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Purpose: To evaluate visual acuity (VA) and injection intervals in patients with neovascular age-related macular degeneration (nAMD) after 12 months of brolucizumab therapy in clinical practice., Design: Retrospective cohort study., Participants: Adults in the United States-based IRIS® Registry (Intelligent Research in Sight) with nAMD who received brolucizumab exclusively for 12 months (2308 eyes of 2079 patients)., Methods: Observational study of eyes with a first injection of brolucizumab (index), followed by 2 or more brolucizumab injections over the following 12 months without switching to another anti-vascular endothelial growth factor (VEGF) agent., Main Outcome Measures: Primary outcomes were change in best recorded VA and, for eyes receiving prior anti-VEGF therapy (treatment-experienced eyes), the difference between the brolucizumab injection interval at 12 months and the anti-VEGF injection interval before switching. The interval before switching was defined as the time between the prior anti-VEGF and index brolucizumab injections; brolucizumab interval was the time between the closest injection to day 365 and the preceding injection. Secondary outcomes included incident adverse events., Results: Overall VA at index was 61.6 ± 18.4 Early Treatment Diabetic Retinopathy Study letters; 83.7% of treatment-naive eyes (184/220) and 86.1% of treatment-experienced eyes (1797/2088) showed stable (< 10 letters gained or lost) or improved (≥ 10 letters gained) VA at 12 months. Among treatment-experienced eyes receiving a prior anti-VEGF injection within 365 days before index, 29.5% (594/2015) showed an interval before switching of 8 weeks or more (mean, 7.6 ± 5.5 weeks), whereas 83.1% (1734/2015) showed a brolucizumab injection interval at 12 months of 8 weeks or more (mean, 10.3 ± 4.0 weeks). In all, 77.1% of treatment-experienced eyes (1554/2015) showed an interval extension of 1 week or more; of these, 55.4% (861/1554) showed an extension of 4 weeks or more., Conclusions: In this community-based study, at 12 months, brolucizumab treatment prolonged the interval between anti-VEGF injections for most treatment-experienced eyes, particularly those with shorter intervals before switching, while maintaining or improving VA. With careful balancing of the benefits and risks, switching to brolucizumab treatment may offer the advantage of extending the treatment interval for patients with a high anti-VEGF therapy burden., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To evaluate factors associated with anti-vascular endothelial growth factor (VEGF) injection interval extension in patients with neovascular age-related macular degeneration (nAMD) switched to brolucizumab treatment., Design: Retrospective, observational cohort study., Participants: Adults in the United States-based IRIS® Registry (Intelligent Research in Sight) with nAMD who switched from another anti-VEGF agent to brolucizumab-only treatment for ≥ 12 months from October 8, 2019, through November 26, 2021., Methods: Univariable and multivariable analyses examined associations of demographic and clinical characteristics with the likelihood of interval extension after switching to brolucizumab therapy., Main Outcome Measures: Eyes were classified as either extenders or nonextenders at 12 months. Extenders were eyes that achieved (1) an extension of ≥ 2 weeks in the brolucizumab injection interval at 12 months versus the interval before switching (time between the last known prior anti-VEGF injection and first [index] brolucizumab injection) and (2) stable (< 10 letters gained or lost) or improved (≥ 10 letters gained) visual acuity (VA) at 12 months versus VA at index injection., Results: Of 2015 eyes among 1890 patients who switched to brolucizumab treatment, 1186 (58.9%) were extenders. In univariable analyses, demographic and clinical characteristics were comparable between extenders and nonextenders, except that extenders had shorter intervals before switching versus nonextenders (mean, 5.9 ± 2.1 weeks vs. 10.1 ± 7.6 weeks, respectively). In multivariable logistic regression modeling, a shorter interval before switching was associated significantly and positively with interval extension with brolucizumab therapy (adjusted odds ratio, 5.6 for interval before switching of < 8 weeks versus ≥ 8 weeks; 95% confidence interval, 4.5-6.9; P < 0.001), and eyes with an index VA of 40 to 65 letters were significantly less likely to be extenders than eyes in the higher (better) index VA categories., Conclusions: Length of the treatment interval before switching was the characteristic associated most strongly with successful interval extension with brolucizumab. Treatment-experienced patients who required more frequent injections (i.e., shorter intervals before switching) showed the greatest extensions when switching to brolucizumab. With careful consideration of benefits and risks, brolucizumab may be a valuable option for patients with higher treatment burdens because of the need for frequent injections., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD)., Design: Phase 3, randomized, multicenter, open-label, active-comparator-controlled trial., Participants: Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy., Methods: Patients were randomized 3:2 to PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Patients were followed through 4 complete refill-exchange intervals (∼2 years)., Main Outcome Measures: Change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline averaged over weeks 44 and 48, weeks 60 and 64, and weeks 88 and 92 (noninferiority margin, -3.9 ETDRS letters)., Results: The PDS Q24W was noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 44/48, 60/64 and 88/92 of -0.2 (95% confidence interval [CI], -1.8 to +1.3), +0.4 (95% CI, -1.4 to +2.1) and -0.6 ETDRS letters (95% CI, -2.5 to +1.3), respectively. Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. The PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events of special interest (AESI) were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. The most common AESI reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations. Serum ranibizumab sampling showed that the PDS continuously released ranibizumab over the 24-week refill-exchange interval and ranibizumab serum concentrations were within the range experienced with monthly ranibizumab., Conclusions: The PDS Q24W showed noninferior efficacy to monthly ranibizumab through approximately 2 years, with approximately 95% of PDS Q24W patients not receiving supplemental ranibizumab treatment in each refill-exchange interval. The AESIs were generally manageable, with learnings continually implemented to minimize PDS-related AEs., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Neovascular (wet) age-related macular degeneration (nAMD) is driven by VEGFs A, C, and D, which promote angiogenesis and vascular permeability. Intravitreal injections of anti-VEGF-A drugs are the standard of care, but these do not inhibit VEGF-C and D, which may explain why many patients fail to respond fully. This trial aimed to test the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti-VEGF-A inhibitor ranibizumab., Design: Dose-ranging, phase 2b, randomized, double-masked, sham-controlled trial., Participants: Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, and the United States., Methods: Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab., Main Outcome Measures: The primary outcome was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks. Secondary outcomes (comparing baseline with week 24) were the proportion of participants gaining or losing ≥ 15 ETDRS BCVA letters; area under the ETDRS BCVA over time curve; change in spectral-domain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT., Results: Of 366 participants recruited from December 1, 2017, to November 30, 2018, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively. Mean (± standard deviation) visual acuity gain in the 2.0 mg OPT-302 group was significantly superior to sham (+14.2 ± 11.61 vs. +10.8 ± 11.52 letters; P = 0.01). The 0.5 mg OPT-302 group was not significantly different than the sham group (+9.44 ± 11.32 letters; P = 0.83). Compared with sham, the secondary BCVA outcomes favored the 2.0 mg OPT-302 group, with structural outcomes favoring both OPT-302 dosage groups. Adverse events (AEs) were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least 1 serious AE. Two unrelated deaths both occurred in the sham arm., Conclusions: Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favorable safety (ClinicalTrials.gov identifier: NCT03345082)., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2023 American Academy of Ophthalmology. All rights reserved.)

