Search

Purpose: To investigate the formation and absorption of avascular subretinal hyperreflective material (avSHRM) in neovascular age-related macular degeneration (nAMD) based on optical coherence tomography angiography (OCTA) characteristics., Design: Prospective cohort study., Methods: This study included patients with treatment-naive nAMD who were followed up for 3 months. Subjects were classified into an avSHRM group and a non-avSHRM group based on the presence of avSHRM at baseline. Quantitative OCTA characteristics including explant area, perimeter, vessel area, density, length, junctions, endpoints, lacunarity, maximum vessel caliber, vessel dispersion, and fractal dimension were assessed, and 3-dimensional volume and optical density ratio (ODR) of avSHRM were measured. Comparison analyses, correlation coefficients, and regression models were applied to explore factors associated with avSHRM formation and absorption., Results: A total of 88 eyes from 88 patients (39 female) were enrolled. Compared to the non-avSHRM group, the avSHRM group exhibited a more intricate vasculature, characterized by higher values of macular neovascularization (MNV) perimeter, vessel area, total vessel length, total number of junctions, and total number of endpoints (all P < .05), as well as the maximum vessel caliber (P < .001). In the multivariate model, which was adjusted for age, sex, and types of medications, avSHRM absorption was correlated with baseline average vessel length, maximum vessel caliber, and avSHRM ODR (standardized β = 0.274, -0.367, and -0.334; P = .049, .010, and .018, respectively), with an adjusted R² of 0.453., Conclusions: Quantitative OCTA measurements can be used for assessing the dynamics of avSHRM in nAMD. Patients with more complex vasculature are at higher risk for avSHRM formation. Average vessel length, maximum vessel diameter, and avSHRM ODR play a role in its absorption., Competing Interests: Conflict of Interest All authors declare no competing interests, financial disclosures, or personal relationships that could potentially influence the objectivity or integrity of this research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the development and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD)., Design: Retrospective, clinical cohort study., Methods: The study included patients with nAMD with anti-vascular endothelial growth factor (VEGF) injections who underwent uneventful cataract surgery between 2007 and 2018 with follow-up until June 2023. Subsequent MA rates were compared between subjects who received a BLF IOL or a non-BLF IOL. All optical coherence tomography scans were manually reviewed in a masked manner regarding patient baseline variables and IOL status by an experienced research technician. By using Heidelberg software, the area of MA was manually evaluated and calculated (mm 2 ) by the program. The overall risk of developing new-onset MA and the effect of IOL type on disease progression were assessed. Death was included as a censoring event., Results: Included were 373 eyes of 373 patients (mean age, 78.6 ± 6.7 years at surgery; 67.4% were female). BLF IOLs were implanted in 206 eyes, and non-BLF IOLs were implanted in 167 eyes with comparable follow-up times (3164 ± 1420 days vs 3180 ± 1403 days, respectively, P = .908) and other baseline parameters (age, gender, corrected distance visual acuity, macular thickness, cumulative number of anti-VEGF injections). Nine preexisting and 77 new-onset MA cases were detected, with similar distribution between BLF and non-BLF eyes (P = .598 and P = .399, respectively). Both univariate Kaplan-Meier (P = .366) and multivariate Cox regression analyses adjusted for age and gender showed that BLF-IOLs were comparable to non-BLF IOLs regarding hazard for new-onset MA (hazard ratio [HR], 1.236; 95% CI, 0.784-1.949; P = .363). Final MA area at the last visit was 5.14 ± 4.71 mm 2 for BLF IOLs and 8.56 ± 9.17 mm 2 for non-BLF IOLs (P = .028), with the mean annual MA area increase of 0.78 ± 0.84 mm 2 and 1.26 ± 1.32 mm 2 , respectively (P = .042)., Conclusions: BLF IOLs did not show added benefit over non-BLF IOLs in terms of MA-free survival but were associated with less progression over time in a cohort of patients with nAMD., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the incidence of blepharoptosis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and compare the rates of blepharoptosis between patients injected with an eyelid speculum and those injected without a speculum., Design: Retrospective cohort study., Methods: International Classification of Diseases, Tenth Revision (ICD-10), codes were used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis after intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as controls. The outcomes were the incidence of ptosis in the injection group compared to the noninjection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without a speculum., Results: We recruited 1100 exudative AMD patients who received at least 1 intravitreal anti-VEGF injection and 2258 nonexudative AMD patients who had not received an injection. In the injection group, 18 of 1100 patients (1.6%) developed ptosis, compared with 52 of 2258 patients (2.3%) in the noninjection group (P = .25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months after the initial injection, and after more than a 1-year injection-free period. Eleven of 537 patients (2.0%) injected without a speculum developed ptosis, compared with 8 of 444 patients (1.8%) injected with a speculum (P = .82)., Conclusions: No statistically significant differences in incidence rates of ptosis were observed. In this analysis, neither intravitreal anti-VEGF injections nor speculum use during injections appears to increase the risk of ptosis., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To evaluate for the presence, severity, and type of exudation at each study visit for a subgroup of patients with neovascular age-related macular degeneration from the Archway and Portal trials., Design: Retrospective analysis of prospectively obtained data., Methods: Spectral-domain optical coherence tomography scans from each study visit of 44 patients from the Port Delivery System (PDS) arm and 32 patients from the monthly injection arm of Archway were evaluated, and composites of horizontal scans through the fovea were created. Each composite was graded for the presence, type, and severity of exudation and impact on best-corrected visual acuity., Results: After PDS implantation, 20 of 44 eyes (45%) never showed any exudation in the fovea, 2 (5%) never showed exudation in the fovea but had several missed visits, whereas 15 (34%), 3 (7%), and 4 (9%) showed mild, moderate, or severe exudation at 1 or more study visits, respectively. When exudation was present, it was most commonly subretinal fluid (50%). Of 32 patients randomized to monthly injections, 15 (47%) had no exudation in the fovea during monthly injections or after PDS implantation. Fluctuation of exudation in the fovea over time was seen in some patients after PDS implantation or during monthly injections with little or no identifiable impact on best-corrected visual acuity. In the 7 eyes with moderate or severe exudation in the fovea after PDS implantation, final vision was good in 5 (20/25 in 3, 20/40 in 1, and 20/50 in 1) and 2 had reduced vision from submacular hemorrhage., Conclusions: The PDS provides excellent control of exudation in the fovea in patients with neovascular age-related macular degeneration, and when exudation occurs, it often resolves without a negative impact on vision., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the outcomes of intentionally suspending anti-vascular endothelial growth factor (anti-VEGF) injections in eyes with advanced neovascular age-related macular degeneration (nAMD)., Design: Retrospective cohort study., Methods: The study sample comprised 93 patients with nAMD and best available Snellen visual acuity (VA) ≤20/400 in which anti-VEGF treatment was suspended by the treating physician. VA and optical coherence tomography (OCT) characteristics were evaluated to determine visual and anatomical outcomes up to 24 months after treatment suspension., Results: A total of 93 eyes from 93 patients who had received a mean of 16 anti-VEGF injections over a mean of 962 (SD 562) days were included. Comparing the treatment suspension visit to 24 months later, no significant change in mean central foveal thickness (163 [SD 118, range 19-704] μm vs 164 [SD 217, range 19-1468], P = .97), greatest lesion diameter (2547 [SD 1294, range 134-5707] μm vs 2442 [SD 1158, range 421-5305] μm, P = .43), greatest lesion thickness (194 [SD 136, range 0-618] μm vs 205 [SD 131, range 0-573] μm, P = .40), or VA (1.87 [SD 0.37], 20/1482, vs 1.94 [SD 0.28], 20/1741, P = .16) was found. In total, 7 eyes (7.5%) restarted treatment following a mean of 977 (SD 450) days after treatment suspension., Conclusions: Suspension of anti-VEGF injections in eyes with advanced nAMD and VA ≤20/400 may be reasonable in cases where the treating physician deems additional treatment is unlikely to provide benefit. Although the visual and anatomical findings remained stable after treatment suspension in most, a small number restarted anti-VEGF therapy, suggesting that eyes should still be monitored for disease progression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To report the incidence and risk factors for fibrosis at 10 years in a large cohort of persons with neovascular age-related macular degeneration (nAMD)., Design: Retrospective, multicenter, cohort study., Methods: We included 225 naive nAMD eyes that underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined by clinically assessing photographs, fundus descriptions, or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as