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Frank G. Holz, Florian Alten, Julia Steinberg, Glenn J. Jaffe, Monika Fleckenstein, Bickol N. Mukesh, Thomas C. Hohman, Steffen Schmitz-Valckenberg, GAP-Study Group; Reticular Drusen associated with Geographic Atrophy in Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3071.
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The morphological substrate of reticular drusen (RD) in contrast to other drusen phenotypes has recently been shown to be an accumulation of highly-reflective material within outer neurosensory retinal layers anterior to the RPE cell monolayer. Herein, we determined the prevalence and topographic distribution of perilesional RD in subjects with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in a prospective, multicenter, natural history study (GAP-Study).
Confocal scanning laser ophthalmoscopy (cSLO) three-field fundus autofluorescence (FAF, exc. 488, em. 500 - 700 nm), near-infrared reflectance (IR 820 nm), and blue reflectance (BR 488) images as well as red-free (RF) and color fundus (CF) camera photographs were recorded in 458 patients with GA. The digital images were evaluated by two independent readers with subsequent senior reader arbitration for prevalence and topographic distribution of RD using a modified Early Treatment Diabetic Retinopathy Study (ETDRS) grid.
RD were detected with at least one cSLO imaging modality in 286 of 458 (62%) subjects in either eye (bilateral 207 [45%]), while they were visible by color fundus photography in 66 of 371 (18%) subjects (bilateral 48 [13%]). Prevalence of RD by cSLO imaging was associated with increasing age (p=0.007) and female gender (p=0.007), but not with GA total lesion area (p=0.38). Cohen kappa statistics showed good interobserver agreement for FAF (Κ = 0.81) and IR (Κ = 0.82) imaging modes, while moderate agreement was found for BR (Κ = 0.48), RF (Κ = 0.48) and CF (Κ = 0.40) (data for right eyes). On three-field FAF images, RD were present most frequently superior to the fovea (99%). In 46% of right eyes, RD were present nasally to the disc.
The results indicate an unexpectedly high prevalence of RD which, thus, represent a common phenotypic hallmark in eyes with GA due to AMD. RD are readily identified by cSLO imaging modalities. The results would explain the high prevalence determined herein, in contrast to previous reports based on fundus photography. Since RD may represent high-risk markers for the progression of AMD, implementation of the above imaging techniques to identify RD appear relevant for future natural history studies, identification of genetic risk variants as well as for interventional trials.
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