Correlation between change in central subfield thickness and change in visual acuity in macular edema due to retinal vein occlusion: post hoc analysis of COPERNICUS, GALILEO, and VIBRANT.

PURPOSE: Assess correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with macular edema due to retinal vein occlusion (RVO) that received intravitreal aflibercept injections (IAI). METHODS: Post hoc analysis of COPERNICUS and GALILEO trials for CRVO and VIBRANT trial for BRVO with relationships determined using Pearson correlation coefficient. RESULTS: In COPERNICUS, correlations (r) between change in CST and change in BCVA from baseline at weeks 12, 24, 52, and 100 were -0.36 (95% CI: -0.52, -0.18; P < 0.001), -0.38 (95% CI: -0.53, -0.20; P < 0.001), -0.44 (95% CI: -0.58, -0.27; P < 0.001), and -0.41 (95% CI: -0.56, -0.23; P < 0.001), respectively. CST changes accounted for only 21% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 2.1-letter increase in BCVA (P = 0.003). Similar findings were noted for GALILEO (r, -0.45 to -0.23) and VIBRANT (r, -0.36 to -0.32) trials. CONCLUSION: In eyes treated with IAI for macular edema due to RVO, correlation between change in CST and change in BCVA was weak to moderate. While change in CST may be helpful in determining the need for anti-VEGF therapy, these findings do not support using changes in CST as a surrogate for changes in visual acuity outcomes.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND RISK OF TRACTION RETINAL DETACHMENT IN EYES WITH PROLIFERATIVE DIABETIC RETINOPATHY: Pooled Analysis of Five DRCR Retina Network Randomized Clinical Trials.

PURPOSE: To investigate whether anti-vascular endothelial growth factor (anti-VEGF) for diabetic macular edema or proliferative diabetic retinopathy (PDR) increases the risk of traction retinal detachment (TRD) among eyes with PDR. METHODS: Pooled analysis of PDR eyes from Protocols I, J, N, S, or T with Early Treatment Diabetic Retinopathy Study level ≥61 (prompt vitrectomy was not planned) randomly assigned to the control group (laser photocoagulation, sham, or intravitreal saline; 396 eyes) or anti-VEGF (487 eyes). The primary outcome was investigator-identified TRD within 1 year of randomization. RESULTS: The 1-year cumulative probability of TRD was 6.8% (95% confidence interval: 4.6%-9.9%, 25 events) in control-group eyes and 4.8% (95% confidence interval: 3.2%-7.3%, 22 events) in anti-VEGF group eyes (hazard ratio = 0.95 [95% confidence interval: 0.54-1.66, P = 0.86]). The cumulative probability of vitrectomy for TRD was 4.4% (16 events) in control-group eyes and 2.2% (9 events) in anti-VEGF group eyes (P = 0.19). Percentage with TRD and vitrectomy for TRD were similar within strata of diabetic retinopathy severity. CONCLUSION: These findings do not support the hypothesis that anti-VEGF therapy for diabetic macular edema or PDR increases the risk of TRD among eyes with PDR similar to those enrolled in five DRCR Retina Network protocols for which prompt vitrectomy was not planned.

PHOTOCOAGULATION VERSUS RANIBIZUMAB FOR PROLIFERATIVE DIABETIC RETINOPATHY: Should Baseline Characteristics Affect Choice of Treatment?

PURPOSE: Among eyes with proliferative diabetic retinopathy, identify whether baseline characteristics impact the benefit of ranibizumab over panretinal photocoagulation (PRP) in DRCR.net Protocol S. METHODS: Participants had proliferative diabetic retinopathy, visual acuity of 20/320 or better, and no previous PRP. Eyes were randomized to PRP or intravitreous 0.5-mg ranibizumab. RESULTS: Ranibizumab was superior to PRP for change in visual acuity and development of vision-impairing central-involved diabetic macular edema over 2 years (P < 0.001). Among 25 characteristics, there were none in which participants assigned to PRP had superior outcomes relative to ranibizumab-assigned participants. The relative benefit of ranibizumab over PRP for change in visual acuity seemed greater in participants with higher mean arterial pressure (P = 0.03), without previous focal/grid laser (P = 0.03), with neovascularization of the disk and elsewhere on clinical examination (P = 0.04), and with more advanced proliferative diabetic retinopathy on photographs (P = 0.02). For development of vision-impairing central-involved diabetic macular edema, the relative benefit of ranibizumab over PRP seemed greater among nonwhite participants (P = 0.01) and those with higher mean arterial pressure (P = 0.01). CONCLUSION: There were no characteristics identified in which outcomes were superior with PRP compared with ranibizumab. These exploratory analyses provide additional support that ranibizumab may be a reasonable alternative to PRP for proliferative diabetic retinopathy over a 2-year period.