subretinal pigment epithelium (RPE), mixed, or subretinal., Results: The mean age at baseline was of 72.1 ± 6.9 years. The incidence rate of fibrosis was estimated to be 8.9 per 100 person-years, with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8%, and subretinal in 22.7%. Independent factors associated with fibrosis included the following: larger central subfield thickness variation (P < .001), submacular hemorrhages (P = .008), higher number of injections (P = .01), and worse baseline visual acuity (VA) (P = .03). Type 2 macular neovascularization was significantly associated with mixed and subretinal fibrosis. VA significantly declined over 10 years (-16.4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), particularly in eyes with mixed and subretinal fibrosis (P < .001)., Conclusions: We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset had a significant impact on final VA. This supports the hypothesis that nAMD patients should be promptly treated with proactive regimens., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To report the diagnosis and definitions, epidemiology, risk factors, and visual outcomes of fibrosis in neovascular age-related macular degeneration (nAMD)., Design: Systematic review and meta-analysis., Methods: The review was performed using the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies and randomized controlled trials were included., Results: Identification of fibrosis is challenging. Optical coherence tomography angiography and polarization-sensitive optical coherence tomography represent novel options in multimodal imaging. The prevalence of fibrosis at baseline, 12, 24, and 60 months was 13%, 32%, 36%, and 56%, respectively. Approximately 60% of the fibrosis burden in nAMD at 5 years was present in the first year of treatment. Fibrosis development was highest in the first 12 months and slowed down over time. The risk factors of fibrosis included classic choroidal neovascularization (CNV), intra-retinal fluid, hemorrhage, hyperreflective material, CNV lesion size, and retinal thickness. Sub-retinal fluid and pigment epithelial detachment may be protective. Treatment-associated factors included disease activity and time to diagnosis. At baseline, the best corrected visual acuity in eyes with fibrosis was poorer than in eyes without fibrosis (-18.50 letters); this difference became larger at 12 months despite treatment (-26.86 letters)., Conclusions: There is a need to identify effective treatment strategies for fibrosis and to closely monitor at-risk patients. More studies involving multimodal imaging are required to clarify the definitions and grading criteria for fibrosis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections compared to controls., Design: Retrospective clinical cohort study., Methods: Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age- and sex-matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP)., Results: There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation between eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD (P = .19) or no-AMD controls (P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes (P = .74) but greater than no-AMD eyes (P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD (P = .03) and more glaucoma laser treatments compared with no-AMD controls (P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10)., Conclusion: Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have increased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To assess the association between treatment interval and likelihood of anti-vascular endothelial growth factor (anti-VEGF) discontinuation among patients with neovascular age-related macular degeneration (nAMD) in a real-world setting in the United States., Design: Retrospective clinical cohort study., Methods: Health insurance claims data from the IBM MarketScan Commercial and Medicare Supplemental databases were retrospectively reviewed to identify adults with nAMD who received anti-VEGF for the first time between July 1, 2011, and June 30, 2017. The proportion of discontinued patients was analyzed using Kaplan-Meier curves. Cox proportional hazards models were used to examine the association between treatment intervals at 24 months and anti-VEGF discontinuation., Results: The analysis included 8167 patients on continuous, unilateral anti-VEGF treatment for at least 24 months. Baseline demographics and clinical characteristics were well balanced between treatment interval groups. The overall rate of discontinuation from 24 months until 60 months after treatment initiation was 30.4%. At 60 months, patients on shorter treatment intervals were more likely to remain on treatment than those on longer intervals, ranging from 76.8% (4-week interval group) to 60.6% (>12-week interval group) and corresponding to a 28% lower likelihood (HR [SE] 0.72 [0.12], P < .01) and 55% higher likelihood of discontinuing treatment (HR [SE] 1.55 [0.07], P < .01), respectively, compared with the 8-week group., Conclusions: nAMD patients on longer anti-VEGF treatment intervals at 24 months had consistently higher discontinuation rates than patients on shorter intervals in the following years. This highlights the need to support and educate patients on long treatment intervals to continue with their treatment., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti-vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration., Design: A phase 2 multicenter randomized double-masked, vehicle-controlled proof-of-concept study., Methods: Trial includes n = 90 patients with active choroidal neovascularization due to neovascular age-related macular degeneration and under anti-vascular endothelial growth factor treatment. All patients received an intravitreal injection of ranibizumab at baseline and were retreated when there was evidence of disease recurrence (rescue). Patients were randomized 1:1 to receive topical LHA510 or vehicle for 12 weeks. Drops were administered twice a day for 8 weeks and then 3 times a day for the last 4 weeks., Main Outcome Measure: The primary outcome was the number of patients requiring rescue over 84 days of topical dosing. Key secondary outcome measures were time to first rescue, total number of ranibizumab injections, changes in central subfield thickness, and changes of visual acuity from baseline to day 84., Results: The extended per protocol set included 70 patients of whom 25 of 33 patients in the LHA510 group (75.8%) and 25 of 37 patients in the placebo group (67.6%) required rescue by day 84 (P = .8466). Secondary and subgroup analysis did not support evidence of efficacy. Twenty-one of 46 patients administered LHA510 developed a reversible corneal haze that resolved with cessation of treatment and did not recur in patients restarted at once daily frequency., Conclusion: In spite of extensive optimization for topical efficacy, LHA510 failed to demonstrate clinical efficacy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Determine correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor agents., Design: A post hoc analysis of VIEW 1 and 2 randomized clinical trials., Methods: This analysis included participants randomized to ranibizumab 0.5 mg every 4 weeks (Rq4), intravitreal aflibercept injection 2 mg every 4 weeks (2q4), and intravitreal aflibercept injection 2 mg every 8 weeks after 3 monthly doses (2q8) to week 52, followed by capped as-needed (at least every 12 weeks) dosing to week 96. Relationship between changes in CST and BCVA was determined using Pearson correlation coefficient., Results: Of 1815 eyes, 595 were assigned to the Rq4, 613 to 2q4, and 607 to 2q8 arms. Correlations (95% confidence intervals [CI]) at weeks 12, 52, and 96 were -0.08 (95% CI, -0.17 to 0.00), -0.05 (95% CI, -0.14 to 0.04), and -0.15 (95% CI, -0.24 to -0.06) for Rq4; -0.13 (95% CI, -0.21 to -0.04), -0.06 (95% CI, -0.14 to 0.03) and -0.04 (95% CI, -0.13 to 0.05) for 2q4, and -0.04 (95% CI, -0.12 to 0.05), -0.01 (95% CI, -0.09 to 0.08), and -0.01 (95% CI, -0.10 to 0.09) for 2q8. Linear regression analysis adjusted for relevant baseline factors showed CST changes accounted for 11% of BCVA changes. Every 100 μm decrease in CST was associated with a 0.3 letter decrease (P = .25) at week 52 and a 0.14 letter decrease (P = .69) at week 96., Conclusions: Weak or no correlation was found between changes in CST and BCVA with either agent or regimen, suggesting changes in CST should not be used as a surrogate for visual acuity outcomes in neovascular age-related macular degeneration., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To compare demographics, visual acuity (VA) and retinal morphology between those with, and without baseline submacular hemorrhage (SMH) for patients enrolled in the Inhibit VEGF in Age-related Choroidal Neovascularization trial (IVAN)., Design: Secondary analyses of a randomized, controlled trial of image and clinical data., Methods: Setting; The IVAN trial collected data in 23 UK hospitals. Study population; IVAN study eyes (with untreated neovascular age-related macular degeneration at randomization) with at least 12 months of follow-up and adequate imaging. Intervention; Study eyes were randomly assigned between monthly ranibizumab, as-needed ranibizumab, monthly bevacizumab, or as-needed bevacizumab. Imaging at baseline was graded independently for the presence, type, position, and extent of SMH. Main outcome measures; The main outcome measures were VA (primary outcome), subretinal fibrosis, atrophic scarring, and retinal thickness outcomes at 12 and 24 months RESULTS: Of 605 IVAN trial participants, 535 were included in this analysis. Patients with SMH at baseline (286 [53%]) were older (P = .010) and affected eyes were more likely to have intraretinal fluid present (P = .038). The VA was