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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.

Purpose To assess the influence of baseline choroidal neovascularization (CNV) features on visual change and fluid resolution after anti–vascular endothelial growth factor (VEGF) treatment of eyes with neovascular age-related macular degeneration (nAMD). Design Post hoc analysis of 52-week data from the phase 3 Vascular Endothelial Growth Factor VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) Studies (VIEW) 1 and 2 clinical trials. Participants One thousand eight hundred four patients with nAMD. Methods Integrated data from VIEW 1 and 2 of 1804 eyes receiving intravitreal aflibercept injections (IAIs) 2 mg every 4 weeks, IAIs 2 mg every 8 weeks after 3 initial monthly doses, and ranibizumab every 4 weeks with documented baseline CNV type, total area, and leakage area were analyzed. Time to an event and cumulative incidence were evaluated by Kaplan-Meier analysis, and relative risks were estimated using proportional hazards analysis. Main Outcomes Measures Cumulative incidence of time to first sustained vision gain of 15 or more Early Treatment Diabetic Retinopathy Study letters, vision loss of more than 5 Early Treatment Diabetic Retinopathy Study letters from baseline, as well as first sustained absence of retinal fluid and intraretinal fluid as evaluated by OCT with respect to CNV type, total CNV, and leakage area. Results Eyes with predominantly classic CNV (mean best-corrected visual acuity [BCVA], 48.2 letters at baseline) showed a higher incidence rate of first sustained gain of 15 letters or more than eyes with occult CNV (mean BCVA, 57.9 letters at baseline; P Conclusions This post hoc analysis provided additional evidence for the role of baseline CNV features (CNV type, total area, and leakage area) in influencing visual and anatomic outcomes in eyes with nAMD after anti-VEGF treatment.

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.

BACKGROUND AND OBJECTIVE: To evaluate impact of baseline systemic dipeptidyl peptidase-4 (DPP-4) inhibitor use in diabetic macular edema (DME). PATIENTS AND METHODS: This was a post hoc exploratory analysis of previously completed randomized, controlled clinical trials (VISTA and VIVID) in patients with DME evaluating intravitreal aflibercept injection (IAI) every 4 weeks (2q4) or every 8 weeks (2q8) or macular laser photocoagulation. RESULTS: Overall, a small number of patients (12.2% [n = 35], 9.7% [n = 28], and 15.4% [n = 44]) in the laser control, 2q4, and 2q8 groups reported baseline DPP-4 inhibitor use. There were no differences in changes from baseline in best-corrected visual acuity, central subfield thickness, or rates of 2-or-greater-step improvement in Diabetic Retinopathy Severity Scale score based on DPP-4 inhibitor use within each treatment group. CONCLUSION: DPP-4 inhibitor use at baseline did not influence the magnitude of visual and anatomic benefit in patients with DME being treated with IAI or laser. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:226–234.]

BACKGROUND AND OBJECTIVE: To determine the safety and efficacy of intravitreal aflibercept injection (IAI) in patients with diabetic retinopathy (DR) in the prevention of macular edema (ME) following cataract surgery. PATIENTS AND METHODS: This phase 2, prospective, interventional, single-masked, randomized trial at a single academic center included 30 patients who were 18 years of age or older with nonproliferative DR and undergoing cataract surgery with phacoemulsification. Patients received 2 mg intravitreal aflibercept (0.05 mL) or sham injection during cataract surgery. Main outcome measures included treatment adverse events (AEs), best-corrected visual acuity (BCVA), and incidence of ME (defined as presence of cystoid abnormalities as detected by optical coherence tomography at any follow-up visit), a 30% or greater increase from preoperative baseline in central subfield macular thickness, or a BCVA decrease of more than 5 ETDRS letters from Day 7 due to retinal thickening. RESULTS: There were similar incidences of AEs between the two groups and no clinically serious ocular AEs in either group. The IAI group had fewer ME events at Day 14 (13% vs. 53%; P = .022), but there was no significant difference in ME events at Day 30 (27% vs. 60%; P = .057), Day 60 (27% vs. 60%; P = .057), or Day 90 (40% vs. 67%; P = .161). Compared to the study group, the control group had a significantly greater increase in central subfield thickness (CST) at Day 30 (50.05 μm vs. 7.95 μm; P = .040) and Day 60 (56.45 μm vs. 3.02 μm; P = .010). However, the difference in CST between groups was no longer significant at Day 90 (50.31 μm vs. 18.48 μm; P = .12). There were no significant differences in BCVA gains between the IAI and sham group at the end of the follow-up period (Day 90, ETDRS letters: 9.88 vs. 8.52; P = .66). CONCLUSIONS: Use of IAI in patients with DR for prevention of ME following cataract surgery showed no significant AEs. Although there were significant differences in ME incidence and retinal thickness at periods of time, there was no clinically meaningful benefit in terms of VA. Further larger trials are needed to validate these findings. [ Ophthalmic Surg Lasers Imaging Retina . 2020;51:170–178.]

