Risk factors associated with reticular pseudodrusen versus large soft drusen.
OBJECTIVE
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.


METHODS
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.
Department of Ophthalmology, New York University School of Medicine, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York.
Sucharita
S
Boddu
Department of Ophthalmology, New York University School of Medicine, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York.
Michele D
MD
Lee
Department of Ophthalmology, New York University School of Medicine, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York.
Marcela
M
Marsiglia
Department of Population Health, New York University School of Medicine, New York, New York.
Michael
M
Marmor
Department of Ophthalmology, New York University School of Medicine, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York.
K Bailey
KB
Freund
Department of Ophthalmology, New York University School of Medicine, New York, New York. Electronic address: roland.smith@nyumc.org.
R Theodore
RT
Smith
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017242:Complement Factor H / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D057092:Geographic Atrophy / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D008297:Male; D009887:Ophthalmoscopy; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics; D015593:Retinal Drusen / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors; D011795:Surveys and Questionnaires; D041623:Tomography, Optical Coherence; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics
C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H