Anti-vascular endothelial growth factor in neovascular age-related macular degeneration – a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems (original) (raw)
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Neovascular age-related macular degeneration (nAMD) leads to visual impairment if not treated timely. Intravitreal anti-VEGF drugs have revolutionized nAMD treatment in two decades. We evaluated visual outcomes of anti-VEGF treatment in nAMD. A real-life population-based cohort study. Data included parameters for age, sex, age at the diagnosis, laterality, chronicity, symptoms, visual outcomes, lens status, and history of intravitreal injections. A total of 1088 eyes (827 patients) with nAMD were included. Visual acuity was stable or improved in 984 eyes (90%) after an average 36±25 months follow-up. Bevacitzumab was the first-line drug in 1083 (99.5%) eyes. Vision improved ≥15 ETDRS letters in 377 (35%), > 5 ETDRS letters in 309 (28%) and was stable (±5 ETDRS letters) in 298 (27%) eyes after anti-VEGF treatment. The loss of 5-<15 ETDRS letters in 44 (4%) and ≥15 ETDRS letters in 60 (6%) eyes was noted. At the diagnosis of nAMD, 110 out of 827 patients (13%) fulfilled the crit...
Psychology, health & medicine, 2015
Current therapy to slow disease progression in patients with neovascular age-related macular degeneration (AMD) often entails intra-vitreal injection of an anti-vascular endothelial growth factor (VEGF) agent, that begins with a three-month loading phase of four weekly injections followed by regular monthly visits with clinician-determined re-treatment. The effects of AMD on quality of life and visual function have been extensively reported in the literature, however, less is known about the burden imposed on patients by the arduous and often indefinite treatment schedule which habitually follows a diagnosis of wet AMD. To date, no systematic review has been conducted of research investigating patients' experiences of anti-VEGF treatment for AMD. A systematic search of the Embase, Medline, PsycINFO and PubMed electronic databases was undertaken to identify all studies between January 2004 and December 2013, published in the English language and involving human participants. A ha...
Ophthalmology, 2018
, MBBS (Hons), 7 for the Fight Retinal Blindness! Study Group* Purpose: To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with neovascular age-related macular degeneration (nAMD) receiving intravitreal antievascular endothelial growth factor (anti-VEGF) agents in daily clinical practice. Design: Observational study. Participants: Treatment-naive eyes starting anti-VEGF therapy for nAMD between 2007 and 2012 tracked in the Fight Retinal Blindness! registry. Eyes had sustained !15 letters of loss from baseline without recovery of visual acuity (VA) at final end point. A subgroup analysis included eyes that sustained !30 letters of loss. Controls had not sustained !15 letters of loss. Methods: KaplaneMeier curves estimated time to first development of loss of !15 letters. Cox proportional hazards models evaluated predictors of loss of !15 letters. Main Outcome Measures: The proportion of eyes with sustained VA loss within 5 years, the time to development of sustained VA loss, and baseline predictors of sustained VA loss. Results: There were 1760 eyes in total and 856 eyes that completed 5 years follow-up. The proportion of eyes with sustained VA loss of !15 letters at 5 years was 22.9% (95% confidence interval [CI], 20.7%e25.1%) and VA loss of !30 letters was 10.8% (95% CI, 9.1%e12.5%). Factors independently associated with higher incidence of sustained !15-letter loss included age >80 years (odds ratio [OR], 1.33 for patients >80 years vs. 80 years; 95% CI, 1.05e1.69; P ¼ 0.02), fewer injections (OR, 0.97 per injection; 95% CI, 0.96e0.98; P ¼ 0.0005), and more visits at which the choroidal neovascularization was graded as active (OR, 1.97 for eyes in upper quartile of active visits vs. eyes in lowest quartile of active visits; 95% CI, 1.39e2.79; P ¼ 0.0001). Baseline VA !70 letters was associated with reduced risk of sustained !30-letter loss (OR, 0.61; 95% CI, 0.38e0.98; P ¼ 0.04). Baseline angiographic lesion criteria were not significantly associated with sustained VA loss. Conclusions: Twenty-three percent of eyes with nAMD developed sustained VA loss of !15 letters over 5 years of anti-VEGF therapy. Baseline predictors of poor outcomes provide more accurate assessment of the potential benefit from anti-VEGF therapy. Ophthalmology 2019;126:735-742 ª 2018 by the American Academy of Ophthalmology Supplemental material available at www.aaojournal.org. Despite the effectiveness of antievascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD), significant loss of vision can still occur. 1e11 The major clinical trials of ranibizumab, Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA), and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR), reported a loss of 15 or more letters of visual acuity (VA) in 8% to 10% of eyes at 2 years. 4,6 In the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD studies
American Journal of Ophthalmology, 2012
PURPOSE-To investigate the potential influences that affect visual acuity (VA) outcome in a clinic-based cohort of age-related macular degeneration (AMD) patients undergoing anti-vascular endothelial growth factor (anti-VEGF) treatment for choroidal neovascularization. DESIGN-Prospective interventional case series. METHODS-Patients with subfoveal choroidal neovascularization (CNV) secondary to AMD were prospectively recruited. A detailed questionnaire was given to patients at time of enrollment, to collect information relating to demographics, history of visual symptoms, visual acuity (VA), and treatment scheduling. Delay from symptoms to treatment ("Treatment delay") was measured in terms of weeks and analyzed in tertiles. Information pertaining to treatment outcomes was collected over a 6-month period. RESULTS-One hundred eighty-five eyes of 185 patients were recruited into the study. Longer delay from first symptoms suggestive of CNV to first injection was a significant predictor (P =. 015) of poorer treatment outcome, when controlling for age, sex, and baseline VA. Patients with a delay in treatment of 21 weeks or more compared to a delay of 7 weeks or less had an odds ratio of 2.62 (1.20, 5.68) for worsening vision after treatment. CONCLUSIONS-Patients experiencing a longer delay between their first symptoms of CNV and their first anti-VEGF treatment have a significantly lower chance of improving vision at 6 months following anti-VEGF therapy. It is critical that this information reach those at potential vision loss from AMD, in order that prompt treatment may be instituted, to maximize the benefits of anti-VEGF treatment. RANIBIZUMAB (LUCENTIS; GENENTECH INC, SOUTH San Francisco, California, USA) and bevacizumab (Avastin; Genentech Inc) are anti-vascular endothelial growth factor (anti-VEGF) drugs that have improved the treatment of neovascular age-related macular Inquiries to Sanjeewa Wickremasinghe,
