Purpose: To evaluate the safety and efficacy of multiwavelength photobiomodulation (PBM) in nonexudative (dry) age-related macular degeneration (AMD). Methods: LIGHTSITE III used a double-masked, randomized, sham-controlled, parallel-group, prospective study design. Subjects were enrolled with a diagnosis of dry AMD and treated with multiwavelength PBM (Valeda Light Delivery System; 590, 660, and 850 nm) or sham treatment. A treatment series included 9 PBM or sham treatments delivered 3x/week over 3 to 5 weeks every 4 months (M) for 24M. Results: A total of 148 eyes (100 subjects) with dry AMD were randomized into the study. LIGHTSITE III met the prespecified primary BCVA efficacy end point at M21 with a significant difference between treatment groups ( P = 0.0036) and a +6.2 letter gain after PBM. At M21, 61.5% of PBM-treated eyes showed ≥5, 23.1% showed ≥10, and 4.4% showed ≥15 letter gains. A favorable safety profile was observed with no signs of phototoxicity. Disease progression to Geographic Atrophy (GA) showed a significant decrease in incidence (Sham, 24.0% vs. PBM, 6.8%; P = 0.007) after PBM treatment at M24. Significant benefit in vision QoL was observed. Conclusion: Multiwavelength PBM represents an interventional therapy that restores visual function and has potential disease-modifying effects in intermediate dry AMD.

Purpose: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) AMD using the LumiThera Valeda ® Light Delivery System. Methods: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were treated with multiwavelength PBM (590, 660 and 850 nm) or Sham treatment delivered 9 treatments over 3-5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. Results: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy BCVA endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 - -0.1, p = 0.02)(PBM alone: 5.4 letters (SE 0.96), CI: 3.5 - 7.3, p < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7 - 5.2, p < 0.0001). The PBM group showed a significant decrease in new onset GA (p = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. Conclusions: LIGHTSITE III provides a prospective, randomized controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM.

To obtain physicians’ “real-world” perspectives on early experiences with triamcinolone acetonide suprachoroidal injection (SCS-TA) for treatment of patients with uveitic macular edema (UME). Twelve retina/uveitis specialists in the United States were surveyed about SCS-TA injection procedure and patient outcomes. Survey participants administered ≥ 291 SCS-TA injections to 243 patients with UME with various disease characteristics (etiologies, chronicity, and anatomical subtypes). Commonly reported reasons for SCS-TA adoption included potential for lowering the risk of steroid-associated intraocular pressure elevations versus intravitreal injections or implants (100

Importance Despite the effectiveness of existing anti-vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME). Objective To evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME. Design, Participants, and Setting This 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021. Intervention Brolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks. Main Outcomes and Measures Participants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52. Results A total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, -0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, -237.8 μm; aflibercept, -196.5 μm; difference, -41.4; 95% CI, -58.9 to -23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion. Conclusions and Relevance In these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified. Trial Registration ClinicalTrials.gov Identifier: NCT03917472.

ImportanceDespite the effectiveness of existing anti–vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME).ObjectiveTo evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME.Design, Participants, and SettingThis 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021.InterventionBrolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks.Main Outcomes and MeasuresParticipants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52.ResultsA total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, −0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, −237.8 μm; aflibercept, −196.5 μm; difference, −41.4; 95% CI, −58.9 to −23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion.Conclusions and RelevanceIn these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified.Trial RegistrationClinicalTrials.gov Identifier: NCT03917472