To evaluate the impact of lipid-lowering medications on diabetic retinopathy and diabetic complications requiring intervention in the US population.Retrospective cohort analysis.Administrative insurance claims were drawn from the Truven MarketScan Commercial Claims and Encounters databases. Population consisted of beneficiaries with type 2 diabetes mellitus (T2DM). Main outcome measurements were any signs of diabetic retinopathy, as measured by diagnosis codes for nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), or diabetic macular edema (DME) and procedure codes for retinopathy treatments (anti-VEGF injections, laser therapy, and vitrectomy).A population of 269,782 patients diagnosed with T2DM between 2008 and 2015 were analyzed. A total of 99,233 patients (37%) were undergoing treatment with lipid-lowering medications. Approximately 6% of patients taking lipid-lowering medications had a diagnosis code for NPDR, PDR, or DME or a procedural code for intravitreal injections, pars plana vitrectomy (PPV) or laser treatment in their record following diagnosis with diabetes compared to 6.5% of patients who did not take lipid-lowering medications (P0.01). In adjusted time-to-event analyses, patients who took lipid-lowering medications prior to diagnosis of T2DM were less likely to progress to any retinopathy diagnosis (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.55-0.65) and less likely to receive any treatment for retinopathy (HR, 0.81; 95% CI, 0.78-0.84). These findings were significant at the aggregate level, at the individual level of diagnosis (NPDR HR, 0.63; 95% CI, 0.57-0.69; PDR HR, 0.45; 95% CI, 0.37-0.54; and DME HR, 0.39; 95% CI, 0.33-0.45), and at the level of each treatment category (anti-VEGF injection HR, 0.81; 95% CI, 0.78-0.84; laser HR, 0.62; 95% CI, 0.47-0.81; and vitrectomy HR, 0.71; 95% CI, 0.59-0.85).This study found consistent evidence that patients taking lipid-lowering medications were less likely to develop NPDR, PDR, or DME and modest evidence that these patients are less likely to receive intravitreal injections of anti-VEGF medication, laser treatments, or vitrectomy. The study validates the findings of studies that have used claims databases in East Asia in relatively homogeneous populations to estimate an association between statin use and retinopathy, replicating them in a US context in a large commercial claims database.

International audience; 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 (kappa = 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.

To evaluate outcomes and disease characteristics in eyes with neovascular age-related macular degeneration that received intravitreal aflibercept injection (IAI) and ranibizumab every 12 weeks or longer (≥q12 weeks) or less than every 12 weeks (q12 weeks) during year 2 of VIEW studies.Post hoc analysis of randomized clinical trial data.In year 1, eyes received ranibizumab q4 weeks (Rq4), IAI 2 mg q4 weeks (2q4), or IAI 2 mg q8 weeks after 3 monthly injections (2q8). In year 2, eyes received pro re nata treatment, with mandatory treatment at least q12 weeks.At week 96, 218 (42.5%), 284 (53.9%), and 245 (47.9%) eyes treated with Rq4, 2q4, and 2q8, respectively, received treatment at ≥q12-week intervals and 295 (57.5%), 243 (46.1%), and 266 (52.1%) eyes at12q-week intervals during the second year. Baseline occult-type choroidal neovascularization (CNV) (P = .0156) and retinal fluid (P.0001) and leakage (P.0001) at week 52 were associated withq12-week dosing. Mean best-corrected visual acuity gains from baseline with Rq4, 2q4, and 2q8 at ≥q12-week interval were 8.7, 9.9, and 9.7 letters at week 52 and 8.5, 8.8, and 9.2 letters at week 96, respectively. The corresponding gains withq12-week dosing were 10.3, 9.7, and 8.9 letters at week 52 and 9.1, 7.7, and 8.1 letters at week 96.Baseline CNV type other than occult and absence of retinal fluid and leakage at week 52 were significantly associated with ≥q12-week dosing. Vision improvements at week 52 following a year of fixed dosing with ranibizumab and IAI were maintained at week 96 in eyes that received treatment ≥q12 weeks andq12 weeks.

BACKGROUND AND OBJECTIVE: The purpose of this study was to assess the real-world incidence of conversion to bilateral neovascular age-related macular degeneration (nAMD) following treatment initiation of nAMD in the initial eye. PATIENTS AND METHODS: This was a retrospective cohort of electronic health records from retinal centers across the United States (Vestrum Database) of all patients with unilateral nAMD treated with anti-vascular endothelial growth factor therapy. RESULTS: A total of 22,553 patients with unilateral nAMD were included. Fellow eyes of 8,522 patients (38%) converted to nAMD. Among these, 2,639 (12%), 2,030 (9%), and 1,802 (8%) patients converted in Years 1, 2, and 3, respectively, after diagnosis in the first eye. Fellow eyes had better vision at conversion and 1 year following conversion. CONCLUSIONS: The fellow eye should be monitored at regular intervals to detect signs of neovascularization. Fellow eyes presented with significantly better vision at diagnosis than the initial eye and maintained better visual acuity with less injections. [ Ophthalmic Surg Lasers Imaging Retina. 2021;52:123–128.]

IMPORTANCE: Anti–vascular endothelial growth factor (VEGF) agents may provide a prophylactic effect in high-risk eyes with intermediate dry age-related macular degeneration (AMD) against conversion to exudative AMD (eAMD), lowering the risk of vision loss. OBJECTIVE: To evaluate intravitreal aflibercept injection (IAI) as prophylaxis against the conversion to eAMD in high-risk eyes at 24 months. DESIGN, SETTING, AND PARTICIPANTS: This single-masked, sham-controlled, randomized clinical trial performed at 4 US clinical sites enrolled patients with intermediate AMD in 1 eye (study eye), defined as presence of more than 10 medium drusen (≥63 to

PURPOSE To evaluate the effect of select baseline characteristics on geographic atrophy (GA) progression in eyes receiving intravitreal pegcetacoplan or sham. DESIGN Phase 2 multicenter, randomized, single-masked, sham-controlled trial. METHODS Patients 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. RESULTS Of 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 < .01), 0.27 (0.27) (P

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 < .001). Mean VA change from the end of year 1 to year 2 for eyes receiving ≤ 6 injections in year 1 generally remained unchanged, irrespective of year 2 dosing frequency. In eyes that received > 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.

