months, 18 months, 36 months, 54 months, and 72 months after LPI. The IOP was measured using Goldmann applanation tonometry before and 1 hour after pharmacological dilation.The mean predilation IOP in the untreated eyes was 14.8 ± 2.7 mm Hg, which increased to 16.4 ± 2.7 mm Hg after pharmacological dilation (P.001). The treated and untreated eyes had similar predilation and postdilation IOP (all P0.05). The average postdilation IOP elevation was 1.5 mm Hg in the treated eyes and 1.6 mm Hg in the untreated eye, without significant differences (P = .802). Lower predilation IOP (P.001), smaller AOD500 (P = 0.001), smaller ARA500 (P = .030), smaller TISA500 (P = .043), and larger Iarea (P0.001) were associated with postdilation IOP elevation of 5 mm Hg and greater. Three untreated eyes (1.04 per 1000 pupil dilation) and 1 treated eye (0.34 per 1000 pupil dilation) developed acute angle closure (AAC) after dilation during the 72-month follow-up.Postdilation IOP elevation was similar among treated and untreated eyes, and the risk of developing AAC was very low, even among patients with PACS. Routine LPI before pupil dilation for people with PACS is not recommended.

PURPOSE To develop deep learning models for identification of sex and age from macular optical coherence tomography (OCT), and to analyze the features for differentiation of sex and age. DESIGN Algorithm development using database of macular OCT. SETTING One eye center in Taiwan. STUDY POPULATION 6147 sets of macular optical coherence tomography (OCT) images from the healthy eyes of 3134 persons. MAIN OUTCOME MEASURES Deep learning based algorithms were used to develop models for identification of sex and age, and 10-fold cross-validation was applied. Gradient-weighted class activation mapping (Grad-CAM) was used for feature analysis. RESULTS The accuracy for sex prediction using deep learning from macular OCT was 85.6±2.1%, compared to the accuracy of 61.9% by using macular thickness and 61.4±4.0% by using deep learning from infrared fundus photography (P

PURPOSE This study is the first to evaluate the prevalence of retinal thinning and the correlation with papilledema and visual acuity (VA) in a large population with craniosynostosis. DESIGN Prospective clinical cohort study. METHODS All and complex patients syndromic and complex with craniosynostosis who visited the only national referral center between 2018 and 2020 were included. Retinal layers were segmented using optical coherence tomography. Patients were seen by an ophthalmologist for VA assessment and fundoscopy. Multivariate regression models were developed to evaluate correlations between retinal thickness, papilledema and VA. RESULTS We included 127 patients. Retinal thinning was most prevalent in the peripapillary retinal nerve fiber layer (≤38%). A longer duration of papilledema in early childhood correlated with an increased peripapillary retinal nerve fiber layer and total retinal thickness optic nerve head later in life (+0.3 ± 0.2, P = .04 and +1.0 ± 1.0, P = .003); however, its thickness was not correlated with the VA (P = .20 and P = .53). Macular retinal thinning was associated with a worse VA (P = .01); however, it was not correlated with the duration of papilledema (P = .95). CONCLUSIONS Following a preventative treatment strategy for syndromic and complex craniosynostosis, the prevalence of retinal ONH thinning is low. Although the prevalence of peripapillary retinal nerve fiber layer thinning is considerable, its thickness is not correlated with VA. In contrast, macular thinning is correlated with worse VA scores and should, therefore, be evaluated during follow-up. Future studies should evaluate the (1) causative mechanism for macular thinning, (2) correlation between the time to surgery and macular thinning, and (3) results of reactive treatment strategies and compare those results to the current study.

Purpose To evaluate the long-term outcomes of the palpebral fissure transfer (PFT) technique without lower eyelid spacer in chronic progressive external ophthalmoplegia (CPEO). DESIGN Retrospective interventional case series. METHODS Consecutive CPEO patients with PFT surgery (2006-2017) and a minimum follow up of 24 months were included. The PFT included simultaneous levator resection or frontalis sling (based on the levator function and Bell's phenomenon) and lower eyelid retractor recession without spacer. Primary outcome measures comprised the change in margin reflex distance 1 (MRD-1), MRD-2, and palpebral fissure height (PFH) in the course of time. Potential predictors of keratopathy were also explored. RESULTS There were 32 patients (64 eyelids) with the mean age and follow up of 34.1 years (15-56) and 37.9 months (24-72), respectively. Mean MRD-1 significantly increased from -0.9 mm to 3.4 mm in the postoperative week 1-2 and 1.8 mm at the last follow up. Mean MRD-2 significantly decreased from 5.6 mm to 3.7 mm in the postoperative week 1-2 and 5 mm at the last follow up. Eyes with frank lower eyelid retraction (MRD-2 > 5 mm) gained more reduction in MRD-2 compared to those with no sclera show (-0.9 mm vs. -0.3 mm, P CONCLUSION Lower eyelid retractor recession without spacer yields significant protective corneal coverage at the critical early postoperative period when the risk of keratopathy is highest.

