Sustained Visual Acuity Loss in the Comparison of Age-Related Macular Degeneration Treatments Trials

Abstract

Although anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration (AMD) results in improved vision overall, loss of substantial vision can occur. Understanding the processes that lead to loss of vision may lead to preventive strategies.OBJECTIVE To determine the incidence, characteristics, causes, and baseline predictors of sustained visual acuity loss after 2 years of treatment with ranibizumab or bevacizumab for neovascular AMD. DESIGN, SETTING, AND PARTICIPANTS A cohort study within a randomized clinical trial of participants in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).INTERVENTIONS Participants were randomly assigned to treatment with ranibizumab or bevacizumab and to 2 years of monthly or as needed injections or monthly injections for 1 year and as needed injections the following year.MAIN OUTCOMES AND MEASURES Sustained visual acuity loss, defined as loss of 15 or more letters from baseline at weeks 88 and 104. RESULTS Among 1030 participants, 61 eyes (5.9%) developed sustained visual acuity loss in 2 years. Within this group, visual acuity decreased gradually over time, with a mean decrease of 2, 19, and 33 letters from baseline at 4 weeks, 1 year, and 2 years, respectively. At 2 years, eyes with sustained visual acuity loss had more scarring (60.0% vs 41.4%, P = .007), more geographic atrophy (GA) (31.6% vs 20.7%, P = .004), larger lesions (16 vs 8 mm 2 , P < .001), and higher proportions of intraretinal fluid (82.5% vs 51.0%, P < .001), subretinal hyperreflective material (84.5% vs 44.2%, P < .001), retinal thinning (43.3% vs 23.0%, P < .001), and thickening (20.0% vs 12.1%, P < .001). Likely causes of sustained visual acuity loss included foveal scarring (44.3%), pigmentary abnormalities (27.9%), and foveal GA (11.5%). Baseline factors independently associated with a higher incidence of sustained visual acuity loss were the presence of nonfoveal GA (odds ratio [OR], 2.86; 95% CI, 1.35-6.08; P = .006), larger area of choroidal neovascularization (OR for a >4-disc area vs Յ1-disc area, 3.91; 95% CI, 1.70-9.03; P = .007), and bevacizumab treatment (OR, 1.83; 95% CI, 1.07-3.14; P = .03).CONCLUSIONS AND RELEVANCE Sustained visual acuity loss was relatively rare in CATT. The development of foveal scar, pigmentary abnormalities, or GA contributed to most of the sustained visual acuity loss. Risk was 3% higher among eyes treated with bevacizumab. Treatment that targeted the prevention of scarring or GA may improve vision outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00593450

The role of indocyanine green angiography imaging in further differential diagnosis of patients with nAMD who are morphologically poor responders to ranibizumab in a real-life setting

“…26 Also some of the baseline characteristics were found to be associated with sustained VA loss, which were presence of non-foveal geographic atrophy, larger CNV area, poor baseline VA, o20/50 baseline VA in the fellow eye, and intraretinal fluid not at the foveal center. 26 The patients' clinical characteristics, lesion type, and misdiagnosis have been evaluated thoroughly and constitute now the main discussed topics in anti-VEGF nonresponse literature. 15,16,26 Factors affecting drug pharmacodynamics and pharmacokinetics such as receptor downregulation, autoantibody formation, change in drug distribution, and absorption have also been shown to be related to nonresponse.…”

“…15 In the pivotal multicenter studies,~5% of the patients were found to be unresponsive to anti-VEGF treatment, and showed sustained VA loss despite treatment; these patients have been called as nonresponders. 11,13,14,26 The sustained VA loss has been attributed to several factors, such as fibrous scar formation, pigmentary anomalies, geographic atrophy, RPE tear, retinal thinning, and thickening. 26 Also some of the baseline characteristics were found to be associated with sustained VA loss, which were presence of non-foveal geographic atrophy, larger CNV area, poor baseline VA, o20/50 baseline VA in the fellow eye, and intraretinal fluid not at the foveal center.…”

“…11,13,14,26 The sustained VA loss has been attributed to several factors, such as fibrous scar formation, pigmentary anomalies, geographic atrophy, RPE tear, retinal thinning, and thickening. 26 Also some of the baseline characteristics were found to be associated with sustained VA loss, which were presence of non-foveal geographic atrophy, larger CNV area, poor baseline VA, o20/50 baseline VA in the fellow eye, and intraretinal fluid not at the foveal center. 26 The patients' clinical characteristics, lesion type, and misdiagnosis have been evaluated thoroughly and constitute now the main discussed topics in anti-VEGF nonresponse literature.…”

“…26 The patients' clinical characteristics, lesion type, and misdiagnosis have been evaluated thoroughly and constitute now the main discussed topics in anti-VEGF nonresponse literature. 15,16,26 Factors affecting drug pharmacodynamics and pharmacokinetics such as receptor downregulation, autoantibody formation, change in drug distribution, and absorption have also been shown to be related to nonresponse. 15,25,26 Suboptimal treatment of the patients with less frequent treatment regimens is another important clinical factor which can affect the treatment success and underlie nonresponse.…”

“…15,16,26 Factors affecting drug pharmacodynamics and pharmacokinetics such as receptor downregulation, autoantibody formation, change in drug distribution, and absorption have also been shown to be related to nonresponse. 15,25,26 Suboptimal treatment of the patients with less frequent treatment regimens is another important clinical factor which can affect the treatment success and underlie nonresponse. Real-life studies showed that many of the patients were undertreated especially in the PRN treatment regimens.…”