Biomarkers for eyes with high injection demand in anti-angiogenic Therapy of nAMD

Purpose: Anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) is a long-term treatment with individually varying injection requirements. Patients with high treatment demand could benefit from new therapeutic approaches involving continuous drug delivery. Suitable predictive biomarkerscould help identify them early. Methods: In a cohort of 744 eyes (mean age 78.4 years, range 43-96; mean follow-up 3.3 years, range 1–10), injection demand was categorized into four groups: ≤4.5 injections/year (n=59), >4.5–≤6.5 (n=203), >6.5–≤8.5 (n=309), and >8.5 injections/year (n=173). Annual optical coherence tomography (OCT) examinations were available for all eyes, with a total of 18,743 OCT scans analyzed. Using recently published algorithms, macular neovascularization (MNV) area and growth as well as central retinal thickness (CRT) were quantified. ANOVA and linear models were applied to assess the relationship between injection frequency in the first year, long-term treatment demand, and morphological parameters. MNV growth was analyzed using grouped growth curve models. Results: Injection frequency during the first year of treatment showed a significant association with long-term annual injection demand (p<0.001). Baseline MNV size and CRT were higher in eyes with higher injection frequency. In addition, MNV growth after one year as well as during follow-up was slower while a lower reduction of CRT was observed in eyes with higher injection frequency. Conclusion: Baseline MNV size and higher CRT and especially injection frequency in the first year may be key biomarkers for high long-term treatment demand. They may facilitate early identification of patients who could benefit from continuous drug delivery therapies.