Reticular Pseudodrusen in Intermediate Age-Related Macular Degeneration: Prevalence, Detection, Clinical, Environmental, and Genetic Associations

Abstract

Purpose: To determine the prevalence of reticular pseudodrusen (RPD) and their detection using multimodal imaging in patients with bilateral large drusen, and examine their clinical, demographic, environmental, and genetic associations.

Methods: Three hundred participants with bilateral large drusen (>125 μm) underwent color fundus photography (CFP), near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT) imaging. Demographic information, smoking, and medical history were recorded, and a blood sample was obtained and genotyped to identify the risk alleles of the CFH and ARMS2 genes.

Results: Reticular pseudodrusen were detected in 28.2% eyes of 29.0% participants using NIR and SD-OCT combined, but CFP and FAF detected only 42% and 89%, respectively, of these eyes with RPD. Participants with RPD were significantly older than those without (P < 0.001), but there was no significant difference in sex distribution, smoking history, cardiovascular factors, and minor allele frequency of the CFH gene (P > 0.173). However, the minor allele frequency of the ARMS2 gene was significantly higher in participants with RPD (P = 0.002). The presence of RPD was also independently associated with the presence of atrophic changes (including nascent geographic atrophy and drusen-associated atrophy detected on SD-OCT; P = 0.043).

Conclusions: Reticular pseudodrusen were detected on NIR and SD-OCT in more than a quarter of participants with bilateral large drusen, being often overlooked with CFP. Those with RPD had a higher frequency of the ARMS2 risk variant, and eyes with RPD were more likely to have atrophic changes. These findings are important to consider when managing patients with intermediate AMD.