Purpose To determine whether wet age-related macular degeneration (AMD) treatment outcomes within prespecified patient subgroups were consistent with overall study results. Additionally, this subanalysis investigated whether there were any relationships between baseline characteristics and evaluated treatment outcomes. Design Post hoc subanalysis of The VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2, 2 similarly designed prospective, multicenter, double-masked, active-controlled, parallel-group, randomized clinical trials. Participants Two thousand four hundred twelve patients with an active subfoveal choroidal neovascularization (CNV) lesion of any subtype secondary to AMD. Methods Primary and key secondary visual end points at week 52 were examined to explore the consistency of effect among prespecified subgroups of 5 baseline characteristics: age, best-corrected visual acuity (BCVA), lesion type, lesion size, and central retinal thickness (CRT). Additionally, within-group analyses were conducted to determine whether the mean changes in BCVA and CRT at 52 weeks were associated positively or negatively with the baseline characteristics of interest. Main Outcome Measures Consistency of treatment outcomes among prespecified subgroups of baseline characteristics. Results For each baseline characteristic, tests for interaction within each prespecified subgroup and among the subgroups were not significant, suggesting that relative visual outcomes for each treatment arm were consistent with overall study outcomes. Within-group analysis revealed a significant association between baseline age, BCVA, and lesion size with BCVA outcomes at 52 weeks; namely, older age, greater BCVA, and larger lesion size were associated with lower mean BCVA gains at 52 weeks. Conclusions Patients in all subgroups of baseline age, BCVA, lesion type, lesion size, and CRT experienced visual outcomes consistent with those of the overall study population. Additionally, baseline older age, better BCVA, and larger CNV lesion size were found to be associated independently with lower mean BCVA gains after 52 weeks of anti–vascular endothelial growth factor therapy. The influence of baseline age, BCVA, and CNV lesion size on treatment outcomes is consistent with other reports from large, prospective trials in wet AMD.

Purpose The effects of repeated intravitreal aflibercept injection (IAI) on the corneal endothelium were studied in patients with unilateral neovascular age-related macular degeneration. Methods RE-VIEW was a phase 4, open-label, single-arm, multicenter study. Patients received IAI every 8 weeks after 3 monthly doses. Slit-lamp biomicroscopy was performed at all study visits. The central corneal endothelial health was evaluated by specular microscopy in the treated versus untreated fellow eyes at baseline and weeks 24 and 52. Results No slit-lamp abnormalities were noted in 154 enrolled patients (eyes). Baseline versus 52-week mean (±SD) endothelial morphometric values (n = 118) for the treated versus untreated fellow eyes were respectively as follows: endothelial cell density was 2410 ± 364 versus 2388 ± 384 cells/mm at baseline and remained unchanged at 2401 ± 353 versus 2376 ± 364 cells/mm at 52 weeks (P = 0.87); the coefficient of variation was 33.5 ± 4.4% versus 34.0 ± 5.0% at baseline and remained unchanged at 34.2 ± 4.7% versus 34.1 ± 4.9% at 52 weeks (P = 0.18); the percentage of hexagonal cells was 59.5 ± 5.8% versus 59.6 ± 6.4% at baseline and remained unchanged at 59.5 ± 6.0% versus 59.5 ± 5.8% at 52 weeks (P = 0.96). Conclusions Repeated IAI for 52 weeks had no apparent corneal endothelial toxicity noted on specular microscopy in patients treated for neovascular age-related macular degeneration.

Purpose To evaluate whether select baseline systemic and ocular factors influence ≥2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) score at week 100 in VISTA and VIVID. Design Post hoc analysis of 2 similarly designed phase 3 trials, VISTA and VIVID. Participants Total of 456 patients with center-involved diabetic macular edema (DME). Methods VISTA and VIVID randomized 872 DME patients to receive intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or macular laser photocoagulation. This post hoc analysis evaluated the influence of select baseline factors on ≥2-step DRSS score improvement by logistic regression in an integrated VISTA and VIVID dataset using observed cases (n = 456) with patients in each treatment group divided into tertiles based on each characteristic. Main Outcome Measures Proportion of patients with ≥2-step improvement in DRSS score from baseline at week 100 by age, duration of diabetes, hemoglobin A1c (HbA1c), body mass index (BMI), best-corrected visual acuity (BCVA), central subfield thickness (CST), and DRSS score. Results At week 100, 10.1%, 34.3%, and 37.6% of patients in the laser, 2q4, and 2q8 groups experienced a ≥2-step DRSS score improvement, respectively. Age, duration of diabetes, HbA1c, BMI, BCVA, and CST had no impact on the ability to achieve ≥2-step improvement in DRSS score. Initial DRSS score was the only factor significantly associated with ≥2-step DRSS score improvement in all treatment groups at weeks 24, 52, 76, and 100. Relatively higher proportions of IAI-treated patients with worse BCVA or thicker CST experienced ≥2-step DRSS score improvement compared with those with better BCVA or thinner CST, respectively, but these associations were not statistically significant. Conclusion A strong association was present between baseline DRSS score and ≥2-step DRSS score improvement at week 100 for DME patients in VISTA and VIVID.

Purpose To examine the relationship between glycemic control at baseline and response to anti–vascular endothelial growth factor treatment for diabetic macular edema (DME). Design Post hoc analysis of 2 similarly designed phase III trials, VISTA and VIVID. Participants Patients with central-involved DME. Methods Both VISTA and VIVID compared efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for DME. Current analysis focused on comparison within each treatment group in an integrated VISTA and VIVID dataset. Baseline hemoglobin A1c (HbA1c) was partitioned into 4 quartiles: 4.5% to Main Outcome Measures Change from baseline best-corrected visual acuity (BCVA), central subfield thickness (CST), and HbA1c. Results In the IAI group, mean BCVA improvement from baseline did not depend on baseline HbA1c at week 52 ( P = 0.1852), but seemed to be dependent at week 100 ( P = 0.0425). The mean CST reduction from baseline was independent of baseline HbA1c at both weeks 52 ( P = 0.1857) and 100 ( P = 0.7346). Mean HbA1c change from baseline in IAI group was small across all HbA1c quartiles. In the laser group, the mean BCVA gain decreased with increasing baseline HbA1c at both weeks 52 ( P = 0.0421) and 100 ( P = 0.0001). Similarly, the mean CST decrease was greater with decreasing baseline HbA1c, at both weeks 52 ( P = 0.0065) and 100 ( P = 0.0162). The mean HbA1c change from baseline in the laser group was minimal across HbA1c quartiles, although glycemic control tended to worsen in upper quartiles. Conclusions The benefit of IAI in patients with DME was less dependent on their presenting glycemic status as opposed to laser.

