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To investigate the relationship of anti-VEGF treatment discontinuation with baseline factors and outcomes in eyes treated initially with aflibercept or bevacizumab for macular edema from central or hemiretinal vein occlusion.Long-term follow-up after a randomized clinical trial from 64 US centers.Analysis included 150 SCORE2 Month 60 completers classified into three groups: discontinued treatment early, treated intermittently, and treated continuously. Outcomes included visual acuity (VA) and central subfield thickness (CST).Those who discontinued treatment early were younger (60.9 years, versus 66.7 and 70.5 for the treated intermittently and treated continuously groups; P=0.001), and 17.4% were black, compared to 19.5% and 4.7% for the treated intermittently and treated continuously groups (P=0.006). At Month 60, the discontinued treatment early group had a higher proportion with complete resolution of macular edema (69.6%) than those treated intermittently (15.0%) and treated continuously (15.7%) (P0.001). Least squares means analyses over follow-up demonstrated that the discontinued treatment early group had lower mean CST (257µm) than the treated intermittently (CST=303µm, P=0.02) and treated continuously (CST=300µm, P=0.01) groups.Compared to those treated continuously, those who discontinued treatment early were younger and more likely black. The discontinued treatment early group had a higher proportion with complete resolution of macular edema at Month 60, and lower mean CST over follow-up, but not better VA, than the treated continuously and treated intermittently groups. Results support the need for continued monitoring and individualized treatment for patients treated with anti-VEGF for macular edema from central or hemiretinal vein occlusion.Clinical trial identifier at clinicaltrials.gov: NCT01969708.

To investigate 5-year outcomes in eyes initially treated with aflibercept or bevacizumab for macular edema due to central retinal or hemiretinal vein occlusion.Long-term follow-up (LTF) after a randomized clinical trial from 64 centers in the United States. Participants were followed up to 60 months and treated at investigator discretion after completing the 12-month treatment protocol. Main outcomes were visual acuity letter score (VALS) and central subfield thickness (CST) on optical coherence tomography.Seventy-five percent (248/330) of eligible participants completed at least 1 visit between months 24 and 60, and 45% completed the month 60 visit. Among participants completing month 60, overall mean VALS improvement over baseline was 13.5 (95% CI: 9.6, 17.5), less than the mean improvement of 20.6 (95% CI: 18.7, 22.4) observed at month 12, with no significant differences between originally assigned study groups. Further, 66% (99/150) had at least 1 treatment between months 48 and 60 with a mean (SD) of 3.41 (3.69) treatments over this period. Mean CST was 671 μm at baseline and 261 μm (95% CI: 241.2, 280.9) at month 60.Although VALS improved substantially when patients were treated per protocol through month 12, improvement lessened when treatment was at investigator discretion and fewer treatments were received although VALS remained markedly improved over baseline through year 5. Most patients continued to receive treatment in year 5. This suggests that continued monitoring and, if warranted, treatment with anti-VEGF therapy benefits patients with macular edema associated with central retinal or hemiretinal vein occlusion. Publication of this article is sponsored by the American Ophthalmological Society.

Retinal nonperfusion (RNP) is an important biomarker for diabetic retinopathy (DR). Data suggest that consistent anti-VEGF pharmacotherapy can slow RNP development. The RECOVERY trial evaluated the impact of aflibercept (Eylea, Regeneron) on RNP among eyes with proliferative DR (PDR).Prospective, randomized clinical trial with treatment crossover in the second year.Eyes with PDR and RNP.At baseline, the subjects were randomized 1:1 to monthly (arm 1) or quarterly (arm 2) intravitreal 2 mg aflibercept. At the beginning of year 2, the treatment arms were crossed over so that the monthly-dosed subjects subsequently received quarterly dosing and the quarterly-dosed subjects subsequently received monthly dosing.Change in total RNP area (mmAmong all subjects, from baseline to year 2, the mean RNP increased from 235 mmThrough year 2 of the RECOVERY trial, both treatment arms experienced significant increases in RNP. Despite the expansion of the RNP area in nearly all subjects, 82% of subjects demonstrated an improvement in DRSS levels from baseline, with no subjects experiencing worsening in DRSS scores.

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

To evaluate macular thickness fluctuations and their association with visual acuity outcome in eyes with macular edema (ME) secondary to central (CRVO) or hemiretinal vein occlusion (HRVO) treated initially with intravitreal aflibercept or bevacizumab. Post hoc analysis of 362 patients with ME secondary to CRVO or HRVO initially randomized to six monthly intravitreal injections of aflibercept or bevacizumab. Three spectral domain optical coherence tomography (SD-OCT) central subfield thickness (CST) fluctuation measures were investigated over Months 1–12: standard deviation (SD), number of turning points (T) for each participant, and a measure denoted as Zigzag reflecting the magnitude of alternating ups and downs in a participant’s CST. Main outcome measure is Month 12 visual acuity letter score (VALS). More fluctuations occurred in eyes randomized to bevacizumab than aflibercept: SD (59.98 vs 32.12; p

Purpose To identify anatomic endpoints altered by intravitreal ranibizumab in central retinal vein occlusion (CRVO) to determine any potential underlying disease modification that occurs with anti-vascular endothelial growth factor (anti-VEGF) therapy beyond best-corrected visual acuity and central optical coherence tomography outcomes. Methods A post hoc analysis of a double-masked, multicenter, randomized clinical trial was performed. A total of 392 patients with macular edema after CRVO were randomized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections. Central reading center-read data were reviewed to explore potential anatomic endpoints altered by therapy. Results At 6 months, there was a reduction in the ranibizumab groups compared with sham groups with respect to total area of retinal hemorrhage (median change from baseline in disc areas: − 1.17 [sham], − 2.37 [ranibizumab 0.3 mg], − 1.64 [ranibizumab 0.5 mg]), development of disc neovascularization (prevalence: 3% [sham], 0% [ranibizumab 0.3 mg], 0% [ranibizumab 0.5 mg]), and presence of papillary swelling (prevalence: 22.9% [sham], 8.0% [ranibizumab 0.3 mg], 8.3% [ranibizumab 0.5 mg], p Conclusions Ranibizumab for CRVO resulted in beneficial disease-modifying effects through a reduction in retinal hemorrhage, neovascularization, and papillary swelling. These findings may form the basis for future work in the development of a treatment response or severity scale for eyes with CRVO.