significantly worse in those with baseline SMH at month 0 (P < .001; estimate of difference 6 letters; 95% CIs, 4-8 letters), but the difference decreased and was not significant at month 12 or 24. No significant association was found between baseline SMH and subretinal fibrosis, atrophic scarring, or central retinal thickness., Conclusions: The presence of SMH at baseline was associated with age, intraretinal fluid, and decreased baseline VA. By month 12, VA was no longer significantly different in those who presented with SMH at baseline., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To identify the risk factors of intraretinal fluid (IRF) development during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD)., Design: Retrospective cohort study., Methods: A total of 425 treatment-naïve patients with neovascular AMD who completed 24 months of follow-up were enrolled. All patients were treated with an initial series of 3 monthly loading doses of anti-VEGF injections, followed by further injections as required. Baseline characteristics were evaluated using multivariate modeling to determine the potential risk factors for IRF development., Results: IRF occurred in 40.2% (171/425 eyes) of all participants during the maintenance phase after the loading injections. The development of IRF during follow-up negatively affected visual outcomes regardless of the presence of IRF at baseline. Multivariate analysis showed that larger areas of choroidal neovascularization (odds ratio [OR] 1.360; P < .001), the presence of IRF at baseline (OR 5.469; P < .001), and the presence of fibrovascular pigment epithelial detachment (OR 2.043; P = .022) were associated with an increased risk of IRF during follow-up. Type 1 (OR 2.005; P = .037) and type 2 macular neovascularization (MNV) (OR 2.643; P = .009) were also associated with a higher risk of IRF than aneurysmal type 1 MNV/polypoidal choroidal vasculopathy., Conclusions: The development of IRF during anti-VEGF treatment for neovascular AMD has additional negative effects on visual outcomes regardless of the presence of IRF at baseline. Baseline risk factors, including choroidal neovascularization size, presence of IRF at baseline, presence of fibrovascular pigment epithelial detachment, and MNV subtype may influence the development of IRF during anti-VEGF treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To investigate the relationship between retinal fluid and vision in ranibizumab-treated patients with neovascular age-related macular degeneration (nAMD)., Design: Clinical cohort study using post hoc analysis of clinical trial data., Methods: We assessed data from HARBOR (NCT00891735), a phase III, randomized, controlled trial. We reviewed 917 patients ≥50 years of age with subfoveal nAMD associated with subretinal (SRF) and/or intraretinal fluid (IRF) at baseline, screening, or week 1. The intervention was intravitreal ranibizumab 0.5 or 2.0 mg (all treatment arms pooled). Outcomes included mean best-corrected visual acuity (BCVA) and BCVA change from baseline at months (M) 12 and 24 evaluated by the presence/absence of SRF and/or IRF., Results: Baseline BCVA was higher with residual vs resolved SRF at M12 (mean [95% confidence interval {CI}] 58.8 letters [57.2-60.4] vs 53.5 [52.4-54.5]) and M24 (59.3 letters [57.8-60.8] vs 53.5 [52.5-54.5]). Mean BCVA change (adjusted for baseline) to M12 was greater with residual vs resolved SRF (mean difference [95% CI], +2.4 letters [+0.1 to +4.7]), but lower with residual vs resolved IRF (-3.5 letters [-5.8 to -1.2]). Eyes with residual SRF (no IRF) exhibited the largest mean BCVA gains (M12, +14.1 letters; M24, +13.2 letters), followed by resolved SRF/IRF (M12, +10.6 letters; M24, +10.0 letters), residual SRF/IRF (M12, +7.2 letters; M24, +8.5 letters), and residual IRF only (M12, +5.5 letters; M24, +3.6 letters)., Conclusions: Vision outcomes (adjusted for baseline BCVA) through M24 were better in ranibizumab-treated eyes with residual vs resolved SRF, and worse with residual vs resolved IRF. Presence of residual retinal fluid requires a more complex and nuanced assessment and interpretation in the context of nAMD management., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: We sought to develop and validate a deep learning model for segmentation of 13 features associated with neovascular and atrophic age-related macular degeneration (AMD)., Design: Development and validation of a deep-learning model for feature segmentation., Methods: Data for model development were obtained from 307 optical coherence tomography volumes. Eight experienced graders manually delineated all abnormalities in 2712 B-scans. A deep neural network was trained with these data to perform voxel-level segmentation of the 13 most common abnormalities (features). For evaluation, 112 B-scans from 112 patients with a diagnosis of neovascular AMD were annotated by 4 independent observers. The main outcome measures were Dice score, intraclass correlation coefficient, and free-response receiver operating characteristic curve., Results: On 11 of 13 features, the model obtained a mean Dice score of 0.63 ± 0.15, compared with 0.61 ± 0.17 for the observers. The mean intraclass correlation coefficient for the model was 0.66 ± 0.22, compared with 0.62 ± 0.21 for the observers. Two features were not evaluated quantitatively because of a lack of data. Free-response receiver operating characteristic analysis demonstrated that the model scored similar or higher sensitivity per false positives compared with the observers., Conclusions: The quality of the automatic segmentation matches that of experienced graders for most features, exceeding human performance for some features. The quantified parameters provided by the model can be used in the current clinical routine and open possibilities for further research into treatment response outside clinical trials., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluated whether the rate of retinal nerve fiber layer (RNFL) thinning is faster in eyes receiving intravitreal injections than in fellow uninjected eyes among patients suspected of having or confirmed to have glaucoma and exudative age-related macular degeneration (AMD)., Design: Retrospective comparative cohort study., Methods: Patients with a diagnosis of unilateral exudative AMD and confirmed to have or suspected of having glaucoma in both eyes receiving unilateral intravitreal injections were identified. Those with ≥3 RNFL optical coherence tomography scans and ≥6 injections were included in the study. Rates of RNFL thinning in the injected eye versus the uninjected eye were estimated using linear mixed models. The main outcome measurement was the differences in rates of RNFL thinning in the injected versus the fellow uninjected eye. The effects of postinjection elevation of intraocular pressure (IOP), injection frequency, and number of injections were also evaluated., Results: A total of 53 patients met the inclusion criteria, receiving 26.4 ± 15.9 intravitreal injections. The average rate of RNFL thinning in uninjected eyes was -0.620 μm/year (P = .029). Injected eyes had an additional incremental loss of -0.385 μm/year, but this value was not statistically significant (95% confidence interval [CI]: -1.147 to 0.379 μm/year; P = .324). Subgroup analysis with only glaucoma patients (n = 33) also demonstrated a nonsignificant effect of injections (-0.568 μm/year; 95% CI: -1.454 to 0.319 μm/year; P = .212). Postinjection IOP elevation, injection frequency, and total number of injections were not associated with faster RNFL loss., Conclusions: Among exudative AMD patients with glaucoma or suspected of having glaucoma, the rate of RNFL thinning in eyes receiving intravitreal injections did not significantly differ from that of fellow uninjected eyes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate retinal fluid volume data extracted from optical coherence tomography (OCT) scans by artificial intelligence algorithms in the treatment of neovascular age-related macular degeneration (NV-AMD)., Design: Perspective., Methods: A review was performed of retinal image repository datasets from diverse clinical settings., Settings: Clinical trial (HARBOR) and trial follow-on (Age-Related Eye Disease Study 2 10-year Follow-On); real-world (Belfast and Tel-Aviv tertiary centers)., Patients: 24,362 scans of 1,095 eyes (HARBOR); 4,673 of 880 (Belfast); 1,470 of 132 (Tel-Aviv); 511 of 511 (Age-Related Eye Disease Study 2 10-year Follow-On). ObservationProcedures: Vienna Fluid Monitor or Notal OCT Analyzer applied to macular cube scans. OutcomeMeasures: Intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) volumes., Results: The fluid volumes measured in neovascular AMD were expressed efficiently in nanoliters. Large ranges that differed by population were observed at the treatment-naïve stage: 0-3,435 nL (IRF), 0-5,018 nL (SRF), and 0-10,022 nL (PED). Mean volumes decreased rapidly and consistently with anti-vascular endothelial growth factor therapy. During maintenance therapy, mean IRF volumes were highest in Tel-Aviv (100 nL), lower in Belfast and HARBOR-Pro Re Nata, and lowest in HARBOR-monthly (21 nL). Mean SRF volumes were low in all: 30 nL (HARBOR-monthly) and 48-49 nL (others)., Conclusions: Quantitative measures of IRF, SRF, and PED are important biomarkers in NV-AMD. Accurate volumes can be extracted efficiently from OCT scans by artificial intelligence algorithms to guide the treatment of exudative macular diseases. Automated fluid monitoring identifies fluid characteristics in different NV-AMD populations at baseline and during follow-up. For consistency between studies, we propose the nanoliter as a convenient unit. We explore the advantages of using these quantitative metrics in clinical practice and research., (Published by Elsevier Inc.)