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 (P0.001 compared with last visit before surgery), respectively. Corresponding change in CRT was a modest increase to 364 μm (P0.05 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.

Purpose To evaluate visual and anatomic outcomes after intravitreal aflibercept injection (IAI) versus laser in diabetic macular edema (DME) patients with and without prior anti–vascular endothelial growth factor (VEGF) treatment for DME. Design Post hoc analysis of eyes from 2 similarly designed, phase 3 trials, VISTA and VIVID. Participants Patients (eyes) with DME with central involvement from VISTA (n = 461) and VIVID (n = 404). Methods Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or macular laser photocoagulation. Main Outcome Measures This study reports exploratory outcomes through week 100. Analyses focused on VISTA because more patients received prior anti-VEGF therapy in VISTA (42.9%) versus VIVID (8.9%). Results Of 42.9% of patients in VISTA who received prior anti-VEGF treatment, 83.3% to 92.6% received ≥ 1 prior injections of bevacizumab, and 71.4% to 82.4% received bevacizumab only as prior anti-VEGF treatment for a duration ranging from 28 days to 3.9 years. In patients with prior anti-VEGF treatment, mean best-corrected visual acuity (BCVA) changes from baseline in the IAI 2q4, IAI 2q8, and laser groups were +10.4 letters, +10.5 letters, and −0.7 letters at week 52 and +10.9 letters, +10.8 letters, and −0.8 letters at week 100, respectively. Corresponding changes in patients without prior anti-VEGF treatment were +14.1 letters, +11.0 letters, and +0.9 letters at week 52 and +12.0 letters, +11.3 letters, and +2.1 letters at week 100. In patients with prior anti-VEGF treatment, mean reductions in central retinal thickness were 180.2 μm, 192.2 μm, and 90.9 μm at week 52 and 180.1 μm, 196.4 μm, and 94.1 μm at week 100. Corresponding reductions in patients without prior anti-VEGF treatment were 190.3 μm, 175.7 μm, and 61.0 μm at week 52 and 200.0 μm, 186.7 μm, and 76.9 μm at week 100. The most frequent serious ocular adverse event was vitreous hemorrhage (1.3%, 0.7%, and 1.9%, respectively). Conclusions Visual and anatomic improvements over laser with both IAI regimens were significant and similar through week 100 in subgroups of patients in VISTA with and without prior anti-VEGF treatment for DME.

BACKGROUND AND OBJECTIVE: To evaluate effect of retinal fluid status at week 12 on visual and anatomic outcomes at week 52 in patients with neovascular age-related macular degeneration from the VIEW studies. PATIENTS AND METHODS: Post-hoc analysis included 1,465 eyes treated with intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) 2 mg every 4 weeks (2q4) or every 8 weeks following three initial monthly injections (2q8) or ranibizumab (Lucentis; Genentech, South San Francisco, CA) 0.5 mg every 4 weeks (Rq4), which had known retinal fluid status at weeks 12 and 52. RESULTS: At 12 weeks, 512 (35%) eyes had fluid and 953 (65%) were fluid-free. Two hundred three (41.5%), 148 (29.8%), and 161 (33.5%) eyes had fluid in Rq4, 2q4, and 2q8, respectively. Best-corrected visual acuity (BCVA) change at week 52 from baseline was independent of retinal fluid status at week 12 or treatment assignment. Eyes were more likely to remain fluid-free at week 52 if absent of fluid at week 12. CONCLUSION: At week 52, 2q4, 2q8, and Rq4 improved BCVA independent of fluid status at week 12. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:238–244.]

BACKGROUND AND OBJECTIVE: To evaluate the effect of baseline factors on differences in vision gains with intravitreal aflibercept injection (IAI) versus laser control in patients with diabetic macular edema (DME). PATIENTS AND METHODS: This was an integrated post-hoc subanalysis of two phase 3 trials (VISTA, VIVID) in patients with DME. Least square (LS) mean differences of patients treated with IAI compared to laser control in best-corrected visual acuity (BCVA) change from baseline at week 100 were evaluated for association with baseline demographics and baseline systemic disease characteristics. RESULTS: At week 100, LS mean differences in BCVA change from baseline with IAI compared to laser control were not significant for association with baseline age, gender, and race or status of glycosylated hemoglobin, body mass index, renal impairment, hypertension, cerebrovascular disease, and ischemic heart disease. CONCLUSION: Vision gains with IAI were significantly greater than laser control and were not influenced by demographics and systemic disease control at baseline. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:167–173.]

