Integrated results from the COPERNICUS and GALILEO studies.

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. RESULTS: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in CONCLUSION: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO

Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy.

To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial.Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA).Patients with GA secondary to age-related macular degeneration (AMD), n = 246.Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period.Time of new eAMD onset in the study eye, history of eAMD in the fellow eye, presence of double-layer sign (DLS) on structural OCT in the study eye, changes in retinal anatomic features by structural OCT and fluorescein angiography (FA), and changes in visual acuity.Exudation was reported in 26 study eyes across treatment groups over 18 months. Mean time to eAMD diagnosis was 256 days (range, 31-555 days). Overall, a higher proportion of patients with a baseline history of eAMD in the fellow eye (P = 0.016) and a DLS in the study eye (P = 0.0001) demonstrated eAMD. Among study eyes in which eAMD developed, 18 of 26 (69%) had history of fellow-eye eAMD and 19 of 26 (73.1%) had DLS at baseline, compared with 76 of 217 study eyes (35%; P = 0.0007) and 70 of 215 study eyes (32.5%; P0.0001), respectively, in which eAMD did not develop. All 21 patients with structural OCT imaging at the time of eAMD diagnosis demonstrated subretinal fluid, intraretinal cysts, or both consistent with exudation. Among 17 patients who underwent FA at eAMD diagnosis, 10 showed detectable macular neovascularization (MNV), all occult lesions. Development of eAMD did not have an appreciable impact on visual acuity, and all patients responded to anti-vascular endothelial growth factor (VEGF) therapy.Intravitreal pegcetacoplan slowed the rate of GA growth and was associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. Exudative AMD seemed to be associated with baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria

Impact of Baseline Retinal Nonperfusion and Macular Retinal Capillary Nonperfusion on Outcomes in the COPERNICUS and GALILEO Studies.

Purpose To evaluate the impact of baseline retinal capillary nonperfusion (RNP) and macular retinal capillary nonperfusion (MNP) status on outcomes at week 24 (W24). Design Post hoc analyses of 2 phase 3, randomized, double-masked, multicenter, sham-controlled studies. Participants Three hundred sixty-six patients with macular edema secondary to central retinal vein occlusion randomized in COPERNICUS and GALILEO. Methods We randomized patients 3:2 to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until W24. RNP and MNP were assessed by a masked independent reading center. Main Outcome Measures Proportion of patients with 10 disc areas (DA) or more of RNP and any degree of MNP at W24, relative risks of 10 DA or more of RNP or any degree of MNP at W24 developing, change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by baseline RNP and MNP status, and relationship between baseline RNP and MNP status. Results At baseline, 24.6% of patients showed 10 DA or more of RNP and 72.6% showed MNP, regardless of baseline RNP status. At W24, the pooled proportions of patients in the intravitreal aflibercept and sham groups with 10 DA or more of RNP were 11.6% and 29.0%, respectively (P = 0.0001); the respective proportions with any degree of MNP were 61.2% and 79.5% (P = 0.0008). Relative risks and 95% confidence intervals for intravitreal aflibercept versus sham were 0.4 (0.25–0.62) for 10 DA or more of RNP and 0.8 (0.68–0.90) for MNP, indicating a lower risk for these outcomes with intravitreal aflibercept than with sham. Mean BCVA change was greater in intravitreal aflibercept- versus sham-treated eyes, with less than 10 DA and 10 DA or more of RNP at baseline (+17.5 vs. +0.8 letters and +18.3 vs. −4.1 letters, respectively) and with and without baseline MNP (+15.7 vs. +0.3 letters and +17.1 vs. +0.4 letters, respectively). Agreement between baseline RNP and MNP status was low (κ = 0.12). The proportions of patients with 1 or more ocular serious adverse event in the intravitreal aflibercept- and sham-treated groups, respectively, were 3.2% and 11.3%. Conclusions At W24, visual and anatomic improvements, including perfusion status, were greater in eyes treated with intravitreal aflibercept than in eyes treated with sham, regardless of baseline RNP or MNP status

Outcomes in Patients with Diabetic Macular Edema Requiring Cataract Surgery in VISTA and VIVID Studies

