Search

Objective: To study the long-term outcomes of anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) in the Netherlands, where off-label bevacizumab is used as the first choice, compared to countries that typically use ranibizumab or aflibercept., Design: Prospective real-world observational study., Methods: A total of 1,617 Dutch eyes were compared with 8,667 eyes from a reference group derived from 13 socio-economically comparable countries. The primary outcome was the mean visual acuity (VA) measured at annual intervals up to 60 months. Secondary outcomes included injection frequency and the rate of switching to an alternative injection type., Results: Dutch eyes exhibited higher VA, received two additional injections annually and switched to alternative treatments more frequently (65.2% vs. 50.1%) and sooner (14.6 months vs. 17.9 months)., Conclusion: Dutch patients achieved higher VA after 60 months compared to the reference group. This higher VA was associated with a greater number of injections and a tendency to switch to a more expensive registered anti-VEGF injection type.

Objectives: To compare visual outcomes for low vision eyes (LVE) (<35 letters LogMAR or <20/200 Snellen) versus non-low vision eyes (NLVE) (>35 letters LogMAR or >20/200 Snellen) at the time of the first injection in a clinical practice setting., Methods: Subgroup analysis of a multicenter national database of treatment- naïve eyes neovascular age related macular degeneration (nAMD) treated with anti-VEGF intravitreal injections divided into LVE and NLVE. Demographics, visual acuity (VA) at baseline and subsequent timepoints (12, 24, and 36 months), number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!)., Results: 3138 eyes were included, 705 LVE and 2433 NLVE. The LVE group had the greatest VA gain (p < 0.001), at 12, 24, and 36 months (+15, +15, and +13 letters respectively). The proportion of patients with VA loss (-5 letters) differed between groups at 12, 24, and 36 and was significantly greater (p < 0.001) in NLVE. The proportion of patients with VA gain (+5 letters) was significantly higher (p < 0.001) in LVE in all timeframes. The proportions of LVE that still had VA ≤ 35 letters at 12, 24, and 36 months were 54%, 54%, and 57%. Conversely, 8%, 9%, and 8% of LVE achieved VA ≥ 70 letters at 12, 24, and 36 months. LVE received fewer intravitreal injections than NLVE throughout follow-up (6, 9, 12 vs 7, 11, 15)., Conclusion: Findings of this study support the need for ongoing therapy in patients with initial visual acuity less than 35 letters since sustained visual improvements can be achieved and maintained for the first 3 years of treatment., Competing Interests: Competing interests: JZV, PCP, and MCG receive funding and consult for Novartis Pharmaceuticals and Bayer. JZV is a member of the Eye editorial board., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes., Design: Multicenter, international, BRVO database study., Subjects: Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting., Methods: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, central subfield thickness (CST), treatments, number of injections, and visits data was collected using a validated web-based tool., Main Outcome Measures: Visual acuity gain at 3 years in logarithm of the minimum angle of resolution letters. Secondary outcome measures included anatomical results, treatment pattern, and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes., Results: Mean adjusted VA change was +11 letters (95% confidence interval 9-13), mean adjusted change in CST was -176 μm (-193, -159). Median number of injections/visits was 16 of 24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n = 677) and as a monotherapy in 71% (n = 538). Few eyes were switched to steroids (11%, n = 83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs. -128 vs. -114 μm; P < 0.001) and significantly lower switching rates (14% vs. 38% vs. 33%; P < 0.001) compared with ranibizumab and bevacizumab, respectively., Conclusions: This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar among the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered., Design: Cohort study., Participants: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry., Methods: Eyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n = 1172) versus Group B with greater than the median (n = 1116)., Main Outcome Measures: Mean visual acuity (VA) change after 12 months of treatment., Results: The mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8-4.4) letters for eyes in Group A versus 5.2 (4.4-5.9) letters for eyes in Group B (P = 0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76 to -61) μm and -85 (-92 to -78) μm for eyes in Group A versus Group B, respectively (P = 0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (P < 0.001). Additionally, eyes that received more injections had a moderately greater CST reduction., Conclusions: This registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. All rights reserved.)

Purpose: The purpose of the study was to assess the association of macular atrophy (MA) according to the activity of macular neovascularization (MNV) (inactive, only subretinal fluid [SRFL], or active, i.e. including intraretinal fluid [IRFL]) using optical coherence tomography (OCT) in patients with neovascular age-related macular degeneration (nAMD)., Methods: Multicentric observational study. Treatment-naïve nAMD eyes without subfoveal MA or subretinal fibrosis (SF) at baseline were included since 1st January 2010 and 30th September 2016 to allow up to 5 years of treatment follow-up. Eyes were grouped based on their predominant activity status as: (1) mostly inactive, (2) mostly active non-SRFL only [IRFL] or (3) mostly active-SRFL only [onlySRFL]. Kaplan-Meier survival curves estimated the time to development of MA or SF. Cox proportional hazards models evaluated predictors of developing subfoveal MA or SF. The main outcome measure was the risk of developing MA according to predominant MNV activity., Results: A total of 973 eyes were eligible for analysis. OnlySRFL eyes had lower risk of developing subfoveal MA (HR [95% CI]: 0.56 [0.36, 0.88]; p = 0.024) and extrafoveal MA (HR [95% CI]: 0.41 [0.27, 0.61]; p < 0.001) than IRFL eyes. IRFL eyes had lower visual acuity (VA) (54.5 letters) and the highest proportion of eyes with vision ≤35 letters (25%) at 5 years while onlySRFL eyes had comparable 5-year VA (63.7 letters) to inactive eyes (63.7 letters)., Conclusion: Subretinal fluid appears to protect against MA. Distinguishing the compartment of retinal fluid and understanding its relationship with MA and SF can guide the management of nAMD., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background/aims: To compare the efficacy of ranibizumab (0.5 mg) with aflibercept (2 mg) in the treatment of cystoid macular oedema due to branch retinal vein occlusion (BRVO) over 12 months., Methods: A multicentre, international, database observational study recruited 322 eyes initiating therapy in real-world practice over 5 years. The main outcome measure was mean change in EDTRS letter scores of visual acuity (VA). Secondary outcomes included anatomic outcomes, percentage of eyes with VA >6/12 (70 letters), number of injections and visits, time to first inactivity, switching or non-completion., Results: Generalised mixed effect models demonstrated that mean (95% CI) adjusted 12-month VA changes for ranibizumab and aflibercept were similar (+10.8 (8.2 to 13.4) vs +10.9 (8.3 to 13.5) letters, respectively, p=0.59). The mean adjusted change in central subfield thickness (CST) was greater for aflibercept than ranibizumab (-170 (-153 to -187) µm vs -147 (-130 to -164) µm, respectively, p=0.001). The overall median (Q1, Q3) of 7 (4, 8) injections and 9 (7, 11) visits was similar between treatment groups. First grading of inactivity occurred sooner with aflibercept (p=0.01). Switching was more common from ranibizumab (37 eyes, 23%) than from aflibercept (17 eyes, 11%; p=0.002)., Conclusion: Visual outcomes at 12 months in this direct comparison of ranibizumab and aflibercept for BRVO in real-world practice were generally good and similar for the 2 drugs, despite a greater effect of aflibercept on CST and time to first grading of inactivity., Competing Interests: Competing interests: MCG and DB are inventors of the software used to collect the data for this analysis. JA, ILMcA and MCG are members of advisory boards for Novartis and Bayer. JA and MCG are also members of advisory boards for Allergan. MCG and JA report personal fees and others from Novartis, others from Bayer, outside the submitted work. DB received a research grant from Novartis., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report the 24-month outcomes of vascular endothelial growth factor (VEGF) inhibitors for myopic choroidal neovascularization (mCNV) in predominantly Caucasian eyes in routine clinical practice., Methods: Retrospective analysis of treatment-naïve eyes starting intravitreal injection of VEGF inhibitors of either bevacizumab (1.25 mg) or ranibizumab (0.5 mg) for mCNV from 1 January 2006 to 31 May 2018 that were tracked in the Fight Retinal Blindness! registry., Results: We identified 203 eyes (bevacizumab-85 and ranibizumab-118) of 189 patients. The estimated mean (95% CI) change in VA over 24 months for all eyes using longitudinal models was +8 (5, 11) letters with a median (Q1, Q3) of 3 (2, 5) injections given mostly during the first year. The estimated mean change in VA at 24 months was similar between bevacizumab and ranibizumab [+9 (5, 13) letters for bevacizumab versus +9 (6, 13) letters for ranibizumab; p = 0.37]. Both agents were also similar in the mCNV activity outcomes, treatment frequency and visit frequency., Conclusions: The 24-month treatment outcomes of VEGF inhibitors for mCNV were favourable in this largest series yet reported of predominantly Caucasian eyes in routine clinical practice, with approximately two lines of visual gain and a median of three injections given mostly during the first year. These outcomes are similar to those reported for predominantly Asian eyes. Bevacizumab appeared to be as safe and effective as ranibizumab., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To assess the impact of disease activity on clinical outcomes in a "real-world" cohort with neovascular age-related macular degeneration over 5 years., Methods: Data were obtained from the prospectively defined Fight Retinal Blindness! registry. Eyes were divided into tertiles based on the proportion of visits where choroidal neovascular lesion was active (low, moderate, and high) up until 5 years., Results: Data from 2,109 eyes were included. The adjusted mean (95% confidence interval) visual acuity change was -0.5 letters (-1.8 to 1.1), 1.8 letters (0.2 to 3.4), and -2.5 letters (-4.2 to -1.3) in the low, moderate, and high activity groups respectively, P < 0.001. Eyes in the low activity group were more likely to develop macular atrophy (56, 47 and 26% in the low, moderate, and high activity groups respectively, P < 0.001) but less likely to develop subretinal fibrosis (27, 35 and 42% in the low, moderate, and high activity groups respectively, P < 0.001)., Conclusion: Eyes with higher and lower levels of disease activity had poorer outcomes than eyes with moderate activity over 5 years, apparently because of the development of subretinal fibrosis or macular atrophy.

