Risk Factors Associated with Reticular Pseudodrusen versus Large Soft Drusen

Purpose To investigate genetic, environmental, and systemic risk factors in prospectively identified subjects with the age-related macular degeneration (AMD) phenotypes of (1) reticular pseudodrusen without large soft drusen and (2) large soft drusen without reticular pseudodrusen. Design Prospective case-case comparison. Methods In a clinical practice setting, patients with AMD were sequentially screened using clinical examination and scanning laser ophthalmoscopy imaging to prospectively identify subjects (n = 73) with the phenotypes of (1) reticular pseudodrusen without large soft drusen (n = 30) or (2) large soft drusen without reticular pseudodrusen (n = 43). Subjects were genotyped for 2 alleles associated with AMD, age-related maculopathy susceptibility 2 ( ARMS2 ) and complement factor H ( CFH ). A questionnaire was administered to collect history of smoking, hypertension, diabetes, and hyperlipidemia, as well as personal and family history of AMD. Results The reticular pseudodrusen group was older (median age 87 vs 81 years, P  = .04) and had more female subjects (83.3% vs 48.8%, P  = .003), later ages of AMD onset (83 vs 70 years, P  = .0005), and a greater frequency of hypertension (76.7% vs 55.8%, P  = .08). No significant differences were found in the distribution of the ARMS2 risk allele ( P  = .4) between the reticular pseudodrusen (homozygous = 20.0%; heterozygous = 56.7%) and large soft drusen (homozygous = 19.0%; heterozygous = 42.9%) phenotypes, or in the distribution of the CHF risk allele ( P  = .7) between the reticular pseudodrusen (homozygous = 26.7%; heterozygous = 56.7%) and large soft drusen (homozygous = 21.4%; heterozygous = 66.7%) phenotypes. Conclusions The reticular pseudodrusen phenotype was associated with increased age, later age of AMD onset, and female sex.