Panretinal Photocoagulation Versus Ranibizumab for Proliferative Diabetic Retinopathy: Factors Associated with Vision and Edema Outcomes.

PURPOSE: To identify baseline factors associated with change in visual acuity or development of vision-impairing central-involved diabetic macular edema (DME) over 2 years when treating proliferative diabetic retinopathy (PDR) with ranibizumab or panretinal photocoagulation (PRP). DESIGN: Post hoc analyses of randomized, multicenter clinical trial data. PARTICIPANTS: Eyes completing the 2-year visit (n = 328) or without vision-impairing central-involved DME at baseline (n = 302) in Diabetic Retinopathy Clinical Research Network Protocol S. METHODS: Intravitreous ranibizumab (0.5 mg/0.05 ml) or PRP. MAIN OUTCOME MEASURES: Change in visual acuity (area under the curve) and development of vision-impairing (20/32 or worse) central-involved DME over 2 years. RESULTS: After multivariable model selection with adjustment for baseline visual acuity and central subfield thickness, no factors were identified as associated with change in visual acuity or development of vision-impairing central-involved DME within the ranibizumab group. In the PRP group, worse change in visual acuity was more likely with higher hemoglobin A1c level (-0.6 letters per 1% increase; 95% confidence interval [CI], -1.2 to -0.1 letters; continuous P = 0.03), more severe diabetic retinopathy (difference between high-risk PDR or worse vs. moderate PDR or better, -2.8 letters [95% CI, -5.5 to -0.2 letters]; continuous P = 0.003), and higher mean arterial pressure (difference between ≥100 mmHg vs. <100 mmHg, -2.0 letters [95% CI, -4.6 to 0.5 letters]; continuous P = 0.009). Development of vision-impairing central-involved DME was more likely with higher hemoglobin A1c level (hazard ratio [HR] per 1% increase, 1.31 [95% CI, 1.13-1.52]; continuous P < 0.001), more severe diabetic retinopathy (HR for high-risk PDR or worse vs. moderate PDR or better, 1.46 [95% CI, 0.73-2.92]; continuous P = 0.03), and the presence of cystoid abnormalities within 500 µm of the macula center (HR, 2.90 [95% CI, 1.35-6.24]; P = 0.006). CONCLUSIONS: For eyes managed with PRP, higher hemoglobin A1c level and more severe diabetic retinopathy were associated with less vision improvement and an increased risk of vision-impairing central-involved DME developing. When managing PDR with ranibizumab, eyes gained vision, on average, with no baseline characteristics identified as associated with visual acuity or central-involved DME outcomes.

CHANGES IN DIABETIC RETINOPATHY SEVERITY WHEN TREATING DIABETIC MACULAR EDEMA WITH RANIBIZUMAB: DRCR.net Protocol I 5-Year Report.

PURPOSE: To explore 5-year changes from baseline in diabetic retinopathy severity among eyes treated with ranibizumab for diabetic macular edema. METHODS: Diabetic retinopathy severity was assessed from study visits and annual fundus photographs among participants in Protocol I (DRCR.net). The proportion of eyes that improved at annual examinations and the cumulative probability of worsening through 5 years were estimated. RESULTS: Among 235 participants with nonproliferative diabetic retinopathy at baseline, there were 29%, 28%, and 32% of eyes with retinopathy improvement at 1, 3, and 5 years, respectively. Among 111 participants with proliferative diabetic retinopathy, corresponding improvement percentages were 38%, 35%, and 23%. The 5-year cumulative probability of worsening was 18% (95% CI: 14%-25%) among nonproliferative diabetic retinopathy eyes and 31% (95% CI: 23%-42%) among proliferative diabetic retinopathy eyes (P = 0.01). In Years 1, 3, and 5, the mean (SD) number of ranibizumab injections was 8.1 (2.5), 2.2 (2.6), and 1.8 (2.6) for nonproliferative diabetic retinopathy eyes, and 9.0 (2.8), 2.3 (2.9), and 1.7 (2.6) for proliferative diabetic retinopathy eyes, respectively. Proportions with improvement or rates of worsening did not change with time. CONCLUSION: Individuals receiving ranibizumab therapy for diabetic macular edema may have favorable changes in DR severity throughout a 5-year period concomitant with sequential reduction in anti-vascular endothelial growth factor therapy.