To evaluate the impact of cataract surgery on visual and anatomic outcomes in patients with diabetic macular edema treated with intravitreal aflibercept injection (IAI) or laser control and who did not require rescue therapy. Post hoc analysis of 2 phase 3 trials, Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA) and Intravitreal Aflibercept Injection in Vision Impairment Due to DME (VIVID). Fifty-four patients (laser treatment, n = 11; IAI, n = 43) who underwent cataract surgery during the study period. In VISTA and VIVID, patients received IAI 2 mg every 4 weeks, IAI 2 mg every 8 weeks after 5 monthly doses, or laser control through week 100. Starting at week 24, if rescue treatment criteria were met, IAI patients received laser therapy, and laser therapy patients received IAI 2 mg every 8 weeks (after 5 monthly doses). Patients who received rescue treatment before cataract surgery were excluded. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in the laser control and pooled IAI groups before and after cataract surgery. The cumulative incidence of cataract surgery did not depend on treatment group assignment (rate ratio, = 1.517; 95% confidence interval, 0.782-2.944; P = 0.2174). At the last study visit before surgery, BCVA was 62.2 and 56.9 letters and CRT was 342 μm and 301 μm in the laser control and IAI groups, respectively. At the first study visit after cataract surgery, BCVA was improved significantly in both the laser control and IAI groups to 73.5 letters (P = 0.010 compared with last visit before surgery) and 67.2 letters (P 0.05 compared with last visit before surgery) and 359 μm (P = 0.013 compared with last visit before surgery), respectively. Incidence of cataract surgery was similar in both treatment groups. Despite a modest worsening in CRT after cataract surgery, BCVA was improved in both treatment groups

Visual Acuity Outcomes in Patients Receiving Frequent Treatment of Neovascular Age-Related Macular Degeneration in Clinical Practice

Purpose: This work evaluates dosing frequency with intravitreal antivascular endothelial growth factor (anti-VEGF) agents over 2 years and visual acuity (VA) outcomes in neovascular age-related macular degeneration (nAMD). Methods: This retrospective analysis assesses electronic medical record data (Vestrum Health treatment and outcomes database) of newly diagnosed nAMD in patients who were initiated on intravitreal anti-VEGF treatment at US clinical sites. Eyes were divided into 2 injection frequency subcohorts (≤ 6 or > 6 injections/y); treatment frequency and change in mean VA (Early Treatment Diabetic Retinopathy Study letters) were evaluated. Results: Overall, 8127 of 213 824 eyes met inclusion criteria in year 1 and 4968 in year 2. During year 1, 77% of the eyes received more than 6 injections (n = 6287), the majority of which received injections at the same frequency during year 2. Mean VA gain from baseline at year 1 was lower in the ≤ 6 than > 6 injections/y subcohort (2.2 vs 6.5, P < .001). Decrease in mean VA from the end of year 1 to year 2 was significantly greater for eyes administered 6 or fewer injections in year 2 than those that received more frequent injections, irrespective of the frequency of injections in the first year. Conclusions: In routine clinical practice, most eyes with nAMD that completed at least 1 year of follow-up were treated with more than 6 injections of anti-VEGF agents during the first year of treatment, resulting in better VA gains than eyes treated less frequently during the same period

Evaluation of Patients Receiving Intravitreal Antivascular Endothelial Growth Factor for Diabetic Macular Edema in Clinical Practice in the United States

Purpose: We assessed the effect of treatment frequency with intravitreal antivascular endothelial growth factor (anti-VEGF) agents on visual acuity (VA) in diabetic macular edema (DME). Methods: This retrospective analysis assessed electronic medical records of eyes newly diagnosed with DME and treated with an anti-VEGF agent at US clinics using the Vestrum Health (Naperville, Illinois) treatment and outcomes database. Eyes were divided into 2 injection frequency subcohorts (≤ 6 vs > 6 injections/y); treatment frequency and change in mean VA (Early Treatment Diabetic Retinopathy Study letters) were evaluated. Results: Among 155 240 eyes assessed, 3028 met inclusion criteria for analysis in year 1 and 1292 in year 2. During year 1 of treatment, 57% (n = 1725) received > 6 injections; most continued to receive the same injection frequency during year 2. Mean VA gain from baseline at year 1 was lower in the ≤ 6 than in the > 6 injections/year subcohort (3.7 vs 8.0 letters, respectively; P 6 injections in year 1, mean VA loss was significantly greater for eyes receiving less-frequent dosing in year 2 than in those maintained on > 6 injections. Conclusions: More than 50% of eyes with DME in routine clinical practice that completed at least 1 year of follow-up received > 6 injections of an anti-VEGF agent during the first year, resulting in better VA gains than eyes treated less frequently

Increasing Incidence and Prevalence of Common Retinal Diseases in Retina Practices Across the United States

