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Key Points: Question: In patients with nonproliferative diabetic retinopathy (NPDR) and good vision but without center-involved diabetic macular edema (CI-DME), does early aflibercept reduce disease progression and improve long-term visual acuity compared with initial observation and treatment only if disease worsens? Findings: This study presents 4-year primary outcomes of a randomized clinical trial that included 328 patients (399 eyes), randomized to 2.0 mg aflibercept injections or sham injections. Among those receiving aflibercept, proliferative diabetic retinopathy or CI-DME developed in 33.9% vs 56.9% among those who received sham—a difference that was statistically significant. Change in visual acuity was −2.7 vs −2.4 letters, a difference that was not statistically significant. Meaning: At 4 years, treatment of NPDR with aflibercept vs sham treatment resulted in statistically significant anatomic improvement, but no improvement in visual acuity. Importance: Anti–vascular endothelial growth factor (VEGF) injections in eyes with nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) reduce development of vision-threatening complications from diabetes over at least 2 years, but whether this treatment has a longer-term benefit on visual acuity is unknown. Objective: To compare the primary 4-year outcomes of visual acuity and rates of vision-threatening complications in eyes with moderate to severe NPDR treated with intravitreal aflibercept compared with sham. The primary 2-year analysis of this study has been reported. Design, Setting, and Participants: Randomized clinical trial conducted at 64 clinical sites in the US and Canada from January 2016 to March 2018, enrolling 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study [ETDRS] severity level 43-53; range, 0 [worst] to 100 [best]) without CI-DME. Interventions: Eyes were randomly assigned to 2.0 mg aflibercept (n = 200) or sham (n = 199). Eight injections were administered at defined intervals through 2 years, continuing quarterly through 4 years unless the eye improved to mild NPDR or better. Aflibercept was given in both groups to treat development of high-risk proliferative diabetic retinopathy (PDR) or CI-DME with vision loss. Main Outcomes and Measures: Development of PDR or CI-DME with vision loss (≥10 letters at 1 visit or ≥5 letters at 2 consecutive visits) and change in visual acuity (best corrected ETDRS letter score) from baseline to 4 years. Results: Among participants (mean age 56 years; 42.4% female; 5% Asian, 15% Black, 32% Hispanic, 45% White), the 4-year cumulative probability of developing PDR or CI-DME with vision loss was 33.9% with aflibercept vs 56.9% with sham (adjusted hazard ratio, 0.40 [97.5% CI, 0.28 to 0.57]; P <.001). The mean (SD) change in visual acuity from baseline to 4 years was −2.7 (6.5) letters with aflibercept and −2.4 (5.8) letters with sham (adjusted mean difference, −0.5 letters [97.5% CI, −2.3 to 1.3]; P =.52). Antiplatelet Trialists' Collaboration cardiovascular/cerebrovascular event rates were 9.9% (7 of 71) in bilateral participants, 10.9% (14 of 129) in unilateral aflibercept participants, and 7.8% (10 of 128) in unilateral sham participants. Conclusions and Relevance: Among patients with NPDR but without CI-DME at 4 years treatment with aflibercept vs sham, initiating aflibercept treatment only if vision-threatening complications developed, resulted in statistically significant anatomic improvement but no improvement in visual acuity. Aflibercept as a preventive strategy, as used in this trial, may not be generally warranted for patients with NPDR without CI-DME. Trial Registration: ClinicalTrials.gov Identifier: NCT02634333 This randomized clinical trial analyzes the effects of aflibercept injections vs sham for reducing disease progression and improving long-term visual acuity in patients with nonproliferative diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Importance: Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown.Objective: To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy.Design, Setting, and Participants: Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020.Interventions: Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria.Main Outcomes and Measures: The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years.Results: Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept.Conclusions and Relevance: Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation.Trial Registration: ClinicalTrials.gov Identifier: NCT02858076. [ABSTRACT FROM AUTHOR]

Importance: Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME [CI-DME]) with visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown.Objective: To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation.Design, Setting, and Participants: Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018.Interventions: Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (≥ 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits.Main Outcomes and Measures: The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists' Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported.Results: Among 702 randomized participants (mean age, 59 years; 38% female [n=264]), 625 of 681 (92% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25% (60/240) and 34% (80/236) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16% (33/205), 17% (36/212), and 19% (39/208) in the aflibercept, laser photocoagulation, and observation groups, respectively (aflibercept vs laser photocoagulation risk difference, -2% [95% CI, -9% to 5%]; relative risk, 0.88 [95% CI, 0.57-1.35; P = .79]; aflibercept vs observation risk difference, -3% [95% CI, -11% to 4%]; relative risk, 0.83 [95% CI, 0.55-1.27; P = .79]; laser photocoagulation vs observation risk difference, -1% [95% CI, -9% to 6%]; relative risk, 0.95 [95% CI, 0.64-1.41; P = .79]). Antiplatelet Trialists' Collaboration vascular events occurred in 15 (7%), 13 (5%), and 8 (3%) participants in the aflibercept, laser photocoagulation, and observation groups.Conclusions and Relevance: Among eyes with CI-DME and good visual acuity, there was no significant difference in vision loss at 2 years whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. Observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME.Trial Registration: ClinicalTrials.gov Identifier: NCT01909791. [ABSTRACT FROM AUTHOR]