Purpose: To report the 36-month treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) receiving vascular endothelial growth factor (VEGF) inhibitors in daily practice who did not develop either subretinal fibrosis (SRFi) or macular atrophy (MA)., Methods: This is a retrospective analysis of data from the Fight Retinal Blindness registry. Treatment-naïve eyes starting intravitreal injection of VEGF inhibitors for nAMD from January 1, 2010, to September 1, 2017, and did not have SRFI and MA at baseline were tracked., Results: We identified 2478 eligible eyes, of which 1712 eyes did not develop SRFi or MA, 291 developed extrafoveal SRFI or MA, and 475 developed subfoveal SRFi or MA over 36 months. The estimated visual acuity stabilized from 6 months to 36 months in eyes that did not develop SRFI or MA with a mean (95% confidence interval [CI]) change in VA of -1 (-2, 0) letters, whereas eyes that developed extrafoveal (-3 [-5, -2] letters) or subfoveal (-10 [-11, -8] letters) SRFi or MA declined in vision in the same period. Eyes with no or extrafoveal SRFi or MA over 36 months were more likely to maintain their visual improvement from six months to 36 months (odds ratio [OR; 95% CI] = 2.3 [1.5, 3.3] for absence vs. subfoveal SRFi or MA, P ≤ 0.01 and OR = 2.0 [1.2, 3.4] for extrafoveal vs. subfoveal MA or SRFi, P = 0.01)., Conclusions: Treatment-naïve nAMD eyes receiving VEGF inhibitors maintain their initial six-month visual improvement over three years if they do not develop SRFI or MA., Translational Relevance: The nAMD is still a major cause of blindness despite antiangiogenic treatments. We found that eyes that did not develop subretinal fibrosis or macular atrophy maintained their initial vision improvement for at least three years, suggesting that identifying treatments for these complications is the final barrier to achieving excellent outcomes in nAMD.

Purpose: To compare treatment outcomes of treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) with bevacizumab as the first-line treatment, according to the guidelines of the Dutch Ophthalmological Society, with those treated first with either ranibizumab or aflibercept, as used in many other countries, all treated using a treat-and-extend strategy., Methods: Data were obtained from the prospectively designed Fight Retinal Blindness! outcomes registry. The primary outcome was the mean change from baseline in visual acuity of all treated eyes, after 12, 24 and 36 months of treatment. Secondary outcomes were the number of injections, the number of visits and the rate of switching to a second anti-VEGF drug., Results: The study included 703 treatment-naïve eyes with nAMD with 12 months follow-up, 373 eyes with 24 months follow-up, and 171 eyes with 36 months follow-up in the Netherlands, and 1131, 652, and 303 treatment-naïve eyes with respectively 12, 24, and 36 months of follow-up in all other countries. The change in visual acuity from baseline did not differ between the Netherlands and the other countries at any follow-up time. The median number of injections, visits and the proportion of eyes switching treatment was significantly higher in the Netherlands than in the other countries., Conclusion: Starting anti-VEGF treatment for nAMD with bevacizumab, as is mandatory in the Netherlands, delivers outcomes similar to those starting treatment with either ranibizumab or aflibercept, but at a cost of more frequent injections, and visits, and more frequent switching treatment to a second drug., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Assess the relationship between subretinal fluid (SRFL), intraretinal fluid, and visual outcomes of neovascular age-related degeneration in routine clinical practice., Methods: Treatment-naive eyes enrolled in the Fight Retinal Blindness! registry after January 2017 were identified. Lesion activity was graded at each visit as inactive, active not SRFL only (A-NSRFL only), or active SRFL only (A-SRFL only). Eyes were grouped based on initial activity as follows: 1) initially A-NSRFL only or 2) initially A-SRFL only, and their predominant activity status over 12 months was as follows: 1) mostly inactive, 2) mostly A-NSRFL only, or 3) mostly A-SRFL only., Results: Seven hundred and three eyes were eligible for analysis. Initially A-NSRFL only had a similar adjusted mean 12-month visual acuity change to initially A-SRFL eyes (5.7 vs. 6.9 letters; P = 0.165), but their final visual acuity was worse (62.5 vs. 67.5 letters at 12 months; P = 0.003). The adjusted mean 12-month visual acuity change between the predominant activity groups was significantly different (P = 0.005), with mostly inactive (7.6 letters) and mostly A-SRFL only (7.5 letters) eyes gaining more than mostly A-NSRFL only eyes (3.6 letters)., Conclusion: Eyes with SRFL only had similar outcomes at 1 year to eyes that were mostly inactive. Intraretinal fluid was associated with worse visual outcomes, highlighting the importance of distinguishing between intraretinal fluid and SRFL when managing neovascular age-related degeneration., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To compare treatment intensity and mean visual acuity gains for first- and second-affected eyes with age-related macular degeneration nAMD over 5 years of treatment. The cumulative incidence of second-eye involvement was assessed., Method: We analyzed data from the Fight Retinal Blindness! project database, a prospectively designed registry of "real-world" outcomes from Australia, New Zealand, Switzerland, and Singapore. Patients with bilateral age-related macular degeneration with ≥5 years of follow-up on treatment were included., Results: Six thousand five hundred and forty-two eyes being treated for age-related macular degeneration were tracked from 2005 to 2017. Thousand two hundred and sixty-one patients had bilateral age-related macular degeneration; of whom, 302 had 5 years of follow-up. Of these, 170 patients started treatment for each eye at least 2 months apart. The mean baseline visual acuity of second-affected eyes was significantly higher than that of first-eyes (20/50 + 2 vs. 20/80; P < 0.01). Second-affected eyes lost a mean of 5.8 (-9.1 to -2.6) logarithm of the minimum angle of resolution letters after 5 years of treatment, whereas the vision of the first-affected eyes remained stable (P = 0.01). Second-affected eyes received fewer injections than the first-affected eyes after the first year of treatment (6.2/year vs. 7.8/year; P < 0.01) and reactivated earlier (376 vs. 507 days; P = 0.04). The cumulative incidence of second eye involvement was 54% over 5 years., Conclusion: Second-affected eyes received fewer treatments and reactivated earlier. Care should be taken to avoid undertreating second-affected eyes.