To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU).Randomized, double-masked, placebo-controlled, phase 2 study.Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis.Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo.The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis.At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 μm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 μm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] μm (P = 0.1317) in the subgroup of eyes with CST ≥300 μm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients).Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

Amelie Pielen,1,2 W Lloyd Clark,3 David S Boyer,4 Yuichiro Ogura,5 Frank G Holz,6 Jean-Francois Korobelnik,7,8 Brigitte Stemper,9,10 Friedrich Asmus,9 Kay D Rittenhouse,11 Christiane Ahlers,9 Robert Vitti,12 Namrata Saroj,12 Oliver Zeitz,9,13,14 Julia A Haller15 On behalf of the COPERNICUS and GALILEO study group 1Eye Center, University Hospital Freiburg, Eye Hospital, Freiburg, 2Hannover Medical School, University Eye Hospital, Hannover, Germany; 3Palmetto Retina Center, Columbia, SC, USA; 4Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA; 5Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 6Department of Ophthalmology, University of Bonn, Bonn, Germany; 7Service d’ophtalmologie, CHU de Bordeaux, 8Service d’ophtalmologie, University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team LEHA, UMR 1219, Bordeaux, France; 9Bayer AG, Berlin, 10Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany; 11Bayer US LLC, Whippany, NJ, 12Regeneron Pharmaceuticals, Tarrytown, NY, USA; 13AKH Eye Clinic, Braunschweig, 14Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Augenheilkunde, Hamburg, Germany; 15Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA 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 2mg every 4weeks 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 6months 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&nbsp

To evaluate benefit of continued treatment in diabetic macular edema (DME) eyes showing a limited early response to treatment.Post hoc analysis of VISTA and VIVID.818 patients (eyes) with DME.Eyes with baseline central subfield thickness (CST) of ≥300 μm that received 2-mg intravitreal aflibercept injection (IAI) every 4 weeks (2q4) or every 8 weeks after 5 monthly injections (2q8) or laser control treatment were included in this analysis if they showed a limited early response at week 12 after 3 monthly injections or a single laser treatment at baseline, as defined by those who met: anatomic criteria (CST reduction ≤10% and CST300 μm); visual criteria (best-corrected visual acuity [BCVA] gain5 letters); or both. Least square (LS) means repeated measures were used to compare outcomes between initial (baseline-week 12) and later (weeks 16-100) periods within each treatment group.Visual outcomes of eyes with limited early response through week 100.In the anatomic subgroup, mean BCVA gains with 2q4 (n = 41) and 2q8 (n = 31) from baseline were 4.3 and 6.6 letters at week 12 and 8.6 and 8.5 letters at week 100, respectively. Corresponding LS mean differences for BCVA gains between initial and later periods were 3.0 (P = 0.0026) and 3.6 letters (P = 0.0017), respectively. In the visual subgroup, mean BCVA gains with 2q4 (n = 53) and 2q8 (n = 49) from baseline were 0.4 and 0.3 letters at week 12 and 6.1 and 4.1 letters at week 100, respectively. Corresponding LS mean differences for BCVA gains between initial and later periods were 5.0 (P0.0001) and 3.1 letters (P = 0.0008), respectively. In the combined subgroup, only a small percentage of IAI-treated eyes (7%) met criteria. Regardless of type of limited early response, continued laser treatment did not result in additional BCVA gains through week 100.Significant vision improvements were observed through week 100 with continued IAI treatment in a small number of DME eyes that showed a limited early response after 3 monthly IAI.

Background/aimsTo understand changes in disease activity as assessed by leakage and retinal fluid status in patients with neovascular age-related macular degeneration (nAMD) receiving fixed dosing with an anti-vascular endothelial growth factor (anti-VEGF) agent.MethodsIn the phase III VIEW 1 (NCT00509795) and VIEW 2 (NCT00637377) studies, eyes with nAMD were treated with intravitreal aflibercept or ranibizumab. Independent, masked reading centres determined the presence/absence of leakage (fluorescein angiography) and retinal fluid (optical coherence tomography) at baseline, week 24 and week 52. In this integrated, post hoc analysis of the VIEW studies, the relationship between leakage/fluid status and best-corrected visual acuity (BCVA) was assessed. The impact of baseline lesion type (predominantly classic (PC), minimally classic (MC), occult) was also evaluated. Data from all treatment groups were pooled.Results2373 eyes were included in this analysis. At baseline, 95.4% of eyes presented with both leakage and fluid. By week 52, leakage and fluid were present in 16.0% of eyes. Mean BCVA gains at week 52 were numerically greater in eyes without leakage and fluid versus eyes with both leakage and fluid (10.3 vs 9.2 letters). At week 52, 11.6%, 15.3% and 20.1% of eyes with PC, MC and occult lesions, respectively, had both leakage and fluid present.ConclusionIn this post hoc analysis, fixed dosing with an anti-VEGF agent over 52 weeks eliminated disease activity (absence of both leakage and fluid) in most eyes. The effect of anti-VEGF treatment on leakage/fluid status favoured PC versus occult lesions.

Importance Information on the effect of anti–vascular endothelial growth factor therapy in eyes with diabetic macular edema (DME) with vision loss after macular laser photocoagulation is clinically valuable. Objective To evaluate visual and anatomic outcomes in a subgroup of macular laser photocoagulation treatment control (hereafter laser control) eyes with substantial vision loss receiving treatment with intravitreal aflibercept injection. Design, Setting, and Participants This investigation was a post hoc analysis of a subgroup of laser control eyes in 2 phase 3 trials—VISTA (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) and VIVID (Intravitreal Aflibercept Injection in Vision Impairment Due to DME)—in a multicenter setting. One hundred nine laser control eyes with center-involving DME were included. Interventions Treatment with intravitreal aflibercept injection (2 mg) every 8 weeks after 5 monthly doses with sham injections on nontreatment visits starting at week 24 was initiated on meeting prespecified criteria of at least a 10-letter visual acuity loss at 2 consecutive visits or at least a 15-letter visual acuity loss from the best previous measurement at 1 visit and vision not better than at baseline. Main Outcomes and Measures Visual and anatomic outcomes in a subgroup of laser control eyes receiving treatment with intravitreal aflibercept injection. Results Through week 100, a total of 63 of 154 eyes (40.9%) in VISTA and 46 of 133 eyes (34.6%) in VIVID initially randomized to laser control received treatment with intravitreal aflibercept injection. The median time from week 24 to the first intravitreal aflibercept injection treatment was 34.0 (VISTA) and 83.5 (VIVID) days. In this subgroup, the mean (SD) visual gain from baseline to week 100 was 2.2 (12.5) (VISTA) and 3.8 (10.1) (VIVID) letters. At the time of intravitreal aflibercept injection initiation, these eyes had a mean (SD) loss of 11.0 (10.1) (VISTA) and 10.0 (6.5) (VIVID) letters from baseline, and they subsequently gained a mean (SD) of 17.4 (9.7) (VISTA) and 13.6 (8.6) (VIVID) letters from the initiation of treatment with intravitreal aflibercept injection through week 100. There was a minimal mean change in central subfield thickness from baseline in these eyes at the time of intravitreal aflibercept injection initiation (an increase of 3.9 μm in VISTA and a decrease of 3.0 μm in VIVID), after which further mean (SD) reductions of 285.6 (202.6) μm (VISTA) and 313.4 (181.9) μm (VIVID) occurred through week 100. Conclusions and Relevance Intravitreal aflibercept injection improves visual and anatomic outcomes in eyes experiencing substantial vision loss after macular laser photocoagulation treatment for DME. Trial Registration clinicaltrials.gov Identifiers:NCT01363440andNCT01331681