Background and Methods: We performed a randomized controlled clinical trial to assess the safety and efficacy of a 1 [mu]g/h ganciclovir implant for the treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients with previously untreated peripheral CMV retinitis were randomly assigne(i either to immediate treatment with the ganciclovir implant or to deferred treatment. Standardized fundus photographs were taken at 2-week intervals and analyze(i in a masked faswon. The study end point was progression of retinitis based on the photographic assessment. Results: Twenty-six patients (30 eyes) were enrolled. The median time to progression of retinitis was 15 days in the defferred treatment group (n=16) vs 226 days in the immediate treatment group (n=14) (P

Objective To investigate the efficacy of verteporfin and photodynamic therapy in the treatment of large retinal capillary hemangiomas. Methods Case reports of 3 patients with large retinal capillary hemangiomas treated with photodynamic therapy using verteporfin. Standard verteporfin dosages (6 mg/m2 of body surface area) were given. Both standard and modified photodynamic protocols were followed. Modified protocols included shorter verteporfin infusion times and longer light exposure times. Results Pretreatment best-corrected Snellen visual acuity of the 3 affected eyes were 20/100, 20/50, and 2/200, respectively. All cases had associated exudative retinal detachments involving the macula. Cases 1 and 2 were classic endophytic retinal capillary hemangiomas. Case 3 was a reactive retinal capillary hemangioma. Case 1 had 2 photodynamic therapy treatments, and after 8 months, visual acuity improved to 20/40. Two years after initiating photodynamic therapy, the visual acuity was 20/30 and there was no reperfusion of the hemangioma. Case 2 had 3 photodynamic therapy treatments. The hemangioma was fibrotic, and 20 months after initiating photodynamic therapy visual acuity improved to 20/30. Case 3 had 1 treatment, 11 weeks later and visual acuity improved to 20/400. Four months after treatment, visual acuity returned to counting fingers because of tractional elevation of the macula as the capillary hemangioma fibrosed. Vitrectomy surgery was performed, and choroidal and retinal neovascularization was discovered. Three months after vitrectomy visual acuity was 20/400. In cases 1 and 2, the capillary hemangioma ultimately regressed, and the exudative detachment resolved. Conclusions Verteporfin and photodynamic therapy were effective in achieving closure of large retinal capillary hemangiomas. In all cases, the hemangioma underwent fibrosis with consequent macular puckering due to retinal traction. In all cases, the visual acuity improved. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Cost-related motivations for conducting research: Participants should be informed," by R.K. Nayak and colleagues.

Importance: Although anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration (AMD) results in improved vision overall, loss of substantial vision can occur. Understanding the processes that lead to loss of vision may lead to preventive strategies., Objective: To determine the incidence, characteristics, causes, and baseline predictors of sustained visual acuity loss after 2 years of treatment with ranibizumab or bevacizumab for neovascular AMD., Design, Setting, and Participants: A cohort study within a randomized clinical trial of participants in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)., Interventions: Participants were randomly assigned to treatment with ranibizumab or bevacizumab and to 2 years of monthly or as needed injections or monthly injections for 1 year and as needed injections the following year., Main Outcomes and Measures: Sustained visual acuity loss, defined as loss of 15 or more letters from baseline at weeks 88 and 104., Results: Among 1030 participants, 61 eyes (5.9%) developed sustained visual acuity loss in 2 years. Within this group, visual acuity decreased gradually over time, with a mean decrease of 2, 19, and 33 letters from baseline at 4 weeks, 1 year, and 2 years, respectively. At 2 years, eyes with sustained visual acuity loss had more scarring (60.0% vs 41.4%, P = .007), more geographic atrophy (GA) (31.6% vs 20.7%, P = .004), larger lesions (16 vs 8 mm2, P < .001), and higher proportions of intraretinal fluid (82.5% vs 51.0%, P < .001), subretinal hyperreflective material (84.5% vs 44.2%, P < .001), retinal thinning (43.3% vs 23.0%, P < .001), and thickening (20.0% vs 12.1%, P < .001). Likely causes of sustained visual acuity loss included foveal scarring (44.3%), pigmentary abnormalities (27.9%), and foveal GA (11.5%). Baseline factors independently associated with a higher incidence of sustained visual acuity loss were the presence of nonfoveal GA (odds ratio [OR],  2.86; 95% CI, 1.35-6.08; P = .006), larger area of choroidal neovascularization (OR for a >4-disc area vs ≤1-disc area, 3.91; 95% CI, 1.70-9.03; P = .007), and bevacizumab treatment (OR,  1.83; 95% CI, 1.07-3.14; P = .03)., Conclusions and Relevance: Sustained visual acuity loss was relatively rare in CATT. The development of foveal scar, pigmentary abnormalities, or GA contributed to most of the sustained visual acuity loss. Risk was 3% higher among eyes treated with bevacizumab. Treatment that targeted the prevention of scarring or GA may improve vision outcomes., Trial Registration: clinicaltrials.gov Identifier: NCT00593450.