Purpose: To perform a societal cost-benefit analysis comparing intravitreal bevacizumab (Avastin), ranibizumab (Lucentis), and aflibercept (Eylea) monotherapies for treating neovascular age-related macular degeneration (NVAMD)., Design: Cost-benefit analysis., Methods: Center for Value-Based Medicine using published clinical trial and Medicare data., Patient Population: 168,400 estimated 2018 U.S. patients with new-onset NVAMD. Procedure(s): cost-benefit analysis using 2018 U.S. real dollars., Outcome Measurements: 11-year direct ophthalmic medical costs expended for bevacizumab, ranibizumab, and aflibercept monotherapies were compared with ophthalmic and nonophthalmic direct medical, direct nonmedical, and indirect medical (productivity) costs saved by the therapies., Results: Bevacizumab monotherapy had an individual, 11-year $14,772 treatment cost and net $357,680 societal return (11-year 2,421% return on investment [ROI]). Ranibizumab therapy cost $106,582 and returned $265,870 to society (249% ROI), whereas aflibercept treatment cost $61,811 and returned $310,611 to society (503% ROI). The 2018 NVAMD overall treatment cohort, 11-year net societal gain was $28.5 billion to patients and insurers, with $24.2 billion (84.9%) coming from bevacizumab therapy, $0.7 billion (2.5%) from ranibizumab therapy, and $3.6 billion (12.6%) from aflibercept therapy. Substituting bevacizumab for ranibizumab and aflibercept in the 2018 new-onset NVAMD patients would save an estimated $1.343 billion over 11 years. Vascular endothelial growth factor-inhibitor (VEGF-I) therapy in 2018 should contribute $12.2 billion to the Gross Domestic Product over 11 years. Late treatment would decrease this by 78% to $2.7 billion., Conclusions: Intravitreal NVAMD bevacizumab, ranibizumab and aflibercept monotherapies accrue considerable financial, ROIs to patients and insurers as they increase national wealth., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The clinic efficiency and cost savings achieved by eliminating formal visual acuity (VA) and dilated fundus examinations (DFEs) were assessed for established patients receiving optical coherence tomography (OCT)-guided intravitreal injections., Design: Comparative cost analysis., Methods: Two different treatment models were evaluated. The first model included patients undergoing routine VA assessment, DFEs, OCT imaging, and intravitreal injections. The second model eliminated the routine VA assessment and DFE while using OCT imaging through an undilated pupil followed by the intravitreal injection. The 2 models incorporated both bevacizumab and aflibercept. The number of patients per clinic day, the cost per visit, and the daily revenues were compared between the 2 models., Results: Optimized schedules with and without VA assessments and DFEs allowed for 48 and 96 patients to be injected per day, respectively. Excluding drug costs, the cost per encounter for the visits with and without a DFE were $39.33 and $22.63, respectively. Including the drug costs, the costs per encounter for the visits with and without a DFE were $85.55 and $68.85 for bevacizumab and $1787.58 and $17770.88 for aflibercept, respectively. Once the reimbursements for each visit type were included, the clinics that eliminated the VA and DFEs were more cost efficient., Conclusion: Eliminating both VA assessments and DFEs for patients undergoing OCT-guided retreatment with intravitreal injections resulted in decreased exposure times between patients and clinic staff, decreased cost per encounter, and increased patient volumes per clinic day, resulting in improved clinic efficiency and safety while seeing more patients in a clinic day., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To perform 11- and 2-year health care sector (ophthalmic) and societal cost perspective reference case, cost-utility analyses comparing bevacizumab, ranibizumab, and aflibercept monotherapies for neovascular age-related macular degeneration (NVAMD)., Design: Cost-utility analysis., Methods: The authors performed 11-year and 2-year ophthalmic and societal cost perspective, cost-utility analyses comparing bevacizumab, ranibizumab, and aflibercept monotherapies for neovascular age-related macular degeneration (NVAMD). We employed patient utilities, bilateral outcomes, 2018 U.S. dollars, vision-related mortality, a Medicare fee schedule, and CATT (Comparison of Age-Related Macular Degeneration Treatments) study and VIEW (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD) trial. Cochrane data were also used., Setting: Center for Value-Based Medicine. Patient/study population: patients with NVAMD., Intervention: Cost-utility analyses using published data. Data-modeled 10-year vision outcomes were modeled forward to year 11., Main Outcome Measurement: These included cost-utility ratios (CURs), costs, and quality-adjusted life-years (QALYs) gained. $100,00/QALY was considered the US cost-effectiveness upper limit., Results: Bevacizumab and ranibizumab each conferred an 11-year, 1.339 QALY gain versus observation. Aflibercept conferred a 1.380 QALY gain. Aflibercept conferred greater QALY gain for less cost than ranibizumab but was not cost-effective compared to bevacizumab ($1,151,451/QALY incremental CUR). The average ophthalmic cost perspective CUR for bevacizumab was $11,033/QALY, $79,600/QALY for ranibizumab, and $44,801/QALY for aflibercept. Eleven-year therapies saved a 1.0 year-of-life loss without treatment from the 11.0-year life expectancy. Early treatment was 138%-149% more cost-effective than late treatment. Two-year therapy prevented a 1-month-of-life loss, and revealed bevacizumab, ranibizumab, and aflibercept conferred 0.141, 0.141, and 0.164 QALY gains, respectively, with corresponding average CURs of $40,371/QALY, $335,726/QALY, and $168,006/QALY, respectively., Conclusions: From an ophthalmic (medical) cost perspective, bevacizumab, ranibizumab, and aflibercept NVAMD monotherapies were all cost-effective over 11 years, with bevacizumab 6.21× more cost-effective than ranibizumab and 3.06× more cost-effective than aflibercept. Two-year modeling revealed bevacizumab was cost-effective, whereas ranibizumab and aflibercept were not. Early treatment was critical for obtaining optimal vision and cost-effectiveness, as is long-term follow-up and adherence to treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To describe the spectral-domain optical coherence tomography (OCT) features of fibrotic lesions associated with neovascular age-related macular degeneration (nAMD) and to outline the progression pathways from initial macular choroidal neovascular lesions (CNVs) to fibrosis., Methods: Patients with nAMD were retrospectively included when macular subretinal fibrosis was present. Fibrosis was categorized using spectral-domain OCT with respect to retinal pigment epithelium (RPE) in 836 spectral-domain OCT slices from 44 eyes of 39 patients. In addition, in 47 distinct eyes, 4181 spectral-domain OCT slices were retrospectively reviewed to longitudinally assess progression from the initial lesion to the final fibrosis., Results: Cross-sectional analysis classified fibrosis on spectral-domain OCT slices, as type A if located underneath the RPE, as type B if located above the RPE, and as type C if the remaining RPE was undistinguishable. The longitudinal analysis series revealed 3 progression pathways from the original CNV: 1) progression to type A, followed by RPE erosion and subretinal hyperreflective material, then type B and type C fibroglial lesion (FGL; 17/47 eyes); 2) progression to type B then type C FGL (17/47 eyes); and 3) persistence of type A with development of a flat, fibroatrophic lesion (13/47 eyes). Subretinal hyperreflective material, macular hemorrhage, or RPE tear occurred in 14 of 47, 13 of 47, and 10 of 47 eyes, respectively., Conclusion: This spectral-domain OCT analysis identified various patterns of macular fibrosis in eyes with nAMD. Three pathways of progression to fibrosis were described including the well-established pathway of type 2 CNV progression to FGL and the progression of type 1 fibrovascular CNV to FGL or fibroatrophic lesion., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate the features of neovascularization (NV) in eyes with neovascular age-related macular degeneration using optical coherence tomography angiography (OCTA) according to the treatment interval of intravitreal aflibercept injection (IVI)., Design: Retrospective, interventional, comparative case series., Methods: Patients with type 1 NV treated with the "pro re nata" regimen after 3 loading IVI were classified into 2 groups based on the numbers of treatments during 12 months, specifically a stable group who required fewer than 2 injections and an unstable group who required more than 3 injections. Quantitative features of OCTA including NV area, NV length, NV density, endpoint density (open-ended vessels per unit length), junction density (vessel junction per unit length), lacunarity, and largest vessel caliber were compared between the 2 groups., Results: Among 71 eyes, 38 and 33 eyes were classified into the stable and unstable groups, respectively. The unstable group had higher endpoint densities (stable vs unstable: 2.72 vs 3.18; P = .03) and higher levels of lacunarity (0.177 vs 0.211; P = .028). The area, density, length of NV, junction density, and largest vessel caliber were not different between the 2 groups (P = .057, P = .184, P = .062, P = .160, and P = .473, respectively). Endpoint density was correlated with the unstable group in both univariate and multivariate analyses (P = .004, P = .002, respectively). A predictive model with an endpoint index demonstrated a sensitivity of 93.75% and a negative predictive value of 89.47% for the unstable group., Conclusions: The characteristics of NV in eyes of exudative age-related macular degeneration with type 1 NV were different according to treatment requirements. Identifying the features of NV on OCTA might be helpful for predicting clinical outcomes and optimal treatment intervals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Swept source optical coherence tomography angiography (SS-OCTA) was used to study the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with unilateral nonexudative age-related macular degeneration., Design: Prospective cohort study., Methods: Patients were imaged using 3- × 3-mm and 6- × 6-mm SS-OCTA scan patterns. MNV was detected using the outer retina to choriocapillaris en face slab. Prevalence and incidence of subclinical MNV, Kaplan-Meier cumulative estimates for the overall risk of exudation, and the association between neovascular lesion size and the risk of exudation were assessed through 2 years., Results: From August 2014 through March 2018, 227 patients (154 intermediate and 73 late age-related macular degeneration eyes) underwent SS-OCTA imaging. Thirty eyes (13.2%) had subclinical MNV at first imaging and 12 eyes (8.9%) developed subclinical MNV during follow-up. Of the 191 eyes with >1 visit, 19 developed exudation. Fourteen of these eyes had pre-existing subclinical MNV. The incidence of exudation from the time of first detection of any subclinical MNV was 34.5%. The relative risk of exudation after detection of subclinical MNV was 13.6 times greater (95% confidence interval 4.9-37.7) than in the absence of subclinical MNV (P < .001). There was no significant risk of exudation based on lesion size alone (P = .91)., Conclusions: By 24 months, the risk of exudation was 13.6 times greater for eyes with subclinical