BACKGROUND AND OBJECTIVE: To facilitate timely surgery and efficient use of operating room time, our practice uses a team-based approach so patients may undergo primary rhegmatogenous retinal detachment (RRD) surgery with a different surgeon instead of the diagnosing surgeon. PATIENTS AND METHODS: This was a retrospective cohort study of 331 eyes that underwent RRD surgery. Patients were divided into two groups: RRD surgery performed by the diagnosing surgon, and RRD surgery performed by a different surgeon. RESULTS: Of 331 eyes, 200 eyes (60.4%) were repaired by the diagnosing surgeon and 131 eyes (39.6%) were repaired by a different surgeon. Primary anatomic success (PAS) rates at 3 months postoperatively were equivalent between the two groups (87.0% and 87.8% in the diagnosing surgeon and different surgeon groups, respectively [ P = .83]). There was no significant difference in preoperative ( P = .08) or final ( P = .28) visual acuity between the groups. Time between diagnosis and RRD repair was shorter in the different surgeon group (median of 1.5 days [IQR: 1.0–3.6] in the surgeon group versus 2.2 days [IQR: 0.8–5.7] in the diagnosing surgeon group) ( P = .03). Logistic regression analysis gave no evidence to suggest that PAS rates depended on day of week, time of day surgery was performed, group, or the interaction between those factors ( P = .93). CONCLUSIONS: Visual and anatomic success in RRD repair are equivalent when surgery is performed by either the diagnosing surgeon or a surgical colleague because time to surgery is reduced. Neither time of day nor day of the week had any influence on the outcomes. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:560–566.]

Purpose To evaluate the association between baseline demographic and spectral domain OCT (SD-OCT) features with visual acuity (VA) in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2) over 2 years. Design Post hoc analysis of prospective clinical trial data. Participants A total of 362 SCORE2 participants with macular edema secondary to central retinal (CRVO) or hemiretinal vein occlusion (HRVO). Methods Spectral domain OCT volume scans were assessed at the SCORE2 reading center at baseline, month 01 (M01), month 06 (M06), month 12 (M12), and month 24 (M24) for central subfield thickness (CST), subretinal fluid, intraretinal fluid, vitreoretinal interface abnormalities, disorganization of retinal inner layers (DRIL), and ellipsoid zone (EZ) within the central subfield (CSF). Main Outcome Measures Visual acuity at M06, M12, and M24. Results Mean baseline age was 68.9 years. Mean VA at M01 was 63.2 letters, and CST was 299.7 μm. At M01, subretinal fluid was seen in 28.5% intraretinal fluid in 67.2%, DRIL was seen in 73.8%, mostly within the CSF, and the EZ was absent in 9.8 and patchy in 31.7%. In multivariate analysis including all M01 demographics and SD-OCT parameters and their association with VA at M06, M12, and M24, VA at M01 remained significant across all time points up to M24 (P Conclusions In this 2-year follow-up of eyes that were treated with both per protocol and off protocol for RVO, VA at M01 was an important predictor of long-term vision and change in vision. Establishing predictors of visual recovery helps identify causes for poor responders to treatment in patients with RVO.

PURPOSE: To assess the relationship between best-corrected visual acuity (BCVA) and anatomic features in patients with macular edema (ME) related to retinal vein occlusion (RVO). DESIGN: Post hoc analysis of 3 clinical trials, which included verified diagnoses, protocol refractions, and the assessment of OCT and fluorescein angiography (FA) images at a masked reading center. PARTICIPANTS: Patients diagnosed with RVO-ME. METHODS: Correlation analyses were performed to determine the correlation between BCVA and macular anatomy at baseline and at 12 and 24 weeks and between changes from baseline to 12 and 24 weeks. MAIN OUTCOME MEASURES: The correlations between BCVA and central subfield thickness (CST), ellipsoid zone (EZ) integrity, intraretinal fluid (IRF), subretinal fluid, central leakage, and ischemia were assessed. RESULTS: In a total of 828 eyes with RVO-ME, the mean age, BCVA, and CST at baseline was 64.7 years, 51.1 letters, and 656.9 μm, respectively. At baseline, a moderate negative correlation was observed between BCVA and CST (r = − 0.56, P < 0.001). At weeks 12 and 24, the mean BCVA of eyes with definitely abnormal (absent) EZ was statistically significantly worse than that of eyes with normal EZ. At week 12, a moderate negative correlation was observed between changes in BCVA and changes in CST (r = − 0.35, P < 0.001), with a similar degree of association noted at week 24 (r = − 0.35, P < 0.001). At weeks 12 and 24, eyes that showed any improvement in central IRF showed a greater improvement in BCVA than eyes that showed no improvement (week 12: 463 eyes, 18.3 letters vs. 177 eyes, 13.0 letters, respectively, P < 0.001) and (week 24: 332 eyes, 20.2 letters vs. 131 eyes, 13.3 letters, respectively, P < 0.001). With respect to the correlation between baseline BCVA and fluorescein leakage or capillary nonperfusion, the Pearson correlation coefficients were – 0.41 (P < 0.001) and – 0.16 (P = 0.060), respectively. CONCLUSIONS: In addition to CST, there are important clinically relevant relationships between BCVA and both OCT and FA anatomic features in patients with RVO-ME.

To evaluate cone photoreceptor density in clinically unremarkable retinal regions in patients with age-related macular degeneration (AMD) using adaptive optics scanning laser ophthalmoscopy (AOSLO).Prospective case series with normal comparison group.Ten eyes of seven patients with intermediate AMD were studied, including four with predominantly subretinal drusenoid deposits (SDD) and three without SDD. Macular regions with a clinical absence of AMD-associated lesions were identified by cone packing structure on AOSLO and optical coherence tomography. Cone density was measured in 1174 clinically unremarkable regions within the central subfield (CSF), the inner (IR), and outer rings (OR) of the Early Treatment Diabetic Retinopathy Study grid over 39.6 ± 3.3 months and compared with age-matched normal values obtained in 17 subjects.Cone density decreased at 98.3% of the examined locations over time in the eyes with AMD. In the CSF, IR, and OR, cones declined by -255 ± 135, -133 ± 45, and -59 ± 24 cones/degreeAOSLO revealed cone photoreceptor loss in regions that appear otherwise unremarkable clinically. These findings may help explain the loss of mesopic sensitivity reported in these areas in eyes with intermediate AMD.

To describe the clinical characteristics and visual outcomes of neovascular age-related macular degeneration (NV-AMD) patients with irregular pigment epithelium detachment (PED) and non-resolving subretinal fluid (SRF) despite continuous monthly injections of anti-vascular endothelial growth factor (VEGF). This is a retrospective case series, including NV-AMD patients treated in a tertiary academic practice. Inclusion criteria were NV-AMD diagnosis, with irregular PED, and non-resolving SRF treated with continuous monthly anti-VEGF intravitreal injections. Data collection included best corrected visual acuity (BCVA), central macular thickness (CMT), sub-foveal choroidal thickness (SFCT), and type and location of PED as seen on optical coherence tomography (OCT). A total of 738 patients with NV-AMD underwent anti-VEGF injections during the follow-up period and 20 eyes of 19 patients (14 females and 5 males) met the inclusion criteria. Average age was 81.7 ± 6.6 years, mean follow-up time was 32.1 ± 23.5 months, and mean number of injections was 31.3 ± 24.2. Mean VA was 0.26 ± 0.21 logMAR (Snellen 20/36) at baseline versus 0.20 ± 0.23 logMAR (Snellen 20/32) at the end of the follow-up (P = 0.28). All eyes presented with sub-foveal, type 1 macular neovascularization (MNV). Average sub-foveal choroidal thickness changed from 189.70 ± 68.46 μm at baseline to 169.00 ± 63.06 μm (P

Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.Multicenter, international, prospective cohort study: ProgStar Study.Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P.001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

AIM: To evaluate the fractal feature of the retinal vasculature of normal eyes on a stereographic projected and montaged ultra-wide field (UWF) fluorescein angiography (FA). METHODS: Prospective, observational, cross-sectional study. Totally 59 eyes of 31 normal subjects were imaged using the Optos 200Tx. Images obtained at different gaze angles stereographically projected and montaged. The early-phase UWF FA frames were processed to segment the retinal vasculature and the results were exported as binary masks. The fractal dimension (FD) was calculated using the box-counting method. RESULTS: The global FD for the entire retina was 1.6±0.04, with no difference between males and females (1.59±0.04 vs 1.61±0.04, P=0.084) or between right and left eyes (1.6±0.04 vs 1.6±0.05, P=0.61). FD was non-uniformly distributed among four quadrants (P0.05). CONCLUSION: Fractal geometry is non-uniformly distributed across the retina in normal eyes and decreases from the fovea to the far-periphery. Subjects with an older age tend to have a smaller FD, however, the FD in the far-periphery does not appear to be influenced by age.

To quantify changes of the retinal vascular bed area (RVBA) in mm2 on stereographically projected ultrawide field fluorescein angiography images in eyes with proliferative diabetic retinopathy after antivascular endothelial growth factor injection.This is a prospective, observational study. The early-phase ultrawide field fluorescein angiography images (Optos 200Tx) of 40 eyes with proliferative diabetic retinopathy and significant nonperfusion obtained at baseline and after six months (NCT02863354) were stereographically projected by correcting peripheral distortion. The global retinal vasculature on ultrawide field fluorescein angiography was extracted for calculating RVBA by summing the real size (mm2) of all the pixels automatically.For the entire cohort, the global RVBA for the entire retina decreased from 67.1 ± 15.5 to 43.6 ± 18.8 mm2 after anti-VEGF treatment at six months (P0.001). In the subgroup receiving monthly anti-VEGF injections, the global RVBA decreased from 68.7 ± 16.2 to 33.9 ± 13.3 mm2 (P0.001). In the subgroup receiving anti-VEGF every three months, the global RVBA decreased from 65.6 ± 15.1 to 50.8 ± 19.3 mm2 (P = 0.004).RVBA seems to be a new biomarker to indicate efficiency of retinal vascular changes after anti-VEGF injection. Eyes with proliferative diabetic retinopathy and significant nonperfusion demonstrate reduced RVBA after anti-VEGF treatment.

To evaluate macular thickness fluctuations and their association with visual acuity outcome in eyes with macular edema (ME) secondary to central (CRVO) or hemiretinal vein occlusion (HRVO) treated initially with intravitreal aflibercept or bevacizumab.Post hoc analysis of 362 patients with ME secondary to CRVO or HRVO initially randomized to six monthly intravitreal injections of aflibercept or bevacizumab. Three spectral domain optical coherence tomography (SD-OCT) central subfield thickness (CST) fluctuation measures were investigated over Months 1-12: standard deviation (SD), number of turning points (T) for each participant, and a measure denoted as Zigzag reflecting the magnitude of alternating ups and downs in a participant's CST. Main outcome measure is Month 12 visual acuity letter score (VALS).More fluctuations occurred in eyes randomized to bevacizumab than aflibercept: SD (59.98 vs 32.12; p 0.0001), T (4.03 vs 3.53; p = 0.02) and Zigzag (24.91 vs 11.60; p = 0.0003). Month 12 VALS is significantly lower for the 4th (highest) quartile of the CST fluctuation measure than for the 1st (lowest) quartile for both SD (mean difference in VALS of 7.87; 95% confidence interval: 3.03, 12.70) and Zigzag (mean difference in VALS of 5.11; 95% confidence interval: 0.29, 9.93). SD and Zigzag quartiles were no longer significantly different after Month 1 VALS was added to the regression analysis.Greater CST fluctuation as assessed by SD and Zigzag was negatively associated with Month 12 VALS. However, early post-treatment VALS is a stronger predictor of VALS outcomes than the CST fluctuation measures.

To correlate fractal dimension (FD) of the retinal vasculature with the extent of retinal nonperfusion area in diabetic retinopathy (DR) on ultrawide-field fluorescein angiography (FA).Cross-sectional study.Baseline Optos 200Tx ultrawide-field FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center. The retinal vasculature was extracted from an early-phase FA frame by exploiting the elongated nature of the vessels and then skeletonized for calculation of FD using a box-counting method. The nonperfusion area was delineated by 2 independent, reading center-certified graders who were masked to the study groups and who were using a standardized protocol and then computed in millimeters squared.While no difference in FD was observed for the entire retina in DR compared with normal control subjects, a significantly smaller FD was found in the far-periphery of the DR eyes (P.001). FD for the entire retina was negatively associated with global nonperfusion area (R = -0.44; P.001), and this relationship was also present within the 3 concentric retinal zones (posterior: R = -0.31, P = .016; midperiphery: R = -0.35, P = .007; and far periphery: R = -0.31, P = .015).Peripheral FD on ultrawide-field FA is reduced in DR eyes compared with normal eyes and is correlated with severity of retinal nonperfusion. FD can be calculated automatically without the need for correction of peripheral distortion, and therefore it may prove to be a useful surrogate biomarker when precise quantification of nonperfusion is not feasible.

Purpose Evaluate the impact of intravitreal aflibercept (Eylea, Regeneron, Tarrytown, NY) on retinal non-perfusion (RNP) in eyes with proliferative diabetic retinopathy (PDR). Design Prospective, randomized clinical trial. Subjects Eyes with treatment-naive PDR and extensive RNP without diabetic macular edema. Methods Patients were randomized 1:1 to intravitreal 2-mg aflibercept every-4-weeks (Monthly) or every-12-weeks (Quarterly). Main Outcome Measures The primary outcome measure was change in total RNP area (mm2) from baseline to year 1. Secondary outcomes included ischemic index (ISI), neovascularization area, diabetic retinopathy severity scale (DRSS) scores, visual acuity, central retinal thickness, visual function questionnaire score, and adverse events. Mean and 95% confidence interval (CI) were calculated for each outcome. Results Through 1-year, the Monthly (n=20) & Quarterly (n=20) cohorts received 11.0 & 3.95 mean aflibercept injections, & DRSS scores improved ≥2 steps in 74% & 67% of patients, respectively. Among all patients through 1-year, mean total area of RNP increased from 235 mm2 (CI, 183-288) to 266 mm2 (CI, 299-303; P=0.18) and ISI increased from 25.8% (CI, 20.9-30.7) to 31.9% (CI, 27.6-36.3; P=0.004). RNP outcomes favored monthly-dosing. Mean total RNP increased from 207 mm2 (CI, 143-270) at baseline to 268 mm2 (CI, 212-324; P=0.01) at 1-year in the Quarterly cohort, and remained stable at 264 mm2 at baseline (CI, 176-351) and 1-year (CI, 209-318; P=0.70) in the Monthly cohort (P=0.05, Monthly vs. Quarterly cohorts), with a difference of 56.8 mm2 in total RNP (CI: -47.8-161; P=0.28) at baseline and -4.19 mm2 (CI: -79.4-71.0; P=0.91) at 1-year between the Monthly and Quarterly cohorts. While many eyes demonstrated increased areas of RNP longitudinally (24, 66.7%), this was more common with Quarterly dosing (14, 77.8%), and a proportion of eyes (12, 33.3%) demonstrated localized areas of apparent reperfusion of non-perfused retina, more commonly in the Monthly cohort (8, 44.4%). Conclusions Widespread evidence of retinal reperfusion with aflibercept-dosing of PDR eyes with extensive RNP was not identified, and therefore the primary outcome of RECOVERY was not met; nevertheless, zones of apparent reperfusion were detected in some patients and a dose-response was identified with a reduction of RNP progression with monthly compared to quarterly dosing.