Purpose: Both ranibizumab and aflibercept improved vision and decreased macular thickness in eyes with diabetic macular edema (DME) in clinical trials. This study compared the 12-month treatment outcomes of each drug in routine clinical practice., Design: Retrospective analysis of data from the prospectively designed observational Fight Retinal Blindness! registry., Participants: Treatment-naive eyes tracked in the registry that initiated treatment with either ranibizumab (0.5 mg) or aflibercept (2 mg) for DME from December 1, 2013, through June 1, 2018., Methods: Visual acuity (VA) was analyzed at 12 months in all eyes (completers, noncompleters, and eyes that switched treatment)., Main Outcome Measures: The primary outcome was the mean change in VA from baseline to 12 months., Results: We identified 383 eyes (ranibizumab, n = 166 eyes; aflibercept, n = 217 eyes) of 291 patients. Eyes receiving aflibercept showed a lower mean VA (mean difference, -3.1 letters) and a thicker maculae (mean difference, +26 μm) at baseline than those receiving ranibizumab, which were not significantly different. Patients receiving ranibizumab were older (mean difference, +2.7 years). The adjusted mean difference in VA change and central subfield thickness (CST) reduction were, respectively, +1 letter (1.4 letters for aflibercept vs. 0.4 letter for ranibizumab; P = 0.4) and -30 μm (-85 vs. -55 μm; P < 0.01) in eyes with initial VA of 20/40 or better and +3 letters (10.6 vs. 7.6 letters; P < 0.01) and -46 μm (-148 vs. -102 μm; P < 0.02) in those with VA of 20/50 or worse. Eyes in the aflibercept group received more median injections over 12 months than the ranibizumab group although this difference was not significant (8 vs. 6 injections; P = 0.13). Treatment switches, albeit low, were more frequent from ranibizumab to aflibercept than vice versa. Significantly more eyes in the aflibercept group were lost to follow-up within 12 months (21% vs. 9% ranibizumab; P < 0.01)., Conclusions: Both drugs were beneficial for DME. Aflibercept-treated eyes, which had borderline worse vision and thicker maculae at baseline, showed larger CST reductions after 12 months of treatment. Larger VA gains were observed with aflibercept treatment when the initial VA was 20/50 or worse., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Ranibizumab and aflibercept are both approved for the treatment of neovascular age-related macular degeneration (nAMD). Herein, we compare the 3-year treatment outcomes of the 2 in routine clinical practice., Design: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness!, Participants: Treatment-naïive eyes starting nAMD treatment from December 1, 2013 through December 31, 2015, with either ranibizumab or aflibercept that were tracked in the registry., Methods: Visual acuity (VA) was analyzed annually in completers (those who completed 3 years of treatment) and in all eyes (completers, noncompleters, and those who switched treatment )., Main Outcome Measures: The primary outcome was mean change in VA (number of letters read on a logarithm of the minimum angle of resolution chart)., Results: A total of 965 eyes of 897 patients (ranibizumab, 499 eyes [469 patients]; aflibercept, 466 eyes [432 patients) were identified. The mean VA and the type of the choroidal neovascularization (CNV) at the start of treatment were similar between the 2 groups. The group receiving ranibizumab was older. The crude mean VA change of +1.5 letters (95% confidence interval [CI], 0-3.1 letters) in the ranibizumab group and of +1.6 letters (95% CI, -0.2 to 3.3 letters; P = 0.97) in the aflibercept group at 3 years in all eyes was similar, as was the adjusted mean VA change, +0.3 letters (95% CI, -1.5 to 2.0 letters) versus +1.0 letters (95% CI, -0.7 to 2.8 letters; P = 0.66). Both treatment groups received a median of 18 injections from a median of 21 clinical visits. The adjusted proportion of clinical visits when the CNV was graded active over 3 years was similar between ranibizumab (43%) and aflibercept (51%; P = 0.9). More switches from ranibizumab to aflibercept (P < 0.001) took place than vice versa. The proportion of eyes that did not complete 3 years of treatment in each of the group was similar (P = 0.21)., Conclusions: Neither ranibizumab nor aflibercept was superior to the other in terms of VA outcomes and treatment frequency at 3 years for nAMD., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate differences in the development of macular atrophy (MA) over 24 months between treat-and-extend (T&E) ranibizumab and aflibercept in patients with neovascular age-related macular degeneration (nAMD)., Design: A phase 4 randomized, partially masked, multicenter study., Participants: Individuals 50 years of age or older diagnosed with active, treatment-naïve subfoveal choroidal neovascularization secondary to nAMD with baseline best-corrected visual acuity (BCVA) of 23 logarithm of minimum angle of resolution letters or more., Methods: Patients were randomized 1:1 to receive either intravitreal injections of ranibizumab 0.5 mg or aflibercept 2.0 mg and were treated according to the same reading center-guided T&E regimen after 3 initial monthly injections., Main Outcome Measures: The primary outcome was mean change in square root area of MA from baseline to month 24. Key secondary outcomes included number of injections and mean change in BCVA from baseline to months 12 and 24., Results: Two hundred seventy-eight patients were included in the analysis (ranibizumab 0.5 mg, n = 141; aflibercept 2.0 mg, n = 137). Mean change in square root area of MA from baseline to month 24 was +0.36 mm (95% confidence interval [CI], 0.27-0.45 mm) for ranibizumab and +0.28 mm (95% CI, 0.19-0.37 mm) for aflibercept (treatment difference, +0.08 mm [95% CI, -0.05 to 0.21 mm]; P = 0.24). The proportion of patients with MA increased from 7% (10/141) to 37% (43/117) for ranibizumab and from 6% (8/137) to 32% (35/108) for aflibercept from baseline to month 24. The average number of injections received per year was similar between both groups: 9.6 (95% CI, 9.2-10.0) for ranibizumab and 9.5 (95% CI, 9.1-9.9) for aflibercept. The mean change in BCVA from baseline to month 24 was +6.6 letters (95% CI,4.7-8.5 letters) for the ranibizumab group and +4.6 letters (95% CI, 2.7-6.6 letters) for the aflibercept group ( P = 0.15). Rates of adverse events (AEs) were similar between both groups., Conclusions: No significant differences in the rate of development or growth of MA over 24 months were observed between ranibizumab and aflibercept in nAMD patients treated using an identical T&E regimen., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report and compare 10-year treatment outcomes of vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration (nAMD) from Australia and New Zealand (ANZ) and Switzerland., Design: Retrospective, comparative, interventional case series., Methods: We analyzed 712 treatment-naive eyes (ANZ, n = 474; Switzerland, n = 321) starting anti-VEGF for nAMD in routine clinical practice between January 1, 2006, and December 31, 2008, tracked in the prospectively designed observational database, the Fight Retinal Blindness! registry. The primary outcome was mean change in visual acuity (VA [in logMAR letters]) in eyes that completed 10 years of treatment., Results: The mean VA in 132 eyes (28%) from ANZ patients who completed 10 years of treatment dropped by 0.9 letters from baseline (95% confidence interval [CI], -4.9 to 3.1; P = 0.7) with 42% achieving ≥20/40, whereas the 37 eyes (12%) from Swiss subjects lost 14.9 letters (95% CI, -24 to -5.7; P < 0.001) with 35% achieving ≥20/40. Eyes from ANZ patients received more injections than eyes from Swiss subjects over 10 years (a median of 53 vs 42, respectively) from fewer visits with better disease control (proportion of visits with active disease: 38% vs 69%, respectively), suggesting a treat-and-extend regimen versus a pro re nata regimen (treatment given only when the lesion is active). Macular atrophy and subretinal fibrosis were the main reasons for 10 letter loss in the subset of eyes analyzed retrospectively. The mean VA of eyes from both regions that discontinued treatment within 10 years had fallen below the baseline at their final visit., Conclusions: Eyes with nAMD may achieve satisfactory long-term visual outcomes if they receive adequate treatment. Central macular atrophy does not develop universally in eyes receiving long-term treatment with VEGF inhibitors as previously feared. Visual outcomes were better in eyes from ANZ patients, likely because they received more injections., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: To compare 24 months outcomes of eyes with retinal angiomatous proliferations (RAPs) treated with antivascular endothelial growth factor (anti-VEGF) with a group of controls diagnosed with other neovascular age-related macular degeneration (nAMD) subtypes in a real-world setting., Methods: Treatment-naïve nAMD eyes that commenced anti-VEGF between January 2006 and November 2015 were identified from a registry of nAMD treatment outcomes. Cases were defined as eyes diagnosed with RAP. Three controls per case were selected among nAMD eyes with non-RAP lesions and matched on baseline visual acuity (VA), year of treatment initiation, anti-VEGF agent first injected and follow-up. Baseline VA was compared with 12 and 24 months VA. Change in VA, number of injections received, proportion of visits with active nAMD and time to first inactivation were compared between RAPs and controls., Results: 157 RAPs and 469 controls were included. Baseline VA (mean (SD)) increased at 12 months (61.4 (15.5) vs 68.7 (14.7) letters, p<0.001) and remained higher (66.6 (17.3) letters) at 24 months (p<0.001) in RAPs. The change from baseline VA (mean(95% CI)) was significantly higher in RAPs than in controls at 12 months (7.3 (5.4 to 9.1) vs 4.1 (2.8 to 5.4) letters, p=0.01) and at 24 months (5.1 (2.8 to 7.3) vs 2.5 (1 to 4) letters, p=0.056). Both groups received a median of 13 injections. RAPs inactivated earlier and were less active than controls (both p<0.001)., Conclusions: RAPs responded well to anti-VEGF, with a significant improvement in VA persisting at 24 months. RAPs had better visual outcomes than controls at 12 and 24 months, tended to inactivate earlier and were less active throughout 2 years follow-up., Competing Interests: Competing interests: Gillies and Barthelmes are inventors of the software used to collect the data for this analysis., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare 5-year real-world outcomes of eyes with classic and occult choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (anti-VEGF) injections., Design: Retrospective analysis from a prospectively designed observational database., Methods: Treatment-naïve eyes diagnosed with occult or minimally or predominantly classic CNV that commenced anti-VEGF treatment between January 2007 and December 2012 were identified from a registry of neovascular age-related macular degeneration (nAMD) treatment outcomes. Baseline characteristics, visual acuity (VA) at 5 years, change in VA, time to first inactivation, number of injections, and proportion of visits graded with active nAMD over the 5 years were compared between the 3 groups., Results: A total of 1929 eyes from 1730 subjects (1196 occult, 289 minimally classic, and 444 predominantly classic CNV) were analyzed. Baseline VA (mean [standard deviation]) was higher in occult CNVs (56.9 [17.4] letters) than in minimally (52.9 [19.7] letters) and predominantly (49.1 [19.9] letters) classic CNVs (P = .003 and P < .0001, respectively). VA change was similar across the groups. At 5 years eyes with occult CNVs still had better VA than other CNVs. Age, lesion size, and baseline VA, but not CNV type, significantly affected final VA in the multivariate model. Predominantly classic CNVs became inactive sooner and were overall less active than other CNV types. The number of injections received was similar across the groups., Conclusions: Eyes with occult CNVs had overall a better VA than other CNVs. The difference in final VA was not significant after adjusting for baseline VA. Five-year outcomes and treatment patterns were not affected by the lesion type., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF., Design: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial., Participants: Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV)., Methods: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 μm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome., Main Outcome Measures: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24., Results: Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P = 0.005)., Conclusions: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely., (Copyright © 2018 American Academy of Ophthalmology. All rights reserved.)

