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Christopher Nathaniel Roybal, Yasser Elshatory, Douglas J Oppedal, Sara E Miller, Edwin M Stone, Elliott H Sohn; A longitudinal study of a large single-family-pedigree with autosomal dominant radial drusen.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3831.
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To characterize a multi-generational family with autosomal dominant radial drusen (ADRD)/Malattia Leventinese and confirmed fibulin-3/EFEMP1 (R345W) mutations longitudinally.
Twenty-eight subjects from a common multi-generational pedigree were ascertained with molecularly confirmed R345W substitutions in fibulin-3. The patients were characterized with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence and color fundus photography. Images were evaluated for presence of radial drusen, macular pigmentation, atrophy and presence of choroidal neovascular membrane (CNVM).
Affected family members were segregated into three phenotypes (mild, intermediate, severe) based on visual acuity and fundus findings. Three patients (aged 27, 34, and 48) with confirmed mutations had no fundus findings consistent with the known phenotype. Five had the mild phenotype (mean age 38 years old, range 19-73); median visual acuity was 20/20. Six had the intermediate phenotype (mean age of 66, range 47-78) and median visual acuity was 20/40 with macular pigment and atrophy present in 50% and 75% of patients, respectively. Radial drusen was present in 83% of intermediate patients and 1 had a CNVM (17%). Eleven patients had the severe phenotype (mean age 61, range 38-80) and mean visual acuity was 20/200. All severe patients had radial drusen and macular RPE atrophy; CNVM occurred in 55%. Eleven patients had greater than 20 year follow-up: all had macular atrophy with early radial drusen defining the extent of late macular atrophy. Large drusen tended to be replaced by atrophy over time. Six of these 11 patients with long term follow-up had disappearance of radial drusen (all 6 were in the severe phenotype category). Early in disease there was a perifoveal drusen-free zone with peripapillary sparing but at 20 years follow-up all patients had peripapillary changes. CNVM manifested in 7 of 11 (64%) patients by 20 year follow-up.
Extent of radial drusen early in the course of ADRD may correlate with location of atrophy up to 20 years later. Large central drusen tend to be replaced by geographic atrophy over time. Phenotypic variability is a prominent feature of the disease, but most patients develop atrophy and/or CNVM.
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