We present an automated method for measuring the lineal density of red blood cells (RBCs) in human retinal capillaries using adaptive optics near-confocal ophthalmoscopy (AONCO). The spatiotemporal traces of RBCs flowing in retinal capillaries were extracted from AONCO images, enhanced using the Gabor filter, the vesselness filter, and the Hough transform. A total of 43 capillary segments (each 50 µm long) were analyzed in 12 eyes of 12 subjects, and the measurement error of the automated method was 0.09 cell over 50 µm compared with results obtained by manual counting. Our method provides a tool for assessing RBC spatial distribution in retinal capillaries.

Purpose: This work compares best-corrected visual acuity (BCVA) and central retinal thickness (CRT) outcome measures following pars plana vitrectomy (PPV) with and without internal limiting membrane (ILM) peel for epiretinal membrane (ERM). Methods: A retrospective cohort study was conducted of 114 eyes of 114 patients with visually significant ERM undergoing PPV with membrane peel (PPV/MP) at a single institution. CRT measurements were collected from Heidelberg and Zeiss spectral-domain optical coherence tomography imaging units. Results compared preoperative and postoperative CRT and BCVA among patients with at least 60 days of follow-up. Results: A total of 114 eyes with ERM met the inclusion criteria. Eighty-one eyes (71%) underwent PPV/MP with ILM peel and 33 eyes (29%) underwent PPV/MP without ILM peel. There was no statistically significant difference between preoperative CRT between the 2 study groups ( P = .95). The mean follow-up time of eyes undergoing PPV/MP without ILM peel and with ILM peel was 391 days and 319 days, respectively. There was no statistical difference in the mean reduction of CRT between the 2 groups ( P = .470). Both groups had improvement of BCVA following surgery and there was no statistical difference in final logMAR visual acuity when comparing the 2 groups ( P = .738). Conclusions: There was an overall improvement of CRT and BCVA among patients undergoing PPV/MP for ERM with or without ILM peel. There was no statistically significant difference in the final BCVA or CRT between the 2 groups.

Purpose To evaluate the association between ellipsoid zone (EZ) on spectral domain optical coherence tomography (SD-OCT) and visual acuity letter score (VALS) in participants with retinal vein occlusion in the Study of Comparative Treatments for Retinal Vein Occlusion 2. Methods SD-OCT scans of 362 participants were qualitatively assessed at baseline and months 1, 6, 12, and 24 for EZ status as normal, patchy, or absent. The thickness of EZ layer in the central subfield was also obtained using machine learning. Results EZ assessments were not possible at baseline due to signal blockage in >75% of eyes. At month 1, EZ was normal in 37.6%, patchy in 48.1%, and absent in 14.3%. EZ was measurable in 48.7% with a mean area of 0.07 ± 0.16 mm2. Mean VALS was better in eyes without an EZ defect compared to eyes with an EZ defect (P < 0.0001 at all visits). EZ defect at month 1 was associated with poorer VALS at all follow-up visits (P < 0.0001). Conclusions Both qualitative and quantitative assessments of EZ status strongly correlated with VALS. Absence of EZ was associated with poorer VALS at both corresponding and future visits, with larger areas of EZ loss associated with worse VALS. Translational Relevance Assessment of EZ can be used to identify patients with potentially poor response in eyes with retinal vein occlusion.

PURPOSE To report the yearly rate of change in macular function in patients with Stargardt disease type 1 (STGD1) over 24 months and to establish a new volumetric visual function index for use in clinical trials investigating the efficacy on retinal sensitivity. METHODS Design: International, multicenter, prospective cohort study with 5 study visits every 6 months over 24 months. PARTICIPANTS A total of 233 individuals with genetically confirmed STGD1 (≥1 disease-causing ABCA4 variant). MAIN OUTCOME MEASURES The total volume (VTOT) beneath the sensitivity surface of a 3-D model of the hill of vision and mean sensitivity (MS) derived from mesopic microperimetry performed with a white stimulus. Changes of VTOT over time and its correlation with the ABCA4 genotype and baseline features. RESULTS At baseline, 440 eyes (233 patients) with a mean (SD) age of 33.7 (15.0) years, mean (SD) visual acuity of 46.08 (16.03) ETDRS letters were analyzed with an average VTOT of 0.91 decibel-steradian (dB-sr) and an MS of 10.73 dB. The overall mean rate of decrease in sensitivity [95% confidence interval] was 0.077 [0.064, 0.090] dB-sr/y for VTOT and 0.87 [0.72, 1.02] dB/year for MS. The progression rate of VTOT depended on baseline visual function (0.029 dB-sr/year for low and 0.120 dB-sr/year for high baseline VTOT; P < .001) and exhibited a difference in the first vs second year of follow-up (0.065 dB-sr/year vs 0.089 dB-sr/year, respectively; P < .001). The absence of pigmentary abnormalities of the retinal pigment epithelium at baseline was found to be associated with a faster progression rate (P < .001), whereas a significant association with the genotype was not detected (P = .7). CONCLUSION In STGD1, both microperimetric outcomes demonstrate statistically significant and clinically meaningful changes after relatively short follow-up periods. Volumetric modeling may be useful in future interventional clinical trials that aim to improve retinal sensitivity or to slow down its decline and for structure-function correlations.

PurposeTo evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes.MethodsThis retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes.ResultsForty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy.ConclusionNon-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.