Purpose: To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with neovascular age-related macular degeneration (nAMD) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in daily clinical practice., Design: Observational study., Participants: Treatment-naive eyes starting anti-VEGF therapy for nAMD between 2007 and 2012 tracked in the Fight Retinal Blindness! registry. Eyes had sustained ≥15 letters of loss from baseline without recovery of visual acuity (VA) at final end point. A subgroup analysis included eyes that sustained ≥30 letters of loss. Controls had not sustained ≥15 letters of loss., Methods: Kaplan-Meier curves estimated time to first development of loss of ≥15 letters. Cox proportional hazards models evaluated predictors of loss of ≥15 letters., Main Outcome Measures: The proportion of eyes with sustained VA loss within 5 years, the time to development of sustained VA loss, and baseline predictors of sustained VA loss., Results: There were 1760 eyes in total and 856 eyes that completed 5 years follow-up. The proportion of eyes with sustained VA loss of ≥15 letters at 5 years was 22.9% (95% confidence interval [CI], 20.7%-25.1%) and VA loss of ≥30 letters was 10.8% (95% CI, 9.1%-12.5%). Factors independently associated with higher incidence of sustained ≥15-letter loss included age >80 years (odds ratio [OR], 1.33 for patients >80 years vs. ≤80 years; 95% CI, 1.05-1.69; P = 0.02), fewer injections (OR, 0.97 per injection; 95% CI, 0.96-0.98; P = 0.0005), and more visits at which the choroidal neovascularization was graded as active (OR, 1.97 for eyes in upper quartile of active visits vs. eyes in lowest quartile of active visits; 95% CI, 1.39-2.79; P = 0.0001). Baseline VA ≥70 letters was associated with reduced risk of sustained ≥30-letter loss (OR, 0.61; 95% CI, 0.38-0.98; P = 0.04). Baseline angiographic lesion criteria were not significantly associated with sustained VA loss., Conclusions: Twenty-three percent of eyes with nAMD developed sustained VA loss of ≥15 letters over 5 years of anti-VEGF therapy. Baseline predictors of poor outcomes provide more accurate assessment of the potential benefit from anti-VEGF therapy., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: To our knowledge, this is the first randomized clinical trial to compare visual outcomes and injection loads between ranibizumab and aflibercept using an identical treat-and-extend (TE) regimen for neovascular age-related macular degeneration (nAMD)., Objective: To report the results of the preplanned 12-month interim analysis of 2 predefined secondary efficacy end points of a randomized clinical trial., Design, Setting, and Participants: The Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients (RIVAL) trial was conducted in 24 sites in Australia and included 281 treatment-naive eyes from 281 participants with active choroidal neovascularization secondary to nAMD and a visual acuity letter score of 23 or greater who were recruited between April 11, 2014, and October 31, 2015. A preplanned interim analysis was performed at month 12. Best-corrected visual acuity (BCVA) assessors and the central reading center, which determined treatment intervals, were masked to treatment assignments., Interventions: Participants were randomized (1:1) to receive intravitreal injections of 0.5 mg of ranibizumab or 2.0 mg of aflibercept. After receiving 3 initial monthly injections, participants entered the TE phase., Main Outcomes and Measures: Mean change in BCVA and the number of injections from baseline to month 12., Results: Of 281 participants, 148 (52.7%) were women and the mean (SD) age was 77.7 (8.1) years. The baseline mean BCVA letter score (approximate Snellen equivalent) was 65.3 (20/50) in the ranibizumab arm and 65.1 (20/50) in the aflibercept arm. One hundred twenty-seven ranibizumab participants (90.1%) and 121 aflibercept participants (88.3%) completed month 12 with a mean (SD [Snellen equivalent]) BCVA letter score of 72.9 (15.5 [20/32]) and 70.5 (14.6 [20/40]), respectively. The mean change in BCVA letter scores from baseline to month 12 was 7.2 (95% CI, 5.5-8.9) for ranibizumab and 4.9 (95% CI, 3.1-6.6) for aflibercept (letter score difference, 2.3; 95% CI, -0.1 to 4.7; P = .06). The mean number of injections from baseline to month 12 was 9.7 in both the ranibizumab (SD, 2.8) and aflibercept (SD, 2.6) arms with a rate ratio of 1.00 (95% CI, 1.0-1.1; P = .86)., Conclusions and Relevance: Our findings suggest that neither aflibercept nor ranibizumab for nAMD are superior to the other regarding the average visual acuity gains and number of injections during 1 year in a TE regimen. Further follow-up to 2 years may determine if advantages of one over the other can be identified., Trial Registration: Clinicaltrials.Gov identifier: NCT02130024.

Introduction: To report 12-month pharmacoepidemiologic data on aflibercept and ranibizumab use in treatment-naïve eyes with neovascular age-related macular degeneration (nAMD)., Methods: Participants were treatment-naïve eyes with nAMD tracked by the Fight Retinal Blindness! registry starting therapy with aflibercept or ranibizumab treatment between January 1st, 2013 and 31st December, 2016. Demographic and clinical characteristics were compared between treatment groups., Results: During the study period, 689 eyes initiated treatment with ranibizumab compared to 568 with aflibercept. We found a similar rate of use of both drugs. Ranibizumab-treated patients were older than aflibercept-treated patients (overall mean [SD] 82.0 [8.4] vs. 78.6 [8.1], P < 0.001). Median (Q1, Q3) lesion size was significantly larger in aflibercept-treated patients (2450 μm [1242, 3000]) compared with ranibizumab patients (2000 μm [1148, 2890], P = 0.008). Eyes treated with ranibizumab and aflibercept received a similar mean number of injections in the first 3 months (3.1 [0.7] vs. 3.0 [0.6]; P = 0.233) and at 12 months (7.3 [2.4] vs. 7.2 [2.2]; P = 0.139). The 12-month switching rates from 2013 onwards for eyes completing 12 months of follow-up were much higher for switching from ranibizumab to aflibercept (19.2%) compared with switching from aflibercept to ranibizumab (5.4%). The proportion of eyes that did not complete 12 months of treatment was 23.2% for ranibizumab and 22.2% for aflibercept-treated groups., Conclusion: A similar rate of use for ranibizumab and aflibercept among Australian practitioners was observed between 2013 and 2016. Ranibizumab was used more often in older patients while aflibercept tended to be used more often in eyes with larger lesions.

Purpose: To assess the effect of intravitreal ranibizumab and aflibercept on retinal pigment epithelial detachment (RPED) in patients with neovascular age-related macular degeneration., Methods: This was a retrospective analysis of data from a prospectively designed and implemented clinical audit. Analysis included change in RPED dimensions and visual acuity in 92/233 treatment-naive eyes with neovascular age-related macular degeneration and RPED 6 months after treatment with either aflibercept or ranibizumab., Results: There was no significant between-group difference in the adjusted mean change for maximum RPED height (P = 0.195), diameter (P = 0.522) or visual acuity (P = 0.836) at 6 months. Injection frequency was the only clinical variable that affected RPED height (P = 0.050) and visual acuity change for both treatment groups (P = 0.004). Around 30% of eyes in each group had complete resolution of RPED at 6 months., Conclusion: Eyes with neovascular age-related macular degeneration and RPED showed significant functional and anatomical responses after 6 months of intravitreal anti-vascular endothelial growth factor injections. However, we found no significant difference in anatomical response or change in visual acuity between eyes treated with ranibizumab compared with aflibercept. Larger, prospectively designed, randomized studies with longer term follow-up may identify a difference between the two drugs that we did not detect.