Factors Associated with Worsening Proliferative Diabetic Retinopathy in Eyes Treated with Panretinal Photocoagulation or Ranibizumab.

PURPOSE: To compare rates and identify predictive factors for events that represent worsening of proliferative diabetic retinopathy (PDR) in eyes treated with panretinal photocoagulation (PRP) or ranibizumab. DESIGN: Randomized clinical trial (55 United States sites). PARTICIPANTS: Three hundred ninety-four study eyes from 305 adults with PDR, visual acuity (VA) 20/320 or better, and no history of PRP. INTERVENTION: Panretinal photocoagulation or intravitreous ranibizumab injections (0.5 mg/0.05 ml). MAIN OUTCOME MEASURES: Time from randomization to a composite PDR-worsening outcome defined as the first occurrence of vitreous hemorrhage, retinal detachment, anterior segment neovascularization, or neovascular glaucoma. RESULTS: Through 2 years, the cumulative probability of worsening PDR was 42% (PRP) versus 34% (ranibizumab; hazard ratio [HR], 1.33; 99% confidence interval [CI], 0.90 to 1.98; P = 0.063). Worse baseline levels of diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study scale) were associated with increased risk of worsening PDR, regardless of treatment group (64% [high-risk PDR or worse] vs. 23% [moderate PDR or better]; HR, 3.97; 99% CI, 2.48 to 6.36; P < 0.001). In the PRP group, eyes receiving pattern scan versus conventional single-spot PRP also were at higher risk for worsening PDR (60% vs. 39%; HR, 2.04; 99% CI, 1.02 to 4.08; P = 0.008), regardless of the number of spots placed or the number of sittings to complete the initial PRP. Eyes in both groups with vision-impairing (VA 20/32 or worse) center-involved diabetic macular edema (DME) at baseline were required to receive ranibizumab for center-involved DME. Therefore the composite outcome was compared by treatment in the subgroup of eyes that did not have vision-impairing center-involved DME at baseline. For these eyes, the rate of PDR-worsening was greater with PRP than ranibizumab (45% vs. 31%; HR, 1.62; 99% CI, 1.01 to 2.60; P = 0.008). CONCLUSIONS: In eyes with PDR, ranibizumab resulted in less PDR worsening compared with PRP, especially in eyes not required to receive ranibizumab for center-involved DME. Although anti-vascular endothelial growth factor therapy requires a more frequent visit schedule than PRP, these findings provide additional evidence supporting the use of ranibizumab as an alternative therapy to PRP for PDR, at least through 2 years.

Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial.

PURPOSE: To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. DESIGN: Randomized clinical trial. PARTICIPANTS: Six hundred sixty participants with visual acuity (VA) impairment from DME. METHODS: Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. MAIN OUTCOME MEASURES: Change in VA, adverse events, and retreatment frequency. RESULTS: Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P < 0.001; aflibercept vs. ranibizumab, P = 0.04; bevacizumab vs. ranibizumab, P = 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA (P = 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P = 0.02; aflibercept vs. ranibizumab, P = 0.18; ranibizumab vs. bevacizumab, P = 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). CONCLUSIONS: All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials.

EFFECTIVENESS OF DIFFERENT MONITORING MODALITIES IN THE DETECTION OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Home Study, Report Number 3.

PURPOSE: To determine the effectiveness of different monitoring modalities to detect incident neovascularization associated with age-related macular degeneration (AMD). METHODS: Secondary analyses compared the rates of detecting incident neovascular AMD in prescheduled office visits versus office visits triggered by monitoring device or by symptom realization in a randomized trial evaluating home telemonitoring device plus standard care (device arm) versus standard care alone. RESULTS: At prescheduled office visits, neovascular AMD was detected in 14/1927 visits (0.7%, 95% confidence interval [CI]: 0.4%-1.1%) and 14/1949 visits (0.7%, 95% CI: 0.3%-1.1%) in the device and standard care alone arms, respectively. Thirty-seven participants with neovascular AMD were detected in 318 office visits (11.6%, 95% CI: 8.1%-15.2%) triggered by device or symptom realization and 17 neovascular AMD in 65 office visits (26%, 95% CI: 15.5%-36.8%) triggered by symptom realization in the device and standard care alone arms, respectively. The home device strategy had a higher neovascular-AMD detection rate than prescheduled office visits (relative risk = 16.0 [95% CI: 8.8-29.3]). Neovascular AMD detected at triggered visits were associated with less vision loss from baseline in the device arm versus standard care alone arm (-3 letters vs. -11.5 letters, respectively, P = 0.03). CONCLUSION: Telemonitoring may alter the management of patients with AMD and improve vision outcomes.

