Ethical considerations limit the feasibility of withholding anti-VEGF therapy and of including untreated high-risk subgroups such as glaucoma patients; therefore, future prospective studies with larger cohorts, longer follow-up durations, and appropriate control or natural-history comparator groups, including glaucoma patients as a separate subgroup, are warranted to better clarify the relationship between anti-VEGF therapy and optic nerve changes. The gene discussed is VEGFA; the disease is glaucoma.