Genetic factors associated with response to as-needed brolucizumab treatment for exudative age-related macular degeneration

To investigate the association between genetic variants susceptible to exudative age-related macular degeneration (AMD) and the treatment response to as-needed intravitreal brolucizumab (IVBr) therapy.

Interventional study METHODS: This retrospective study included 103 treatment-naïve eyes with exudative AMD. All eyes received three monthly IVBr injections (6.0 mg/0.05 mL) followed by a pro re nata regimen for 12 months. Seven major AMD-associated single nucleotide polymorphisms-ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH rs1329428, C2-CFB-SKIV2L rs429608, C3 rs2241394, CETP rs3764261, and ADAMTS9 rs6795735-were genotyped using TaqMan assays. The requirement for retreatment, the number of additional injections, and visual outcomes were compared across genotypes.

Of the 103 patients, 68 (66.0%) required additional injections. The T allele of ARMS2 A69S was significantly more frequent in the retreatment group than in the retreatment-free group (65.0% vs. 42.9%, p = 1.9 × 10⁻³) and remained independently associated with retreatment after adjustment for age, sex, and baseline visual acuity (p = 3.0 × 10⁻³). Eyes with the TT genotype required significantly more additional injections than those with the TG or GG genotypes (2.4 ± 1.7 vs. 1.3 ± 1.6 and 1.3 ± 1.5, respectively; p = 5.0 × 10⁻³). Kaplan-Meier analysis demonstrated a significant difference in retreatment-free survival among ARMS2 genotypes (p = 4.1 × 10⁻⁴). Visual outcomes did not differ across any genotypes.

ARMS2 A69S may serve as a predictor of recurrence and number of additional injections in as-needed brolucizumab therapy for exudative AMD.