The introduction of antivascular endothelial growth factor agents such as ranibizumab and aflibercept has revolutionized the management of neovascular age-related macular degeneration. A number of randomized clinical trials have shown that ranibizumab and aflibercept produce similar efficacy and safety outcomes. Most of the switching studies published to date show that efficacy benefits are uncontrolled, retrospective trials with limitations in terms of their selection, monitoring, numbers, and assessment criteria. Based on the published literature to date, we propose arguments for and against switching antivascular endothelial growth factor agents, provide our own perspective on this topic, and suggest a focus for future research., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The combination of steroid and anti-vascular endothelial growth factor (VEGF) intravitreal therapeutic agents could potentially have synergistic effects for treating diabetic macular oedema (DMO). On the one hand, if combined treatment is more effective than monotherapy, there would be significant implications for improving patient outcomes. Conversely, if there is no added benefit of combination therapy, then people could be potentially exposed to unnecessary local or systemic side effects., Objectives: To assess the effects of intravitreal agents that block vascular endothelial growth factor activity (anti-VEGF agents) plus intravitreal steroids versus monotherapy with macular laser, intravitreal steroids or intravitreal anti-VEGF agents for managing DMO., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 21 February 2018., Selection Criteria: We included randomised controlled trials (RCTs) of intravitreal anti-VEGF combined with intravitreal steroids versus intravitreal anti-VEGF alone, intravitreal steroids alone or macular laser alone for managing DMO. We included people with DMO of all ages and both sexes. We also included trials where both eyes from one participant received different treatments., Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane.Two authors independently reviewed all the titles and abstracts identified from the electronic and manual searches against the inclusion criteria. Our primary outcome was change in best corrected visual acuity (BCVA) between baseline and one year. Secondary outcomes included change in central macular thickness (CMT), economic data and quality of life. We considered adverse effects including intraocular inflammation, raised intraocular pressure (IOP) and development of cataract., Main Results: There were eight RCTs (703 participants, 817 eyes) that met our inclusion criteria with only three studies reporting outcomes at one year. The studies took place in Iran (3), USA (2), Brazil (1), Czech Republic (1) and South Korea (1). Seven studies used the unlicensed anti-VEGF agent bevacizumab and one study used licensed ranibizumab. The study that used licensed ranibizumab had a unique design compared with the other studies in that included eyes had persisting DMO after anti-VEGF monotherapy and received three monthly doses of ranibizumab prior to allocation. The anti-VEGF agent was combined with intravitreal triamcinolone in six studies and with an intravitreal dexamethasone implant in two studies. The comparator group was anti-VEGF alone in all studies; two studies had an additional steroid monotherapy arm, another study had an additional macular laser photocoagulation arm. Whilst we judged these studies to be at low risk of bias for most domains, at least one domain was at unclear risk in all studies.When comparing anti-VEGF/steroid with anti-VEGF monotherapy as primary therapy for DMO, we found no meaningful clinical difference in change in BCVA (mean difference (MD) -2.29 visual acuity (VA) letters, 95% confidence interval (CI) -6.03 to 1.45; 3 RCTs; 188 eyes; low-certainty evidence) or change in CMT (MD 0.20 μm, 95% CI -37.14 to 37.53; 3 RCTs; 188 eyes; low-certainty evidence) at one year. There was very low-certainty evidence on intraocular inflammation from 8 studies, with one event in the anti-VEGF/steroid group (313 eyes) and two events in the anti-VEGF group (322 eyes). There was a greater risk of raised IOP (Peto odds ratio (OR) 8.13, 95% CI 4.67 to 14.16; 635 eyes; 8 RCTs; moderate-certainty evidence) and development of cataract (Peto OR 7.49, 95% CI 2.87 to 19.60; 635 eyes; 8 RCTs; moderate-certainty evidence) in eyes receiving anti-VEGF/steroid compared with anti-VEGF monotherapy. There was low-certainty evidence from one study of an increased risk of systemic adverse events in the anti-VEGF/steroid group compared with the anti-VEGF alone group (Peto OR 1.32, 95% CI 0.61 to 2.86; 103 eyes).One study compared anti-VEGF/steroid versus macular laser therapy. At one year investigators did not report a meaningful difference between the groups in change in BCVA (MD 4.00 VA letters 95% CI -2.70 to 10.70; 80 eyes; low-certainty evidence) or change in CMT (MD -16.00 μm, 95% CI -68.93 to 36.93; 80 eyes; low-certainty evidence). There was very low-certainty evidence suggesting an increased risk of cataract in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 4.58, 95% 0.99 to 21.10, 100 eyes) and an increased risk of elevated IOP in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 9.49, 95% CI 2.86 to 31.51; 100 eyes).One study provided very low-certainty evidence comparing anti-VEGF/steroid versus steroid monotherapy at one year. There was no evidence of a meaningful difference in BCVA between treatments at one year (MD 0 VA letters, 95% CI -6.1 to 6.1, low-certainty evidence). Likewise, there was no meaningful difference in the mean CMT at one year (MD - 9 μm, 95% CI -39.87μm to 21.87μm between the anti-VEGF/steroid group and the steroid group. There was very low-certainty evidence on raised IOP at one year comparing the anti-VEGF/steroid versus steroid groups (Peto OR 0.75, 95% CI 0.16 to 3.55).No included study reported impact of treatment on patients' quality of life or economic data. None of the studies reported any cases of endophthalmitis., Authors' Conclusions: Combination of intravitreal anti-VEGF plus intravitreal steroids does not appear to offer additional visual benefit compared with monotherapy for DMO; at present the evidence for this is of low-certainty. There was an increased rate of cataract development and raised intraocular pressure in eyes treated with anti-VEGF plus steroid versus anti-VEGF alone. Patients were exposed to potential side effects of both these agents without reported additional benefit. The majority of the evidence comes from studies of bevacizumab and triamcinolone used as primary therapy for DMO. There is limited evidence from studies using licensed intravitreal anti-VEGF agents plus licensed intravitreal steroid implants with at least one year follow-up. It is not known whether treatment response is different in eyes that are phakic and pseudophakic at baseline.

Purpose: To investigate when retinal pigment epithelium (RPE) tears occur and their associated treatment patterns and long-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) during anti-vascular endothelial growth factor (VEGF) treatment., Design: Case-control analysis from a prospectively designed observational database., Participants: Treatment-naïve eyes enrolled in the Fight Retina Blindness! observational study that commenced anti-VEGF treatment for nAMD between January 2006 and January 2017 were identified. Cases were defined as eyes in which an RPE tear developed during treatment. Three control eyes per case were matched for age, baseline visual acuity (VA), lesion size, treatment duration before tearing, and duration of follow-up., Methods: Cases were classified as having early or late tears using a segmented regression model. Baseline characteristics were compared between the 2 groups. Comparisons of VA and injections received between tear eyes and control eyes were performed at baseline, before and immediately after the tear, and then 12 and 24 months later. Visual acuity also was compared among different visits within each group., Main Outcome Measures: Visual acuity, time to tear, and injections received., Results: Fifty-five cases and 165 matched control eyes were included. The segmented regression estimated a breakpoint for the time to tear at 182 days. We therefore defined eyes as having early tears if they tore before the breakpoint (38/55 eyes [69%]), and as late tears if they tore afterward (17/55 eyes [31%]). Baseline VA was significantly lower in early compared with late tears (53.6 vs. 63.4 letters; P = 0.009). Visual acuity had improved in early tears before the tear (+5.6 letters from baseline; P = 0.01), decreased immediately after the tear (-8.3 letters; P = 0.002), then recovered with no difference compared with control eyes 12 and 24 months later (P > 0.05 for both). Late tear eyes had significantly lower VA than control eyes before tearing (55.5 vs. 66.9 letters; P < 0.001). Visual acuity did not decrease significantly after the tear, but continued to decline compared with control eyes at all end points. Both early and late tear eyes received more injections than control eyes after tearing., Conclusions: Retinal pigment epithelium tears act differently depending on when they occur. Long-term visual outcomes in eyes affected by RPE tearing may be related more to the patient's response to therapy than to the tear itself., (Copyright © 2017 American Academy of Ophthalmology. All rights reserved.)