To determine the relationship of intraocular pressure (IOP) control with subsequent retinal nerve fiber layer (RNFL) thinning in patients with primary angle closure disease (PACD).Prospective cohort study.The study monitored 517 treated PACD eyes from 280 Chinese patients at least 24 months. IOP was measured every 3 months using Goldmann applanation tonometry, and RNFLs were measured by spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering) every 6 months. IOP mean and fluctuation were calculated as the average and the coefficient of variation of IOP measurements during the first 18 months of the study period. The relationship between IOP and subsequent RNFL changes over time were examined using multivariable linear mixed models. Intraclass correlations at the patient and eye levels were also controlled using nested random intercepts in the models.IOP mean (β = -1.20 µm/y per 1 mm Hg, P.001) and IOP fluctuation (β = -3.10 µm/y per 10% unit change in the coefficient of variation, P.001) were independently negatively associated with subsequent progressive global RNFL changes, after adjustment for age, sex, and baseline RNFL thickness. In the sectoral analysis, both higher mean IOP and IOP fluctuation predicted progressive RNFL thinning in the inferotemporal, superotemporal, superonasal, and temporal sectors in the order of strength of association. In the subgroup analysis by disease category, IOP fluctuation showed greater association with global RNFL thinning in eyes with primary angle closure glaucoma (P = .010) than in eyes without glaucomatous changes (P = .07).In treated PACD eyes, large IOP fluctuation is an independent predictor for subsequent progressive RNFL thinning in addition to high mean IOP during follow-up.

Purpose To evaluate the relationship between the occurrence of optic disc hemorrhages (DH) and glaucoma progression as determined by multiple glaucoma testing modalities. Design A prospective cohort study. Methods A longitudinal study of 124 open angle glaucoma patients who had yearly disc photography (DP), visual fields (VFs), spectral-domain optical coherence tomography (SD-OCT) retinal nerve fiber layer (RNFL) thickness scans, and optic nerve volume scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany), all performed on the same day over a 5-year period. The minimum distance band (MDB) thickness, a 3D neuroretinal rim parameter, was calculated from optic nerve volume scans. Patients were classified as glaucoma progressors or non-glaucoma progressors using event-based analysis. Results Out of 124 open angle glaucoma patients, 19 (15.3%) had one or more DHs on yearly DPs. Presence of a DH was associated with localized 3D neuroretinal rim thickness progression (superior MDB progression; OR 3.96, P = 0.04), but not with global or inferior MDB progression (P = 0.14 and 0.81 respectively), DP progression (P = 0.08), VF progression (P = 0.45), or RNFL global, inferior or superior progression (P = 0.17, 0.26 and 0.76 respectively). In the majority of patients with MDB progression (14/17, or 82%), the progression was noted before or concurrently with the first instance of DH. Conclusions Glaucoma progression detected by high-density 3D SD-OCT neuroretinal rim measurements preceded DH occurrence in the majority of patients. These findings support the hypothesis that DHs are indicators of ongoing glaucoma progression rather than discrete events that cause subsequent progression.

PURPOSE: To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials. DESIGN: Single-center, prospective case series. METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 [86%]), cone-rod dystrophy (2 [9%]), or isolated macular dystrophy (1 [5%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up. CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.

