Graefe's Archive for Clinical and Experimental Ophthalmology · 7 authors, 3 centres
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This study found a 9.7% prevalence of subretinal drusenoid deposits (SDD) in first-degree relatives of SDD patients, with older age as the main determinant. A trend toward higher body mass index in relatives with SDD and a higher polygenic risk score for AMD in individuals with SDD suggest a hereditary component. Clinically, relatives of SDD patients should be monitored for retinal changes, especially at older age.
**Background:** Subretinal drusenoid deposits (SDDs) are extracellular alterations anterior to the retinal pigment epithelium, distinct from conventional drusen. They are associated with age-related macular degeneration (AMD) and functional impairments such as scotopic vision loss. Given their uniform phenotype, a hereditary predisposition is suspected, but data on SDD prevalence in relatives of affected individuals are scarce. This study aimed to evaluate the prevalence and determinants of SDD in first-degree relatives of patients with SDD and to explore associations with AMD-linked genetic polymorphisms.
**Methods:** The study recruited 195 participants: 123 index patients with SDD (mean age 81.4 ± 7.2 years, 67% women) and 72 first-degree relatives (mean age 52.2 ± 14.2 years, 56% women) from the university eye hospital Bonn. All participants underwent a full ophthalmic examination including spectral domain–optical coherence tomography (SD-OCT) and near-infrared (IR) imaging. SDD presence and disease stage were graded, and the percentage of IR en face area affected by SDD was measured. Genetic sequencing was performed on 189 individuals using an Illumina GSA array, and a polygenic risk score (PRS) for AMD was calculated based on 69 SNPs. Multivariable logistic and linear regression models were used to assess determinants of SDD presence and area, controlling for age, sex, BMI, smoking, spherical equivalent, cataract surgery, hypertension, and diabetes. Genetic associations were analyzed using generalized linear mixed models adjusting for age, sex, and family ID.
**Key Results:** SDD was present in 7 of 72 relatives (9.7% prevalence). Relatives with SDD had a mean age of 60.1 ± 7.6 years, mean BMI of 32.8 ± 9.4, and all but one were former or current smokers. In contrast, relatives without SDD had a mean age of 51.4 ± 14.5 years, mean BMI of 26.8 ± 7.0, and 46% never smoked. In the total cohort, older age was significantly associated with SDD presence (OR per year 1.27, 95% CI 1.17–1.41, P < 0.001) and larger affected area (beta per year 0.92, 95% CI 0.13–1.72, P = 0.02). In relatives, higher BMI showed a borderline association with SDD presence (OR 1.16, 95% CI 1.00–1.45, P = 0.08). No significant associations were found for sex, smoking, spherical equivalent, cataract surgery, hypertension, or diabetes. For genetic analyses, the AMD PRS was borderline associated with AMD presence (OR 4.99, 95% CI 0.95–26.23, P = 0.057). Individuals with SDD tended to have a higher PRS, but this was not statistically significant in multivariable models (OR 1.87, 95% CI 0.61–5.76, P = 0.27). No individual SNP was significantly associated with SDD after Bonferroni correction.
**Clinical Implications:** This study provides the first prevalence estimate of SDD in first-degree relatives of affected patients (9.7%), suggesting a hereditary component. Age was confirmed as the main determinant, and a trend toward higher BMI in younger relatives may indicate metabolic contributions. The higher AMD PRS in SDD individuals, though not statistically significant, supports a genetic link. Clinically, relatives of SDD patients should be monitored for retinal changes, especially at older age, and preventive measures such as smoking cessation and healthy lifestyle should be emphasized. Limitations include a relatively young relative cohort, potential selection bias, and limited statistical power for genetic analyses. Larger longitudinal studies are needed to confirm these findings and clarify the genetic predisposition of SDD.