Objective: To evaluate treatment patterns and outcomes of patients in the United States who received antivascular endothelial growth factor (anti-VEGF) agents for wet age-related macular degeneration (AMD)., Design: Retrospective study PARTICIPANTS: Patients with wet AMD., Methods: Using the Intelligent Research in Sight Registry, we studied patients with wet AMD who received ≥1 anti-VEGF injection, who were ≥50 years old, and with ≥1.5 years of follow-up. Patients were grouped based on follow-up duration (in years): ≥1.5 (cohort 1), ≥2.5 (cohort 2), and ≥3.5 (cohort 3)., Results: Patient characteristics were similar between treatment groups. 36.8%, 34.5%, and 39.2% of ranibizumab, aflibercept, and all anti-VEGF eyes, respectively, had an injection interval <8 weeks in length at the end of year 1. Results were similar at year 2 and 3. In cohorts 1-3, visual acuity (VA) changes from baseline ranged from 0.3 to 0.7 (year 1), -1.3 to -1.7 (year 2), and -2.8 to -3.1 (year 3) Early Treatment Diabetic Retinopathy Study letters. By the end of year 3, 41%, 39%, and 42% of ranibizumab, aflibercept, and all anti-VEGF eyes, respectively, had discontinued treatment (no injection for >6 months)., Conclusion: Approximately one-third of eyes had injection intervals <8 weeks in length at the end of year 1. VA was slightly better at the end of year 1 and declined after the first year despite treatment. By the end of year 3, more than one-third of eyes had discontinued treatment. Given the high treatment burden, wet AMD patients may benefit from more durable approaches that require less frequent dosing., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyse the morphological characteristics of eyes with neovascular age-related macular degeneration (AMD) with good long-term visual acuity after anti-VEGF (vascular endothelial growth factor) therapy., Methods: Retrospective, observational study of 175 patients with neovascular AMD with >5 years of follow-up after initiating anti-VEGF therapy. Spectral-domain optical coherence tomography images were assessed for thickness of pigment epithelial detachment (PED), subretinal hyper-reflective material (SHRM), subretinal fluid and subfoveal choroidal, as well as the integrity of the outer retinal bands., Results: The final analysis cohort included 203 eyes (175 patients) followed for a mean of 7.84±1.70 years (range: 5-11). The maximum PED thickness in the foveal central subfield (FCS) was significantly lower (p<0.001) in the poor vision group (13.11 μm) compared with the intermediate (86.25 μm) or good (97.92 μm) vision groups, respectively. In contrast, the maximum thickness of SHRM in the FCS was significantly thicker (p<0.001) in eyes with poor vision (149.46 μm) compared with eyes with intermediate vision (64.37 μm) which in turn were significantly thicker (p<0.001) than eyes with good vision (9.35 μm). The good vision group also had better continuity of all outer retinal bands (external limiting membrane, ellipsoid zone, and retinal pigment epithelium) compared with the other two groups (all p<0.001)., Conclusion: A thicker PED and thinner SHRM were correlated with better vision in eyes with neovascular AMD following long-term anti-VEGF therapy. If replicated in future prospective studies, these findings may have implications for design of optimal anatomic endpoints for neovascular AMD treatment., Competing Interests: Competing interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. CW reported receiving grants, personal fees or nonfinancial support from Adverum, Aerie Pharmaceuticals, Aldeyra, Alimera Sciences, Allergan, Apellis, Arctic Vision, Arrowhead, Bausch + Lomb, Bayer, Bionic Vision Technologies, Boehringer Ingelheim, Chengdu Kanghong Biotechnologies (KHB), Clearside Biomedical, EyePoint, Gemini Therapeutics, Genentech, Graybug Vision, Gyroscope, IONIS Pharmaceutical, IVERIC Bio, Kato DSRC, Kodiak Sciences, LMRI, Neurotech Pharmaceuticals, NGM Biopharmaceuticals, Novartis, OccuRx, Ocular Therapeutix, ONL Therapeutics, Opthea, Outlook Therapeutics, Oxurion (formerly Thrombogenics), Palatin, Pentavision, PolyPhotonix, RecensMedical, Regeneron, RegenXBio, Roche, SAI MedPartners, SamChunDang Pharm., Santen, Senju, Taiwan Liposome Company, Takeda, Thea Open Innovation, Verana Health, Visgenx, Xbrane BioPharma. DS reported receiving grants, personal fees, or nonfinancial support from Amgen, Genentech, Heidelberg, Optovue, Regeneron, Topcon, Bayer, Iveric Bio, Novartis. SS reported receiving grants, personal fees, or nonfinancial support from Carl Zeiss Meditec, Nidek, Topcon, Heidelberg, Optos, Centervue, Amgen, Allergan, Genentech/Roche, Oxurion, Novartis, Regeneron, Bayer, 4DMT, Merck, Apellis, Astellas., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To identify optical coherence tomography (OCT) biomarkers, including thin and thick double-layer sign (DLS) for the progression from intermediate AMD (iAMD) to exudative macular neovascularization (MNV) over 24 months., Design: Retrospective cohort study., Methods: Setting: Retina consultants of Texas., Patient Population: 458 eyes of 458 subjects with iAMD in at least 1 eye with 24 months of follow-up data., Main Outcomes Measures: The following biomarkers were assessed at baseline: high central drusen volume (≥0.03 mm 3 ), intraretinal hyper-reflective foci (IHRF), subretinal drusenoid deposits, hyporeflective drusen cores, thick DLS, thin DLS, and central choroidal thickness. A binary logistic regression was computed to investigate the association between baseline OCT covariates and the conversion to exudative MNV within 24 months. In addition, fellow eye status was also included in the model., Results: During follow-up, 18.1% (83 of 458) of eyes with iAMD progressed to exudative MNV. Thick DLS, IHRF, and fellow eye exudative MNV were found to be independent predictors for the development of exudative MNV within 2 years. The baseline frequencies, odds ratios, 95% confidence intervals, and P values for these biomarkers were as follows: thick DLS (9.6%, 4.339, 2.178-8.644; P < .001), IHRF (36.0%, 2.340, 1.396-3.922; P = 0.001), and fellow eye exudative MNV (35.8%, 1.694, 1.012-2.837; P = .045)., Conclusions: Thick DLS, IHRF, and fellow eye exudative MNV were associated with an increased risk of progression from iAMD to exudative MNV. These biomarkers, which are readily identified by the review of OCT volume scans, may aid in risk prognostication for patients and for identifying patients for early intervention trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related macular degeneration (nAMD). MEDLINE, CENTRAL, and