gms | German Medical Science

Background: Complement genes are strongly linked to age-related macular degeneration (AMD). Little is known about disease progression in AMD patients carrying rare variants in these genes. We assessed short-term disease progression in AMD patients with rare variants in the complement factor H (CFH) or factor I (CFI) genes.

Methods: We selected AMD patients carrying a rare (mean allele frequency <1%), protein-altering or splice-site variant in either the CFH or CFI gene, excluding protective or neutral variants. Patients were followed over time for at least 12 months. The following parameters were obtained at every visit: changes in visual appearance of drusen load compared to baseline (no change/substantial change/regression) on color fundus photography, area (in mm2) of geographic atrophy (GA) on fundus autofluorescence (FAF), mean retinal sensitivity (RS) in decibels (dB) on mesopic microperimetry and visual acuity (VA) in logMAR.

Results: We included 44 patients (88 eyes) with a mean (IQR) age of 61.3 (16.5). There were 29 and 15 patients with a rare variant in the CFH and CFI gene, respectively. The majority of eyes (73/87) showed no substantial change in drusen load after 12 months. The mean area (SD) of GA was 4.5mm2 (5.6) at baseline and 5.5mm2 (6.5) after 12 months in 19 eyes with exclusive signs of GA on FAF (p = 0.499). Mean growth rate (SD) was 1.50mm2 (1.49)/year. VA and mean RS did not change significantly over 12 months, however, subgroup analysis over 20 months showed significant decline in mean RS.

Conclusion: Over this short follow-up period we were not able to detect significant changes in VA, drusen load and GA growth. Mean RS significantly declined over 20 months, and may be a useful biomarker for clinical trials. More data is necessary to compare the progression of these rare variant carriers to regular AMD patients.