MNV detected by SS-OCTA compared with eyes without subclinical MNV. For eyes with subclinical MNV in the absence of symptomatic exudation, we recommend close follow-up without treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the outcomes of patients with exudative age-related macular degeneration (AMD) treated with intravitreal antivascular endothelial growth factors (VEGF) using a telemedicine system., Design: Interventional case series., Methods: This study examined all patients with exudative AMD who were receiving intravitreal anti-VEGF injections from September 1, 2015, through August 31, 2017, using electronic consultations at a single academic center and health system. Patients were managed initially by a retinal specialist and then allowed to receive further care with their local ophthalmologist. There were 200 electronic consultations placed during this time period for 83 eyes of 59 patients. Data collected included the retina specialist's recommendations: intravitreal agent, interval between injections, number of injections, and when the patient was to follow-up. All occurrences of recommendations that were not completed were reported., Results: The mean age of the patients at the time of electronic consultations was 82.3 ± 7.3 years with a mean follow-up time of 2.4 ± 0.81 years. The mean distance from the home of the patient to the retina specialist was 70 ± 44 miles. There were 14 consultations (7.1%) that did not comply with the recommendations of the retina specialist. Most of these were due to other medical comorbidities leading to missed appointments or scheduling errors., Conclusions: In an integrated health care setting, 59 patients with exudative AMD were identified who were able to be effectively managed using a telemedicine system. In the appropriate setting, telemedicine may be able to assist in the management of patients with wet AMD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the incidence of fellow eye (FE) neovascular age-related macular degeneration (nAMD) in patients with unilateral nAMD according to FE drusen type., Design: Retrospective cohort study., Methods: Between January 2013 and June 2016, 434 consecutive patients with naïve nAMD were enrolled. We selected 280 eligible patients with treatment-naïve, unilateral nAMD for analysis (280/280 = 100% patients were followed up at 2 years; 50/280 = 17.9% patients were followed up at 5 years). The incidence and hazard ratios (HR) of FE nAMD according to age, sex, choroidal thickness, nAMD subtype, and drusen type were analyzed., Results: The 5-year incidence of FE nAMD was 20.9%. The incidences of the soft plus subretinal drusenoid deposits (SDD), soft drusen only, and SDD only groups were 76.4%, 46.2%, and 25.7%, respectively; they were significantly higher than the no drusen group (vs 3.6%; P < .001, P < .001, P < .001). There was no significant difference between the pachydrusen and no drusen groups (7.1% vs 3.6%; P = .101). The multivariate Cox regression hazard model revealed older age (HR, 1.053; P = .031) and drusen type were significant (P = .001). Compared with the no drusen group, the soft drusen plus SDD, soft drusen only, and SDD groups showed an HR of 18.460 (P = .001), 8.302 (P = .015), and 5.465 (P = .082), respectively. Pachydrusen was not shown to be a significant risk factor compared to the no drusen group (HR, 2.417; P = .281)., Conclusion: The incidence of FE nAMD was significantly different with respect to drusen type. Soft drusen plus SDD had the highest risk of neovascular AMD, followed by soft drusen only and SDD only., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess whether publication of Comparison of Age-related macular degeneration Treatment Trial (CATT) results and introduction of aflibercept to the marketplace affected intravitreal bevacizumab and ranibizumab utilization., Design: Retrospective analysis of treatment patterns., Methods: We calculated weekly bevacizumab and ranibizumab utilization during 3 timeframes: (1) before CATT publication, (2) between CATT publication (April 28, 2011) and assignment of a unique aflibercept billing code (January 1, 2013), and (3) afterward for 164,188 Medicare beneficiaries with neovascular macular degeneration receiving ≥1 anti-vascular endothelial growth factor injection(s) from January 1, 2008 to December 31, 2014. We identified ophthalmologists who predominantly (≥80%) administered bevacizumab or ranibizumab and evaluated changes in preferences over the 3 periods. We replicated analyses on 881,381 commercially insured beneficiaries., Results: Among 317 ophthalmologists administering predominantly ranibizumab to Medicare beneficiaries pre-CATT, 221 (69.7%) reduced ranibizumab use post-CATT, whereas 96 (30.3%) continued using ranibizumab ≥80% of the time. Findings were reversed among 1041 ophthalmologists who predominantly administered bevacizumab pre-CATT-777 (74.6%) continued bevacizumab-predominant use while 264 (25.4%) reduced bevacizumab use post-CATT. Among the 145 ophthalmologists who predominantly administered ranibizumab before aflibercept's availability, 77 (53.1%) reduced ranibizumab utilization and 68 (46.9%) continued using ranibizumab ≥80% of the time after aflibercept became available. Corresponding numbers among the 909 ophthalmologists who predominantly administered bevacizumab pre-aflibercept were 381 (41.9%) reducing and 528 (58.1%) continuing bevacizumab-predominant use. Similar results were observed for commercially insured patients., Conclusions: Many ophthalmologists who favored ranibizumab switched to bevacizumab after CATT publication, while most who favored bevacizumab before CATT publication continued favoring it afterward. Aflibercept's introduction had little impact on preferences for ranibizumab or bevacizumab., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcomes and disease characteristics in eyes with neovascular age-related macular degeneration that received intravitreal aflibercept injection (IAI) and ranibizumab every 12 weeks or longer (≥q12 weeks) or less than every 12 weeks (

Purpose: To evaluate practice patterns for bilateral same-day intravitreal anti-vascular endothelial growth factor (VEGF) injections and determine the rate of unilateral and bilateral postinjection endophthalmitis after bilateral same-day intravitreal anti-VEGF injections., Design: Retrospective cohort study., Methods: The records of a large academic private practice were electronically queried for all office visits, during which bilateral intravitreal anti-VEGF injections were performed between April 1, 2012 and August 21, 2017 for patients with a diagnosis of neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion. Demographic information and indication for injection were recorded for each patient and office visit. Charts of patients with endophthalmitis were reviewed, and information was collected on presentation examination, culture data, and visual outcomes., Results: During the study period, 101 932 bilateral same-day intravitreal anti-VEGF injections were performed over 50 966 office visits for 5890 patients. The mean (standard deviation) age of patients in this cohort was 74.2 (14.1) years and 60.6% of patients were female. The 2 most common indications for injection were neovascular age-related macular degeneration (54.3% of patients) and diabetic macular edema (35.4% of patients). Twenty-eight cases of endophthalmitis (0.027% of total injections) occurred during the study period. There were no cases of bilateral endophthalmitis, and no patients had more than 1 occurrence of endophthalmitis., Conclusions: In this large cohort of patients undergoing bilateral same-day intravitreal anti-VEGF injections, there were no cases of bilateral endophthalmitis. Additionally, the overall rate of unilateral endophthalmitis was low and comparable to prior studies of unilateral injections. These results support the safety of bilateral same-day intravitreal anti-VEGF treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To assess outcomes of the treat-and-extend (T&E) injection regimen for neovascular age-related macular degeneration (AMD) as compared to either a monthly or a pro re nata (PRN) treatment strategy., Design: Systematic review and meta-analysis., Methods: Studies that compared the T&E regimen with either monthly or PRN dosing for treatment-naïve AMD were included. Trial eligibility, data extraction, and risk of bias were assessed according to Cochrane review methods. Estimates were pooled using random-effects meta-analysis., Results: Four eligible studies were identified, all using ranibizumab (total N = 940 eyes), including 2 randomized controlled trials comparing T&E to monthly and 2 retrospective reviews comparing T&E to PRN. No studies evaluating aflibercept were identified. Improvements in vision and central retinal thickness were similar between T&E and monthly at 12 months, with a mean difference of -1.79 letters (95% confidence interval [CI]: 3.70, 0.13) and 3.76 μm (95% CI: -13.78, 21.30) in favor of monthly injections. In contrast, visual gains were higher in the T&E compared to the PRN group (difference of +6.18 letters, 95% CI: 3.28, 9.08). Fewer injections were required using the T&E regimen when compared to monthly (mean of -1.6 and -6.9 injections at 12 and 24 months, respectively). A mean of 1.44 more injections was required for the T&E compared to PRN regimen at 12 months; however, this was achieved with fewer visits., Conclusion: Despite the growing preference for the T&E regimen, there is limited head-to-head evidence comparing dosing strategies. The evidence available, however, suggests that at 12 months, T&E is comparable to monthly and superior to PRN dosing for both efficacy and safety outcomes when using ranibizumab., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate whether having macular fluid on optical coherence tomography (OCT) prior to cataract surgery adversely affected vision or anatomic outcomes after cataract surgery in patients with exudative age-related macular degeneration (AMD)., Design: Retrospective cohort study., Methods: We examined all patients who underwent cataract surgery and were receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections from January 1, 2012 through December 31, 2016. There were 81 eyes that underwent cataract surgery and had received at least 1 intravitreal anti-VEGF injection for a diagnosis of exudative AMD within 6 months prior to surgery. Data collected included the development of subretinal or intraretinal macular fluid, or subretinal hemorrhage, in the 6 months following surgery; number of injections; best-corrected visual acuity (BCVA); and central subfield thickness (CST)., Results: There was a significant improvement between preopertive and postoperative BCVA when comparing all patients (P values < .0001) and no significant difference in CST before and after surgery (P > .05). There were 23 eyes with fluid on the preoperative OCT. There were no differences in final BCVA or CST and no difference in the development of fluid postoperatively when compared to patients without fluid preoperatively (all P values > .05). These patients also saw a significant improvement in BCVA (P = .006)., Conclusion: In a real-world setting, patients with both cataracts and wet AMD may safely undergo cataract surgery. Patients with stable preoperative fluid on OCT should be considered for cataract surgery, as these patients did well postoperatively, with no worsening of their neovascular process., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.)