JAMA Ophthalmology
IMPORTANCE Although multiple imputation models for missing data and the use of mixed-effects models generally provide better outcome estimates than using only observed data or last observation carried forward in clinical trials, such approaches usually cannot be applied to visual outcomes from retrospective analyses of clinical practice settings, also called real-world outcomes. OBJECTIVE To explore the potential usefulness of survival analysis techniques for retrospective clinical practice visual outcomes. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study covered a 12-year observation period at a tertiary eye center. Of 10 744 eyes with neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor (VEGF) therapy between October 28, 2008, and February 1, 2020, 7802 eyes met study criteria (treatment-naive, first-treated eyes starting anti-VEGF therapy). Eyes were excluded from the analysis if they received photodynamic therapy or macular laser, any previous anti-VEGF therapy, treatment with anti-VEGF agents other than ranibizumab or aflibercept, or had an unknown date or visual acuity (VA) value at first injection. MAIN OUTCOMES AND MEASURES Kaplan-Meier estimates and Cox proportional hazards modeling were used to consider VA reaching an Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 70 (Snellen equivalent, 20/40) or better, duration of VA sustained at or better than 70 (20/40), and VA declining to 35 (20/200) or worse. RESULTS A total of 7802 patients (mean [SD] age, 78.7 [8.8] years; 4776 women [61.2%]; and 4785 White [61.3%]) were included in the study. The median time to attaining a VA letter score greater than or equal to 70 (20/40) was 2.0 years (95% CI, 1.87-2.32) after the first anti-VEGF injection. Predictive features were baseline VA (hazard ratio [HR], 1.43 per 5 ETDRS letter score or 1 line; 95% CI, 1.40-1.46), baseline age (HR, 0.88 per 5 years; 95% CI, 0.86-0.90), and injection number (HR, 1.12; 95% CI, 1.10-1.15). Of the 4439 of 7802 patients (57%) attaining this outcome, median time sustained at an ETDRS letter score of 70 (20/40) or better was 1.1 years (95% CI, 1.1-1.2). CONCLUSIONS AND RELEVANCE In this cohort study, patients with neovascular age-related macular degeneration beginning anti-VEGF therapy were more likely to experience positive visual outcomes within the first 2.0 years after treatment, typically maintaining this outcome for 1.1 years but then deteriorating to poor vision within 8.7 years. These findings demonstrate the potential usefulness of the proposed analyses. This data set, combined with the statistical approach for retrospective analyses, may provide long-term prognostic information for patients newly diagnosed with this condition.
BMC Ophthalmology
Background Anti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD. Methods Two clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial. Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included. Results Mean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained...
American Journal of Ophthalmic Clinical Trials, 2018
Anti-vascular endothelial growth factor (anti-VEGF) agents are the mainstay of therapy for treatment of neovascular age-related macular degeneration (nvAMD), one of the leading causes of blindness in the developed world. There have been a variety of different treatment regimens that have been examined for the administration of anti-VEGF therapies, including continuous fixed dosing, pro re nata administration, and treat and extend (TAE) protocols. There is no clear consensus on which dosing regimen optimizes visual and anatomical outcomes while accounting for factors such as cost and patient burden. Based on recent surveys in 2014 and 2017 by the American Society of Retina Specialists (ASRS), the majority of ophthalmology providers are utilizing TAE protocol for anti-VEGF dosing for the management of nvAMD. Although there are a number of clinical trials that have examined TAE dosing, the ALTAIR study is the first, large, prospective randomized controlled trial to compare two differen...
Ophthalmology Retina, 2019
Purpose-To analyze best-corrected visual acuity (BCVA) outcomes after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). Design-Prospective cohort study of participants enrolled in a clinical trial of oral supplements and receiving anti-VEGF therapy in routine clinical practice. Participants-Age-Related Eye Disease Study 2 (AREDS2) participants (50-85 years) whose eyes met AREDS2 inclusion criteria at baseline (no late AMD; BCVA ≥20/100; no previous anti-VEGF injections) but received at least one anti-VEGF injection for incident neovascular AMD during follow-up.
Journal of Clinical Medicine, 2022
Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) have become the standard of care for age-related macular degeneration (AMD). Although most pivotal trials have used monthly injections, alternative strategies that enable the injections to be administered on a more flexible schedule, including pro re nata (PRN) and treat-and-extend (T&E) regimens, are being applied more frequently. This review sought to provide further scientific evidence about the visual outcomes and treatment burden among the currently available anti-VEGF agents and regimens, including aflibercept, ranibizumab, abicipar and brolucizumab. To this end, a systematic review of published randomized studies was conducted from the MEDLINE and EMBASE databases and the Cochrane library, and a meta-analysis was applied to the obtained data using single-means modeling to compare the efficacy and maintenance among the different available treatments and regimens at Years 1 and 2. Quality analy...