Background/aimsOASIS is a Phase IIIb trial (NCT01429441) assessing long-term outcomes in subjects with symptomatic vitreomacular adhesion (VMA). The purpose of this study is to report on the frequency, severity, location and time course of ellipsoid zone (EZ) alterations in ocriplasmin-treated and sham control eyes in the OASIS study.Methods220 patients (146 ocriplasmin, 74 sham) subjects with VMA were enrolled in this masked post hoc analysis phase IIIb, randomised, sham-controlled double-masked multicentre clinical trial. A masked post hoc analysis of OCT images was performed at the Doheny Image Reading Center from subjects enrolled in the OASIS trial. The status of the EZ band was assessed in three different macular regions: the central subfield (CS) (≤1 mm diameter), the parafoveal area (PAA) (>1 to ≤3 mm) and the perifoveal area (PEA) (>3 to ≤6 mm). The EZ band was rated as normal/intact, full thickness macular hole (FTMH), abnormal but continuous, discontinuous/disrupted or absent at visits from baseline (pretreatment) to week 1 (day 7), month 1 (day 28), month 3, month 6, month 12 and the final follow-up at month 24. EZ band status was compared in both study and control eyes.ResultsA total of 208 patients (138 ocriplasmin, 70 sham) were included in this analysis. At baseline, FTMH was present in 48.6%, 8.0%, 0% and 52.8%, 2.9%, 0% in the CS, PAA and PEA of the ocriplasmin and sham groups, respectively. The EZ was graded to be abnormal but continuous, discontinuous/disrupted or absent at Baseline in 21.0%, 4.3%, 2.8% in the CS, PAA and PEA, respectively, of the ocriplasmin group; and 12.9%, 10.0%, 4.3% in the CS, PAA and PEA of the sham group. For the ocriplasmin group in the PAA, this frequency increased to 6.6% at week 1, was 9.8% at month 1, but improved to 3.8% at month 3, and remained stable to 1.6% at month 24. These differences, however, were not statistically significant.ConclusionsOcriplasmin treatment for symptomatic VMA was associated with EZ abnormalities in a small percentage of patients that was best assessed in regions (PEA) relatively unaffected by the VM interface disease at baseline. The EZ abnormalities were apparent by week 1, persisted at month 1, and appeared to resolve in the majority of cases by month 3.Trial registration numberNCT01429441

Purpose: To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of choroidal vascularity index (CVI) analysis. Design: Prospective cohort study Methods: Of 741 patients prescribed PPS within a large university database, 100 (13.4%) with any consumption agreed to participate in a prospective screening investigation. Multimodal retinal imaging including near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) was performed in all patients. Characteristic findings of affected patients were identified, and affected and unaffected cohorts were compared. CVI, defined as stromal choroidal area (SCA) divided by the total choroidal area, was analyzed. Results: The prevalence of PPS maculopathy was 16%. NIR illustrated punctate hyperreflective lesions with early presentation. FAF illustrated a speckled macular network of hypo- and hyperautofluorescence colocalized with multifocal hyperreflective retinal pigment epithelial lesions on SD-OCT. Advanced cases demonstrated varying degrees of atrophy. The affected cohort exhibited significantly greater mean PPS therapy duration, mean daily dosage, and mean cumulative dosage (19.5±5.5 years, 433.9±137.6 mg, 3,103.1±1,402.2 g) compared with the unaffected cohort (7.1±6.6 years, 291.6±177.6 mg, 768.4±754.8 g). SCA was significantly lower and CVI was significantly greater in the affected vs the unaffected group. Conclusions: This prospective cohort study identified a prevalence of PPS maculopathy of 15%-20% among PPS users who agreed to participate. A spectrum of findings may be observed with multimodal retinal imaging. Significant choroidal abnormalities associated with this characteristic maculopathy may provide surrogate markers of macular toxicity.

PURPOSE This study assessed relationships between best-corrected visual acuity (BCVA), central subfield thickness (CST), and ellipsoid zone (EZ) integrity in macular edema (ME) patients. DESIGN Post hoc analysis of 6 clinical trials, which included verified diagnoses, protocol refractions, and reading center assessment of OCT images. PARTICIPANTS Participants (n = 1063) were diagnosed with ME from retinal vein occlusion (RVO), diabetic retinopathy (DR; diabetic macular edema, DME), or noninfectious uveitis (NIU). METHODS For CST, 2 clinical trials for each disorder were analyzed. For EZ, 3 studies across 2 disorders were analyzed. MAIN OUTCOME MEASURES Primary outcomes were correlations between BCVA and CST, and between BCVA and 4 central subfield EZ grades. RESULTS For baseline BCVA and CST, Pearson correlation coefficients were: ME from RVO, -0.56 (774 eyes; 95% confidence interval [CI], -0.61 to -0.51; P < 0.001); DME, -0.50 (91 eyes; 95% CI, -0.64 to -0.33; P < 0.001); and ME from NIU, -0.38 (198 eyes; 95% CI, -0.49 to -0.26; P < 0.001). Regarding change from baseline to 24 weeks for both BCVA and CST, Pearson correlation coefficients were: ME from RVO, -0.35 (95% CI, -0.43 to -0.27; P < 0.001); DME, -0.30 (95% CI, -0.48 to -0.09; P = 0.006); and ME from NIU, -0.42 (95% CI, -0.53 to -0.29; P < 0.001). Acute and chronic ME showed similar baseline and 24-week change linear correlations. With lower baseline CST, a trend of decreased baseline and 24-week change correlations was found. For central subfield EZ at baseline, mean BCVA progressively worsened with each of 4 EZ grades in 185 eyes with gradable EZ (DME, 41 eyes; NIU, 144 eyes; P ≤ 0.050 for all pairwise comparisons except between normal and questionably abnormal EZ grades). Eyes with normal baseline central subfield EZ showed greater 24-week change in BCVA than those with abnormal baseline EZ (15.00 letters vs. 8.16 letters; P = 0.0005, with baseline BCVA, CST, and age as covariates). CONCLUSIONS Despite these correlations, CST and EZ integrity, as graded herein, account for the minority of BCVA variation in patients with ME resulting from RVO, DR, and NIU.

PURPOSE: To assess whether early visual acuity letter score change from baseline (ΔVALS) and early spectral domain optical coherence tomography (SD-OCT) measures of center point thickness (CPT) are associated with later ΔVALS in eyes with macular edema due to central or hemiretinal vein occlusion treated with intravitreal aflibercept or bevacizumab. METHODS: Secondary analysis of a randomized clinical trial of 362 participants. RESULTS: Considered separately at Month 3, CPT (categorized as ≤300 microns, >300 microns) and ΔVALS (categorized as

This study assessed relationships between best-corrected visual acuity (BCVA), central subfield thickness (CST), and ellipsoid zone (EZ) integrity in macular edema (ME) patients.Post hoc analysis of 6 clinical trials, which included verified diagnoses, protocol refractions, and reading center assessment of OCT images.Participants (n = 1063) were diagnosed with ME from retinal vein occlusion (RVO), diabetic retinopathy (DR; diabetic macular edema, DME), or noninfectious uveitis (NIU).For CST, 2 clinical trials for each disorder were analyzed. For EZ, 3 studies across 2 disorders were analyzed.Primary outcomes were correlations between BCVA and CST, and between BCVA and 4 central subfield EZ grades.For baseline BCVA and CST, Pearson correlation coefficients were: ME from RVO, -0.56 (774 eyes; 95% confidence interval [CI], -0.61 to -0.51; P0.001); DME, -0.50 (91 eyes; 95% CI, -0.64 to -0.33; P0.001); and ME from NIU, -0.38 (198 eyes; 95% CI, -0.49 to -0.26; P0.001). Regarding change from baseline to 24 weeks for both BCVA and CST, Pearson correlation coefficients were: ME from RVO, -0.35 (95% CI, -0.43 to -0.27; P0.001); DME, -0.30 (95% CI, -0.48 to -0.09; P = 0.006); and ME from NIU, -0.42 (95% CI, -0.53 to -0.29; P0.001). Acute and chronic ME showed similar baseline and 24-week change linear correlations. With lower baseline CST, a trend of decreased baseline and 24-week change correlations was found. For central subfield EZ at baseline, mean BCVA progressively worsened with each of 4 EZ grades in 185 eyes with gradable EZ (DME, 41 eyes; NIU, 144 eyes; P ≤ 0.050 for all pairwise comparisons except between normal and questionably abnormal EZ grades). Eyes with normal baseline central subfield EZ showed greater 24-week change in BCVA than those with abnormal baseline EZ (15.00 letters vs. 8.16 letters; P = 0.0005, with baseline BCVA, CST, and age as covariates).Despite these correlations, CST and EZ integrity, as graded herein, account for the minority of BCVA variation in patients with ME resulting from RVO, DR, and NIU.