Purpose To assess long-term safety and efficacy of intraocular ranibizumab injections in patients with macular edema after retinal vein occlusion (RVO). Design Open-label extension trial of the 12-month Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) trials. Participants We included 304 patients who completed BRAVO and 304 patients who completed CRUISE. Methods Patients were seen at least every 3 months and given an intraocular injection of 0.5 mg ranibizumab if they met prespecified retreatment criteria. Main Outcome Measures Primary outcomes were incidence and severity of ocular and nonocular adverse events (AEs). Key efficacy outcomes included mean change from baseline best-corrected visual acuity (BCVA) letter score by Early Treatment Diabetic Retinopathy Study protocol and central foveal thickness. Results In patients who completed month 12, the mean number of injections (excluding month 12 injection) in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5 (central RVO), respectively. The incidence of study eye ocular serious AEs (SAEs) and SAEs potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to 9% and 1% to 6%, respectively. The mean change from baseline BCVA letter score at month 12 in branch RVO patients was 0.9 (sham/0.5 mg), −2.3 (0.3/0.5 mg), and −0.7 (0.5 mg), respectively. The mean change from baseline BCVA at month 12 in central RVO patients was −4.2 (sham/0.5 mg), −5.2 (0.3/0.5 mg), and −4.1 (0.5 mg), respectively. Conclusions No new safety events were identified with long-term use of ranibizumab; rates of SAEs potentially related to treatment were consistent with prior ranibizumab trials. Reduced follow-up and fewer ranibizumab injections in the second year of treatment were associated with a decline in vision in central RVO patients, but vision in branch RVO patients remained stable. Results suggest that during the second year of ranibizumab treatment of RVO patients, follow-up and injections should be individualized and, on average, central RVO patients may require more frequent follow-up than every 3 months. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Assess the 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO).Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial.We included 392 patients with macular edema after CRVO.Eligible patients were randomized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections. After 6 months, all patients with BCVA ≤20/40 or central subfield thickness ≥250 μm could receive ranibizumab.Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 12, additional parameters of visual function, central foveal thickness (CFT), and other anatomic changes were assessed.Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 13.9 (11.2-16.5) and 13.9 (11.5-16.4) in the 0.3 mg and 0.5 mg groups, respectively, and 7.3 (4.5-10.0) in the sham/0.5 mg group (P0.001 for each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 47.0% and 50.8% in the 0.3 mg and 0.5 mg groups, respectively, and 33.1% in the sham/0.5 mg group. On average, there was a marked reduction in CFT after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group to the level of the ranibizumab groups, which was sustained through month 12. No new ocular or nonocular safety events were identified.On average, treatment with ranibizumab as needed during months 6 through 11 maintained the visual and anatomic benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after CRVO, with low rates of ocular and nonocular safety events. After sham injections for 6 months, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT in the sham/0.5 mg group to a level similar to that in the 2 ranibizumab treatment groups and an improvement in BCVA, but not to the same level as that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after CRVO.Proprietary or commercial disclosure may be found after the references.

Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion (BRVO).Prospective, randomized, sham injection-controlled, double-masked, multicenter trial.A total of 397 patients with macular edema after BRVO.Eligible patients were randomized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, all patients with study eye best-corrected visual acuity (BCVA) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met.The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12. Additional visual and anatomic parameters were assessed.Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 16.4 (14.5-18.4) and 18.3 (15.8-20.9) in the 0.3 mg and 0.5 mg groups, respectively, and 12.1 (9.6-14.6) in the sham/0.5 mg group (P0.01, each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0% and 60.3% in the 0.3 mg and 0.5 mg groups, respectively, and 43.9% in the sham/0.5 mg group. On average, there was a marked reduction in central foveal thickness (CFT) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group, which was sustained through month 12. No new ocular or nonocular safety events were identified.At month 12, treatment with ranibizumab as needed during months 6-11 maintained, on average, the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO, with low rates of ocular and nonocular safety events. In the sham/0.5 mg group, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA, but not to the extent of that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO.Proprietary or commercial disclosure may be found after the references.

