Onset of Retinal Pigment Epithelium Atrophy Subsequent to Anti-VEGF Therapy in Patients with Neovascular Age-Related Macular Degeneration

Abstract

Purpose: The aim of this study was to evaluate risk factors for the development of retinal pigment epithelium (RPE) atrophy in patients with neovascular age-related macular degeneration (nAMD). Procedures: This post hoc analysis of the prospective RESPONSE study includes 52 therapy-naive nAMD patients without baseline RPE atrophy, who were treated with ≥9 anti-vascular endothelial growth factor (VEGF) injections for ≥3 years. RPE atrophy was assessed via multimodal imaging. Baseline aqueous VEGF and serum complement levels (C3d/C3) were measured. Risk factors for atrophy development were evaluated via logistic regression analysis. Results: Atrophy onset was significantly associated with the duration of nAMD (mean 5.34 years; odds ratio = 1.83, p = 0.012). Anti-VEGF injection number, age, C3d/C3 ratio, baseline intraocular VEGF, or delay to the first treatment had no influence on RPE atrophy. Conclusions: The duration of treatment-requiring nAMD was identified as primary risk factor for the onset of concomitant RPE atrophy after commencing therapy. Targeting concomitant atrophy in nAMD patients might improve the long-term prognosis of the disease.

Anti–Vascular Endothelial Growth Factor Use and Atrophy in Neovascular Age-Related Macular Degeneration

“…Two publications reported atrophy outcomes using CFP, FA, and spectral-domain (SD) OCT from IVAN (The Inhibition of VEGF in Age-related choroidal Neovascularisation; Current Controlled Trials ISRCTN92166560). 10,27 Over 2 years, 30% of eyes demonstrated GA. 10 An analysis of 11,13e24 Color fundus photography and fluorescein angiography* HARBOR 12,25,26 Color fundus photography and fluorescein angiography IVAN 10,27 Color fundus photography, fluorescein angiography, and OCT RESPONSE 28 Color fundus photography, fluorescein angiography, SD OCT, FAF, and infrared imaging SEVEN-UP 29,30 Fluorescein angiography and FAF y TREX-AMD 31,32 SD OCT, FAF, and infrared imaging Chang et al (2015) 33 Color fundus photography and fluorescein angiography, FAF, and SD OCT Saito et al (2017) 34 Color fundus photography and short-wavelength autofluorescence Thavikulwat et al (2017) 35 Color fundus photography, fluorescein angiography, FAF, and SD OCT Zandi et al (2017) 36 FAF and SD OCT Mantel et al (2018) 37 Color fundus photography, fluorescein angiography, FAF, and SD OCT Mantel et al (2018) 38 Color fundus photography, fluorescein angiography, FAF, and SD OCT 13 Cohort study within CATT (N ¼ 1030; patients who completed 2 yrs of follow-up)…”

“…A post hoc analysis of RESPONSE (Genetics in Nonresponse to Anti-VEGF Treatment in Exudative AMD [RESPONSE]; ClinicalTrials.gov identifier: NCT01213667) assessed atrophy using CFP, FA, SD OCT, fundus autofluorescence (FAF), and infrared imaging. 28 Retinal pigmented epithelium atrophy (RPEA) developed in 21.2%, 28.8%, 40.4%, 44.2%, and 57.7% of patients at 6 months, year 1, year 2, year 3, and the final visit, respectively. Baseline central retina thickness was the only significant predictor of RPEA development.…”

A Review of Macular Atrophy of the Retinal Pigment Epithelium in Patients with Neovascular Age-Related Macular Degeneration: What is the Link? Part II

“…The reported figures show that the highest MA incidence was within the first year of the study. Thavikulwat et al [40], Sadda et al [27], Li et al [47] and Sitnilska et al [48] reported percentages of MA incidence within the first year of 85%, 75%, 65% and 50%, respectively. Over a follow-up period of 4 years, Domalpally also noted that most new occurrences of MA were within the initial 2 years [49].…”

“…For some studies the expressed percentage was out of the group of study eyes that had no atrophy at the start of the study, whilst for others it was out of the whole cohort of study eyes. For some studies, eyes with baseline MA were excluded from either the analysis or from the whole study [14,21,27,35,36,40,46,48,51], others excluded eyes that did not develop MA by the end of the study [50], while the majority of the remaining reports included eyes with and without MA at baseline and also with and without MA at end of study.…”

“…CATT excluded eyes with baseline MA from the analysis [14], and so did others [35,46,48,51], and in another report CATT excluded eyes with subfoveal GA at baseline [21], and others have followed as well [36,40]. Again, Sadda et al also excluded eyes with subfoveal atrophy at baseline, yet atrophy immediately within, adjacent and nonadjacent to CNV lesions (active or regressed) was included [27].…”