To investigate the relationship between intraretinal macular hemorrhage and visual acuity outcomes in eyes with central retinal vein occlusion or hemiretinal vein occlusion managed with aflibercept, bevacizumab, or observation.Retrospective analysis of data from 2 randomized clinical trials.A total of 362 participants were randomized in the Study of Comparative Treatments for Retinal Vein Occlusion 2, and 88 participants randomized to observation in the Standard Care vs Corticosteroid in Retinal Vein Occlusion Study. Participants received monthly intravitreal aflibercept or bevacizumab through month 6 or observation through month 8. The main outcome was visual acuity letter score (VALS).Reduced area of hemorrhage by month 6 was observed in 70.7% (116 of 164) of aflibercept-treated eyes, 63.8% (104 of 163) of bevacizumab-treated eyes, and 42.2% (27 of 64) of observation eyes by month 8 (P.01). Relative to eyes with hemorrhage during follow-up, aflibercept-treated eyes without hemorrhage at month 6 had a mean VALS improvement of 8.0 (99% confidence interval [CI]: 1.9, 14.2); bevacizumab-treated eyes without hemorrhage at month 6 had a mean VALS improvement of 3.2 (99% CI: -4.6, 11.0); and observation eyes without hemorrhage at month 8 had a mean VALS improvement of 13.5 (99% CI: 0.4, 26.5). At month 6, the presence of hemorrhage and the change in central subfield thickness (CST) were significantly associated with the change in VALS; however, CST was a more important predictor.Improvement in hemorrhage during follow-up was associated with visual acuity improvements and predicted visual acuity changes beyond what was explained by CST. These findings suggest that intraretinal macular hemorrhage is an important indicator of disease severity in retinal vein occlusion.

Background/AimsTo better understand the pattern of degeneration progression in cases with choroideremia.MethodsA cohort of genotypically confirmed choroideremia cases who underwent optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging was studied. Using HEYEX review software, the foveal centre was marked on FAF images under guidance of corresponding OCT images, followed by application of an ETDRS grid. The boundaries of preserved autofluorescence (AF) were manually segmented in each individual ETDRS subfield. The regional distribution of preserved AF was assessed by comparing its area among the various subfields.ResultsA total of 168 eyes from 84 choroideremia cases were enrolled. There was a statistically significant difference in the amount of preserved AF area between inner subfields as determined by one-way analysis of variance (F (3,668)=9.997, pConclusionThe asymmetric spatial distribution of preserved AF in choroideremia (corresponding to the stellate shaped nature of these regions) suggests that the progression of degeneration has directional preference.

We present two novel approaches to state detection of qubits defined with trapped ions. The first uses simple pulse sequences from a mode-locked laser to induce state-dependent excitations in less than 1 ns. The resulting atomic fluorescence occurs in the dark, allowing the placement of non-imaging detectors right next to the atom to improve the qubit state detection efficiency and speed.The second employs the long lived F state in Yb+ which has been used in quantum information science almost exclusively for clocks and optical-frequency qubits. We describe how this resource can be used in conjunction with the ground state S1/2 manifold to aid in the scaling of trapped ion quantum information science. Narrow-band optical pumping into the 2F7/2 from one of the conventional 2S1/2 qubit states is projected to achieve a higher state preparation and measurement (SPAM) fidelity than any other demonstrated technique.

Purpose To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design Multicenter, international, prospective cohort study. Methods Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Prog ression of Star gardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

AimsTo evaluate the choriocapillaris (CC) flow alterations around geographic atrophy (GA) in eyes with dry age-related macular degeneration.MethodsUsing a swept-source optical coherence tomography angiography (SS-OCTA) device, two volume 6×6 mm scans were acquired in patients with GA presenting between June and December 2017 at the Doheny-UCLA Eye Centers. The area of GA was delineated on the en face structural OCT fundus images. For each eye, the en face OCTA slabs at the level of the CC from the two acquisitions were averaged and compensated for signal loss using the corresponding structural en face images. The resulting images were binarised and analysed for the percentage of flow voids in the para-atrophy zone (a 500 µm wide ring around the immediate edge of the atrophy) and in the peri-atrophy zone (a 500 µm wide ring around the para-atrophy zone edge), the latter considered as a reference in the comparative analysis.ResultsThirty eyes of 20 patients were enrolled. The percentage of flow voids in the para-atrophy zone was 27.23%±6.29% and was significantly higher than in the surrounding peri-atrophy zone (23.4%±6.01%; pConclusionsA significant impairment of the CC flow is present in the zone immediately surrounding the GA lesions strengthening the hypothesis that CC alterations may be relevant to the progression of GA.

PURPOSE: Assess systemic vascular endothelial growth factor-A (VEGF) levels after treatment with intravitreous aflibercept, bevacizumab or ranibizumab. DESIGN: Comparative-effectiveness trial with participants randomly assigned to 2-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab following a retreatment algorithm. PARTICIPANTS: Participants with available plasma samples (N=436) METHODS: Plasma samples were collected before injections at baseline, 4-week, 52-week and 104-week visits. In a pre-planned secondary analysis, systemic free-VEGF levels from an ELISA immunoassay were compared across anti-VEGF agents and correlated with systemic side effects. MAIN OUTCOME MEASURES: Changes in the natural log (ln) of plasma VEGF levels. RESULTS: Baseline free-VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were −0.30±0.61, −0.31±0.54, −0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted CI; P-value) were −0.01 (−0.12, +0.10; P=0.89), −0.31 (−0.44, −0.18; P