Vision-threatening lesions developing with longer-term follow-up after treatment of neovascular age-related macular degeneration.

PURPOSE: To assess the development of vision-threatening lesions at least 3.5 years after initiating anti-vascular endothelial growth factor (VEGF) for choroidal neovascularization (CNV) in eyes with age-related macular degeneration (AMD). DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 75 patients (81 eyes) with CNV secondary to AMD who received intravitreous anti-VEGF treatment and were followed for at least 3.5 years after initiating treatment. METHODS: Retrospective record review of patients initiating anti-VEGF treatment between November 2005 and June 2008 at a university-based institution for whom at least 3.5 years of follow-up was available at the same institution. MAIN OUTCOME MEASURES: Predominantly hemorrhagic lesions or geographic atrophy (GA). RESULTS: Among 75 patients (81 eyes; 59% were women; median age, 78 years), mean follow-up was 4.9 years and at least 6 years for 40%. Median visual acuity (VA) was 20/80 (interquartile range [IQR], 20/50-20/100) initially, 20/63 (IQR, 20/40-20/160) at 2 years, 20/80 (IQR, 20/40-20/200) at 3.5 years, and 20/63 (IQR 20/32-20/200) at 6 years. Six eyes (7%) had predominantly hemorrhagic lesions initially, whereas this developed in an additional 3 eyes (4%, 95% confidence interval [CI], 1% to 10%) in 3.5 years and in 1 additional eye (1%, 95% CI, 0.03% to 7%) at more than 3.5 years of follow-up. Initially, GA within or overlapping the boundary of the entire CNV was present in 4 eyes (5%) and outside this boundary in 8 eyes (10%). Geographic atrophy enlarged in each eye over time. The only eyes that developed GA outside the CNV boundary were those that had GA outside the lesion at baseline. Additional atrophy within the boundary of CNV defined at baseline, termed "atrophic disciform scars," developed in 5 eyes (6%), all within 4 years of treatment initiation. CONCLUSIONS: Longer-term follow-up of neovascular AMD managed with anti-VEGF therapy suggests that predominantly hemorrhagic lesions may develop within 3.5 years of initiating therapy and more than 3.5 years after initiating therapy. In contrast, new areas of GA beyond the boundaries of the CNV lesion as defined at initiation of anti-VEGF therapy seem unlikely to develop if there is no GA outside of the CNV lesion initially.

RANIBIZUMAB PLUS PROMPT OR DEFERRED LASER FOR DIABETIC MACULAR EDEMA IN EYES WITH VITRECTOMY BEFORE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

BACKGROUND: The approach to managing diabetic macular edema in eyes with previous vitrectomy is based on limited evidence. Therefore, an exploratory post hoc assessment of 3-year data from eyes with and without vitrectomy before randomization in a DRCR.net trial that evaluated ranibizumab + prompt or deferred laser for diabetic macular edema is presented. METHODS: Visual acuity and optical coherence tomography outcomes were compared between eyes with and without previous vitrectomy. RESULTS: At baseline, eyes with previous vitrectomy (n = 25) had longer duration of diabetes, worse visual acuity, less thickened central subfield measurements on optical coherence tomography and were more apt to have worse diabetic retinopathy severity level or previous treatment for macular edema or cataract surgery than eyes without a history of vitrectomy (n = 335). Analyses adjusted for these baseline imbalances did not identify substantial differences between eyes with and without previous vitrectomy at each annual visit through 3 years for the favorable visual acuity, optical coherence tomography central subfield thickness, or volume outcomes, although optical coherence tomography improvement appeared slower in vitrectomy eyes during the first year. CONCLUSION: This study provides little evidence that the beneficial clinical outcomes for patients with center-involved diabetic macular edema treated with anti-vascular endothelial growth factor are affected in the long term by previous vitrectomy.

Randomized trial of a home monitoring system for early detection of choroidal neovascularization home monitoring of the Eye (HOME) study.

