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OBJECTIVE/PURPOSE: To describe the frequency of long-term morphological features and their relationships with visual function in participants who exited the inhibition of VEGF in age-related choroidal neovascularization (IVAN: ISRCTN92166560) trial. DESIGN: Multicenter cohort study up to 7 years after enrolment. PARTICIPANTS: Patients enrolled in IVAN excluding participants who died or withdrew during the trial. METHODS: Multimodal fundus images, best corrected (BCVA) and low luminance visual acuity (LLVA) were obtained in a subset of 199 participants who attended a research visit. Clinical sites (n=20) also provided all visual acuity and clinical information from usual care records for 532 participants and submitted most recent color, OCT and other fundus images for 468 participants to a reading center. MAIN OUTCOME MEASURES: Assessed from most recent images: intralesional macular atrophy (ILMA) within the footprint of the neovascular lesion; hyperreflective material (HRM); intraretinal fluid (IRF); subretinal fluid (SRF); pigment epithelial detachment (PED); disorganization of outer retinal layers (DROL). Cross sectional relationships between morphological features and BCVA/LLVA were estimated. RESULTS: ILMA was present in 31.8% of study eyes at IVAN exit (mean follow-up 1.96 years) and 89.5% at the most recent imaging visit (6.18 years). HRM, IRF, SRF, PED and DROL were present in 78.8%, 47.7%, 7.6%, 94.5% and 55% respectively. In the subset with complete imaging data, in eyes without DROL, BCVA was worst in the thinnest outer fovea tertile (thinnest minus middle and thickest tertiles, -19.7 and -19.5 letters respectively) whereas in eyes with DROL, BCVA was worst in the thickest (thinnest and middle tertiles minus thickest, 12.5 and 12.2 respectively). Regression models showed that presence of ILMA and HRM were independently associated with BCVA (22 letters worse (95% CI 11.2, 32.8, p<0.001) and 9.8 letters worse (95% CI 0.1, 19.4, p=0.047), respectively). SRF and foveal PED were associated with better BCVA (5.9 letters, 95% CI -7.9, 19.7, p<0.399; and 6.4 letters, 95% CI -1.1, 14.0, p=0.094 respectively). The model with LLVA was similar. Sensitivity analysis including the entire eligible cohort yielded similar estimates. CONCLUSIONS: Macular atrophy and HRM were common after 7 years of follow-up and strongly associated with visual outcomes.

Original publication




Journal article


Ophthalmol Retina

Publication Date



IVAN trial, disorganization of outer retina, long-term follow-up, macular atrophy, spectral domain OCT