PURPOSE To compare anterior segment and angle parameters between pseudoexfoliation syndrome (PEX) and PEX glaucoma (PEXG) and normal control subjects using anterior segment optical coherence tomography (AS-OCT) imaging. DESIGN Cross-sectional study. METHODS One hundred and two subjects with PEXG, PEX, and normal eyes as the control group were recruited from an academic referral institution. All subjects underwent a complete ophthalmologic examination, axial length measurement, and AS-OCT imaging. Anterior segment and angle parameters were evaluated. RESULTS After excluding 4 eyes because of poor imaging of the scleral spur, data from 34 eyes with PEXG, 33 eyes with PEX, and 31 eyes of normal control subjects were analyzed. Anterior chamber depth was significantly shallower in eyes with PEXG compared with eyes of control subjects (P < .001). The differences in anterior chamber angle parameters (AOD500, AOD750, TISA500,and TISA750) were significant among study groups, with lower values in the PEXG group compared with the PEX and control subject groups. Lens vault (mean [mm]±SD) was higher in the PEXG (0.46 ±0.21) and PEX (0.427 +0.28) groups compared with the control group (0.305+ 0.20). CONCLUSIONS PEXG eyes have the narrowest anterior chamber angle parameters. There is a progressive decrease in angle parameters from control subjects to the PEX group to the PEXG group. Narrow anterior chamber angle and anterior chamber depth may have a role in the progression of PEX to PEXG. Detection of narrow angle in these patients may help clinicians manage the disease more properly.

To investigate the diagnostic performance of multicolor imaging for detection of retinal nerve fiber layer (RNFL) defects in myopic eyes with glaucoma.Comparative diagnostic analysis.A total of 150 myopic eyes of 138 patients (-1.00 diopter or axial length24 mm) underwent multicolor imaging by Spectralis (Heidelberg Engineering GmbH) optical coherence tomography (OCT). Two independent observers graded the RNFL visibility score and determined the location of the RNFL defect on each image. Readings were taken from the superior and inferior areas. The diagnostic performances of multicolor, green-reflectance, and blue-reflectance images for detection of the RNFL defect were compared with those of conventional fundus and red-free RNFL photographs.The interobserver agreement on the RNFL visibility score was substantial for fundus and RNFL photographs and multicolor and green-reflectance images and was perfect for blue-reflectance images. The interobserver agreement on the location of the RNFL defect was better when using multicolor imaging than when using conventional photography. The green-reflectance image (2.89 ± 0.31) showed the highest RNFL visibility score, followed by blue-reflectance (2.88 ± 0.32) and multicolor (2.57 ± 0.63) images. The sensitivity of multicolor imaging (94.9%, 93.2%, and 91.5% for green-reflectance, blue-reflectance, and multicolor images, respectively) was significantly higher than that of fundus photography (83.1%) for detection of superotemporal RNFL defects (all P.05). It was significantly higher for inferotemporal defects than those of fundus and RNFL photographs (all P.05).Multicolor imaging can visualize the glaucomatous RNFL defects in myopic eyes that are indistinguishable on conventional photography.

Purpose No approved therapies directly target retinal ganglion cells (RGCs) for neuroprotection or neuroenhancement in glaucoma. Recombinant human nerve growth factor (rhNGF) has been shown to promote RGC survival and function in animal models of optic neuropathy. Here we evaluate safety, tolerability, and efficacy of short-term, high-dose rhNGF eye drops versus placebo in a cohort of glaucoma patients. Methods This study is a single-center, randomized, double-masked, vehicle-controlled, parallel group study designed to assess safety and tolerability as well as short-term neuroenhancement of structure and function (Clinicaltrials.gov NCT02855450). Sixty open-angle glaucoma patients were randomized 40:20 to receive either 180 μg/ml rhNGF or vehicle control eye drops in both eyes, three times daily for 8 weeks, with a 24-week post-treatment follow-up. One eye was officially selected as the study eye, although both eyes were studied and dosed. Primary endpoints were safety, as assessed through adverse events, and tolerability, as assessed through patient reported outcomes. Secondary outcome measures included best corrected visual acuity (BCVA), Humphrey visual field (HVF), electroretinogram (ERG), and optical coherence tomography (OCT) of retinal nerve fiber layer (RNFL) thickness at baseline, after 8 weeks of treatment, and at 4 and 24 weeks after treatment (12- and 32-weeks total). Results Of the 60 randomized subjects, 23 were female (38%) and the average age was 66.1 years. Through week 32, there were no treatment-related serious adverse events, including no unexpectedly severe progression of optic neuropathy, no adverse events affecting ocular function or pressure, and no drug-related systemic toxicity. Topical high-dose rhNGF was tolerated well, with low level of symptom burden mainly eliciting periocular ache (in 52% of treated, 5% of placebo) and only 3 patients (7.5%) discontinuing treatment due to discomfort, out of whom 1 patient (2.5%) prematurely withdrawing from the study. There were no statistically significant differences in global indices of HVF, and no meaningful differences in total, quadrant, or clock-hour mean RNFL thickness between the groups, although both of these function and structure measures showed non-significant trends towards significance in favor of rhNGF. Real-world participant data was used to generate an estimate of cohort size needed to power subsequent studies. Conclusions rhNGF is safe and tolerable in a topical 180 μg/ml formulation. Although no statistically significant short-term neuroenhancement was detected in this trial, given the strong effects of NGF in preclinical models and trends detected in this study, analysis for efficacy in a neuroprotection trial is warranted.

