Importance Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes and decreased treatment burden. Objective To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD. Design, Setting, and Participants The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021. Interventions Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 μL) or 2 mg (50 μL) of aflibercept followed by doses at weeks 20 and 32. Main Outcomes and Measures Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety. Results All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n = 53), or aflibercept, 2 mg (n = 53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n = 27) vs 34.0% (n = 18) (difference, 17.0 [95% CI, –1.6 to 35.5] percentage points; P = .08) at week 16 and 39.6% (n = 21) vs 28.3% (n = 15) (difference, 11.3 [95% CI, –6.6 to 29.2] percentage points; nominal P = .22) at week 44. At week 44, mean (SE) change in central retinal thickness was –159.4 (16.4) vs –137.2 (22.8) μm with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, –9.5 [95% CI, –51.4 to 32.4]; nominal P = .65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 [95% CI, –1.4 to +7.0]; nominal P = .20). No differences in safety profiles between the groups were observed. Conclusions and Relevance Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema. Trial Registration ClinicalTrials.gov Identifier: NCT04126317

Patients with neovascular age-related macular degeneration who developed endophthalmitis after an intravitreal anti–vascular endothelial growth factor injection required less frequent treatment for neovascular age-related macular degeneration after the resolution of the infection. In 13.3% of patients, the neovascular age-related macular degeneration became quiescent, but most patients had better anatomical and functional outcomes if treatment was reinitiated. Purpose: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections. Methods: Multicenter, retrospective series. Results: From April 2013 to October 2018, 196,598 intravitreal anti–vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001). Conclusion: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

Purpose: To report mortality of patients who were eligible for enrollment in the Collaborative Ocular Melanoma Study (COMS) clinical trials of medium-sized choroidal melanoma or large-sized choroidal melanoma but chose to defer treatment or receive no melanoma treatment. Design: Prospective nonrandomized multicenter cohort study as an adjunct to COMS randomized clinical trials. Methods: Patient follow-up procedures included examinations, correspondence, telephone contacts, and National Death Index searches. Primary outcome was patient death measured by all-cause mortality. Secondary outcomes were melanoma treatment and melanoma metastasis. Results: Of 77 patients eligible for COMS clinical trials who chose to defer or receive no melanoma treatment, 61 were appropriate candidates and 45 (74%) enrolled in the natural history study (NHS). In all, 42 patients (42 eyes) had medium melanoma, and the median follow-up was 5.3 years (range, 4-10.7 years). In all, 22 patients (52%) had subsequent melanoma treatment, and 20 (48%) had no melanoma treatment. For the 42 patients, Kaplan-Meier estimate of 5-year mortality was approximately 30% [95% confidence interval (CI), 18%-47%]. For COMS medium melanoma trial, 5-year mortality was 18% (95% CI, 16%-20%), not statistically significantly different from the NHS patients. After adjusting for differences in age and longest basal diameter, the 5-year risk of death for NHS patients versus COMS trial patients was 1.54 (95% CI, 0.93-2.56). Three patients had large melanoma. Melanoma metastasis was confirmed or suspected in 8 (42%) of 19 deaths. Conclusion: Greater mortality and higher risk of death for NHS patients are probative but not conclusive evidence of a beneficial, life-extending effect of medium melanoma treatment.

Purpose: To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery.Design: Retrospective case series.Subjects: Eleven eyes of 6 patients from 6 different institutions.Methods: Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis.Main Outcome Measures: Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes.Results: Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes.Conclusions: Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma. (C) 2015 by the American Academy of Ophthalmology.

PURPOSE:To determine the safety and efficacy of bovine hydroxyapatite as an orbital implant material.METHODS:Prospective, consecutive case series of patients undergoing enucleation, evisceration, or secondary orbital implantation. A motility peg was placed in all consenting candidates. Patients were followed 1 week, 1 month, and several months after surgery for signs of inflammation, infection, extrusion, or other complication.RESULTS:Twenty-seven patients received a bovine hydroxyapatite orbital implant. Magnetic resonance imaging was obtained in 3 patients (3 orbits) approximately 4 weeks after surgery and showed signs of peripheral fibrovascular ingrowth in all three cases. Magnetic resonance imaging was obtained in 9 patients (9 orbits) 4 to 12 months after surgery and showed signs of incomplete fibrovascular ingrowth in 1 of 9 (11%) cases, subtotal fibrovascular ingrowth in 2 of 9 (22%) cases, and complete fibrovascular ingrowth in 6 of 9 (67%) of cases. Complications included postoperative chemosis in 3 cases (11%) and exposure requiring reoperation in 2 cases (7%). Motility peg placement was performed successfully in 5 patients (5 orbits).CONCLUSIONS:Bovine hydroxyapatite appears to be a safe and effective orbital implant material. The material appears to be biocompatible and nonallergenic. Bovine hydroxyapatite allows for fibrovascular integration and motility peg placement.

Acquired immune deficiency syndrome (AIDS) is associated with a wide spectrum of systemic and ocular infectious diseases. Little information is known about herpes simplex virus type 1 (HSV-1) keratoconjunctivitis in association with AIDS. The authors present six cases of recurrent HSV keratitis occurring in AIDS patients. Features of the herpetic keratitis in these patients included unilateral dendritic or geographic epithelial keratopathy; predilection for peripheral versus central corneal involvement; one to three recurrences per patient over a mean observation period of 17 months, with a median dendritefree interval of 7 months; and a moderately prolonged clinical course with a median healing time of 3 weeks using topical antiviral therapy. Only one of six cases had stromal infiltrative involvement. These cases raise the question of whether the immunologic abnormalities associated with AIDS may affect the clinical characteristics and course of HSV keratitis.