Aim: To report the natural history of subretinal fluid (SRF) causing foveal detachment in macular telangiectasia type 2 (MacTel) and our experience of therapeutic intervention with intravitreal steroids or antivascular endothelial growth factor inhibitor (anti-VEGF) agents in some cases., Methods: Retrospective case series. Three of the MacTel study's largest registries were searched to identify eyes with foveal detachment., Results: We identified 7 eyes from 6 exclusively female patients. The prevalence of foveal detachment was low, present in 1.4% of the assessed MacTel population. Age at presentation ranged from 50 to 66 years. Follow-up ranged from 2 to 8 years. There was late-phase leakage on fluorescein angiography from what was presumed to be ectatic capillaries. The SRF fluctuated without a rapid decline in visual acuity in cases that were not treated. When they were, intravitreal anti-VEGF and steroid therapy in general reduced SRF, at least temporarily, but did not halt the gradual long-term decrease in visual acuity. In one case, optical coherence tomography angiography showed significant reduction in the extent of the predominantly deep intraretinal vascular complex 1 month after anti-VEGF therapy., Discussion and Conclusions: As the natural history of this unusual MacTel phenotype is not characterised by rapid visual decline, intervention with intravitreal anti-VEGF or steroid therapy may not be necessary., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of retinal vascular diseases. However, constitutive VEGF also acts as a trophic factor on retinal nonvascular cells. We have studied the effects of aflibercept and ranibizumab on human Müller cells and photoreceptors exposed to starvation media containing various concentrations of glucose, with or without CoCl2-induced hypoxia. Cell survival was assessed by calcein-AM cell viability assays. Expression of heat shock proteins (Hsp) and redox proteins thioredoxin 1 and 2 (TRX1, TRX2) was studied by Western blots. The production of neurotrophic factors in Müller cells and interphotoreceptor retinoid-binding protein (IRBP) in photoreceptors was measured by enzymelinked immunosorbent assays. Aflibercept and ranibizumab did not affect the viability of both types of cells. Neither aflibercept nor ranibizumab affected the production of neurotrophic factors or expression of Hsp60 and Hsp90 in Müller cells. However, aflibercept but not ranibizumab affected the expression of Hsp60, Hsp9, TRX1 and TRX2 in photoreceptors. Aflibercept and ranibizumab both inhibited the production of IRBP in photoreceptors, aflibercept more so than ranibizumab. Our data indicates that the potential influence of aflibercept and ranibizumab on photoreceptors should be specifically monitored in clinical studies.

Purpose: To directly compare visual acuity (VA) outcomes with ranibizumab vs. aflibercept for eyes with neovascular age-related macular degeneration (nAMD) treated in routine clinical practice., Design: Database observational study., Participants: Treatment-naïve eyes with nAMD tracked by the Fight Retinal Blindness outcome registry that commenced anti-vascular endothelial growth factor therapy with ranibizumab or aflibercept between December 1, 2013, and January 31, 2015. Eyes were matched at baseline for VA, age, and choroidal neovascular membrane (CNV) size., Methods: Locally weighted scatterplot smoothing curves were used to display VA results. Eyes that switched or discontinued treatment were included with their last observation carried forward., Main Outcome Measures: Change in mean VA (number of letters read on a logarithm of the minimum angle of resolution chart); number of injections and visits; proportion of eyes with inactive CNV over 12 months., Results: We identified 394 eyes (197 treated with ranibizumab and 197 with aflibercept) from 372 patients who received treatment from 34 practitioners. Baseline parameters were well matched. The mean (standard deviation [SD]) VA of ranibizumab-treated eyes increased from 58.6 (20.3) letters at baseline to 62.3 (23.9) (+3.7 [95% confidence interval {CI} 1.4-6.1]) letters (P = 0.001), compared with 58.9 (19.2) letters at baseline to 63.1 (21.5) (+4.26 [95% CI 2.0-6.5]) letters (P < 0.001) for eyes receiving aflibercept. The difference in change in crude VA of 0.6 letters between the 2 groups was not statistically significant (P = 0.76), nor was the difference in adjusted mean VA of the 2 groups (P = 0.26). In completers, the mean (SD) numbers of injections (8.1 [2.1] vs. 8.0 [2.3]; P = 0.27) and visits (9.6 [3.0] vs. 9.5 [3.1]; P = 0.15) did not differ between the 2 groups. The adjusted proportion of eyes in which the CNV lesion was graded as inactive during the study was similar between the eyes receiving ranibizumab and aflibercept (74% vs. 77%, respectively; P = 0.63)., Conclusions: Visual acuity outcomes at 12 months did not differ between ranibizumab and aflibercept used for nAMD in this large observational study, nor was a difference in treatment frequency found., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aims: To examine 12-month outcomes of eyes switching from intravitreal ranibizumab to aflibercept for neovascular age-related macular degeneration (nAMD)., Methods: Database observational study of eyes with nAMD tracked by the Fight Retinal Blindness outcome registry that received ranibizumab for at least 12 months before switching to aflibercept and followed for at least 12 months after the switch. Visual acuity (VA) recorded at 12 months after the switch was analysed using locally weighted scatterplot smoothing curves. Lesion activity was graded according to a prospectively identified definition. Main outcomes were change in VA and treatment intervals 12 months after the treatment switch. Secondary outcomes included change in activity grading, effect of duration of treatment before switching and analysis of eyes that switched back., Results: A total of 384 eyes switched from ranibizumab to aflibercept after a mean duration of 39.8 months on the original treatment. The mean VA did not change from the time of switching treatment (63.4, SD 15.9 logarithm of the minimum angle of resolution letters) to 12 months later (63.3, SD 16.7). While 10% of eyes gained 10 or more letters 12 months after the switch, 13% lost the same amount. The mean number of injections decreased by around one injection in the 12 months after switching (p<0.001), with a decrease in the proportion of choroidal neovascular membrane lesions that were graded as active. Eyes that had been treated for the longest time (49 or more months) before switching had worse vision at the point of switch but neither change in VA nor treatment interval was different between groups. The small proportion (6.9%) of eyes that switched back again to ranibizumab had already lost a mean of 5.2 letters from the first switch to the switch back and continued to lose vision at a similar rate for at least 6 months., Conclusions: The mean VA of eyes that switched treatments from ranibizumab to aflibercept was not different 12 months later. There was a modest increase in treatment intervals and a somewhat greater proportion of eyes that were graded as inactive after the switch., Competing Interests: JJA, RG, APH, ILM and MCG are members of advisory boards for Novartis and Bayer. JJA and MCG are also members of advisory boards for Allergan. MCG, JJA, APH and RG report personal fees and others from Novartis, others from Bayer, outside the submitted work. DB and APH received a research grant from Novartis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To present the treatment patterns, disease activity, and visual outcomes of eyes in the maintenance phase of a treat-and-extend regimen for neovascular age-related macular degeneration (nAMD). To compare the maintenance phase behavior of eyes with a shorter induction phase (≤3 injections) with those requiring a longer induction phase (>3 injections)., Design: Database observational study., Participants: Eyes with nAMD receiving anti-vascular endothelial growth factor (VEGF) treatment using a treat-and-extend protocol. Persistently active eyes were excluded, as were eyes with <12 months follow-up during the maintenance phase., Methods: Clinical information from a large prospective international voluntary registry of nAMD was analyzed. The maintenance phase was defined as starting at the first clinician-reported grading of lesion inactivity., Main Outcome Measures: For analyses by eye: treatment interval at first reactivation; time to first reactivation; and visual acuity change during the study period. For analyses by visit: choroidal neovascular membrane activity graded by the treating physician; time since previous injection; and visual acuity loss since previous injection (>0 letters and ≥15 letters)., Results: The mean change in visual acuity during the maintenance phase was +1.0 letters at 12 months -0.6 letters at 24 months and -1.5 at 36 months. Median treatment interval increased from 35 days at study entry to 63 days at 12 months and was 60 days at 36 months. 38.5% of eyes remained inactive at all observed visits during the maintenance phase (minimum 1 year follow-up, mean 945 days). The most common treatment interval at first reactivation was 8 weeks. Treatment intervals beyond 12 weeks seemed to be associated with increased risk of disease reactivation, with risk of reactivation reaching 37.4% at treatment intervals of ≥20 weeks. Eyes with a longer induction phase had worse visual outcomes in the maintenance phase, and earlier and more-frequent disease reactivation, although they received injections less frequently., Conclusions: The detailed behavior of eyes in the maintenance phase of treat-and-extend management for nAMD is presented. Visual acuity was well maintained during the study period. The most common interval at which reactivation first occurred was 8 weeks. Longer duration of induction phase was associated with worse visual acuity outcomes and earlier disease reactivation, perhaps because of undertreatment., (Copyright © 2016 American Academy of Ophthalmology. All rights reserved.)