Purpose: The Medicare cost savings from the use of bevacizumab in the United States for the treatment of exudative age-related macular degeneration (AMD) were estimated by replacing the use of bevacizumab with ranibizumab and aflibercept., Design: Retrospective trend study., Methods: Main outcome measures were spending by Medicare as tracked by Current Procedural Terminology (CPT) codes for intravitreal injections (67028) and treatment-specific J-codes (J0178, J2778, J9035, J3490, and J3590) for inhibitors of vascular endothelial growth factor. These claims were identified from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services among fee-for-service (FFS) Medicare beneficiaries from 2012 to 2015. The 2008 claims were acquired from the 100% fee-for-service (FFS) Part B Medicare Claims File., Results: The use of bevacizumab from 2008 to 2015 resulted in an estimated savings of $17.3 billion, which corresponded to a $13.8 billion savings to Medicare and a $3.5 billion savings to patients. This amount underestimated the actual cost savings to Medicare providers, since approximately 30% of Medicare-eligible recipients received care within Medicare Advantage plans and were not included in this analysis., Conclusions: The cost savings from the use of bevacizumab from 2008 to 2015 for Medicare fee-for-service patients undergoing treatment for exudative AMD was estimated at $17.3 billion. Additional savings over the $17.3 billion would have accrued from the use of bevacizumab if diagnostic categories such as diabetic macular edema and retinal vein occlusion were included in this study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcomes and predictive factors of visual acuity (VA) change after cataract surgery in patients being treated for neovascular age-related macular degeneration (nAMD)., Design: Retrospective, matched case-control study., Methods: We studied eyes undergoing cataract surgery that had been tracked since they first started treatment for nAMD. These eyes were compared with a cohort of unoperated phakic eyes being treated for nAMD (3 per case) matched for treatment duration before cataract surgery, baseline VA, age, and length of follow-up., Results: We included 124 patients that had cataract surgery and 372 matched controls. The mean (95% confidence interval) VA gained was 10.6 letters (7.8, 13.2; P < .001) 12 months after surgery; 26.0% had gained ≥3 lines and 1.6% had lost ≥3 lines of VA. Visual acuity (mean [standard deviation]) 12 months after surgery was higher in eyes that had cataract extraction compared with controls (65.8 [17.1] vs 61.3 [20.8] letters, respectively, P = .018). The proportion of visits where the choroidal neovascular (CNV) lesion was graded active and the mean number of injections were similar before and after surgery (P = .506 and P = .316, respectively), whereas both decreased in the control group, suggesting that surgery modestly increased the level of activity of the CNV lesion. Mean [SD] VA prior to surgery was lower in eyes that gained ≥15 letters compared with eyes that gained 0-14 letters (40.2 [21.4] vs 62.1 [15.1], P < .001). Patients undergoing cataract surgery within the first 6 months of anti-VEGF therapy were more likely to lose rather than gain vision (20.8% lost vision vs 12.8% and 4.4% gaining ≥15 or 0-14 letters respectively, P = .023). Age, receiving an injection at least 2 weeks before surgery, and the CNV lesion type had no discernible association with VA outcomes., Conclusions: We found evidence of a modest effect of cataract surgery on CNV lesion activity in eyes being treated for nAMD. Despite this, visual outcomes were reassuringly good. Cataract surgery within 6 months of starting treatment for nAMD should be avoided if possible., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To identify factors influencing visual outcome in patients with neovascular age-related macular degeneration (NVAMD) and subfoveal hemorrhage (SFH) treated with anti-vascular endothelial growth factor (VEGF) agents., Design: Retrospective case series., Methods: Anti-VEGF-treated eyes with SFH > 1 disc area (DA) were identified (n = 16) and changes in visual acuity (VA) and central subfield thickness (CST) from baseline to last follow-up, along with SFH area, thickness, minimum distance from fovea to SFH border, and time to resolution, were determined., Results: At baseline, mean (± standard error of the mean) size and thickness of SFH were 14.9 ± 2.8 DA and 386.6 ± 46.9 μm, and mean Snellen VA and CST were 20/250 and 591.7 ± 57.0 μm. Median follow-up was 47.6 months. While more than 50% of patients had VA ≤ 20/200 at baseline and all time points through week 48, the percentage of patients with VA ≥ 20/50 increased to 30%-40% at months 6 and 12 and remained stable through month 48. Spearman rank correlation demonstrated 2 independent variables that correlated with good visual outcome, smaller area of SFH at baseline (r = -0.630; P = .009), and high frequency of anti-VEGF injections (r = 0.646; P = .007). In exceptional patients with good visual outcome despite large baseline SFH, shortest distance between the fovea and hemorrhage border significantly correlated with baseline VA (r = -0.503, P = .047) and final VA (r = -0.575, P = .02)., Conclusions: Patients with NVAMD and thick SFH, but short distance between fovea and uninvolved retina, can have good visual outcomes when given frequent anti-VEGF injections., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To determine if use of antiplatelet or anticoagulant (AP/AC) medication influences visual acuity in patients with active neovascular age-related macular degeneration (N-AMD)., Design: Retrospective analysis of data from a randomized controlled trial., Methods: Setting: Multicenter., Study Population: Total of 330 patients with active N-AMD from the BRAMD study, a comparative trial between bevacizumab and ranibizumab in the Netherlands., Observation Procedures: Patients underwent an extensive ophthalmic examination. Visual acuity was categorized into functional vision (best-corrected visual acuity [BCVA] ≥ 0.5), visual impairment (BCVA < 0.5), and severe visual impairment (BCVA < 0.3). Fundus photographs were graded for presence of retinal or subretinal hemorrhages. Information on AP/AC medication was obtained through interview. Logistic regression analysis was used to determine associations between AP/AC medication and outcomes. Frequency of hemorrhages in users and non-users stratified for visual acuity categories was analyzed with ANCOVA., Main Outcome Measures: BCVA and presence of hemorrhages., Results: In total, 40.9% of the patients used AP/AC medication, of which 73.3% was aspirin. AP/AC use was not associated with visual impairment (adjusted odds ratio [OR] 0.79; 95% confidence interval [CI] 0.43-1.44) or severe visual impairment (adjusted OR 0.75; 95% CI 0.40-1.43). Patients on AP/AC presented with comparable frequencies of hemorrhages (27% vs 32%, P = .32, respectively). Similar results were found when analyses were restricted to aspirin users only., Conclusion: In our study, use of AP/AC medication was associated neither with visual decline nor with the occurrence of hemorrhages in patients with active N-AMD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To analyze the long-term growth patterns of type 1 neovascularization (NV) in eyes with age-related macular degeneration (AMD) receiving anti-vascular endothelial growth factor (VEGF) therapy., Design: Retrospective cohort study., Methods: Patients were enrolled from 2 eye centers and underwent optical coherence tomography angiography (OCTA) imaging with follow-up greater than 1 year. Choroidal neovascularization (CNV) was manually segmented on OCTA images and compared between time points. CNV growth was subdivided into 3 categories based on OCTA area measurement: CNV doubling, modest growth of less than 50%, and shrinkage. These growth rates were correlated with OCTA morphologic features., Results: Forty-one eyes were analyzed. Mean CNV area was 1.60 ± 1.84 mm 2 at baseline and 1.80 ± 1.84 mm 2 at 1 year. Thirty-three eyes (80%) displayed an increase in CNV area at 1 year with a mean increase of 0.20 ± 0.38 mm 2 (P = .001). Eleven eyes (27%) underwent CNV doubling, 19 eyes (46%) illustrated modest growth, and 6 (15%) showed shrinkage. Anatomic features including a capillary fringe (odds ratio [OR] = 5.3, P = .036) and immature lesion morphology (OR = 4.2, P = .015) were significantly associated with CNV doubling. CNV growth occurred in 3 predominant patterns: "symmetric" growth, "asymmetric" growth, and "finger-like projections," which reflected the orientation of expansion of CNV. "Symmetric" and "asymmetric" growth together correlated with greater frequency of CNV doubling (OR = 15, P = .0048)., Conclusion: OCTA provides noninvasive measurement of the area of neovascular lesions in AMD. Sustained growth of type 1 NV can be identified in the majority of lesions (80%) that display characteristic patterns of progression despite ongoing anti-VEGF therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To compare patient and Medicare savings from the use of optical coherence tomography (OCT) in guiding therapy for neovascular age-related macular degeneration (nvAMD) to the research investments made in developing OCT by the National Institutes of Health (NIH) and the National Science Foundation (NSF)., Design: Observational cohort study., Methods: Main outcome measures were spending by Medicare as tracked by Current Procedural Terminology codes on intravitreal injections (67028), retinal OCT imaging (92134), and anti-vascular endothelial growth factor (anti-VEGF) treatment-specific J-codes (J0178, J2778, J9035, J3490, and J3590). These claims were identified from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services among fee-for-service (FFS) Medicare beneficiaries from 2012 to 2015; 2008 claims were acquired from the 100% FFS Part B Medicare Claims File. OCT research costs were determined by searching for grants awarded by NIH and NSF from inception to 2015. All costs and savings were discounted by 3% annually and adjusted for inflation to 2015 dollars., Results: From 2008 to 2015, the United States government and nvAMD patients have accrued an estimated savings of $9.0 billion and $2.2 billion, respectively, from the use of OCT to guide personalized anti-VEGF treatment. The $9.0 billion represents a 21-fold return on government investment into developing the technology through NIH and NSF grants., Conclusions: Although an overall cost-benefit ratio of government-sponsored research is difficult to estimate