Purpose To evaluate the diagnostic performance of swept-source anterior segment optical coherence tomography (SS-OCT) in differentiating eyes with primary angle closure disease (PACD) from eyes of control subjects, as well as eyes with PAC and PAC glaucoma (PACG) from eyes with PAC suspect (PACS) disease. Design Multicenter cross-sectional study. Methods Chinese patients were classified into control, PACS, and PAC/PACG groups. The area under the receiving operating characteristic curve (AUC) from logistic regression models was used to evaluate discriminating ability. Sensitivity and specificity were calculated, and performance of the models was validated using an independent dataset. Results A total of 2928 SS-OCT images from 366 eyes of 260 patients were recruited to develop diagnostic models. The validation dataset included 1176 SS-OCT images from 147 eyes of 143 patients. For distinguishing PACD from control eyes, average anterior chamber depth had the highest AUC (0.94). With a cutoff of 2.2 mm for average anterior chamber depth, the sensitivity and specificity were 90.2% and 85.2% in the training set. For distinguishing PAC/PACG from PACS, a multivariate model had an AUC of 0.83, with sensitivity and specificity of 82.0% and 62.8% in the training set. The validation set confirmed the findings. Conclusions SS-OCT of the anterior segment showed excellent diagnostic performance distinguishing PACD from normal eyes and moderate diagnostic ability distinguishing eyes with PAC/PACG from eyes with PACS. ACD alone may provide a simple and effective way to diagnose PACD from control subjects. As ACD can be obtained using other more available modalities, this has implications for the early diagnosis of PACD.

Purpose : To evaluate the effect of loss to follow up (LTFU) on outcomes in eyes with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF). Design : Retrospective cohort study Methods : Single-center study of 90 eyes of 73 patients with non-proliferative diabetic retinopathy (NPDR) and DME treated with anti-VEGF injections who were LTFU for >6 months. Main outcomes were the change in mean visual acuity (VA) and central foveal thickness (CFT) at the return and final visits compared to the visit before LTFU. Results : Mean age was 64.5 years, mean LTFU duration was 322 days, and mean follow-up duration after return was 502 days. Compared to the mean VA at the visit before LTFU (0.42, Snellen ∼20/52), mean VA worsened at the return visit (0.54, Snellen ∼20/69, p=0.004). No significant change in the mean VA was noted at the 3-month after return visit (0.50, Snellen ∼20/63), the 6-month after return visit (0.46, Snellen ∼20/57), the 12-month after return visit (0.42, Snellen ∼20/52) and the final follow up (0.47, Snellen ∼20/59). When analyzed by NPDR severity before LTFU, no difference in VA was found from the visit before LTFU to the final visit. Mean CFT increased when comparing the visit before LTFU (270 μm) to the return visit (305 μm, p=0.012), but no difference was found by the final visit [247 μm, p=0.07]. Conclusions : Anti-VEGF treated DME patients who were LTFU for a prolonged period experienced a modest decline in VA that recovered after restarting treatment.

Purpose: To quantitatively evaluate the retinal structural parameters of pediatric patients who were determined to be deficient in vitamin D. Design: Prospective, cross-sectional study. Methods: Retinal structural parameters, including the peripapillary retinal nerve fiber layer (RNFL), central macula, retinal layer, and choroidal thicknesses, central retinal artery equivalent (CRAE), and central retinal vein equivalent (CRVE), in pediatric subjects with vitamin D deficiency (group 1) and those without (group 2) were compared. Results: Group 1 comprised 70 individuals, while group 2 comprised 80 individuals. The mean peripapillary RNFL (except for the nasal superior sector [P = .037]), central macula, and retinal layer thicknesses were also determined to be similar in both groups (P > .05 for both groups). The mean choroidal thickness was lower in the subfoveal (P = .006) and nasal 3000-µm–diameter areas (P = .004) in group 1. The mean CRAE was determined to be lower (P = .031) and the CRVE was higher in group 1 (P = .005); it was determined that there was a significant correlation between the vitamin D level and both the CRAE (r = 0.447, P < .001) and CRVE (r = −0.320, P = .013). Conclusion: Choroidal thinning, a decrease in the CRAE, and increase in the CRVE were structural changes that occurred in the pediatric subjects who had vitamin D deficiency. The alterations in these parameters became more prominent in pediatric subjects who were determined to have lower vitamin D levels.