OBJECTIVE: To determine whether home monitoring with the ForeseeHome device (Notal Vision Ltd, Tel Aviv, Israel), using macular visual field testing with hyperacuity techniques and telemonitoring, results in earlier detection of age-related macular degeneration-associated choroidal neovascularization (CNV), reflected in better visual acuity, when compared with standard care. The main predictor of treatment outcome from anti-vascular endothelial growth factor (VEGF) agents is the visual acuity at the time of CNV treatment. DESIGN: Unmasked, controlled, randomized clinical trial. PARTICIPANTS: One thousand nine hundred and seventy participants 53 to 90 years of age at high risk of CNV developing were screened. Of these, 1520 participants with a mean age of 72.5 years were enrolled in the Home Monitoring of the Eye study at 44 Age-Related Eye Disease Study 2 clinical centers. INTERVENTIONS: In the standard care and device arms arm, investigator-specific instructions were provided for self-monitoring vision at home followed by report of new symptoms to the clinic. In the device arm, the device was provided with recommendations for daily testing. The device monitoring center received test results and reported changes to the clinical centers, which contacted participants for examination. MAIN OUTCOME MEASURES: The main outcome measure was the difference in best-corrected visual acuity scores between baseline and detection of CNV. The event was determined by investigators based on clinical examination, color fundus photography, fluorescein angiography, and optical coherence tomography findings. Masked graders at a central reading center evaluated the images using standardized protocols. RESULTS: Seven hundred sixty-three participants were randomized to device monitoring and 757 participants were randomized to standard care and were followed up for a mean of 1.4 years between July 2010 and April 2013. At the prespecified interim analysis, 82 participants progressed to CNV, 51 in the device arm and 31 in the standard care arm. The primary analysis achieved statistical significance, with the participants in the device arm demonstrating a smaller decline in visual acuity with fewer letters lost from baseline to CNV detection (median, -4 letters; interquartile range [IQR], -11.0 to -1.0 letters) compared with standard care (median, -9 letters; IQR, -14.0 to -4.0 letters; P = 0.021), resulting in better visual acuity at CNV detection in the device arm. The Data and Safety Monitoring Committee recommended early study termination for efficacy. CONCLUSIONS: Persons at high risk for CNV developing benefit from the home monitoring strategy for earlier detection of CNV development, which increases the likelihood of better visual acuity results after intravitreal anti-VEGF therapy.

Visual acuity after cataract surgery in patients with age-related macular degeneration: age-related eye disease study 2 report number 5.

OBJECTIVE: To evaluate visual acuity outcomes after cataract surgery in persons with varying degrees of severity of age-related macular degeneration (AMD). DESIGN: Cohort study. PARTICIPANTS: A total of 1232 eyes of 793 participants who underwent cataract surgery during the Age-Related Eye Disease Study 2, a prospective, multicenter, randomized controlled trial of nutritional supplements for treatment of AMD. METHODS: Preoperative and postoperative characteristics of participants who underwent cataract extraction during the 5-year trial were analyzed. Both clinical data and standardized red-reflex lens and fundus photographs were obtained at baseline and annually. Photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Cataract surgery was documented at annual study visits or by history during the 6-month telephone calls. Analyses were conducted using multivariate repeated-measures regression. MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. RESULTS: Adjusting for age at time of surgery, gender, interval between preoperative and postoperative visits, and type and severity of cataract, the mean changes in visual acuity were as follows: eyes with mild AMD (n = 30) gained 11.2 letters (95% confidence interval [CI], 6.9-15.5), eyes with moderate AMD (n = 346) gained 11.1 letters (95% CI, 9.1-13.2), eyes with severe AMD (n = 462) gained 8.7 letters (95% CI, 6.7-10.7), eyes with noncentral geographic atrophy (n = 70) gained 8.9 letters (95% CI, 5.8-12.1), and eyes with advanced AMD (central geographic atrophy, neovascular disease, or both; n = 324) gained 6.8 letters (95% CI, 4.9-8.8). The visual acuity gain across all AMD severity groups was statistically significant from preoperative values (P < 0.0001). CONCLUSIONS: Mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity.

Ranibizumab for macular telangiectasia type 2 in the absence of subretinal neovascularization.