Intravitreal anti-vascular endothelial growth factor (VEGF) injections are commonly used to treat eyes with macular edema secondary to hemiretinal vein occlusion (HRVO) or central retinal vein occlusion (CRVO). Information on whether differences exist in outcomes after anti-VEGF therapy can help guide treatment for each of the different disease types.To compare baseline characteristics, treatment burden, and outcomes of macular edema treatment in participants with HRVO with those of participants with CRVO.This post hoc outcome analysis from the Study of Comparative Treatments for Retinal Vein Occlusion 2 randomized clinical trial included 362 participants with macular edema caused by HRVO or CRVO treated at 66 US sites. Randomization began in September 2014, and the last month 24 follow-up visit occurred in February 2018. Data were analyzed from April 2020 to May 2021.Eyes were initially randomized to 6 monthly intravitreal injections of aflibercept or bevacizumab and were treated according to protocol between months 6 to 12 depending on 6-month outcome. After month 12, patients were treated per investigator discretion and observed through month 60.Mean visual acuity letter score (VALS).Of 362 included patients, 157 (43.4%) were female, and the mean (SD) age was 68.9 (12.0) years. Outcome data were analyzed up to month 24 owing to substantial missing data at later visits. A significantly greater proportion of participants with HRVO than those with CRVO were Black (37% vs 11%). Treatment rates between months 12 to 23 were 0.36 (95% CI, 0.32-0.40) injections per month for patients with CRVO and 0.28 (95% CI, 0.19-0.36) for patients with HRVO (P = .11). The mean VALS from months 1 to 24 of an HRVO study eye exceeded that of a CRVO study eye by 5.5 (95% CI, 1.5-9.5; P = .01), consistent with the magnitude of the VALS difference between eyes with CRVO and HRVO at baseline. Eyes with CRVO presented at baseline with more macular edema than eyes with HRVO (difference in central subfield thickness [CST], 86 μm; 95% CI, 48-124; P < .001), with no difference in CST between the groups throughout months 1 to 24.Black race was more prevalent among participants with HRVO than CRVO, and no differences were observed in the frequency of treatments for macular edema between eyes with CRVO and HRVO. Although eyes with CRVO presented with worse visual acuity and more macular edema on average than did eyes with HRVO, the magnitude of VALS improvement, central retinal thickness in response to anti-VEGF therapy, and treatment burden were similar between the groups.

ImportanceTwo-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.ObjectiveTo investigate outcomes 1 year after cessation of the SCORE2 treatment schedule.Design, Setting, and ParticipantsIn 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.InterventionsSCORE2 participants completed the treatment protocol at month 12, were subsequently treated at investigator discretion, and underwent assessment at month 24.Main Outcomes and MeasuresVisual acuity letter score (VALS) and central subfield thickness (CST) on spectral-domain optical coherence tomography.ResultsAmong 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 RelevanceNo 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 RegistrationClinicalTrials.gov identifier: NCT01969708.

PURPOSE: To determine treatment outcomes of intravitreal ocriplasmin in symptomatic vitreomacular adhesion.DESIGN: Retrospective interventional case series.METHODS: SETTING: Private practice. STUDY POPULATION: Thirty-five eyes (35 subjects) with symptomatic vitreomacular adhesion. INTERVENTION/OBSERVATION: Intravitreal ocriplasmin injection from February to November 2013. MAIN OUTCOME MEASURE: Vitreomacular adhesion resolution rate. Secondary endpoints included postinjection visual acuity and rates of outer retinal attenuation and full-thickness macular hole (MH) closure.RESULTS: The 35 subjects included were of mean age 69 years, 66% female, and 71% phakic. Eleven subjects (31%) had macular comorbidities. Average adhesion diameter was 571 pm, with mean 7.9 months duration of symptoms. Nine subjects (26%) had epiretinal membrane and 6 (17%) had MH (mean diameter 186 mu m). Mean preinjection logarithm of the minimal angle of resolution visual acuity was 0.46, and improved to 0.33 at final follow-up. Fifteen eyes (43%) achieved adhesion release at mean 10 days post injection. One of 6 MH (17%) closed. Transient outer retinal attenuation occurred in 10 of 35 cases (29%), with 8 of 10 (80%) achieving adhesion release. One subject (3%) developed a retinal detachment. Adhesion resolution Was more likely in patients with younger age (P = .04), absence of comorbidities (P = .02), small adhesion diameter (P = .005), short adhesion duration (P = .03), and transient outer retinal attenuation (P = .008).CONCLUSIONS: Intravitreal ocriplasmin efficacy in the private practice setting, while including patients with macular comorbidities, is similar to that of previous studies. Transient toxicity to the outer retina occurs frequently-typically with adhesion resolution-necessitating careful postinjection spectral-domain optical coherence tomography monitoring. (C) 2015 by Elsevier Inc. All rights reserved.

