Genetic Polymorphisms and the Phenotypic Characterization of Individuals with Early Age-Related Macular Degeneration

While the importance of risk polymorphisms for the pathogenesis of age-related macular degeneration (AMD) is well established, their impact on morphological and functional phenotypes is largely unclear. We aimed to characterize individual phenotypes in patients who were either homozygous for a risk allele in the CFH gene, ARMS2 gene, or both as compared to non-carriers.

Patients with early AMD (n = 85) were assessed during a follow-up examination of a prospective study (MARS) with multimodal diagnostics including SD-OCT and microperimetry.

Compared to non-carriers, OCT scans revealed lower retinal thickness in patients homozygous for CFH or ARMS2, which was caused by a significantly reduced photoreceptor layer. The number and ultrastructure of drusen were also significantly different.

These findings indicate that patients with risk alleles demonstrate distinct phenotypic differences of morphology and function as compared to non-carriers. In particular in the CFH group, a loss of photoreceptors occurred concomitantly with reduced retinal sensitivity. Further studies might help to better understand the pathophysiology.