EMBASE were searched. Randomized-controlled trials and observational studies comparing T&E to PRN or fixed dosing for treatment-naïve AMD patients were included. Mean difference (MD) for visual acuity (VA) and number of injections are presented. Risk of bias was assessed according to Cochrane guidelines. Methodology was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). VA improvement was similar with T&E and fixed dosing at one (MD -0.08 letters, p = 0.95) and two years (MD 0.58 letters, p = 0.62). In contrast, VA improvements were significantly greater for T&E when compared against a PRN regimen at one (MD 3.95 letters, p < 0.0001) and two years (MD 4.08 letters, p < 0.001). Significantly fewer ranibizumab injections were administered in the T&E arm at one (MD -2.42 injections, p < 0.0001) and two years (MD -6.06 injections, p < 0.00001) relative to fixed dosing. Fewer aflibercept injections were likewise administered to patients on a T&E regimen versus fixed dosing at one year (MD -0.78 injections, p < 0.0001). Low-certainty evidence from the present synthesis implies that T&E preserves VA similar to fixed schedules with significantly fewer injections at one and two years. Also, patients with T&E dosing achieved better VA outcomes than those on PRN regimen but T&E dosing was associated with more injections., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To assess the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks compared with aflibercept 2 mg dosed every 4 weeks in eyes with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid., Design: Multicenter, randomized, double-masked phase 3a study., Participants: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment)., Methods: Eyes were randomized (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks up to and including week 100., Main Outcome Measures: The primary end point was analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 52 (margin, 4 letters). Other key end points included change in central subfield thickness (CST) from baseline to week 52, fluid-free status (no intraretinal fluid and no subretinal fluid), and safety., Results: At week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline (least squares mean difference, -0.6 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -2.1 to 0.9; P < 0.001). A total of 4.8% and 1.7% of participants reported a 15-letter or more BCVA loss from baseline at week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared with those treated with aflibercept, the CST was reduced significantly (P < 0.001), and a significantly greater proportion of eyes were fluid free at week 52 (40.4% brolucizumab vs. 19.0% aflibercept; 95% CI, 13.9-29.0; P < 0.001). Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab versus 4.5% (0% and 0%) for aflibercept, respectively., Conclusions: Visual acuity outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed every 4 weeks were noninferior to aflibercept 2 mg dosed every 4 weeks, with superior anatomic outcomes. However, incidences of IOI, including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To determine the association between central subfield thickness (CST) variability and visual outcomes in eyes with neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor therapies., Methods: In this post hoc, treatment-agnostic analysis, patients (N = 1,752) were grouped into quartiles of increasing CST variation. The association between CST variability and best-corrected visual acuity was measured from baseline, or from the end of the loading phase, until the end of the study using a multilevel modeling for repeated-measures model. The association between CST variability and the presence of retinal fluid was also assessed., Results: Increased CST variability was associated with worse best-corrected visual acuity outcomes at the end of study, with a least-square mean difference in best-corrected visual acuity of 8.9 Early Treatment Diabetic Retinopathy Study letters between the quartiles with the lowest and highest CST variability at the final visit. Increased variability was also associated with a higher mean fraction of visits with the presence of fluid., Conclusion: More stable CST was associated with better visual outcomes at the end of treatment suggesting that CST variability may provide a more reliable prognostic marker of visual outcomes than the presence of fluid alone, with the potential to enhance the clinical care of neovascular age-related macular degeneration patients., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Objectives: To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial., Design: Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA)., Subjects: Patients with GA secondary to age-related macular degeneration (AMD), n = 246., Intervention: Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period., Main Outcome Measures: 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., Results: 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%; P < 0.0001), 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., Conclusions: 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., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration, as evidenced by clinical trials that have used these features for inclusion criteria, retreatment criteria, and outcome measures of the efficacy of intravitreal injections of anti-vascular endothelial growth factor agents., Methods: A literature review of anatomical measures of disease activity was conducted., Results: Treatment goals for neovascular age-related macular degeneration include improving/maintaining vision by drying the retina, and several analyses have evaluated the relationship between visual function and anatomy. The change in retinal thickness has been found to correlate with the change in the visual acuity, and variation in retinal thickness may predict visual acuity outcomes. In addition, specific fluid compartments may have different prognostic values. For example, the presence of intraretinal fluid has been associated with poorer visual acuity, whereas the presence of subretinal fluid has been associated with better visual acuity. Retinal fluid and thickness are important for selecting dosing interval durations in clinical trials and clinical practice., Conclusion: Retinal thickness and retinal fluid are common anatomical measures of disease activity in neovascular age-related macular degeneration. Further research is required to fully elucidate the relationship between anatomical features and visual outcomes in neovascular age-related macular