Purpose: To report nine cases of pachychoroid pigment epitheliopathy.Methods: An observational case series of nine patients who underwent comprehensive ophthalmic examination, fundus photography, fundus autofluorescence, spectral-domain optical coherence tomography, and enhanced depth imaging optical coherence tomography.Results: Eighteen eyes of 9 patients, aged 27 years to 89 years, were diagnosed with pachychoroid pigment epitheliopathy based on the characteristic funduscopic appearance of reduced fundus tessellation with overlying retinal pigment epithelial changes in one or both eyes, fundus autofluorescence abnormalities, and increased subfoveal choroidal thickness confirmed by enhanced depth imaging optical coherence tomography (mean, 460.2 mu m). The five older patients had been previously diagnosed with age-related macular degeneration, while the four younger subjects were referred for possible inflammatory chorioretinitis, pattern dystrophy, or nonspecific drusen. No subjects had a history of or subsequently developed subretinal fluid.Conclusion: Pachychoroid pigment epitheliopathy falls within a spectrum of diseases associated with choroidal thickening that includes central serous chorioretinopathy and polypoidal choroidal vasculopathy, and it should be suspected in eyes with a characteristic fundus appearance related to choroidal thickening and associated retinal pigment epithelial abnormalities but no history of subretinal fluid. Enhanced depth imaging optical coherence tomography confirming an abnormally thick choroid and characteristic retinal pigment epithelial changes on fundus autofluorescence support the diagnosis. Because these patients are frequently misdiagnosed, the recognition of pachychoroid pigment epitheliopathy may avoid unnecessary diagnostic testing and interventions.

PURPOSE: To describe the clinical and pathologic characteristics of mucin-producing sweat gland carcinoma of the eyelid and to determine whether neuroendocrine differentiation is of prognostic significance.DESIGN: Retrospective interventional case series.METHODS: Search of the New York Eye and Ear Infirmary pathology database between 1990 and 2011 identified 16 patients with mucin-producing sweat gland carcinoma. Clinical, histopathologic, and immunohistochemical analyses were performed on all identified cases.RESULTS: The patients presented with vascularized, focally cystic, nonulcerated eyelid margin lesions. Histopathologic evaluation showed that 4 lesions (25%) had a cystic, papillary, and solid growth pattern with an in situ component, 7 (44%) were pure invasive mucinous carcinomas, and 5 (31%) demonstrated both growth patterns. Immunohistochemical analysis of 15 tumors showed that pure cystic/papillary lesions had a significantly greater percentage of synaptophysin-immunoreactive cells (P = .036). There was no significant difference in the number of neuroendocrine markers expressed or in the intensity of immunostaining among the 3 different growth patterns. Re-excision for margin clearance was performed in 8 of 13 cases (61.5%). Two of 13 lesions recurred (15%); 1 of these was an in situ tumor with cystic morphology and neuroendocrine differentiation and the other was pure invasive mucinous carcinoma. None of the lesions metastasized.CONCLUSIONS: Mucin-producing sweat gland carcinoma pathologically represents a continuum, from an in situ lesion to a classic, invasive mucinous carcinoma. Immunohistochemical evidence of neuroendocrine differentiation can be observed in all lesions and does not appear to have a prognostic significance, arguing against the utility of immunohistochemical subtyping of mucinous sweat gland carcinomas. (Am J Ophthalmol 2013;155:585-592. (C) 2013 by Elsevier Inc. All rights reserved.)

Purpose: To determine the prevalence of herpes simplex virus type 1 (HSV-1) DNA in failed Descemet membrane stripping automated endothelial keratoplasty (DSAEK) grafts.Methods: A retrospective interventional case series of patients with DSAEK graft failure treated at the New York Eye and Ear Infirmary between January 2009 and July 2012 was performed. Repeat DSAEK, penetrating keratoplasty, or keratoprosthesis procedure was subsequently performed on eyes with failed grafts. All failed grafts were examined immunohistochemically and with qualitative real-time polymerase chain reaction for HSV-1 DNA. In HSV-1-positive cases, corneoscleral donor rims from the original DSAEK procedures were also examined immunohistochemically and with polymerase chain reaction.Results: Fifty-one failed DSAEK grafts from 50 eyes of 49 patients were identified. Indications for DSAEK were pseudophakic bullous keratopathy (28/51, 55%), Fuchs corneal endothelial dystrophy (12/51, 23%), failed penetrating keratoplasty (7/51, 14%), corneal decompensation from glaucoma (2/51, 4%), herpetic endotheliitis (1/51, 2%), and failed DSAEK (1/51, 2%). Forty-three grafts (83%) were primary DSAEK graft failure. HSV-1 DNA was isolated from 2 of 51 failed DSAEK grafts (4.0%). The corresponding corneoscleral donor rims did not demonstrate the presence of HSV-1.Conclusions: Based on our results, HSV-1 infection plays a minor role in DSAEK graft failure. The data suggest that recipient reactivation, rather than donor transmission, plays a role in HSV infection.