because the benefit may be diffuse and delayed, the investment in OCT over 2 decades has been recouped many times over in just a few years through better personalized therapy., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine demographic and geographic variation in the use of ranibizumab and bevacizumab for the treatment of neovascular age-related macular degeneration (AMD) among Medicare beneficiaries., Design: Retrospective cohort study., Methods: Using a 100% sample of Medicare claims data, we evaluated Medicare beneficiaries (N = 195 812) with an index claim for neovascular AMD between July 1, 2006, and June 30, 2009, to determine whether beneficiaries first received ranibizumab or bevacizumab following initial diagnosis., Results: The overall proportion of beneficiaries that first received ranibizumab for neovascular AMD was 35%, and varied significantly (0.9%-84.6%) across the 306 US hospital referral regions (median = 33%, interquartile range = 17%-49%). Based on hierarchical logistic regression models, the likelihood of receiving ranibizumab declined over time (adjusted odds ratio (aOR) comparing treatment in 2009 vs 2006 = 0.39, P < .001). After we controlled for year of treatment, black beneficiaries were 45% less likely to receive ranibizumab compared to non-blacks (P < .0001). Beneficiaries residing in urban areas (aOR vs isolated rural towns = 1.12, P < .001), in zip codes with higher median incomes, and in the New England and East South Central census regions (aOR vs Pacific census region = 5.57, P < .001; aOR = 3.58, P < .001, respectively) had increased odds of receiving ranibizumab., Conclusions: The odds of receiving bevacizumab vs ranibizumab as initial therapy for neovascular AMD among US Medicare beneficiaries varied substantially across geographic and demographic groups. Relatively fewer patients received ranibizumab for initial neovascular AMD treatment in 2009 vs 2006. Future research should study the drivers of variation in utilization of these interventions, the extent this variation indicates differential access to these agents, and whether treatment choice impacts patient outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate flow signal within subretinal hyperreflective material (SHRM) using optical coherence tomography angiography (OCTA) and its association with aflibercept treatment responses in treatment-naïve neovascular age-related macular degeneration (nAMD)., Design: Prospective consecutive interventional case series., Methods: Forty-four eyes of 44 patients with treatment-naïve nAMD manifesting SHRM on OCT were studied. All patients underwent OCTA and received 3 monthly aflibercept injections. The intrinsic flow signals within SHRM were quantitatively analyzed using OCTA, and eyes were classified into the vascular and avascular SHRM groups., Results: Of 44 eyes, 21 (47.7%) and 23 (52.3%) showed vascular SHRM and avascular SHRM, respectively. Compared with eyes with avascular SHRM, eyes with vascular SHRM showed higher rates of external limiting membrane (ELM) disruption owing to SHRM (P = .015), classic choroidal neovascularization (CNV) (85.7% vs 26.1%, P = .87 × 10 -4 ), and intraretinal fluid (P = .008) at baseline. After 3 aflibercept injections, 38 eyes (86.4%) showed dry macula despite persistent SHRM in 24 eyes (54.5%). Compared with the eyes with resolved SHRM, those with persistent SHRM showed higher rate of vascular SHRM (75.0% vs 15.0%, P = .86 × 10 -4 ), classic CNV (P = .032), absence of polypoidal lesion (P = .020), ELM disruption owing to SHRM (P = .042), and intraretinal fluid (P = .008). Dry macula after loading injections was significantly associated with SHRM resolution (P = .025)., Conclusions: In nAMD, SHRM can be categorized as vascular and avascular by quantitative OCTA analysis. Vascular SHRM persisted after treatment and was associated with failure to achieve dry macula, suggesting that vascular SHRM is predictive of lower response to anti-VEGF therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To determine the efficacy and durability of aflibercept used in a treat-and-extend (TAE) regimen for neovascular age-related macular degeneration (NVAMD)., Design: Multicenter, prospective, open label, noncomparative, interventional study., Methods: Forty eyes of 40 patients with treatment-naïve NVAMD were managed with a TAE regimen of intravitreal aflibercept. The main endpoints were the change in mean and median best-corrected visual acuity from baseline at years 1 and 2. Other endpoints included mean number of annual injections and treatment intervals., Results: Thirty-five (87.5%) and 31 patients (77.5%) completed year 1 and year 2, respectively. The mean letter gain was 7.2 (P < .001) and 2.4 (P = .269) letters at 1 and 2 years, respectively, from a mean baseline of 58.9 letters (20/63 Snellen equivalent). The median visual gain was 11.5 and 7.5 letters at 1 and 2 years, respectively, from a median baseline of 59.0 letters (20/63 Snellen equivalent). The mean number of injections was 8.0 and 6.5 during the first and second year, respectively. Twelve-week or longer treatment intervals were used in 35% and 38% of patients during the first- and second-year time points, respectively., Conclusion: Intravitreal aflibercept TAE therapy led to significant visual improvement in eyes with NVAMD at 1 year, with some loss in the visual gains at the end of year 2 that was not related to loss of exudative control. TAE therapy with aflibercept is a rational strategy to reduce treatments and clinic evaluations over 2 years with satisfactory outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate the relationship between best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in eyes receiving ranibizumab for 3 common retinal diseases., Design: Retrospective analysis of clinical trial data., Methods: Early Treatment Diabetic Retinopathy Study BCVA and spectral-domain optical coherence tomography-measured CRT of 387 eyes of 345 patients enrolled in 6 prospective clinical trials for management of neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were evaluated by Pearson correlation and linear regression., Results: At baseline, there was a small correlation between BCVA and CRT in pooled AMD trial data (r = -0.24). A medium correlation was identified in pooled DME trial data (r = -0.42). No correlation was found in pooled RVO trial data. At month 12, no correlation was found between changes from baseline in BCVA and CRT in pooled AMD trial data. Medium correlations were identified in both pooled DME (r = -0.45) and pooled RVO (r = -0.35) trial data at month 12. Changes in BCVA and CRT associated with edema recurrence upon transition from monthly to pro re nata (PRN) dosing were correlated in AMD (r = -0.27) and RVO (r = -0.72) trials, but not in DME trial data., Conclusion: DME demonstrated a convincing relationship between BCVA and CRT. Correlations appear to be more complex in AMD and RVO. At the inflection point between monthly and PRN dosing, when recurrence of edema is anticipated in many patients, CRT appears strongly correlated with loss of BCVA in RVO., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To develop a near-real-time data warehouse (DW) in an academic ophthalmologic center to gain scientific use of increasing digital data from electronic medical records (EMR) and diagnostic devices., Design: Database development., Methods: Specific macular clinic user interfaces within the institutional hospital information system were created. Orders for imaging modalities were sent by an EMR-linked picture-archiving and communications system to the respective devices. All data of 325 767 patients since 2002 were gathered in a DW running on an SQL database. A data discovery tool was developed. An exemplary search for patients with age-related macular degeneration, performed cataract surgery, and at least 10 intravitreal (excluding bevacizumab) injections was conducted., Results: Data related to those patients (3 142 204 diagnoses [including diagnoses from other fields of medicine], 720 721 procedures [eg, surgery], and 45 416 intravitreal injections) were stored, including 81 274 optical coherence tomography measurements. A web-based browsing tool was successfully developed for data visualization and filtering data by several linked criteria, for example, minimum number of intravitreal injections of a specific drug and visual acuity interval. The exemplary search identified 450 patients with 516 eyes meeting all criteria., Conclusions: A DW was successfully implemented in an ophthalmologic academic environment to support and facilitate research by using increasing EMR and measurement data. The identification of eligible patients for studies was simplified. In future, software for decision support can be developed based on the DW and its structured data. The improved classification of diseases and semiautomatic validation of data via machine learning are warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate detailed patient experiences specific to receiving vascular endothelial growth factor inhibitors (anti-VEGF) for wet age-related macular degeneration (wAMD), and to acquire a snapshot of the frequency of clinically significant levels of depression, anxiety, and posttraumatic stress among patients and levels of burden in patients' carers., Design: Observational cross-sectional mixed-methods study., Methods: Three hundred patients with wAMD receiving anti-VEGF treatment and 100 patient carers were recruited. Qualitative data on patients' experience of treatment were collected using a structured survey. Standardized validated questionnaires were used to quantify clinically significant levels of anxiety, depression, and posttraumatic stress, as well as cognitive function and carers' burden., Results: Qualitative data showed that 56% of patients (n = 132) reported anxiety related to anti-VEGF treatment. The main sources of anxiety were fear of going blind owing to intravitreal injections and concerns about treatment effectiveness, rather than around pain. From validated questionnaires, 17% of patients (n = 52) showed clinical levels of anxiety and 12% (n = 36) showed clinical levels of depression. Depression levels, but not anxiety, were significantly higher in patients who received up to 3 injections compared with patients who received from 4 to 12 injections (analysis of variance [ANOVA] P = .027) and compared with patients who received more than 12 injections (ANOVA P = .001)., Conclusions: Anti-VEGF treatment is often experienced with some anxiety related to treatment, regardless of the number of injections