degeneration., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD)., Design: Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data., Participants: The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters., Methods: At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630)., Main Outcome Measures: Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs)., Results: For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 μm, -146 μm, and -142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively., Conclusions: Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide and is the most common cause of blindness in developed countries. Despite antivascular endothelial growth factor (anti-VEGF) therapy demonstrating improvements in visual and anatomical outcomes, unmet needs remain. Brolucizumab-dbll (ie, brolucizumab), a VEGF inhibitor for treatment of neovascular (wet) AMD and recently approved by the FDA for its treatment of wet AMD, attempts to mitigate treatment burden through less frequent injections. OBJECTIVE: To assess the incremental cost-effectiveness of brolucizumab compared with aflibercept and ranibizumab, given similar costs per injection and the potential for longer dosing intervals based on phase 3 clinical trial data. METHODS: A Markov model was developed to model the treatment of wet AMD patients with brolucizumab vs aflibercept and vs ranibizumab over a lifetime time horizon (base case) and 5-year time horizon (scenario analysis). The Markov model consisted of 3 primary health states: on treatment, off treatment, and death. Markov substates (5 total) described visual acuity (VA) ranging from no vision impairment to blindness. These VA-based substates were defined by best-corrected visual acuity (BCVA) values measured using Early Treatment Diabetic Retinopathy Study letters. Fixed-dosing regimens for each therapy were included in the model: dosing every 4 weeks (q4w) for the first 3 months followed by dosing q8w/q12w for brolucizumab, dosing q4w for the first 3 months followed by dosing q8w for aflibercept, and q4w for ranibizumab. RESULTS: In the base case, brolucizumab was less costly than aflibercept ($63,614 vs $72,189), and brolucizumab generated 0.0079 more quality-adjusted life-years (QALYs) than aflibercept (4.580 vs 4.572). Lower total costs with brolucizumab were driven by reduced drug costs ($56,432 vs $64,057), reduced administration costs ($6,013 vs $6,825), and reduced monitoring costs ($1,168 vs $1,306). When evaluating the cost-effectiveness of brolucizumab over a 5-year time horizon, brolucizumab was less costly than aflibercept ($44,644 vs $50,772) and generated an additional 0.0049 QALYs (2.953 vs 2.948). Additionally, brolucizumab was less costly than ranibizumab ($63,614 vs $128,163) and generated 0.0078 more QALYs than ranibizumab (4.580 vs 4.572) in the base case. Lower total costs with brolucizumab were driven by reduced drug costs ($56,432 vs $114,516), reduced administration costs ($6,013 vs $11,541), and reduced monitoring costs ($1,168 vs $2,107). When evaluating the cost-effectiveness of brolucizumab over a 5-year time horizon, brolucizumab was less costly than ranibizumab ($44,644 vs $89,665), and brolucizumab generated an additional 0.0046 QALYs (2.953 vs 2.948). CONCLUSIONS: Brolucizumab can be cost saving and cost-effective compared with aflibercept and ranibizumab in the treatment of wet AMD. DISCLOSURES : Novartis Pharmaceuticals Corporation provided funding to Xcenda for the cost-effectiveness analysis and preparation of this manuscript. Carlton is an employee of Xcenda. Agashivala is employed by Novartis Pharmaceuticals Corporation; Yu was an employee of Novartis Pharmaceutical Corporation at the time of this study. Hassan reports personal fees from iOPEN, BVI/Visitrec, ArcticDx, Bayer, F. Hoffmann-La Roche Ltd, Broadspot, BMC, Katalyst Surgical, Alcon, Vitreq, Surgicube, personal Ocugenix, Regeneron, Allergan, Oculus Surgical, Novartis, Genentech, and Eyepoint, unrelated to this work. Wykoff reports personal fees from Corcept Therapeutics, DORC, EyePoint, Gyroscope, IVERIC Bio, Merck, Notal Vision, ONL Therapeutics, Oxurion, Palatin, PolyPhotonix, Takeda, Thea Open Innovation; grants from Aerie Pharmaceuticals, Aldeyra, Gemini Therapeutics, Graybug Vision, IONIS Pharmaceutical, LMRI, Mylan, Neurotech Pharmaceuticals, Outlook Pharmaceuticals, Samsung Bioepis, Senju, Taiwan Liposome Company, Xbrane BioPharma, Santen; and grants and personal fees from Adverum, Allergan, Apellis, Chengdu Kanghong Biotechnologies (KHB), Clearside Biomedical, Genentech, Kodiak Sciences, NGM Biopharmaceuticals, Novartis, Opthea, Recens Medical, Regenxbio, Roche, and Regeneron, unrelated to this work. This research was presented as a virtual poster at the AMCP 2020 Annual Meeting, April 2020.

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 <125 μm), at least 1 large druse (≥125 μm), and/or retinal pigmentary changes, and eAMD in the fellow eye. Patients were treated from June 23, 2015, to March 13, 2019., Interventions: Intravitreal aflibercept injection (2 mg) or sham quarterly injection for 24 months (1:1 randomization)., Main Outcomes and Measures: The primary end point was the proportion of patients with conversion to eAMD at month 24 characterized by development of choroidal neovascularization, as assessed by leakage on fluorescein angiography and fluid on spectral-domain optical coherence tomography by an independent masked reading center., Results: Of 128 patients enrolled, 127 (63 in the IAI group and 64 in the sham group) were included in the primary analysis (68 men [53.5%]; mean [SD] age, 76.5 [8.1] years). Baseline demographic and clinical characteristics were balanced between the groups. By month 24, 6 patients (9.5%) in the IAI group and 7 (10.9%) in the sham group developed eAMD (P = .98). Patients with a history of eAMD for longer than 2 years in their fellow eye at baseline showed a lower rate of conversion to eAMD in the study eye compared with those with a history of eAMD for 2 years or less in the fellow eye. Safety was consistent with previous studies involving intravitreal anti-VEGF injections., Conclusions and Relevance: In this evaluation of quarterly anti-VEGF exposure as prophylaxis to reduce conversion of eyes with high-risk dry AMD to eAMD, the rates of conversion were not lower in the IAI group compared with the sham treatment group at month 24. Understanding the mechanism of conversion to eAMD and therapies that could prevent this event remains an important unmet need., Trial Registration: ClinicalTrials.gov Identifier: NCT02462889.