Importance Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are used to treat a variety of posterior segment conditions, including some associated with glaucoma, such as macular edema due to central retinal vein occlusion (CRVO). Therefore, information regarding intraocular pressure (IOP)-related events associated with anti-VEGF therapies is important to help balance the risks and benefits over the course of therapy. Objective To investigate IOP-related events among participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). Design, setting, and participants Secondary analysis of a randomized clinical trial that included 312 participants with macular edema secondary to CRVO or hemiretinal vein occlusion (HRVO) who were not taking IOP-lowering medications at baseline. First randomization occurred on September 14, 2014, and contained data through data freeze on April 1, 2020. Analysis took place from April 2020 through December 2020. Interventions Study participants were initially randomized to 6 monthly intravitreal injections of aflibercept or bevacizumab. At month 6, protocol-defined good responders were rerandomized to continued monthly or treat-and-extend dosing of their originally assigned study drug, and protocol-defined poor or marginal responders were switched to alternative treatment. After month 12, participants were treated as per investigator discretion. Main outcomes and measures Three different outcomes: (1) IOP elevation more than 10 mm Hg from baseline, (2) IOP to a level higher than 35 mm Hg, and (3) IOP-lowering incisional or laser surgery. Results Of the 312 participants meeting inclusion criteria (138 [44.2%] were female; mean [SD] age, 67.8 [12.1] years), 25 (8.0%) had IOP elevation more than 10 mm Hg over baseline through month 60, and 5 (1.6%) had IOP higher than 35 mm Hg. The 60-month Kaplan-Meier cumulative incidence of IOP elevation more than 10 mm Hg over baseline was 0.13 (95% CI, 0.08-0.19), and the 60-month Kaplan-Meier cumulative incidence of IOP higher than 35 mm Hg was 0.02 (95% CI, 0.01-0.06), and did not differ among participants initially randomly assigned to receive aflibercept or bevacizumab. Three participants (1.0%) underwent IOP-lowering incisional surgery, and 3 participants (1.0%) underwent IOP-lowering glaucoma laser surgery. Conclusions and relevance Intravitreal anti-VEGF injections are used to treat some conditions associated with glaucoma, such as macular edema due to CRVO, and the rates of IOP-related events in this trial support monitoring IOP in eyes treated with anti-VEGF therapy for macular edema associated with CRVO or HRVO for up to 60 months. Trial registration ClinicalTrials.gov Identifier: NCT01969708.

To describe baseline vision-related function, measured with the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), in patients with macular edema secondary to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2); evaluate the baseline relationship between NEI VFQ-25 scores with visual acuity letter score (VALS) and central retinal thickness; and compare baseline NEI VFQ-25 scores in SCORE2 participants with those in normal-vision reference populations and patients in other retinal vein occlusion trials.Multicenter, noninferiority randomized controlled trial.SCORE2 was designed to assess whether intravitreal bevacizumab is noninferior to intravitreal aflibercept for treatment of decreased vision attributable to macular edema owing to CRVO or HRVO. SCORE2 enrolled 362 participants, including 305 with CRVO and 57 with HRVO. Analyses were of cross-sectional baseline data. The main outcome measures were baseline NEI VFQ-25 composite and subscale scores.SCORE2 participants' baseline NEI VFQ-25 composite and subscale scores are significantly lower compared with 3 normal-vision reference populations (P.01; except for ocular pain score) and similar to patients in other retinal vein occlusion clinical trials. Baseline VALS in the better eye was correlated with baseline NEI VFQ-25 composite and subscale scores of general vision, near activities, role difficulties, dependency, and color vision, with correlations ranging from 0.19 to 0.26 (P.05 for each score).CRVO and HRVO patients in SCORE2 had significantly worse baseline patient-reported vision-related function than normal vision populations, despite the disease being primarily unilateral with typically excellent vision in the fellow eye.

Purpose To investigate the clinical importance of changes in diabetic retinopathy severity score (DRSS) in patients with diabetic macular edema (DME) treated with intravitreal ranibizumab. Design Post hoc analysis of the phase III RIDE and RISE studies of ranibizumab for treatment of DME. Participants Four hundred sixty-eight eyes treated with ranibizumab from randomization with gradable DRSS on baseline fundus photographs. Methods Visual and anatomic outcomes were examined in eyes grouped according to DRSS change from baseline to month 24. Main Outcome Measures Mean best-corrected visual acuity (BCVA) letter score change, proportion of patients with 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letter score change, mean contrast sensitivity change, proportion of patients with resolved macular edema, and leakage on fluorescein angiography. Results Most (56.8%) patients treated with ranibizumab experienced 1-step or more improvement in DRSS from baseline to month 24; 40.0% had no change, and 3.2% experienced DRSS worsening. Patients with DRSS stability or improvement had greater mean BCVA letter score changes (+15.1, +14.2, +11.3, and +11.2 letters for ≥3-step improvement, ≥2-step improvement, 1-step improvement, and no DRSS change, respectively) compared with +5.0 letters in patients who had any DRSS worsening. Best-corrected visual acuity letter score gain of 15 letters or more was more common in patients with 2-step or 3-step or more DRSS improvement (51.9% and 44.6%, respectively) compared with those with a 1-step DRSS improvement, no change, or worsening (37.9%, 39.6%, and 26.7%, respectively). A loss of 15 letters or more in BCVA was more common in patients with any DRSS worsening (13.3%) compared with patients who had stable or improved DRSS (0%–2.8%). Resolution of macular edema was more common in patients with DRSS improvement: 84.2%, 87.7%, and 92.3% of patients with 1-step, 2-step or more, and 3-step or more improvement in DRSS achieved central foveal thickness of 250 μm or less, compared with 65.2% and 53.3% of patients who had no DRSS change or any DRSS worsening. Conclusions These findings provide further support that improvement in DRSS is a clinically important outcome that should be evaluated as a measure of treatment effectiveness in future studies of diabetic eye disease.

Purpose To describe the design and baseline characteristics of participants in the S tudy of CO mparative Treatments for RE tinal Vein Occlusion 2 (SCORE2) and to compare with cohorts from other retinal vein occlusion trials. Design Phase III prospective, multicenter, randomized clinical trial designed to assess whether intravitreal bevacizumab is noninferior to intravitreal aflibercept for treatment of decreased vision attributable to macular edema associated with central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO). Participants Total of 362 participants: 307 with CRVO and 55 with HRVO. Methods Demographic and study eye characteristics are summarized and compared between CRVO and HRVO study participants. Main Outcome Measures Baseline ophthalmic characteristics, including visual acuity and retinal thickness, and medical history characteristics, including hypertension, diabetes mellitus, and coronary artery disease. Results The mean age of participants was 69 years, 76% of participants were white, and 90% were non-Hispanic. There was a racial disparity with respect to disease type, with 38% of HRVO patients being black compared with 11% of CRVO patients ( P value adjusted for multiple testing = 0.0001). This is similar to findings from the previous SCORE Study. Comorbidities included hypertension (77%), diabetes mellitus (31%), and coronary artery disease (15%). At baseline, mean visual acuity letter score was 50 (20/100) (range, 19–73 [20/400 to 20/40]), mean optical coherence tomography (OCT)–measured central subfield thickness was 678 μm (range, 300–1203 μm), and mean number of months from diagnosis of macular edema to randomization was 6 (range, 0–104 months). One hundred twenty (33%) SCORE2 participants had been treated previously with anti–vascular endothelial growth factor (anti-VEGF) therapy, with these participants having baseline visual acuity letter score and OCT-measured central subfield thickness similar to those without prior anti-VEGF treatment, but longer mean duration of macular edema before randomization (18 months vs. 1 month for those without prior anti-VEGF treatment; P Conclusions The SCORE2 cohort is a heterogeneous population, including both CRVO and HRVO eyes and both treatment-naive eyes and eyes treated previously with anti-VEGF, which will allow study results to have broad applicability to CRVO and HRVO patients receiving treatment for macular edema. Similarities of the baseline characteristics of the SCORE2 population to other CRVO trial cohorts will allow meaningful comparisons of outcome results across trials.