The purpose of this study was to investigate if monthly intravitreal ranibizumab decreases risk of macular hemorrhages in patients with choroidal neovascularization secondary to age-related macular degeneration.Incidences of macular hemorrhages in the control and ranibizumab groups from three, multicenter, randomized, clinical trials (MARINA, ANCHOR, and PIER) were compared. Two time intervals (Months 0-3 and 5-17) were evaluated to account for transition from monthly to quarterly injections in PIER. Time interval after Month 17 was excluded because of crossover from control to active treatment in all trials.Months 0-3: All trials showed higher incidence rates of hemorrhages in control compared with ranibizumab groups (ANCHOR: photodynamic therapy [27.3%], 0.3 mg [8.0%], 0.5 mg [8.6%]; MARINA: sham [18.6%], 0.3 mg [8.8%], 0.5 mg [8.8%]; and PIER: sham [16.1%], 0.3 mg [3.4%], 0.5 mg [3.3%]). In ANCHOR and MARINA, data of Months 5-17 showed higher incidence rates in control compared with monthly ranibizumab groups (ANCHOR: photodynamic therapy [47.8%], 0.3 mg [12.5%], 0.5 mg [12.3%]; and MARINA: sham [38.0%], 0.3 mg [13.2%], 0.5 mg [13.0%]), but this was not seen for quarterly ranibizumab groups in PIER (sham [22.4%], 0.3 mg [23.7%], 0.5 mg [28.3%]).Treatment with monthly intravitreal ranibizumab was associated with reduced risk of new macular hemorrhages when compared with photodynamic therapy (ANCHOR) or sham (MARINA and PIER). There was no difference between PIER quarterly ranibizumab-treated and sham patients.

To evaluate visual and anatomic outcomes after intravitreal aflibercept injection (IAI) versus laser in diabetic macular edema (DME) patients with and without prior anti-vascular endothelial growth factor (VEGF) treatment for DME.Post hoc analysis of eyes from 2 similarly designed, phase 3 trials, VISTA and VIVID.Patients (eyes) with DME with central involvement from VISTA (n = 461) and VIVID (n = 404).Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or macular laser photocoagulation.This study reports exploratory outcomes through week 100. Analyses focused on VISTA because more patients received prior anti-VEGF therapy in VISTA (42.9%) versus VIVID (8.9%).Of 42.9% of patients in VISTA who received prior anti-VEGF treatment, 83.3% to 92.6% received ≥ 1 prior injections of bevacizumab, and 71.4% to 82.4% received bevacizumab only as prior anti-VEGF treatment for a duration ranging from 28 days to 3.9 years. In patients with prior anti-VEGF treatment, mean best-corrected visual acuity (BCVA) changes from baseline in the IAI 2q4, IAI 2q8, and laser groups were +10.4 letters, +10.5 letters, and -0.7 letters at week 52 and +10.9 letters, +10.8 letters, and -0.8 letters at week 100, respectively. Corresponding changes in patients without prior anti-VEGF treatment were +14.1 letters, +11.0 letters, and +0.9 letters at week 52 and +12.0 letters, +11.3 letters, and +2.1 letters at week 100. In patients with prior anti-VEGF treatment, mean reductions in central retinal thickness were 180.2 μm, 192.2 μm, and 90.9 μm at week 52 and 180.1 μm, 196.4 μm, and 94.1 μm at week 100. Corresponding reductions in patients without prior anti-VEGF treatment were 190.3 μm, 175.7 μm, and 61.0 μm at week 52 and 200.0 μm, 186.7 μm, and 76.9 μm at week 100. The most frequent serious ocular adverse event was vitreous hemorrhage (1.3%, 0.7%, and 1.9%, respectively).Visual and anatomic improvements over laser with both IAI regimens were significant and similar through week 100 in subgroups of patients in VISTA with and without prior anti-VEGF treatment for DME.

To investigate whether extremes in visual acuity (very good or very poor) of the fellow eye (FE) influence visual acuity of the study eye in patients receiving intravitreal ranibizumab treatment for neovascular age-related macular degeneration.From 2 randomized, controlled, clinical trials (MARINA and ANCHOR), we performed a retrospective analysis of ranibizumab-treated patients who maintained stable FE visual acuity (±5 letters from baseline at each of Months 1, 4, 6, and 12), comparing patients with untreated FE visual acuity that was either 20/32 or better (very good) or 20/200 or worse (very poor). Visual acuity of the treated study eyes, which received monthly intravitreal ranibizumab (0.3 mg or 0.5 mg), was compared between the 2 FE cohorts at the Month 6 and Month 12 visits.A total of 145 patients were analyzed. In the cohort with very poor FE visual acuity (n = 55), there were 35 patients in MARINA and 20 patients in ANCHOR; in the cohort with very good FE visual acuity (n = 90), there were 52 patients in MARINA and 38 patients in ANCHOR.The mean (standard deviation) gain of the study eye visual acuity in the very good FE cohort was 10.3 (13.3) and 10.8 (13.7) letters at Months 6 and 12, respectively, compared with a lesser mean visual acuity gain of 4.6 (12.2) and 6.7 (11.7) letters at Months 6 and 12 in the very poor vision FE cohort. There was no statistically significant difference (adjusted) in the study eye visual acuity change between the 2 cohorts at either 6 months (P = 0.11) or 12 months (P = 0.26).This retrospective analysis of the MARINA and ANCHOR study data did not support the hypothesis that FE visual acuity plays a significant role in driving visual acuity of patients receiving monthly intravitreal ranibizumab injections for neovascular age-related macular degeneration. Visual acuity of the FE by itself is, therefore, not a useful parameter in predicting visual acuity in a majority of ranibizumab-treated patients.