Purpose: To evaluate the real-world utility of the ForeseeHome monitoring device (Notal Vision, Ltd., Tel Aviv, Israel) for the detection of conversion from intermediate age-related macular degeneration (iAMD) to neovascular AMD (nAMD) and to compare with results published by the Home Monitoring of the Eye (HOME) study., Design: Retrospective analysis of electronic health records., Participants: Eyes prescribed use of the ForeseeHome device across 4 retinal practices in the United States., Methods: Usage information was collected from the online ForeseeHome portal for all eyes prescribed the device. For a predetermined subset of eyes, additional clinical information was collected through chart review and analyzed for clinical utility., Main Outcome Measures: Frequency and length of use, number of eyes that used the device, number of eyes that established a baseline measurement, number of eyes that converted to nAMD, and number of alerts., Results: Seven hundred seventy-five eyes of 448 patients were prescribed use of the ForeseeHome device. Six hundred forty-nine eyes (83.7%) used the device at least once; among this population, 478 (73.7%) established a baseline measurement. Patients who established a baseline measurement were significantly younger than those who did not (P < 0.001). Among eyes that established a baseline measurement, 126 (26.4%) had an overall inadequate frequency of use (≥2 tests per week), and 250 (52.3%) did not use the device as frequently as instructed by the manufacturer (≥3 tests per week); 24.7% of eyes discontinued use within 1 year. Of the 136 eyes that established a baseline measurement among 211 eyes prescribed the device at 1 clinical site, 52 alerts were recorded; 3 (6.8%) correctly identified conversion to nAMD and 47 (93.2%) represented false-positive alerts., Conclusions: Compared with the prospective HOME study, the utility of the ForeseeHome device in the current analysis of clinical practice application was limited. A meaningful proportion of eyes never used the device or could not establish a baseline measurement. Overall frequency of use was low, and continuous use of the device decreased over time. A need exists for improvement in home monitoring technology for eyes with iAMD at risk of conversion to nAMD., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) versus ranibizumab every 4 weeks in treatment-naïve patients with neovascular age-related macular degeneration (AMD)., Design: Two randomized, multicenter, double-masked, parallel-group, active-controlled, phase 3 clinical trials (CEDAR, SEQUOIA) with identical protocols were conducted. Data from both trials were pooled for analysis., Participants: Patients with active choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) of 24-73 Early Treatment Diabetic Retinopathy Study letters in the study eye were enrolled., Methods: Patients (n = 1888) were randomized in a 1:1:1 ratio to study eye treatment with abicipar 2 mg every 8 weeks after 3 initial doses at baseline and weeks 4 and 8 (Q8), abicipar 2 mg every 12 weeks after 3 initial doses at baseline and weeks 4 and 12 (Q12), or ranibizumab 0.5 mg every 4 weeks (Q4)., Main Outcome Measures: The primary efficacy end point was proportion of patients with stable vision (defined as <15-letter loss in BCVA from baseline) in the study eye at week 52. Secondary end points included change from baseline in BCVA and central retinal thickness (CRT) at week 52. Safety measures included adverse events (AEs)., Results: The proportion of patients with stable vision at week 52 was 93.2%, 91.3%, and 95.8% in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively, with both abicipar Q8 and Q12 noninferior to ranibizumab Q4. Week 52 mean change from baseline in BCVA was 7.5, 6.4, and 8.4 letters and in CRT was -144, -145, and -144 μm in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3%, respectively. The IOI AEs were typically mild or moderate in severity and treated with topical corticosteroids; 62 of 192 patients (32.3%) received oral and/or injectable corticosteroids., Conclusions: Abicipar Q8 and Q12 were both noninferior to ranibizumab Q4 in the primary end point of stable vision at week 52. Intraocular inflammation was more frequent with abicipar. Quarterly and Q8 abicipar reduce nAMD disease and treatment burden compared with monthly treatment., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To assess anti-vascular endothelial growth factor (VEGF) management patterns and anatomic and visual acuity (VA) outcomes among patients with neovascular age-related macular degeneration (nAMD) in United States clinical practice., Design: Retrospective observational cohort study., Participants: Patients (N = 30 106) initiating intravitreal anti-VEGF treatment for nAMD between October 2009 and November 2016., Methods: Analysis of longitudinal electronic health records from USRetina., Main Outcome Measures: Number of intravitreal injections, OCT examinations, and fluorescein angiography (FA) examinations per study eye during the first 12 months; corrected VA and central retinal thickness (CRT) at 12 months; and number of ophthalmologist visits, stratified by index anti-VEGF agent., Results: Over the first 12 months, patients made a mean of 8.1 (range, 1-39) ophthalmologist visits, received a mean of 6.0 (range, 1-27) anti-VEGF injections, and underwent 7.2 OCT and 5.3 FA examinations per study eye. For eyes with paired baseline and 12-month readings, mean CRT declined from 320 to 271 μm (mean change, -48 μm), and mean VA increased from 60.3 to 61.0 approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letters (mean change, +0.6 letters). Twelve months after initiating index treatment with bevacizumab, ranibizumab, and aflibercept, 19.3%, 15.8%, and 15.5% of eyes, respectively, showed greater than 10-letter gain, whereas 13.2%, 14.7%, and 14.4% of eyes, respectively, showed greater than 10-letter loss. Mean change from baseline VA at 12 months increased linearly with cumulative anti-VEGF injection count: +1.79 versus -0.95 approximate ETDRS letters for eyes receiving 7 or more injections versus fewer than 7 injections. Similarly, the magnitude of the reduction from baseline CRT at 12 months tended to increase linearly with increasing number of anti-VEGF injections. Multivariate linear regression analysis, adjusted for covariates, indicated a significant association between cumulative number of anti-VEGF injections and change from baseline in VA at 12 months, with each unit increase producing an estimated gain of 0.37 approximate ETDRS letters., Conclusions: This analysis of combined morphologic and functional outcomes of anti-VEGF therapy, the largest conducted to date in nAMD, identified relatively low anti-VEGF injection frequencies, coupled with moderate anatomic and limited VA improvements, in United States clinical practice., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the efficacy and safety of intravitreal