To compare the long-term results of Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK) in fellow eyes for treatment of Fuchs endothelial corneal dystrophy.This study is a 2-centered, retrospective case series of 64 patients (128 eyes) with DSAEK followed by DMEK. The main outcomes measured were best spectacle-corrected visual acuity (BSCVA) and duration of time to achieve BSCVA as well as eye preference.Preoperative median logarithm of the minimum angle of resolution (logMAR) BSCVA was similar in eyes receiving DMEK 0.36 ± 0.26 and DSAEK 0.42 ± 0.34 (P = .266). The average follow-up time needed for the DMEK eyes to achieve BSCVA was faster than that of DSAEK (277 days vs 490 days, P = .0014). With long-term follow-up, the BSCVA of the DMEK eyes [0.09 ± 0.10 logMAR] and DSAEK eyes [0.11 ± 0.16 logMAR] did not show a statistically significant difference (P = .069). Twenty-two of the 64 preferred the DMEK eye, 17 patients preferred the DSAEK eye (P = .423), and 25 patients did not have a preference. In the DMEK group, the average spherical equivalent was -0.08 compared with the DSAEK group at 0.06 (P = .2854).In our fellow eye study with long-term follow-up, DMEK and DSAEK had comparable levels of BSCVA and patient satisfaction. The DMEK eyes reached their BSCVA sooner, whereas the DSAEK eyes improved over a longer time frame. A greater number of patients had 20/25 and 20/20 vision in the DMEK group; however, the difference was not statistically significant. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

PURPOSE: To characterize long-term clinical outcomes of monotherapy selective laser trabeculoplasty (SLT) in Afro-Caribbean patients with open-angle glaucoma (OAG). DESIGN: This was a post hoc analysis of nearly 8 years (median 3.2, interquartile range 2.1–7.1) of pooled data from the West Indies Glaucoma Laser Study (WIGLS) and its preliminary study. METHODS: SETTING: Three eye care practices in Saint Lucia and Dominica. PARTICIPANTS: Afro-Caribbean adults with mild-moderate OAG treated with ≤2 medications (61 in preliminary study, 72 in WIGLS). INTERVENTION: Participants underwent medication washout, baseline IOP determination, and bilateral 360° SLT. Participants were followed for up to 94 months. Repeat SLT was performed according to pre-specified criteria. MAIN OUTCOME MEASURES: The primary outcome was mean intraocular pressure (IOP) reduction from baseline. The secondary outcome was medication-free survival with SLT repeated as needed. RESULTS: The pooled data set included 265 eyes of 133 Afro-Caribbean participants. Mean (standard deviation) baseline IOP was 21.2 (3.4) and 21.2 (3.9) mmHg in right and left eyes, respectively. Over 8 years, mean IOP ranged from 12.8–15.7 mmHg and from 13.1–15.8 mmHg, respectively (p

To investigate the clinical characteristics of optic nerve head (ONH) prelaminar schisis in eyes with advanced glaucoma.Cross-sectional study.One hundred sixteen eyes with advanced glaucoma (30-2 mean deviation-12 dB) were included. ONH prelaminar schisis was identified using the spectral-domain optical coherence tomography independently by 2 evaluators and only eyes that reached consensus for the presence of ONH prelaminar schisis were included. Bruch membrane opening-minimum rim width (BMO-MRW), thickness and depth of lamina cribrosa (LC), peripapillary retinal nerve fiber layer (RNFL) thickness, macular thickness (total, RNFL, ganglion cell layer, inner plexiform layer), and peripapillary and subfoveal choroidal thickness were additionally obtained. Clinical characteristics were compared between the 2 groups based on the presence of ONH prelaminar schisis.ONH prelaminar schisis was identified in 48 of 116 eyes. Multivariate logistic regression analysis revealed that short axial length, thin and deep LC, and thick macula were associated with the presence of ONH prelaminar schisis. When the structure-function relationships were determined, macular structural parameters tended to have a better relationship with functional parameters than the BMO-MRW and peripapillary RNFL thickness parameters in eyes with ONH prelaminar schisis.The ONH prelaminar schisis was associated with thin and deep LC, short axial length, and generally thick macula. In patients with this features, the macular measurements, rather than peripapillary or ONH measurements, better predict the functional status of the eye. Our findings may have significant clinical implications for management of advanced glaucoma eyes with and without ONH prelaminar schisis.

