Genomics of Reticular Pseudodrusen in Age-related Macular Degeneration

Abstract

 

Purpose:

 

To study the incidence and distribution pattern of reticular pseudodrusen and correlate its presence to various stages of AMD and known AMD risk alleles.

 

Methods:

 

Photographic and clinical records of all patients enrolled in the ongoing AMD genetic study was evaluated. All available color, red free, autofluorescence and fluorescein images were analyzed. The associated AMD features including drusen, geographic atrophy, choroidal neovascularization (CNVM), retinal pigment epithelial hyper /hypopigmentation were documented. The distribution of the pseudodrusen was grouped into nine regions (four quadrants in the macular region, four quadrants straddling the arcades, and nasal to the optic disc).

 

Results:

 

Records from a total of 754 participants were evaluated. Seventy patients (110 eyes) had pseudodrusen (10%). The age ranged between 59-94 years (mean 80). There were 57 women and 13 men. Pseudodrusen lesions were bilateral in 42 and unilateral in 28 AMD patients (19 right eyes & 9 left eyes). The associated AMD lesions were grade 2 in 7 eyes, grade 3 in 44 eyes, grade 4 in 18 eyes and grade 5 in 41 eyes. In 45 patients with grade 5 in one or both eyes, 25 eyes had pseudodrusen without CNVM. In 11 patients with unilateral CNVM, pseudodrusen was seen only in the less severely affected fellow eye with AMD grades of 2 in one, 3 in nine and 4 in one eye. The prevalence of pseudodrusen was 20% in grade 3, 17% in grade 4 and 12% in grade 5 eyes. Pseudodrusen was present in the less severely affected fellow eye when not present in the eye with neovascular AMD in 19% of participants. The genotype distribution (CFH, CFB, ARMS2, C3 and mtDNA) was comparable in all eyes with pseudodrusen irrespective of the AMD grade or extent of pseudodrusen, although there was a trend towards significance for ARMS2.

 

Conclusions:

 

The presence and extent of pseudodrusen may not necessarily be a risk factor for neovascular AMD. No association was found between pseudodrusen and known AMD risk alleles in this small sample.

 

Keywords: age-related macular degeneration • genetics • drusen