Bilateral choroidal thinning during unilateral aflibercept for neovascular age-related macular degeneration: 5-year mixed-effects analysis.

PURPOSE: To evaluate 5-year choroidal changes in eyes with unilateral neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVA) and to compare longitudinal changes among treated, fellow untreated, and control eyes using mixed-effects modeling. METHODS: Sixteen patients with unilateral nAMD (16 treated and 16 fellow untreated eyes) and 20 age-matched and sex-matched control eyes were included. Best-corrected visual acuity (BCVA), central subfield thickness (CST), central choroidal thickness (CCT), and choroidal vascularity index (CVI) were assessed. Absolute and proportional CCT changes were analyzed. Annual rates of change were estimated using linear mixed-effects models. RESULTS: Over 5 years, control eyes showed mild age-related choroidal thinning (- 3.7 μm/year). In contrast, CCT declined significantly faster in treated eyes (- 11.5 μm/year; p < 0.01 vs. control); fellow untreated eyes also demonstrated accelerated thinning (- 8.2 μm/year; p < 0.05 vs. control). Proportional analyses showed a similar graded pattern. BCVA worsened and CST decreased in treated eyes, while remaining stable in fellow eyes. CVI increased modestly and similarly in treated and fellow eyes (approximately + 0.8%/year). CONCLUSION: In this 5-year three-group longitudinal analysis, treated eyes showed the greatest annual reduction in CCT, fellow untreated eyes showed an intermediate reduction, and age-matched control eyes showed the smallest decline. The inclusion of a control group indicated that fellow-eye thinning exceeded that expected from physiological aging alone, supporting bilateral choroidal change during long-term unilateral IVA therapy.