PURPOSE To assess the diagnostic accuracy of optical coherence tomography angiography (OCTA) compared with multimodal imaging for choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC) eyes and to determine the features that predicted CNV. DESIGN Prospective cross-sectional study. METHODS Consecutive CSC patients were recruited from retina clinic. The reference standard for CNV was determined by interpretation of multimodal imaging with OCTA, structural OCT line scan, fluorescein angiography (FA), indocyanine green angiography (ICGA), ultra-widefield fundus photography and fundus autofluorescence (FAF). Two independent masked graders examined OCTA without FA and ICGA to diagnose CNV. Univariate and multivariate analyses were performed to evaluate factors associated with CNV. RESULTS CNV was detected in 69 eyes in 64 out of 277 CSC patients according to reference standard. The two masked graders who examined OCTA had sensitivity of 81.2% (95% Confidence Interval [CI], 71.9%-90.4%) and 78.3% (95% CI, 68.5%-88.0%), specificity of 97.3% (95% CI, 95.9%-98.8%) and 96.2% (95% CI, 94.5%-98.0%), positive predictive values of 82.4% (95% CI, 73.3%-91.4%) and 76.1% (95% CI, 66.1%-86.0%), and negative predictive values of 97.1% (95% CI, 95.6%-98.7%) and 96.7% (95% CI, 95.0%-98.3%). Their mean area under the receiver operating characteristic curve (AUC) was 0.88 with good agreement (Kappa coefficient 0.80 [95% CI, 0.72-0.89]). Flat irregular pigment epithelial detachment on structural OCT, neovascular network on OCTA and ill-defined late leakage on FA significantly correlated with CNV in CSC from multiple regression (P CONCLUSIONS There is discordance between OCTA and multimodal imaging in diagnosing CNV in CSC. This study demonstrated the caveats in OCTA interpretation, such as small extrafoveal lesions and retinal pigment epithelial alterations. Comprehensive interpretation of OCTA with dye angiography and structural OCT is recommended.

PurposeTo investigate the characteristics and rate of central visual field loss after optic disc hemorrhage (DH).DesignProspective cohort study.MethodsThree hundred forty-three eyes of 220 subjects who had ≥3 years of follow-up with a 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 predefined zones were compared using linear mixed-effects models in DH and non-DH eyes. Clustered pointwise regression analysis was also used to define central VF progressors and compared with 24-2 VF loss using guided progression analysis.ResultsThirty-nine 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 MD loss that were 3 times faster than non-DH eyes (mean difference -0.36 dB/year [95% confidence interval 0.54-0.18]; P < .001) and were 3.7 times more likely to progress (P=.002). A larger proportion of glaucomatous eyes showed central VF progression rather than peripheral VF progression in the DH group (30.8% vs. 20.5%) compared with the 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 < .001). Superonasal and superotemporal central VF regions progressed more rapidly than other regions, especially in DH eyes.ConclusionCentral VF loss is accelerated in glaucoma eyes with DH and it corresponds topographically to the DH location. In patients with glaucoma with DH, one should consider supplementing 10-2 VFs with 24-2 VFS to monitor the disease.

Purpose To assess changes in outer retinal layer (ORL) thickness before the development of exudative macular neovascularization (MNV) in eyes with age-related macular degeneration. Design Retrospective observational case series. Methods Eyes with age-related macular degeneration that eventually developed exudative MNV followed with sequential optical coherence tomography for ≥2 years before the exudation occurred were enrolled. The ORL thickness was automatically calculated by the optical coherence tomography software for each sector of the early treatment diabetic retinopathy study map at each follow-up visit. The ORL thickness change from baseline to the day when the exudative MNV developed was compared between sectors that eventually developed exudative MNV and those that did not. Results Forty-seven eyes (47 patients) were included. At baseline (24 ± 3 months before exudative MNV), mean (standard deviation) ORL thickness of sectors that eventually developed exudative MNV was similar to that of sectors that did not (85.2 [8.2] µm vs 86.8 [5.7] µm, P = .08). ORL thickness significantly increased in sectors that developed exudative MNV compared with those that did not (+5.8 [10.4] µm vs −2.8 [3.6] µm, P Conclusion Thickening of the ORL begins in the area where exudative MNV will develop long before the exudation, accelerating significantly in the last 2 months. The occurrence of exudative MNV could be predicted by 2 months using this simple analysis.