BACKGROUND AND OBJECTIVE: To provide an updated estimate of incidence and prevalence of the foremost retinal diseases in the U.S. PATIENTS AND METHODS: Retrospective study of the Vestrum Health Database evaluating eyes with diagnoses of wet or dry age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), branch or central retinal vein occlusion (BRVO; CRVO) from January 2014 to December 2019 across 58 retina practices. RESULTS: Of the 3,086,791 eyes examined, 490,881 (15.9%) had dry AMD, 294,041 (9.5%) wet AMD, 270,703 (8.8%) DME, 254,690 (8.3%) DR without DME, 73,617 (2.4%) BRVO, and 50,670 (1.6%) CRVO. Dry AMD had the highest incidence. These diseases comprised 61.0% of total prevalence and 54.3% of incidence among patients at the retina practices analyzed. CONCLUSIONS: Based on a diverse database, these diseases comprised the majority of U.S. retina practice cases, with increasing annual incidences. AMD is the most common diagnosis, then diabetic eye disease

Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections (QUALITII): Development of a patient-reported measure to assess treatment burden of repeat intravitreal injections

Objective To understand patient burden of treatment of repeated intravitreal injections (IVI) in the management of exudative retinal diseases.Methods and analysis Participants were sampled from a large urban retina specialty practice in Houston, Texas, USA, based on history of ongoing receipt of IVI. The 50-item Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections questionnaire was developed to evaluate the patient experience including discomfort, anxiety, inconvenience and satisfaction. Categorial principal components analysis (CATPCA) was performed to assess construct validity and internal consistency. A subset of these items was used to establish a measure of total treatment burden, referred to as the IVI Treatment Burden Score (TBS).Results 142 patients participated in this study. CATPCA analysis revealed five dimensions of patient burden: disruption of normal routine or capacity, anxiety, frequency of visits, chronicity of disease and perceived treatment value or satisfaction. Together, these dimensions accounted for 67% of variance explained. Cronbach’s alpha was 0.97. The most frequently cited cause of discomfort was the feeling after anaesthetic wore off. The most common source of anxiety was fear of injection and associated discomfort or pain. Regarding inconvenience, patients reported temporary postinjection debilitation, requiring an average of 8 hours for recovery per treatment. The most frequently identified sources of satisfaction were confidence in the provider or treatment and interactions with staff.Conclusions Understanding and quantifying the patient burden associated with repeated IVI for exudative retinal diseases can reveal opportunities to improve delivery methods. The TBS could serve to inform strategies to maximise treatment adherence and optimise patient experiences

Epidemiology of rhegmatogenous retinal detachment in commercially insured myopes in the United States

Abstract Myopia is a known risk factor for rhegmatogenous retinal detachment (RRD). Given global trends of increasing myopia, we aimed to determine the absolute risk (incidence rate) of RRD in non-myopes, myopes and high myopes in the United States over ten years. We performed a retrospective cohort study of 85,476,781 commercially insured patients enrolled in the Merative™ Marketscan® Research Database. The incidence rate of RRD in phakic patients in the United States was 39-fold higher in high myopes than non-myopes (868.83 per 100,000 person-years versus 22.44 per 100,000 person-years) and three-fold higher in myopes than non-myopes (67.51 per 100,000 person-years versus 22.44 per 100,000 person-years). The incidence rate was significantly higher in males in each category (P < 0.01). Combined, the incidence rate of RRD in phakic patients in the United States from 2007 to 2016 was 25.27 RRDs per 100,000 person-years, a rate higher than those in prior published studies in North America, South America, Europe, Asia, and Australia. The absolute risk of myopia and high myopia increased from 2007 to 2016. The risk of RRD in phakic high myopes rose with increasing age. Notably, the magnitude of increased risk of RRD in myopes varied substantially according to the minimum follow-up period in our models and should be accounted for when interpreting data analyses

Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan.

PurposeTo evaluate the effect of select baseline characteristics on geographic atrophy (GA) progression in eyes receiving intravitreal pegcetacoplan or sham.DesignPhase 2 multicenter, randomized, single-masked, sham-controlled trial.MethodsPatients with GA received 15 mg pegcetacoplan monthly or every other month (EOM), or sham injection monthly or EOM for 12 months. Primary efficacy endpoint was change in GA lesion size (square root) from baseline. Post hoc analysis evaluated the effects of age; gender; lesion size, focality, and location (extrafoveal vs foveal); pseudodrusen status; best-corrected visual acuity (BCVA); and low-luminance deficit (LLD) on GA progression at Month 12.ResultsOf 246 randomized patients, 192 with 12-month data were included in this analysis. Overall mean (standard deviation) change in lesion size (mm) was 0.26 (0.17) (P ConclusionsExtrafoveal lesions and larger LLD are potential risk factors for GA progression. Pegcetacoplan treatment significantly controlled GA progression even after accounting for these risk factors