Incidence and Risk Factors of Reticular Pseudodrusen Using Multimodal Imaging

Although retinal multimodal imaging is needed for diagnosing reticular pseudodrusen (RPD), the incidence of RPD in the general population typically has been assessed only using fundus photographs, which may underestimate their incidence.

To describe the incidence of RPD using retinal color photographs, spectral-domain optical coherence tomography scans, fundus autofluorescence, and near-infrared reflectance images among individuals 77 years of age or older and to analyze the associated risk factors of RPD.

The ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires) Study is a cohort of French individuals 77 years of age or older. Data for this study were collected between February 22, 2011, and February 15, 2017, with a mean (SD) follow-up of 3.7 (1.0) years (range, 1.2-5.6 years). At baseline, 501 individuals were eligible to participate. Of 1002 eyes, 197 had prevalent RPD, advanced age-related macular degeneration, or ungradable images. Of the remaining 805 eyes, 333 were missing follow-up data; therefore, the statistical analyses included data from 472 eyes. Data management and statistical analyses were performed between March 15, 2017, and April 5, 2019.

Reticular pseudodrusen were considered as present if detected by at least 2 of the following imaging methods: color fundus photographs, fundus autofluorescence, near-infrared reflectance, and spectral-domain optical coherence tomography images.

Of the 472 eyes analyzed, 263 (55.7%) were from female participants, and the mean (SD) age was 81.9 (3.2) years. Forty-three eyes developed RPD, corresponding to an annual incidence rate of 2.9% (95% CI, 1.9%-4.4%) per participant and an estimated 5-year risk of 13.5%. In multivariable analysis, 4 risk factors of incident RPD were identified: subfoveal choroidal thinning (hazard ratio [HR], 0.99; 95% CI, 0.99-1.00 per 10-μm decrease in thickness; P = .02) and the presence of the minor allelic variants rs10490924 for ARMS2 (HR, 3.57; 95% CI, 1.80-7.10; P < .001), rs1061170 for CFH (HR, 2.12; 95% CI, 1.02-4.41; P = .04), and rs10468017 for LIPC (HR, 2.57; 95% CI, 1.37-4.82; P = .003). Lipophilic statin therapy was associated with a lower incidence of RPD (HR, 0.13; 95% CI, 0.02-0.74; P = .02).

With the use of multimodal imaging, the RPD incidence rate was higher than previously reported in other population-based studies using fundus color images. Individuals with subfoveal choroidal thinning or carrying minor allelic variants for ARMS2, CFH, or LIPC had an increased risk for RPD, whereas lipophilic statin therapy was associated with a lower incidence.