Purpose To report the anterior segment clinical features and histopathologic and histochemical characteristics of explanted corneas from the largest reported cohort of patients with Hurler syndrome and other variants of mucopolysaccharidosis (MPS) I undergoing corneal transplantation. Design Retrospective observational case series. Methods This institutional study reviewed 15 corneas from 9 patients with MPS I spectrum disease who underwent corneal transplant to treat corneal clouding between May 2011 and October 2020. We reviewed the clinical data, hematoxylin-eosin–stained sections, and histochemical stains, including those for mucopolysaccharides (Alcian blue and/or colloidal iron). The main outcome measures were pathology observed under light microscopy and postsurgical clinical outcomes. Results Nine patients underwent 15 corneal transplants for corneal clouding (14/15 procedures were deep anterior lamellar keratoplasty). All corneas had mucopolysaccharide deposition visible on hematoxylin-eosin–stained sections, which was highlighted in blue with histochemical stains. All corneas also showed alterations in Bowman's layer and the majority also showed epithelial abnormalities. Conclusion MPS I shows significant corneal clouding that is successfully treated with deep anterior lamellar keratoplasty. The excised corneas show characteristic epithelial changes, disruption or breaks in Bowman's membrane, and amphophilic collections of stromal granular mucopolysaccharides which are visible on hematoxylin-eosin–stained sections and highlighted by special histochemical stains (Alcian blue and collodial iron). These changes, although subtle, should alert the pathologist to the possibility of an underlying lysosomal storage disorder.

To investigate the etiology and long-term surgical prognosis of the abnormal epithelium for partial limbal stem cell deficiency (LSCD), following superficial keratectomy DESIGN: Retrospective, interventional case series METHODS: This single-center, retrospective study was conducted to assess the prognosis of consecutive patients who underwent superficial keratectomy, with or without amniotic membrane transplantation (AMT), for the treatment of partial LSCD, from 2010 to 2019. We analyzed the etiologies of partial LSCD, surgical success rate, prognosis for recurrent cases, and the improvement in visual acuity.We included 40 patients (51 eyes) with partial LSCD. All eyes were in clinical stage II without dense fibrovascular tissue. Idiopathy was the most common etiology (39%), followed by multiple surgeries involving the corneoscleral limbus (19%). All eyes attained corneal reepithelialization and transparency. Furthermore, the visual acuity improved or remained unchanged postoperatively. We observed recurrence in 19 eyes (37%) with a mean follow-up period of 26.3 months. Despite no significant difference in the recurrence rates among different etiologies, postoperative delayed epithelialization and extensive limbal involvement were identified as risk factors for recurrence (P.001 and P = .013, respectively). Repeat surgeries were performed in 16 eyes. The final success rate was 84%.Superficial keratectomy is useful for the treatment of partial LSCD of varied etiologies, with an expected improvement in visual acuity postoperatively. Although the procedure can be repeated and have a high success rate, there have been several cases of recurrence in the long-term postoperative course.

Purpose To investigate the long-term effects of corticosteroid pulse therapy (CPT) for the treatment of acute-stage Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients with severe ocular involvement. Design Retrospective, comparative case series. Methods This study retrospectively reviewed the medical records of 116 SJS/TEN patients who developed the disease between 2002 and 2018. Patients with severe ocular disorders (ie, ocular surface epithelial defect, pseudomembranous formation, or both) at the acute stage and who were followed for >1 year post SJS/TEN onset were enrolled. In those patients, the treatments administered for acute-stage SJS/TEN and associated ocular sequelae were examined, including the best-corrected visual acuity (BCVA) in the patient's worse eye and the incidence of the ocular complications at the final follow-up examination. Results A total of 85 patients were enrolled. Of those, 36 received CPT within 4 days post disease onset (group A) and 49 patients did not receive CPT within 4 days post disease onset (group B). The percentage of eyes with a BCVA in the worse eye of ≥ 1.0 were 52.8% in group A and 14.3% in group B. Severe ocular sequelae (ie, a worsening of BCVA and corneal and conjunctival complications) were significantly less in group A than in group B. Conclusions In SJS/TEN patients with acute ocular involvement, CPT initiated within 4 days from disease onset may help reduce severe ocular sequelae.