aflibercept + anti-platelet-derived growth factor receptor β (PDGFRβ) combination with intravitreal aflibercept injection (IAI) monotherapy in patients with treatment-naïve neovascular age-related macular degeneration (nAMD)., Design: Phase 2, randomized, double-masked study., Participants: A total of 505 patients (eyes) with nAMD., Methods: Patients were randomized 1:2:2 to low-dose combination intravitreal anti-PDGFRβ 1 mg and aflibercept 2 mg (LD combo), high-dose combination intravitreal anti-PDGFRβ 3 mg and aflibercept 2 mg (HD combo), or IAI alone every 4 weeks through week 12. At week 12, patients in the HD combo and IAI groups were re-randomized to continue as assigned or switch to HD combo → IAI or IAI → HD combo and dosed every 4 weeks through week 28. During weeks 28 to 52, patients received treatment as needed per prespecified criteria. This report presents efficacy through week 28 and safety through week 52., Main Outcome Measures: Mean best-corrected visual acuity (BCVA) change from baseline at week 12 (primary end point)., Results: At week 12, mean BCVA gains from baseline were 5.8, 5.8, and 7.5 letters with LD combo, HD combo, and IAI, respectively (P = 0.21 for LD combo and P = 0.10 for HD combo vs. IAI). The corresponding proportions of eyes that gained ≥15 letters were 12%, 19%, and 22%, respectively. Mean reductions in central retinal thickness from baseline were 126.1, 127.1, and 126.9 μm, respectively. Proportions of eyes with complete resolution of fluid from baseline were 35%, 24%, and 42%, respectively. Vision and anatomic outcomes at week 28 were consistent with the week 12 results. Through week 52, the incidence of intraocular inflammation was 1.0%, 7.5%, 2.1%, 2.1%, and 0%, respectively. The incidence of Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events was 1.9%, 0.9%, 1.1%, 2.1%, and 1.9%, respectively., Conclusions: Intravitreal aflibercept + anti-PDGFRβ did not improve BCVA over IAI alone. Anatomic outcomes evaluating complete fluid resolution favored IAI. Adverse events were consistent with the reported IAI safety profile, except for a higher frequency of intraocular inflammation in the HD combo group., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Characterize eyes managed with quarterly intravitreal anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration (nAMD)., Patients and Methods: Treatment-naïve nAMD eyes managed predominately using a treat-and-extend approach that received five or more consecutive quarterly injections from 2005 to 2017., Results: One hundred fifty eyes were retrospectively identified. During quarterly dosing, a mean of 9.8 injections were given over a mean of 29 months. Ninety-one eyes (61%) had no exudative disease recurrence during quarterly dosing. Thirty-three eyes (22%) experienced exudative activity recurrence, with a mean cumulative yearly recurrence rate of 12% and a mean 6-letter loss of visual acuity (VA). Twenty-four eyes (16%) stopped quarterly treatments; nine (38%) of these subsequently experienced exudative activity recurrence with a mean 8-letter VA loss., Conclusion: In this real-world analysis of nAMD managed with quarterly dosing over a mean of more than 2 years' follow-up, 22% experienced disease recurrence during quarterly dosing, and 38% of eyes that stopped quarterly dosing experienced subsequent exudative disease recurrence. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e250-e256.]., (Copyright 2019, SLACK Incorporated.)

Purpose: To quantify the extent of topographic correspondence between baseline (BSL) choroidal neovascularization (CNV) and macular atrophy (MA) at follow-up in eyes with neovascular age-related macular degeneration (NVAMD)., Design: Post hoc analysis of randomized controlled clinical trial data., Methods: Sixty treatment-naïve NVAMD patients from the TREX-AMD trial were followed for 18 months. Regions of month 18 macular atrophy (MA) were graded on fundus autofluorescence (FAF) with guidance of spectral-domain optical coherence tomography (SDOCT). CNV lesions were graded manually on fluorescein angiography (FA) with lesion components including classic and occult CNV delineated. FAF and FA images were registered to quantitate area and location of overlap between CNV and MA. Outcome measures included overlap of month 18 MA to BSL CNV subtype and progression of MA from BSL to month 18., Results: Twenty-six eyes had both MA at month 18 and CNV at BSL. A total of 84.6% of eyes showed evidence of MA and CNV overlap. MA appeared by month 18 in regions corresponding to BSL classic CNV in 36.4% of eyes and occult CNV in 40.9%, and in both regions in 22.7%, with more area of MA (AMA) in regions of occult than classic CNV. MA position at BSL corresponded to BSL classic CNV in 76.9% of eyes and occult CNV in 61.5%, and to both regions in 15.4%, with more AMA in regions of occult than classic CNV. Among eyes with MA and CNV at BSL but with no overlap, 50% progressed to involve regions with BS -CNV. Six eyes had no BSL MA but developed MA at month 18 within regions of BSL CNV., Conclusions: In ranibizumab-treated eyes with NVAMD, more MA lesions develop within the region of baseline CNV (type 1, CNV-based MA) than outside (type 2, CNV-independent MA). Baseline-MA also tends to be located within regions of CNV in the pretreatment phase., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Our purpose was to evaluate the relationship between subfoveal choroidal thickness (SCT) and development of macular atrophy (MA) in eyes with age-related macular degeneration (AMD)., Methods: This was a prospective, multicenter study. Sixty participants (120 eyes) in the TREX-AMD trial (NCT01648292) with treatment-naïve neovascular AMD (NVAMD) in at least one eye were included. SCT was measured by certified reading center graders at baseline using spectral domain optical coherence tomography (SDOCT). The baseline SCT was correlated with the presence of MA at baseline and development of incident MA by month 18. Generalized estimating equations were used to account for information from both eyes., Results: Baseline SCT in eyes with MA was statistically significantly less than in those without MA in both the dry AMD (DAMD) (P = 0.04) and NVAMD (P = 0.01) groups. Comparison of baseline SCT between MA developers and non-MA developers revealed a statistically significant difference (P = 0.03). Receiver operating characteristic curve (ROC) analysis showed the cut-off threshold of SCT for predicting the development of MA in cases without MA at baseline was 124 μm (AUC = 0.772; Sensitivity = 0.923; Specificity = 0.5). Among eyes without MA at baseline, those with baseline SCT ≤124 μm were 4.3 times more likely to develop MA (Odds ratio: 4.3, 95% confidence interval: 1.6-12, P = 0.005) than those with baseline SCT >124 μm., Conclusions: Eyes with AMD and MA had less SCT than those without MA. Eyes with less baseline SCT also appear to be at higher risk to develop MA within 18 months.