Purpose: To report the efficacy and safety of intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD) in real-world practice., Methods: Metaanalysis of ∼26,360 patients from 42 real-world observational studies reporting outcomes of intravitreal ranibizumab for nAMD published between 2007 and 2015. Baseline demographics, lesion type, and visual acuity (VA) were recorded. The weighted mean was calculated for change in VA and frequency of injections and visits during year 1, year 2, and ≥3 years. Local and systemic adverse events were recorded., Results: The mean change in VA for patients receiving a treat-and-extend regimen was +8.8 (95% confidence interval [CI]: 5.8 to 11.8), +6.7 (95% CI: 3.2 to 10.1), and +5.4 (95% CI: -4.1 to 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 1 year (n = 1,539), 2 years (n = 2,521), and ≥3 years (n = 1,298), in comparison with +3.5 (95% CI: 2.0 to 5.0), +1.3 (95% CI: -1.6 to 4.2), and -1.9 (95% CI: -9.8 to 6.0) ETDRS letters for pro re nata at 1 year (n = 20,247), 2 years (n = 14,408), and ≥3 years (n = 11,714). Treat-and-extend patients received on average more injections (6.9 vs. 4.7) but had fewer visits (7.6 vs. 9.2) in the first year. Baseline characteristics were similar between the regimens. The reported rate of endophthalmitis was 17 of 66,176 intravitreal injections (0.026%)., Conclusion: Intravitreal ranibizumab for nAMD prevents severe visual loss in real-world practice. Patients can achieve visual gain from baseline, but the extent to which these are maintained in the long term may depend on the frequency of injections.

Purpose: To compare 12‐month treatment outcomes of eyes receiving aflibercept or ranibizumab for macular oedema secondary to central retinal vein occlusion (CRVO) in routine clinical practice. Methods: 296 treatment‐naïve eyes receiving either aflibercept (171 eyes, 2 mg) or ranibizumab (125 eyes, 0.5 mg) for macular oedema secondary to CRVO were recruited retrospectively from centres using the prospectively designed FRB! registry. The primary outcome measure was the mean change in LogMAR letter scores of visual acuity (VA). Secondary outcomes included change in central subfield thickness (CST), injections and visits, time to first grading of inactivity, switching and non‐completion from baseline to 12 months. Results: Baseline VA (SD) was somewhat better in aflibercept‐ versus ranibizumab‐treated eyes (42.5 ± 25.5 letters versus 36.9 ± 26 letters; p = 0.07) with similar CST (614 (240) μm versus 616 (234) μm: p = 0.95). The 12‐month adjusted mean (95%CI) VA change was +16.6 (12.9, 20.4) letters for aflibercept versus +9.8 (5.5, 14.1) letters for ranibizumab (p = 0.001). The mean (95%CI) adjusted change in CST was significantly greater in aflibercept‐ versus ranibizumab‐treated eyes: −304 (−276, −333) µm versus −252 (−220, −282) µm (p < 0.001). Both groups had a median (Q1, Q3) of 7 (5, 9) injections and 10 (8,13) visits. Aflibercept‐treated eyes became inactive sooner than ranibizumab (p = 0.02). Switching occurred more commonly from ranibizumab (26 eyes, 21%) than from aflibercept (9 eyes, 5%) (p < 0.001). Conclusion: Both aflibercept and ranibizumab improved VA and reduced CST in eyes with CRVO in routine clinical practice, with aflibercept showing significantly greater improvements in this comparative analysis. [ABSTRACT FROM AUTHOR]

Background To study the visual outcomes of neovascular AMD (nAMD) treated with anti‐vascular endothelial growth factor (VEGF) drugs at national level. Methods: Multicenter national database of nAMD eyes treated with anti‐VEGF intravitreal injections (ranibizumab, aflibercept, bevacizumab) in fixed bimonthly (FB) or treat‐and‐extend (TAE) regimens. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) ETDRS letters at baseline and subsequent visits, number of injections and visits data were collected using a validated web‐based tool (Fight Retinal Blindness!). Results: 1273 eyes (1014 patients) were included, 971 treatment naïve (TN) and 302 previously treated (PT). Baseline VA (mean ± SD) was 57.5 (±19.5) and 62.2 (±17) (p > 0.001), and 24 months final VA was 60.4 (±21.2) and 58.8 (±21.1) (p = 0.326), respectively. Mean VA change at 12/24 months was +4.2/+2.9 letters in TN eyes and +0.1/−3.4 letters in PT eyes (p < 0.001/p < 0.001). The percentage of ≥15 letters gainers/losers at 24 months was 24.8%/14.5% in TN, and 10.3%/15.7% in PT eyes. The median number of injections/visits at 12 months was 7/9 in TN and 6/8 in PT (p = 0.002/p < 0.001) and at 24 months was 11/16 in TN and 11/14 in PT (p = 0.329/p < 0.001). Study drugs included ranibizumab (39.5%), aflibercept (41.2%) and bevacizumab (19.3%). Conclusion: Independent, large‐scale national audits are feasible if committed health care professionals are provided with efficient information technology systems to do them. The results described here represent an adequate measurement of the quality of care delivered nationwide and benchmark the clinical management of nAMD at a country level compared to other real‐world international cohorts. [ABSTRACT FROM AUTHOR]

Importance: To assess early outcomes of intravitreal vascular endothelial growth factor (VEGF) inhibitor treatment in neovascular age‐related macular degeneration (nAMD) before patients have a chance to miss or discontinue treatment. Background: Intravitreal VEGF inhibitors used to treat nAMD have been compared in various ways. The present study compared the 4‐week responses to the first injection of either aflibercept, bevacizumab, or ranibizumab. Design: Observational study. Participants: Treatment‐naïve nAMD patients with visual acuity (VA) taken 22 to 48 days after the first treatment with an intravitreal VEGF inhibitor. Methods: An observational study from a prospectively designed database. Main outcome measures: VA change from baseline and proportion of eyes judged active 22 to 48 days after the first treatment. Results: The overall mean (95% confidence interval [CI]) VA change at 4 weeks was +3.7 (3.3, 4.0) letters. No pairwise comparisons in crude VA change or VA change after multivariate adjustment between the three agents were significant. However, after multivariate adjustment, more eyes treated with bevacizumab (90%) had active disease 4 weeks after the first injection than ranibizumab (84%; P =.013) and aflibercept (82%; P =.004). Older age, higher baseline vision and larger lesions were associated with lower VA change. Conclusion: There was no significant difference in VA gains amongst all three drugs but ranibizumab and aflibercept seemed to be more efficacious in quelling disease activity 4 weeks after the first treatment. VA change after the first injection was driven largely by baseline characteristics such as age, baseline VA and lesion size. [ABSTRACT FROM AUTHOR]

Background: Retinal pigment epithelium (RPE) is known to secrete factors important for retinal homeostasis. How this secretome changes in diabetic eyes treated with anti‐vascular endothelial growth factor (VEGF) inhibitors is unclear. Methods: Diabetic conditions were simulated in vitro using ARPE‐19 cell‐line culture, with high glucose (25 mM) culture media, and hypoxia was chemically induced using cobalt chloride. Stress was assessed using cell viability assays as well as Western blots and enzyme‐linked immunosorbent assay (ELISA) for production of HIF‐1a and VEGF‐A. Production of neurotrophic factors was quantified once conditions were established using ELISA under stress with and without the addition of VEGF inhibitors. Changes were analysed with one‐way ANOVA. Results: Hypoxia downregulated pigment epithelium‐derived factor (PEDF) expression. The addition of bevacizumab, ranibizumab and aflibercept in normoxic conditions all led to a significant downregulation of PEDF. Glucose concentration had no effect on secretion of PEDF. Brain‐derived neurotrophic factor (BDNF) secretion was downregulated in high glucose and was upregulated in hypoxia. Placental growth factor (PlGF) secretion by ARPE‐19 was undetectable by ELISA. Conclusions: We found that hypoxia, high glucose or VEGF inhibitors affected secretion of neurotrophic factors. This variation under different conditions may influence neuron and photoreceptor survival in the diabetic state and VEGF inhibitor treated eyes. [ABSTRACT FROM AUTHOR]