PURPOSE: To investigate hemiretinal asymmetry in radial peripapillary capillary vessel area density (VAD) of healthy, glaucoma suspect, and glaucoma eyes of varying severity and its diagnostic utility for glaucoma. DESIGN: Population-based, cross-sectional study. METHODS: 6×6-mm optic disc scans were collected on optical coherence tomography angiography (OCTA) to obtain VAD and on OCT to measure circumpapillary retinal nerve fiber layer (RNFL) thickness. Hemiretinal difference in VAD (hdVAD) was defined as the absolute difference between superior and inferior hemiretinal VAD. Age-adjusted multivariable linear regression of hdVAD on glaucoma severity was performed. Area under curves (AUCs) were calculated from predicted probabilities generated by multiple logistic regression of glaucoma severity on age-adjusted single and combined parameters. RESULTS: 1043 eyes of 1043 participants (587 healthy, 270 suspect, 67 mild, 54 moderate, 65 severe glaucoma) were included. After age adjustment, mean hdVAD was similar between healthy and suspect (P = 0.225), higher in mild versus suspect (P < 0.001), higher in moderate versus mild (P = 0.018), but lower in severe versus moderate (P = 0.001). AUCs of hdVAD were highest for discriminating mild (0.685) and moderate (0.681) glaucoma from healthy. Combining hdVAD and global RNFL (gRNFL) yielded the highest AUCs of all parameters for mild (0.817) and any POAG (0.859) and resulted in significantly better diagnostic accuracy than either hdVAD or gRNFL alone (P < 0.05 for all comparisons). CONCLUSIONS: hdVAD is higher in early glaucoma and may help with early detection when damage is focal, but its diagnostic ability appears less robust in advanced glaucoma when damage is diffuse.

PURPOSE To investigate the corneal endothelium damage in Graves ophthalmopathy (GO) and its role as a promising quantitative index to evaluate GO activity. DESIGN Cross-sectional study. METHODS This study included 128 eyes of 64 patients with GO. All subjects underwent ophthalmologic examinations, including proptosis, tear break-up time (BUT), corneal fluorescein staining, and Schirmer test. Corneal endothelium was measured by noncontact specular microscope and ocular biometric parameters were measured by IOLMaster 700. Each eye was assigned a specific clinical activity score (CAS), then grouped as active (CAS ≥3 points) or inactive (CAS

Purpose To investigate the effects of preoperative Lipiflow (Johnson & Johnson, Jacksonville, FL, USA) treatment before cataract surgery on meibomian gland dysfunction (MGD) and dry eye induced by surgery. Design Prospective, randomized controlled study. Methods This study comprised 124 eyes of 124 patients with planned surgery for senile cataract. Participants were randomly allocated into control and Lipiflow groups based on administration of Lipiflow treatment 3 weeks before cataract surgery. For meibomian gland (MG) evaluation, MG atrophy, degree of gland expressibility, and quality of gland secretions were examined at the baseline visit and 1 and 3 months postoperatively. Ocular surface parameters of tear film break-up time, Oxford corneal staining score, and tear film lipid layer thickness were measured at each visit. Ocular Surface Disease Index and Dry Eye Questionnaire were also assessed. Results The control group exhibited a significant decrease in MG expressibility, worsened meibum quality, decreased lipid layer thickness, and worsened corneal staining after cataract surgery. Also, dry eye symptom showed significant worsening. Conversely, the Lipiflow group showed significantly improved MG patency and meibum quality, increased tear film break-up time, and reduced corneal staining, and presented improved subjective outcomes reported on both Ocular Surface Disease Index and Dry Eye Questionnaire. The improvement of each parameter in the Lipiflow group showed a linear correlation with baseline MGD grade. In addition, patients without baseline MGD showed less worsening or improvement of MGD and dry eye induced by surgery, with preoperative Lipiflow treatment. Conclusions Preoperative Lipiflow treatment conducted before cataract surgery may be a safe and effective intervention for relieving MGD and dry eye induced by surgery. It might be recommended not only for the patients with preoperative MGD but also for those without baseline MGD, to prevent the development of MGD and dry eye induced by ocular surgeries.