Intralesional Macular Atrophy in Anti–Vascular Endothelial Growth Factor Therapy for Age-Related Macular Degeneration in the IVAN Trial

Purpose: To report on the development and progression of macular atrophy (MA) and its relationship with morphologic and functional measures in study and fellow eyes in the Inhibition of vascular endothelial growth factor (VEGF) in Age-related Choroidal Neovascularisation trial. Design: Reading center analysis of data from a randomized controlled trial. Participants: Participants with previously untreated neovascular age-related macular degeneration (nAMD) in the study eye. Methods: Color, fluorescein angiography (FA) and OCT images acquired at baseline and during the 2-year follow-up were graded systematically for presence of MA. Regression models were constructed to explore relationships between MA and lesion morphology and vision measures (best-corrected distance and near acuity, reading speed and index, contrast sensitivity). Main Outcome Measures: Primary outcome was development of intralesional MA (≥175 μm greatest linear dimension of choroidal vessels seen on FA and/or color, aided by OCT) lying within the maximum footprint of the neovascular lesion. Results: Study eye data were available for 594 of 610 participants; 57 (9.6%) showed intralesional MA at baseline. Incident intralesional MA occurred in 24.4% by the final visit and extralesional MA in only 1.54%. In fellow eyes, an established nAMD lesion was present at baseline in 248 of whom 42 (16.9%) showed intralesional MA at baseline and 32 (12.9%) developed incident intralesional MA. The odds of incident intralesional MA by final visit were lower in study eyes that had ≥50% classic CNV at baseline (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.19–0.80; P = 0.010), subretinal fluid at final visit (OR, 0.41; 95% CI, 0.25–0.76; P = 0.004), or pigment epithelial detachment at final visit (OR, 0.40; 95% CI, 0.21–0.74; P = 0.004). Secondary analyses of incident or progressed intralesional MA in study eyes supported these findings, with odds increasing if the fellow eye had baseline intralesional MA (OR, 2.43; 95% CI, 1.09–5.44; P = 0.030). No significant associations were observed between development of intralesional MA and any other morphologic or visual function measure. Conclusions: Macular atrophy frequently develops within an nAMD lesion in eyes receiving anti–VEGF therapy over 2 years. No associations between incident MA and drug or treatment frequency or visual function were detected, providing some reassurance to clinicians; however, the longer-term effects remain unknown.