PURPOSE: To evaluate the effects of 0.3 mg or 0.5 mg of ranibizumab in eyes with macular telangiectasia type 2 without subretinal neovascularization. METHODS: Ten eyes were randomized to either 0.3 mg or 0.5 mg ranibizumab group in 1 eye only. Study eye received ranibizumab at baseline and at Months 1 and 2. Injections at Months 3, 4, and 5 were at investigator's discretion. Participants were followed monthly through 6 months with best-corrected visual acuity, fluorescein angiography, and optical coherence tomography. RESULTS: For study eyes at baseline, median best-corrected visual acuity letter score was 60 (20/64 Snellen equivalent) and central subfield retinal thickness was 181.5 µm. Median number of injections was six. Median change in best-corrected visual acuity at Month 3 was 4 letters (range: -5 to 9 letters) at both doses in the study eye and 3 letters (range: -10 to 5 letters) in the untreated fellow eye. At Month 3, retinal leakage decreased 0.87 disk area and 0.76 disk area for 0.3 mg and 0.5 mg ranibizumab, respectively. Median change in central subfield retinal thickness was 1 µm and -11 µm for 0.3 mg and 0.5 mg ranibizumab, respectively. CONCLUSION: Ranibizumab (0.3 mg or 0.5 mg) decreases leakage secondary to macular telangiectasia type 2, but accompanying improvements in best-corrected visual acuity appear similar to improvements in the untreated fellow eye where retinal thickness is relatively unchanged.

Retinal characteristics in eyes with pathologic myopia among individuals self-identifying as Black.

OBJECTIVE: Investigate retinal characteristics of pathologic myopia (PM) among patients self-identifying as Black. DESIGN: Retrospective cohort single-institution retrospective medical record review. METHODS: Adult patients between January 2005 and December 2014 with International Classification of Diseases (ICD) codes consistent with PM and given 5-year follow-up were evaluated. The Study Group consisted of patients self-identifying as Black, and the Comparison Group consisted of those not self-identifying as Black. Ocular features at study baseline and 5-year follow-up visit were evaluated. RESULTS: Among 428 patients with PM, 60 (14%) self-identified as Black and 18 (30%) had baseline and 5-year follow-up visits. Of the remaining 368 patients, 63 were in the Comparison Group. For the study (n = 18) and Comparison Group (n = 29), median (25th percentile, 75th percentile) baseline visual acuity was 20/40 (20/25, 20/50) and 20/32 (20/25, 20/50) in the better-seeing eye and 20/70 (20/50, 20/1400) and 20/100 (20/50, 20/200), respectively, in the worse-seeing eye. In the eyes that did not have choroidal neovascularization (CNV) in the study and Comparison Group, median study baseline optical coherence tomography central subfield thickness was 196 µm (169, 306 µm) and 225 µm (191, 280 µm), respectively, in the better-seeing eye and 208 µm (181, 260 µm) and 194 µm (171, 248 µm), respectively, in the worse-seeing eye. Baseline prevalence of CNV was 1 Study Group eye (3%) and 20 Comparison Group eyes (34%). By the 5-year visit, zero (0%) and 4 (15%) additional eyes had CNV in the study and Comparison Group, respectively. CONCLUSION: These findings suggest that the prevalence and incidence of CNV may be lower in patients with PM self-identifying as Black when compared with individuals of other races.

Severe Intraocular Inflammation Following Intravitreal Faricimab.

Importance: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. Objective: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. Design, Setting, and Participants: In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Exposure: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Main Outcomes and Measures: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. Results: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. Conclusions and Relevance: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema: The INSIGHT Randomized Clinical Trial.

Importance: Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME). Objective: To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME. Design, Setting, and Participants: This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021. Interventions: Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52. Main Outcomes and Measures: The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs). Results: A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) µm vs -124 (7) µm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 µm; 90% CI, -3 to 26 µm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms. Conclusions and Relevance: MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept. Trial Registration: ClinicalTrials.gov Identifier: NCT03610646.

Long-term follow-up of vascular endothelial growth factor inhibitor therapy for neovascular age-related macular degeneration.