Introduction: To report 12-month pharmacoepidemiologic data on aflibercept and ranibizumab use in treatment-naïve eyes with neovascular age-related macular degeneration (nAMD).Methods: Participants were treatment-naïve eyes with nAMD tracked by the Fight Retinal Blindness! registry starting therapy with aflibercept or ranibizumab treatment between January 1st, 2013 and 31st December, 2016. Demographic and clinical characteristics were compared between treatment groups.Results: During the study period, 689 eyes initiated treatment with ranibizumab compared to 568 with aflibercept. We found a similar rate of use of both drugs. Ranibizumab-treated patients were older than aflibercept-treated patients (overall mean [SD] 82.0 [8.4] vs. 78.6 [8.1], P < 0.001). Median (Q1, Q3) lesion size was significantly larger in aflibercept-treated patients (2450 μm [1242, 3000]) compared with ranibizumab patients (2000 μm [1148, 2890], P = 0.008). Eyes treated with ranibizumab and aflibercept received a similar mean number of injections in the first 3 months (3.1 [0.7] vs. 3.0 [0.6]; P = 0.233) and at 12 months (7.3 [2.4] vs. 7.2 [2.2]; P = 0.139). The 12-month switching rates from 2013 onwards for eyes completing 12 months of follow-up were much higher for switching from ranibizumab to aflibercept (19.2%) compared with switching from aflibercept to ranibizumab (5.4%). The proportion of eyes that did not complete 12 months of treatment was 23.2% for ranibizumab and 22.2% for aflibercept-treated groups.Conclusion: A similar rate of use for ranibizumab and aflibercept among Australian practitioners was observed between 2013 and 2016. Ranibizumab was used more often in older patients while aflibercept tended to be used more often in eyes with larger lesions. [ABSTRACT FROM AUTHOR]

Anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of retinal vascular diseases. However, constitutive VEGF also acts as a trophic factor on retinal non-vascular cells. We have studied the effects of aflibercept and ranibizumab on human Müller cells and photoreceptors exposed to starvation media containing various concentrations of glucose, with or without CoCl2-induced hypoxia. Cell survival was assessed by calcein-AM cell viability assays. Expression of heat shock proteins (Hsp) and redox proteins thioredoxin 1 and 2 (TRX1, TRX2) was studied by Western blots. The production of neurotrophic factors in Müller cells and interphotoreceptor retinoid-binding protein (IRBP) in photoreceptors was measured by enzyme-linked immunosorbent assays. Aflibercept and ranibizumab did not affect the viability of both types of cells. Neither aflibercept nor ranibizumab affected the production of neurotrophic factors or expression of Hsp60 and Hsp90 in Müller cells. However, aflibercept but not ranibizumab affected the expression of Hsp60, Hsp9, TRX1 and TRX2 in photoreceptors. Aflibercept and ranibizumab both inhibited the production of IRBP in photoreceptors, aflibercept more so than ranibizumab. Our data indicates that the potential influence of aflibercept and ranibizumab on photoreceptors should be specifically monitored in clinical studies. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes of intravitreal therapy from an observational study cohort with those of participants receiving treatment in the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab (MARINA) for the treatment of neovascular age-related macular degeneration (wet AMD). Design: Database observational study. Participants in the observational cohort were chosen to match demographic features and entry criteria of the treatment group from MARINA. Outcomes over 12 months were compared. Participants: Eight hundred twenty-one anti–vascular endothelial growth factor (anti-VEGF)-naïve eyes treated with ranibizumab with 12 months or more of follow-up were included in the total Fight Retinal Blindness! (FRB-All) cohort, whereas a subset of this cohort of 401 eyes who were matched to the MARINA treatment group were included as the FRB-MARINA cohort. Intervention: Intravitreal ranibizumab therapy of 0.5 mg for wet AMD. Methods: Visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) letters and treatments given were recorded continuously and anonymously in an electronic database for 12 months. Locally weighted scatterplot smoothing (LOESS) regression was used to plot change in visual acuity data over the course of 12 months for both the FRB-All cohort and the FRB-MARINA cohort, whereas results from the MARINA trial were taken from the published study report. Main Outcome Measures: Change in VA in logMAR letters over 12 months, treatment, and visit intensity. Results: Mean visual acuity improvement after 12 months in FRB-MARINA (+5.5 letters) was similar to that of the 0.5-mg group from MARINA (+7.2 letters). Improvement in FRB-ALL was slightly less (+4.9 letters). Mean treatment effect compared with the MARINA control group was similar for the MARINA treated group (+17.6 letters) and the FRB-MARINA cohort (+15.9 letters). A mean of 7.3 injections in 12 months was received by the observational cohorts. Conclusions: Similarity of mean VA improvement in the matched observational cohort with that of the phase 3 clinical trial suggests that these results can be achieved in real-world clinical practice with a modified treatment regimen. [ABSTRACT FROM AUTHOR]

Purpose To characterize in more detail routine treatment patterns of intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD), we analyzed the length of time and the number of injections required until lesions with choroidal neovascularization (CNV) were first graded inactive. Design Database observational study. Participants Treatment-naïve eyes receiving predominantly ranibizumab for nAMD in routine clinical practice that were tracked in the Fight Retinal Blindness! observational registry. Methods Eyes treated with ranibizumab were followed until CNV was first reported to be “inactive” (i.e., absence of intraretinal fluid and hemorrhages). Main Outcome Measures The length of time until lesion inactivation occurred and the number of injections required. Results A total of 1096 eyes (65.8% from women) were included in the study. The median number of weeks until a lesion was graded as inactive after beginning treatment was 15 weeks. One to 3 injections were sufficient to inactivate the lesion in 61.1% of eyes. A mean change in visual acuity of +5.5 logarithm of the minimum angle of resolution letters (95% confidence interval, 4.8–6.3) was found from treatment initiation to the time that eyes were reported as inactive. In eyes with a mean treatment frequency less than every 5.3 weeks, a median of only 3 injections (mean = 3.7) were required before lesions with CNV were graded as inactive, but if the mean treatment interval extended beyond 5.3 weeks, the median number of injections required increased sharply to 6 injections (mean, 7 injections). Occult lesions became inactive more slowly than classic lesions. Conclusions Most lesions with CNV became inactive with 3 injections of ranibizumab, but a small proportion remained active for more than 12 months. Injection frequency and lesion type were the main factors that predicted the time and number of injections required to render lesions inactive. [ABSTRACT FROM AUTHOR]

The article presents a clinical study which examines the efficacy of efficacy of intravitreal 0.5 miligram (mg) ranibizumab, antineoplastic agent, for the treatment of center-involving macular edema secondary to branch retinal vein occlusion (BRVO) as compare to standard-of-care grid laser. The study concluded that ranibizumab is significantly efficient as compare to standard care grid laser.

Purpose To assess the incidence, cumulative rate, and long-term outcomes of infectious and noninfectious endophthalmitis after intravitreal injections (IVTs) of anti-vascular endothelial growth factor (VEGF) agents. Design Database study, prospectively designed. Participants Treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) tracked by the Fight Retinal Blindness! (FRB!) registry that commenced anti-VEGF therapy between January 1, 2006, and November 30, 2016. Methods Cumulative rate of endophthalmitis and survival curves were measured using Cox-proportional hazards models. Locally weighted scatterplot smoothing curves were used to display visual acuity (VA). Main Outcome Measures Incidence and cumulative rate of endophthalmitis, and change in VA 12 months after endophthalmitis. Results Infectious endophthalmitis developed in 18 of 88 150 injections (1/4897 injections [0.020%]; 95% confidence interval [CI], 0.012–0.032) with no difference found between types of anti-VEGF medications ( P = 0.896). The cumulative rate of infectious endophthalmitis per patient was 0.055%, 0.183%, 0.360%, 0.360%, 0.555%, and 0.843% after 10, 20, 30, 40, 50, and 60 IVTs, respectively. However, the “risk” of infectious endophthalmitis did not increase with each successive injection ( P = 0.202). Noninfectious endophthalmitis developed in 11 of 88 150 injections (1/8013 injections [0.012%]; 95% CI, 0.006–0.022). The cumulative rate of noninfectious endophthalmitis per patient was 0.087% and 0.228% after 10 and 20 IVTs, respectively, and then remained stable up to 60 IVTs. The incidence of noninfectious endophthalmitis was higher for bevacizumab (8/9931, 0.081%) compared with ranibizumab (3/54 776, 0.005%; P = 0.005) and aflibercept (0/23 425; P = 0.016), and no differences were observed between ranibizumab and aflibercept ( P = 1.0). The 12-month VA in infectious and noninfectious endophthalmitis was within ±2 lines of before endophthalmitis in 53% and 75% of eyes, respectively; a loss >2 lines was observed in 31% and 25% of eyes, respectively. Conclusions The incidences of infectious and noninfectious endophthalmitis after IVT were low, and the risk did not increase with each successive injection. We found higher rates of noninfectious endophthalmitis with bevacizumab compared with ranibizumab or aflibercept. Three quarters of cases with infectious and two thirds of cases with noninfectious endophthalmitis retained vision within 10 letters of the pre-endophthalmitis level. [ABSTRACT FROM AUTHOR]