received. Clinical levels of depression seem to be more frequent in patients at early stages of anti-VEGF treatment. Strategies to improve patient experience of treatment and minimize morbidity are suggested., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the incidence rate of massive submacular hemorrhage (SMH) in patients with polypoidal choroidal vasculopathy (PCV) and analyze the associated risk factors., Design: Retrospective cohort study., Methods: Patients diagnosed with PCV from May 2003 to May 2014 were included. Two hundred forty-five eyes of 245 patients were enrolled. The time between the initial visit to the clinic with subjective visual symptoms and the date of massive SMH was recorded. SMH larger than 4 disc diameters was defined as massive SMH. Age; hypertension; visual acuity (VA); indocyanine green angiography findings, including the greatest linear dimension, largest polyp size, and PCV type (cluster vs non-cluster); and treatment methods were reviewed for risk factor analysis using Kaplan-Meier survival and Cox regression analyses., Results: The incidence rate of massive SMH within 1 year after the initial visit was 2.45%. Massive SMH occurred within 3, 5, and 10 years after the first visit in 6.17%, 11.09%, and 29.85% of patients, respectively. Cox regression analysis revealed that the cluster type of PCV was significantly associated with massive SMH (hazard ratio [HR], 3.418; P = .003). Photodynamic therapy followed by anti-vascular endothelial growth factor injection lowered the risk of massive SMH (HR = .242; P = .047]. Final VA in eyes with massive SMH was significantly lower than that in patients without massive SMH (1.34 ± 0.66 vs 0.63 ± 0.53 logMAR; P < .001)., Conclusions: Patients with PCV who develop massive SMH experience severe vision loss. The incidence rate of massive SMH in PCV increases with time. The cluster type of polyp in PCV is a significant risk factor for massive SMH., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To compare time to retreatment and visual function between patients with treatment-naïve neovascular age-related macular degeneration (AMD) treated with either intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA) in routine clinical practice., Design: Retrospective, interventional comparative case series., Participants: A total of 200 eyes of 197 patients with neovascular AMD., Methods: A total of 99 patients in the IVR group and 101 patients in the IVA group who met the inclusion criteria with 12 months of follow-up were included in the present study. All patients received 3 consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab or 2.0 mg/0.05 mL aflibercept as loading doses. Retreatment was allowed if evidence of clinical deterioration or the presence of intraretinal edema or subretinal fluid on spectral-domain optical coherence tomography examination performed at the 1-month follow-up was noted. The time to retreatment after the third injection during the loading phase to the first recurrence during the maintenance phase was compared between treatments using the Kaplan-Meier analysis. Functional and anatomic outcomes were also compared between the IVR and IVA groups., Results: The median time to retreatment after the last induction dose was 5 months in both groups. The proportion of IVR patients who required injection retreatment was not significantly higher than that of IVA patients (67.7% and 63.4%, respectively, at the 12-month follow up; log-rank test, P = .554). In both groups, significant improvements in postoperative best-corrected visual acuity (BCVA) compared with preoperative visual acuity was observed over the 12-month follow-up period (P < .05 for both). Central foveal thickness (CFT) decreased from the baseline values in both groups during the follow-up period (P < .001 for both). Although there was a trend toward greater BCVA improvements in the IVA group, no significant differences in BCVA or CFT were observed between the treatment groups., Conclusions: Both IVR and IVA were well tolerated and demonstrated efficacy in improving the visual acuity in treatment-naïve patients with AMD. Despite a trend toward greater BCVA improvements in the IVA group, a similar injection burden was observed following the loading phases of both ranibizumab and aflibercept., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine the 24-month results of patients who had pro re nata (PRN) aflibercept treatment owing to recurrent or resistant neovascular macular degeneration., Design: Retrospective, interventional, consecutive case series., Methods: Eighty-one eyes of 78 patients with resistant or multiple recurrences of intraretinal or subretinal fluid while receiving monthly bevacizumab or ranibizumab injections and were switched to strict, as-needed aflibercept treatment with every-8-weeks spectral-domain optical coherence tomography (SDOCT)-guided monitoring were included. If there was a persistence of fluid despite this treatment, more frequent aflibercept injections were considered. Anatomic outcomes including maximum retinal thickness, central macular thickness, maximum pigment epithelial detachment height, maximum fluid height, and visual acuity (VA) were assessed at given follow-ups., Results: All anatomic endpoints significantly improved following 3 consecutive aflibercept injections, which were maintained through 24 months (P < .05 for all endpoints at all visits). Thirty-seven eyes (45.6%) required more frequent injections with monthly SDOCT-guided monitoring at a median of 37 weeks (interquartile range, 30-62 weeks) to adequately treat the retinal fluid. Seventy-one of 81 eyes (87.7%) became completely dry on at least 1 follow-up visit; however, there was no significant improvement in VA during the study period., Conclusion: Aflibercept injection with an as-needed regimen was effective in many eyes previously treated with monthly bevacizumab or ranibizumab injections that had persistent or recurrent fluid. Despite significant improvement in anatomic outcomes, vision remained stable throughout the 2-year follow-up, likely because this cohort of patients had advanced choroidal neovascular membrane upon enrollment (recurrent or resistant)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate macular retinal ganglion cell thickness in patients with neovascular age-related macular degeneration (AMD) and intravitreal anti-vascular endothelial growth factor (VEGF) therapy., Design: Retrospective case series with fellow-eye comparison., Methods: Patients with continuous unilateral anti-VEGF treatment for subfoveal and juxtafoveal neovascular AMD and a minimum follow-up of 24 months were included. The retinal nerve fiber (RNFL) and retinal ganglion cell layer (RGCL) in the macula were segmented using an ETDRS grid. RNFL and RGCL thickness of the outer ring of the ETDRS grid were quantified at baseline and after repeated anti-VEGF injections, and compared to the patients' untreated fellow eye. Furthermore, best-corrected visual acuity (BCVA), age, and retinal pigment epithelium (RPE) atrophy were recorded and correlated with RNFL and RGCL., Results: Sixty eight eyes of 34 patients (23 female and 11 male; mean age 76.7 (SD ± 8.2) with a mean number of 31.5 (SD ± 9.8) anti-VEGF injections and a mean follow-up period of 45.3 months (SD ± 10.5) were included. Whereas the RGCL thickness decreased significantly compared to the noninjected fellow eye (P = .01), the decrease of the RNFL was not significant. Visual acuity gain was significantly correlated with RGCL thickness (r = 0.52, P < .05) at follow-up and negatively correlated (r = -0.41, P < .05) with age. Presence of RPE atrophy correlated negatively with the RGCL thickness at follow-up (r = -0.37, P = .03)., Conclusion: During the course of long-term anti-VEGF therapy there is a significant decrease of the RGCL in patients with neovascular AMD compared to the fellow (untreated) eye., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the therapeutic response of pigment epithelial detachment (PED) to anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (nAMD), and identify predictive factors for PED resolution after treatment., Design: Retrospective, interventional case series., Methods: A total of 202 treatment-naïve nAMD eyes presenting PED at baseline were retrospectively included and analyzed. All patients were treated with an initial series of 3 monthly loading injections of ranibizumab or aflibercept, followed by additional injections as required., Results: After 12 months of treatment, the mean PED height decreased from 453 ± 261 μm at baseline to 230 ± 142 μm (P = .002), and the mean best-corrected visual acuity improved from 0.71 ± 0.41 logarithm of the minimal angle of resolution (Snellen equivalent, 20/102) to 0.60 ± 0.36 (20/79) (P = .024). The proportion of complete PED resolution after treatment was 19.3% (39 eyes). Multivariate logistic regression analysis was used to find baseline characteristics associated with a higher chance of PED resolution, including lower PED height at baseline (P = .018), polypoidal choroidal vasculopathy (P = .015), or retinal angiomatous proliferation (P = .010) compared to typical nAMD; serous PED (P = .022) compared to fibrovascular PED; and aflibercept (P = .039) compared to ranibizumab., Conclusions: PEDs secondary to nAMD showed significant functional and anatomic improvement after intravitreal anti-VEGF injections over 12 months. However, the anti-VEGF treatment showed limited efficacy for the complete resolution of PED. The PED type, nAMD subtype, baseline PED height, and anti-VEGF drug type was associated with a higher probability of PED resolution after treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device., Design: Comparative analysis of diagnostic instruments., Methods: Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of <.05 were considered statistically significant., Results: Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type 1, 2 eyes (14.3%) as type 2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS OCT and SD OCT 3 mm × 3 mm OCTA were 0.949 ± 1.168 mm(2) and 0.340 ± 0.301 mm(2), respectively (P = .001). For the 6 mm × 6 mm OCTA the total CNV area using SS OCT and SD OCT were 1.218 ± 1.284 mm(2) and 0.604 ± 0.597 mm(2), respectively (P = .0019). The field of view did not significantly affect the measured CNV area (P = .19 and P = .18 for SS OCT and SD OCT, respectively)., Conclusion: SS OCTA yielded significantly larger CNV areas than SD OCTA. It is possible that SS OCTA is better able to demarcate the full extent of CNV vasculature., (Copyright © 2016 Elsevier Inc. All rights reserved.)