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Ethan A Rossi, Hongxin Song, Lisa Latchney, Margaret A Folwell, William Fischer, Mina M Chung; Adaptive Optics Imaging of AREDS2 Patients Reveals a Variety of Photoreceptor Layer Morphologies. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5236.
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The Age-Related Eye Disease Study 2 (AREDS2), a randomized controlled trial to determine whether the addition of nutrients to the AREDS formulation reduces the risk of progression to advanced age-related macular degeneration (AMD), evaluated 4203 patients characterized by fundus photographic features according to a standardized severity scale. Despite a carefully executed study design, AREDS2 found no statistically significant risk reduction among the treatment groups. It is possible that finer metrics of AMD severity are needed to detect disease progression and evaluate treatments more efficiently. Adaptive optics scanning light ophthalmoscopy (AOSLO) can provide high-resolution retinal images in patients with AMD. In this study, we imaged 5 AREDS2 study participants with AOSLO and compared these results to AREDS2 fundus photographic grades.
The photoreceptor layer of five AREDS2 study patients was imaged with AOSLO. Imaging was targeted to the central macula with fundus photograph guided fixation target control software. AO imaging results were compared to clinical imaging including color fundus photography, commercial confocal SLO fundus autofluorescence, spectral domain OCT (HRA Spectralis+OCT), and AREDS2 grading. AOSLO images were compared between subjects, and characteristic features identified in each.
AO imaging revealed several distinct photoreceptor morphologies including: 1) clustered “dark” cones near the fovea, 2) regional variegated reflectance, 3) isolated peripheral “dark” cones, 4) residual cones overlying drusen, 5) residual cone like structures within small GA lesions, and 6) web like patterns within large GA lesions. AREDS2 fundus photographic grades ranged from 6-10. Three patients within the same AREDS2 grade (8) showed wide variability in features identified with AO.
AO imaging offers promise as a sensitive method for characterizing patient populations participating in clinical trials, such as the AREDS2 study. As high resolution imaging devices become more widespread, standardized imaging protocols and analysis methods are needed to take advantage of the richness of information available in these images. Further study, including development of quantitative analysis and automated identification methods may enable the use of AOSLO features as biomarkers to facilitate clinical trials and longitudinal studies of AMD progression.
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