PURPOSE OF REVIEW: To discuss the most recent literature regarding the long-term use (≥52 weeks of follow-up) of antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (NVAMD). RECENT FINDINGS: Intravitreal ranibizumab has been demonstrated to provide outstanding vision outcomes relative to the standard therapy in patients with NVAMD. The VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD studies showed that patients managed with intravitreal aflibercept achieved visual acuity and anatomic improvements similar to individuals managed with monthly ranibizumab while receiving an average of five fewer injections during the first 12 months of treatment. In the Comparison of AMD Treatment Trials, intravitreal bevacizumab dosed monthly met noninferiority to ranibizumab monthly, as well as noninferiority to ranibizumab dosed as-needed with respect to change in visual acuity 1 year after the treatment initiation. Furthermore, patients switched to as-needed regimens in their second year of follow-up from monthly dosing during the first year demonstrated an incremental loss of visual acuity during the second year of follow-up irrespective of the drug used. To date, trials evaluating anti-VEGF therapy for NVAMD demonstrate a low incidence of serious ocular or systemic adverse events. However, the potential for deleterious effects of long-term (beyond 2 years) pan-VEGF blockade remains unknown. SUMMARY: Patients with NVAMD enjoy heretofore unprecedented vision gains when managed with anti-VEGF therapy, and the limited body of evidence to date regarding long-term anti-VEGF treatment shows these vision gains can be maintained through 2 years. Further investigation is needed to explore the effects of long-term anti-VEGF therapy beyond 2 years.

Green or yellow laser treatment for diabetic macular edema: exploratory assessment within the Diabetic Retinopathy Clinical Research Network.

PURPOSE: Explore differences in green compared with yellow focal/grid laser treatment on functional and anatomical endpoints in eyes with diabetic macular edema. METHODS: Data from two randomized clinical trials were evaluated for differences in visual acuity and optical coherence tomography parameters for eyes assigned to sham injection + prompt laser, ranibizumab + prompt laser, or prompt laser only: among subgroups of eyes treated exclusively and electively with either green or yellow laser. RESULTS: In the sham injection + prompt laser group, the mean visual acuity letter score change for eyes receiving green and yellow laser treatment, respectively, was +2.4 ± 14 and +5.1 ± 13 at the 52-week visit (P = 0.06) and +2.4 ± 15 and +6.0 ± 13 at the 104-week visit (P = 0.13), with no corresponding evidence of differences in optical coherence tomography thickness. When comparing wavelength groups in the ranibizumab + prompt laser and prompt laser-only groups, meaningful differences in visual acuity and optical coherence tomography thickness were not detected at 1 year or 2 years. CONCLUSION: A trend toward improved vision outcome with yellow laser observed in one trial was not corroborated by anatomical outcomes or by the other trial. In this study, without random assignment to different wavelengths controlling for bias and confounding, it is not possible to determine whether one wavelength is better than the other.

Accuracy of Artificial Intelligence in Estimating Best-Corrected Visual Acuity From Fundus Photographs in Eyes With Diabetic Macular Edema.

Importance: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely. Objective: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information. Design, Setting, and Participants: Deidentified color fundus images taken after dilation were used post hoc to train AI systems to perform regression from image to BCVA and to evaluate resultant estimation errors. Participants were patients enrolled in the VISTA randomized clinical trial through 148 weeks wherein the study eye was treated with aflibercept or laser. The data from study participants included macular images, clinical information, and BCVA scores by trained examiners following protocol refraction and VA measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Main Outcomes: Primary outcome was regression evaluated by mean absolute error (MAE); the secondary outcome included percentage of predictions within 10 letters, computed over the entire cohort as well as over subsets categorized by baseline BCVA, determined from baseline through the 148-week visit. Results: Analysis included 7185 macular color fundus images of the study and fellow eyes from 459 participants. Overall, the mean (SD) age was 62.2 (9.8) years, and 250 (54.5%) were male. The baseline BCVA score for the study eyes ranged from 73 to 24 letters (approximate Snellen equivalent 20/40 to 20/320). Using ResNet50 architecture, the MAE for the testing set (n = 641 images) was 9.66 (95% CI, 9.05-10.28); 33% of the values (95% CI, 30%-37%) were within 0 to 5 letters and 28% (95% CI, 25%-32%) within 6 to 10 letters. For BCVA of 100 letters or less but more than 80 letters (20/10 to 20/25, n = 161) and 80 letters or less but more than 55 letters (20/32 to 20/80, n = 309), the MAE was 8.84 letters (95% CI, 7.88-9.81) and 7.91 letters (95% CI, 7.28-8.53), respectively. Conclusions and Relevance: This investigation suggests AI can estimate BCVA directly from fundus photographs in patients with DME, without refraction or subjective visual acuity measurements, often within 1 to 2 lines on an ETDRS chart, supporting this AI concept if additional improvements in estimates can be achieved.