To assess long-term safety and efficacy of intraocular ranibizumab injections in patients with macular edema after retinal vein occlusion (RVO).Open-label extension trial of the 12-month Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) trials.We included 304 patients who completed BRAVO and 304 patients who completed CRUISE.Patients were seen at least every 3 months and given an intraocular injection of 0.5 mg ranibizumab if they met prespecified retreatment criteria.Primary outcomes were incidence and severity of ocular and nonocular adverse events (AEs). Key efficacy outcomes included mean change from baseline best-corrected visual acuity (BCVA) letter score by Early Treatment Diabetic Retinopathy Study protocol and central foveal thickness.In patients who completed month 12, the mean number of injections (excluding month 12 injection) in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5 (central RVO), respectively. The incidence of study eye ocular serious AEs (SAEs) and SAEs potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to 9% and 1% to 6%, respectively. The mean change from baseline BCVA letter score at month 12 in branch RVO patients was 0.9 (sham/0.5 mg), -2.3 (0.3/0.5 mg), and -0.7 (0.5 mg), respectively. The mean change from baseline BCVA at month 12 in central RVO patients was -4.2 (sham/0.5 mg), -5.2 (0.3/0.5 mg), and -4.1 (0.5 mg), respectively.No new safety events were identified with long-term use of ranibizumab; rates of SAEs potentially related to treatment were consistent with prior ranibizumab trials. Reduced follow-up and fewer ranibizumab injections in the second year of treatment were associated with a decline in vision in central RVO patients, but vision in branch RVO patients remained stable. Results suggest that during the second year of ranibizumab treatment of RVO patients, follow-up and injections should be individualized and, on average, central RVO patients may require more frequent follow-up than every 3 months.

To assess the efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO).Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial.A total of 392 patients with macular edema after CRVO.Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections.The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT).Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 12.7 (9.9-15.4) and 14.9 (12.6-17.2) in the 0.3 mg and 0.5 mg ranibizumab groups, respectively, and 0.8 (-2.0 to 3.6) in the sham group (P0.0001 for each ranibizumab group vs. sham). The percentage of patients who gainedor =15 letters in BCVA at month 6 was 46.2% (0.3 mg) and 47.7% (0.5 mg) in the ranibizumab groups and 16.9% in the sham group (P0.0001 for each ranibizumab group vs. sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg = 43.9%; 0.5 mg = 46.9%) had BCVA ofor = 20/40 compared with sham patients (20.8%; P0.0001 for each ranibizumab group vs. sham), and CFT had decreased by a mean of 434 microm (0.3 mg) and 452 microm (0.5 mg) in the ranibizumab groups and 168 microm in the sham group (P0.0001 for each ranibizumab group vs. sham). The median percent reduction in excess foveal thickness at month 6 was 94.0% and 97.3% in the 0.3 mg and 0.5 mg groups, respectively, and 23.9% in the sham group. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with CRVO.Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO, with low rates of ocular and nonocular safety events.

To assess efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema following branch retinal vein occlusion (BRVO).Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial.A total of 397 patients with macular edema following BRVO.Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections.The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT).Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 16.6 (14.7-18.5) and 18.3 (16.0-20.6) in the 0.3 mg and 0.5 mg ranibizumab groups and 7.3 (5.1-9.5) in the sham group (P0.0001 for each ranibizumab group vs sham). The percentage of patients who gainedor =15 letters in BCVA at month 6 was 55.2% (0.3 mg) and 61.1% (0.5 mg) in the ranibizumab groups and 28.8% in the sham group (P0.0001 for each ranibizumab group vs sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg, 67.9%; 0.5 mg, 64.9%) had BCVA ofor =20/40 compared with sham patients (41.7%; P0.0001 for each ranibizumab group vs sham); and CFT had decreased by a mean of 337 microm (0.3 mg) and 345 microm (0.5 mg) in the ranibizumab groups and 158 microm in the sham group (P0.0001 for each ranibizumab group vs sham). The median percent reduction in excess foveal thickness at month 6 was 97.0% and 97.6% in 0.3 mg and 0.5 mg groups and 27.9% in the sham group. More patients in the sham group (54.5%) received rescue grid laser compared with the 0.3 mg (18.7%) and 0.5 mg (19.8%) ranibizumab groups. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with BRVO.Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid, effective treatment for macular edema following BRVO with low rates of ocular and nonocular safety events.

Purpose To explore whether monthly intravitreal ranibizumab injections are associated with a lower rate of new choroidal neovascularization (CNV) in fellow eyes of patients with unilateral neovascular age-related macular degeneration. Design Retrospective data analysis of randomized, controlled clinical trials. Methods Incidence of new CNV in fellow eyes was calculated at 12 and 24 months from 2 clinical trials (the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration [MARINA] study and the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration [ANCHOR] study), based on fluorescein angiographic reading center criteria and investigator evaluation. Patients treated with monthly ranibizumab (0.3 and 0.5 mg) were compared with those receiving a sham injection (MARINA) or photodynamic therapy (ANCHOR). Results In MARINA, new CNV developed in fellow eyes in 20.3% of the 0.3-mg ranibizumab group by 12 months and in 30.4% by 24 months. The conversion rate in the 0.5-mg ranibizumab group was 21.1% and 38.0% by 12 and 24 months, respectively. In the sham group, 26.4% converted by 12 months and 36.3% converted by 24 months. In ANCHOR, fellow eyes in 15.9% of the 0.3-mg ranibizumab group converted by 12 months and fellow eyes in 23.8% converted by 24 months. The conversion rate in the 0.5-mg ranibizumab group was 24.3% and 35.1% by 12 and 24 months, respectively. In the photodynamic therapy group, 25.4% converted by 12 months and 38.8% converted by 24 months. Differences in conversion rates at 12 and 24 months between the 0.3-mg or 0.5-mg ranibizumab groups and respective controls (sham or photodynamic therapy) were not statistically significant. Conclusions Results of this study do not support the hypothesis that monthly ranibizumab injections reduce the rate of CNV development in untreated fellow eyes.

Purpose To assess efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema following branch retinal vein occlusion (BRVO). Design Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial. Participants A total of 397 patients with macular edema following BRVO. Methods Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections. Main Outcome Measures The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT). Results Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 16.6 (14.7–18.5) and 18.3 (16.0–20.6) in the 0.3 mg and 0.5 mg ranibizumab groups and 7.3 (5.1–9.5) in the sham group ( P P P P Conclusions Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid, effective treatment for macular edema following BRVO with low rates of ocular and nonocular safety events. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.