Purpose: To compare the enlargement rate of macular atrophy (ERMA) in eyes treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for neovascular age-related macular degeneration (AMD) or fellow control eyes, as well as analyze risk factors for macular atrophy (MA) development and progression., Design: Eighteen-month, multicenter, randomized, controlled clinical trial., Participants: Sixty patients with treatment-naïve neovascular AMD in 1 eye randomized 1:2 to monthly or TREX ranibizumab., Methods: Patients' study and fellow eyes were followed for 18 months using spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was quantified on FAF images using Heidelberg Region Finder software (Heidelberg Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by SD OCT and infrared reflectance imaging. For eyes without baseline MA yet developed MA by 18 months, intervening visits were assessed to determine the first visit at which MA appeared to define progression rates. Foveal choroidal thickness (FCT), subretinal hyperreflective material (SHRM), and pigment epithelial detachment (PED), were assessed at baseline to determine whether they influenced MA progression., Main Outcome Measures: Mean ERMA at 18 months. Relationship between visual acuity and MA, and the baseline risk factors for ERMA were also assessed., Results: The final analysis cohort included 88 eyes in 3 groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean ERMA over 18 months was 0.39±0.67 (monthly), 1.1±1.9 (TREX), and 0.49±1 mm 2 (control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline patients with MA was 0.9±1, 1.9±2.2, and 1±1.3 mm 2 , respectively (P = 0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%, respectively. Mann-Whitney U test revealed a statistically significant association between baseline FCT (127±46 vs. 155±55 μm, P = 0.01) and SHRM thickness (106±131 vs. 50±85 μm, P = 0.02) on MA. In eyes with no baseline MA, presence of SHRM, SHRM, and PED thickness, and presence of baseline hemorrhage were all significant predictors of new MA development (P = 0.04, 0.01, 0.04, 0.004, 0.01, respectively)., Conclusions: Ranibizumab did not show a statistically significant influence on new MA development in eyes with neovascular AMD, whether dosed monthly or per TREX regimen. The FCT, SHRM thickness, and hemorrhage at baseline were all significant predictors of new MA., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess prospectively a treat-and-extend (TREX) management strategy compared with monthly dosing of intravitreal ranibizumab in treatment-naïve neovascular age-related macular degeneration (AMD) patients., Design: Phase IIIb, multicenter, randomized, controlled clinical trial., Participants: Sixty patients with treatment-naïve neovascular AMD randomized 1:2 to monthly or TREX management., Methods: Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) from 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or according to a TREX protocol. The TREX patients were treated monthly for at least 3 doses, until resolution of clinical and spectral-domain optical coherence tomography evidence of exudative disease activity; the interval between visits then was individualized according to a strict prospective protocol., Main Outcome Measures: Mean ETDRS BCVA change from baseline., Results: At baseline, mean age was 77 years (range, 59-96 years), mean BCVA was 20/60 (Snellen equivalent), and mean central retinal thickness (CRT) was 511 μm. Fifty-seven eyes (95%) completed month 12, at which point mean BCVA improved by 9.2 and 10.5 letters in the monthly and TREX cohorts, respectively (P = 0.60). The mean number of injections administered through month 12 was 13.0 and 10.1 (range, 7-13) in the monthly and TREX cohorts, respectively (P < 0.0001). Among TREX patients, 7 (18%) were maximally extended, 4 (10%) demonstrated fluid at every visit, and at month 12, 18 (45%) had achieved an extension interval of 8 weeks or more; the mean maximum extension interval between injections after the first 3 monthly doses was 8.4 weeks (range, 4-12 weeks). Most TREX patients who demonstrated recurrent exudative disease activity (17/24 [71%]) were unable to extend beyond their initial maximum extension interval., Conclusions: The TREX neovascular AMD management strategy used in this prospective, randomized, controlled trial resulted in visual and anatomic gains comparable with those obtained with monthly dosing., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Assess the efficacy of intravitreal aflibercept on pigment epithelial detachments (PED) associated with previously treated patients with neovascular age-related macular degeneration (AMD)., Design: Retrospective study., Participants: Sixty eyes., Methods: Patients with persistent PED who were treated with intravitreal aflibercept (2.0 mg) with ≥2 previous injections of bevacizumab (1.25 mg) or ranibizumab (0.5 mg) were analyzed., Results: Mean number of prior injections was 24.8 during a mean of 32 months of management (range 3-77 months). Baseline mean PED height was 258 µm (range 80-687 µm), which decreased at 1, 6, and 12 months upon switching to aflibercept to 226 µm (-14%, range 34-701 µm), 215 µm (-18%, range 0-666 µm), and 208 µm (-22%, range 0-752 µm), respectively. The majority of eyes experienced a decrease in PED height after switching to aflibercept: 50/58 (86%), 38/47 (81%), and 37/47 (79%) at months 1, 6, and 12, respectively. Reduction in PED height was weakly correlated with improved visual acuity (R(2) = 0.11)., Conclusions: Intravitreal aflibercept resulted in significant reduction in PED height in previously treated eyes with neovascular AMD., (Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Aim: To determine the efficacy of 2.0 mg aflibercept in the management of patients with recalcitrant exudative age-related macular degeneration (AMD)., Methods: In this prospective, open-label, single-arm clinical trial, patients were seen monthly and given mandatory 2.0 mg aflibercept at baseline, months 1, 2 and 4. Pro re nata (PRN) retreatment at months 3 and 5 was performed upon evidence of disease on spectral domain-optical coherence tomography (SD-OCT). End point at month 6: mean change in Early Treatment Diabetic Retinopathy Study best corrected visual acuity (ETDRS BCVA) and central subfield thickness (CST), mean number of aflibercept injections, percentage of PRN injections required, patients with no fluid on SD-OCT and patients losing >15 letters., Results: At baseline, 46 patients with a mean of 42 prior antivascular endothelial growth factor-A (anti-VEGF) intravitreal treatments had a mean of 74.2 letters (Snellen equivalent 20/32) and mean CST of 347 µm. ETDRS letters remained stable throughout the trial; at month 6, mean BCVA change was +0.2 letters (range -10 to +13, p=0.71). Anatomically, mean CST improved significantly from baseline at each study visit including -23.6 µm at month 1 and -27.3 µm at month 6 (p=0.018). Seventy-one of 90 (79%) possible PRN injections were required and a mean of 5.6 aflibercept injections out of the maximum six were administered. Ten of 45 (22%) patients had no retinal fluid on SD-OCT at month 6. No patient lost >15 letters., Conclusions: Aflibercept 2.0 mg treatment maintained mean visual acuity improvements previously achieved with high-dose 2.0-mg ranibizumab injections in recalcitrant wet AMD patients. Aflibercept 2.0 mg treatment led to significant anatomic improvement and was required monthly in most patients., Clinical Trials Registration: FDA IND#12462. NCT 01543568., Trial Details: IND 12462, NCT 01543568 http://clinicaltrials.gov/show/NCT01543568., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To compare the sensitivity of commonly used time-domain (TD-OCT) and spectral-domain optical coherence tomography platforms and scanning modalities in the management of neovascular age-related macular degeneration in a population with a high prevalence of exudative disease activity., Methods: Fifty consecutive patients within the prospective SAVE (Super-dose Anti-Vascular Endothelial growth factor) trial, which analyzed the utility of 2.0 mg intravitreal ranibizumab for the treatment of recalcitrant neovascular age-related macular degeneration, were enrolled in a comparison trial of 3 different optical coherence tomography (OCT) platforms. Stratus TD-OCT radial scan (Carl Zeiss Meditec, Inc) was compared with 3 Heidelberg Spectralis Heidelberg Retinal Angiograph+OCT (Heidelberg Engineering) acquisition settings (radial, 7-line raster, volumetric) and 2 Cirrus high definition (HD)-OCT (Carl Zeiss Meditec, Inc) acquisition settings (5-line raster, volumetric)., Results: Using every imaging platform and acquisition setting, evidence of exudative disease activity was positively identified in 163 of 191 patient visits (85.3%). Intraretinal cysts were identified in 83 of 191 visits (43.5%), and subretinal fluid was identified in 116 of 191 visits (60.7%). Of these positive visits, the Stratus TD-OCT radial scanning technology demonstrated a significantly lower rate of detection (71.8%) when compared with the Spectralis HRA+OCT spectral domain scanning modalities (radial 87.1%, P < 0.001; 7-line raster 92.0%, P < 0.001; volumetric 94.5%, P < 0.001) or the Cirrus HD-OCT spectral domain scanning modalities (5-line raster 81.6%, P = 0.001; volumetric 92.0%, P < 0.001). Intraretinal cysts and subretinal fluid were identified in 83 visits (43.5%) and 116 visits (60.7%), respectively, with 36 eyes (18.8%) having fluid in both locations. No individual imaging modality demonstrated a diagnostic advantage for detecting subretinal fluid versus intraretinal cysts (e.g., Cirrus volume detected 86.7% of intraretinal cysts and 88.8% of subretinal fluid, P = 0.33)., Conclusion: In this neovascular age-related macular degeneration patient population, spectral-domain ocular coherence tomography was a superior diagnostic tool when compared with TD-OCT, with each spectral domain platform and acquisition setting identifying significantly more exudative disease activity. The two spectral domain platforms (Cirrus and Spectralis) were not directly compared because identical image acquisition parameters were not used. No individual imaging modality demonstrated a diagnostic advantage for detecting subretinal fluid versus intraretinal cysts.

Objectives: To assess durability of visual and anatomic gains with 2.0 mg ranibizumab in recalcitrant neovascular age-related macular degeneration (AMD)., Methods: Phase I-II trial of 88 patients with recalcitrant neovascular AMD treated as needed every 4 (cohort A) or 6 weeks (cohort B) following three monthly doses. ETDRS refraction and spectral-domain OCT-guided as-needed re-treatments., Results: Seventy-nine patients completed the 12-month endpoint and were given 11.6 (cohort A) and 8.6 (cohort B) mean treatments. Mean best corrected visual acuity gains of 4.1 letters following three monthly doses were sustained for 12 months for both cohorts. Anatomic improvements were sustained for 12 months for cohort A, but not for cohort B; cohort B demonstrated a gradual increase in mean central retinal thickness (P = .03)., Conclusion: Visual and anatomic gains achieved with 2.0 mg ranibizumab in recalcitrant neovascular AMD were sustained for 1 year with monthly treatment. In comparison, anatomic gains were diminished with less than monthly treatment., (Copyright 2013, SLACK Incorporated.)