Purpose Sensitive, reproducible visual function biomarkers are necessary to evaluate the efficacy of emerging treatments for Stargardt disease type 1 in clinical trials. We previously demonstrated that fixation stability may serve as a secondary outcome parameter for visual function loss. However, the test duration and protocol have an unknown effect on the assessment of fixation stability. Here, we hypothesize that separate fixation testing with a single target is different from combined fixation testing using the same target with simultaneous perimetry testing. Design International, multicenter, prospective, cross-sectional study. Methods Microperimetry data from the international, multicenter, prospective Progression of Atrophy Secondary to Stargardt Disease (ProgStar, NCT01977846 ) study were analyzed. Patients underwent various types of fixation testing including static testing and dynamic testing, and a duration-corrected dynamic test was generated (30sEpoch). Results A total of 437 eyes from 235 patients were included (mean age, 33.8 ± 15.1 years; 55.3% female). The mean 1SD-BCEA (bivariate contour ellipse area), which is the smallest ellipse encompassing 1 standard deviation of all fixation events, was smaller for the static fixation test compared to the 30sEpoch (4.5 ± 6.9 deg2 vs 5.3 ± 7.0 deg2; P = .02) and the number of points within both the 2-degree and 4-degree circles was larger (P Conclusions Our results suggest that differences in static and dynamic assessment of fixation stability are dependent not only on different test durations but also on the testing protocol of a single fixation target vs fixation target plus simultaneous perimetry testing and provide information on the conduct of fixation testing for clinical trials.

Background and objectiveTo develop a semi-automated, machine-learning based workflow to evaluate the ellipsoid zone (EZ) assessed by spectral domain optical coherence tomography (SD-OCT) in eyes with macular edema secondary to central retinal or hemi-retinal vein occlusion in SCORE2 treated with anti-vascular endothelial growth factor agents.MethodsSD-OCT macular volume scans of a randomly selected subset of 75 SCORE2 study eyes were converted to the Digital Imaging and Communications in Medicine (DICOM) format, and the EZ layer was segmented using nonproprietary software. Segmented layer coordinates were exported and used to generate en face EZ thickness maps. Within the central subfield, the area of EZ defect was measured using manual and semi-automated approaches via a customized workflow in the open-source data analytics platform, Konstanz Information Miner (KNIME).ResultsA total of 184 volume scans from 74 study eyes were analyzed. The mean±SD area of EZ defect was similar between manual (0.19±0.22 mm2) and semi-automated measurements (0.19±0.21 mm2, p = 0.93; intra-class correlation coefficient = 0.90; average bias = 0.01, 95% confidence interval of limits of agreement -0.18-0.20).ConclusionsA customized workflow generated via an open-source data analytics platform that applied machine-learning methods demonstrated reliable measurements of EZ area defect from en face thickness maps. The result of our semi-automated approach were comparable to manual measurements.

Purpose To determine if crowdsourced ratings of oculoplastic surgical outcomes provide reliable information compared to professional graders and oculoplastic experts. Methods In this prospective psychometric evaluation, a scale for the rating of postoperative eyelid swelling was constructed using randomly selected images and topic experts. This scale was presented adjacent to 205 test images, including 10% duplicates. Graders were instructed to match the test image to the reference image it most closely resembles. Three sets of graders were solicited: crowdsourced lay people from Amazon Mechanical Turk marketplace, professional graders from the Doheny Image Reading Center (DIRC), and American Society of Ophthalmic Plastic and Reconstructive Surgery surgeons. Performance was assessed by classical correlational analysis and generalizability theory. Results The correlation between scores on the first rating and the second rating for the 19 repeated occurrences was 0.60 for lay observers, 0.80 for DIRC graders and 0.84 for oculoplastic experts. In terms of inter-group rating reliability for all photos, the scores provided by lay observers were correlated with DIRC graders at a level of r = 0.88 and to experts at r = 0.79. The pictures themselves accounted for the greatest amount of variation among all groups. The amount of variation in the scores due to the rater was highest in the lay group at 25%, and was 20% and 21% for DIRC graders and experts, respectively. Conclusions Crowdsourced observers are insufficiently precise to replicate the results of experts in grading postoperative eyelid swelling. DIRC graders performed similarly to experts and present a less resource-intensive option.

Importance Two-year outcomes are reported comparing eyes originally assigned to aflibercept or bevacizumab to assess the need for continued anti–vascular endothelial growth factor (VEGF) therapy for macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) from participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) trial. Objective To investigate outcomes 1 year after cessation of the SCORE2 treatment schedule. Design, Setting, and Participants In this secondary analysis of the SCORE2 randomized clinical trial, follow-up included 117 participants originally randomized to aflibercept and 119 participants originally randomized to bevacizumab between September 17, 2014, and November 18, 2015. Data for the analyses were frozen on September 13, 2018. Interventions SCORE2 participants completed the treatment protocol at month 12, were subsequently treated at investigator discretion, and underwent assessment at month 24. Main Outcomes and Measures Visual acuity letter score (VALS) and central subfield thickness (CST) on spectral-domain optical coherence tomography. Results Among 362 participants randomized to aflibercept or bevacizumab, 65.2% (236 of 362) completed a protocol visit at month 24 (mean [SD] age, 68.5 (12.0) years; 53.8% male). The mean (SD) VALS improved from baseline to 12 months by 21.6 (14.5) in the aflibercept group compared with 21.9 (16.6) in the bevacizumab group (difference, −0.3; 99% CI, −5.6 to 4.9), then worsened from those values by a mean (SD) VALS of 7.6 (17.5) in the aflibercept group and 7.5 (14.5) in the bevacizumab group (difference, −0.1; 99% CI, −5.6 to 5.3) at month 24. The mean (SD) CST improved from baseline to 12 months by 394 (231) μm in the aflibercept group compared with 420 (274) μm in the bevacizumab group (difference, 26 μm; 99% CI, −62 to 114 μm), then worsened from those values by a mean (SD) of 58 (192) μm in the aflibercept group compared with 48 (186) μm in the bevacizumab group (difference, 10 μm; 99% CI, −58 to 78 μm) at month 24. Conclusions and Relevance No differences in VALS or CST outcomes at month 24 were identified when participants originally assigned to aflibercept were compared with those assigned to bevacizumab. Caution in interpretation is needed because of loss to follow-up. In both groups, VALS and CST improved through month 12 and then worsened somewhat during the second year, when treatment was at investigator discretion. This analysis suggests that CRVO and HRVO warrant close monitoring and treatment as needed over at least 2 years to optimize outcomes in eyes treated with anti-VEGF therapy. Trial Registration ClinicalTrials.gov identifier:NCT01969708