Disease Progression in Age-Related Macular Degeneration Patients Carrying Rare Variants in the Complement Factor H or...

Rare variants in CFI and CFH genes are associated with AMD. This study aimed to compare the incidence of late AMD in carriers of these variants to a reference cohort using a long follow-up cohort (LF-cohort) and to examine short-term AMD progression in a short follow-up cohort (SF-cohort).

This cohort study included two groups: the LF-cohort, observed for more than five years retrospectively and the SF-cohort, observed for one year prospectively, with patients attending in-hospital visits. One hundred twelve AMD patients with rare CFH/CFI or variants were invited from the European Genetic Database. The LF-cohort's outcome was the incidence of late AMD per 100 person-years compared to a matched reference cohort. In the SF-cohort, geographic atrophy (GA), retinal sensitivity, and visual acuity were measured.

The LF-cohort included 28 patients (median [interquartile range {IQR}] age, 71.3 [24.3] years; 18 females [64%]) with an incidence rate of 6.2 per 100 person-years which was higher than the reference cohort (1.8 per 100 person years (P = 0.01)). The SF-cohort consisted of 44 patients (median [IQR] age 70.5 [16.5] years; 29 (65% female). Mean annual GA growth (SD) was 0.22 mm (0.13) in 19 eyes of 12 patients. Retinal sensitivity changed for late-staged eyes (right eye: 17.2 dB to 15.7 dB, P = 0.03; left eye 17.3 dB to 16.4 dB, P = 0.06) whereas visual acuity did not.

Carriers of rare CFI or CFH variants show a higher incidence of late AMD. These patients may benefit from personalized gene therapy and complement inhibition in future trials.