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Longitudinal Analysis of Age-Related Macular Degeneration (AMD) in the AMD Ryan Initiative Study (ARIS)


Journal Article

Pak, J.W.; Ayala, G.; Hurtenbach, C.; Orndahl, C.; Keenan, T.D.L.; Ferris, F.L.; Clemons, T.E.; Chew, E.Y.; Domalpally, A.

Invest. Ophthalmol. & Vis. Sci.




AMD; ARIS; autofluorescence; drusen; RPD

Purpose : ARIS is a 5-year observational study of participants with early AMD or reticular pseudodrusen (RPD) to identify novel biomarkers of disease progression. The AMD characteristics were followed longitudinally using multimodal imaging evaluation. Methods : Baseline (BL), M12, and M24 followup images were evaluated for both eyes for four cohorts: early AMD, RPD only, RPD with large drusen, and healthy controls. Optical coherence tomography (OCT) images were graded for drusen, hyperreflective foci/dots (HRF/HRD), iRORA /cRORA, and RPD. Fundus autofluorescence (FAF) images were graded for hypo and hyperautofluorescence abnormalities. Color fundus photography (CFP) images were graded for drusen size and area, and AMD severity scale. Results : The cohorts with 3 visits comprised 44 eyes with early AMD, 22 eyes with combined RPD, and 48 healthy control eyes. Among eyes with Early AMD, drusen were mostly hyperreflective (61%), dome-shaped (43%) with no HRF at BL and M12. One eye developed HRF at M24. Drusen area was <0.5mm2 in 82% at BL. There were no FAF abnormalities in 70% at BL and no changes developed over time. The RPD cohort had a mean RPD area of 35.3 mm2 at BL, 39.2 at M12, and 42.7 at M24. This cohort also had drusen that were hyperreflective (64%) and dome-shaped (50%). HRF were seen in 14% at BL, and 28% by M24. Drusen area was <0.5mm2 in 68% at BL. FAF abnormality, besides RPD, was absent in 86% at BL and no changes developed over time. One eye in the early AMD cohort developed iRORA at M24 and no eyes developed cRORA. In the RPD cohort, 2 eyes developed iRORA and 1 eye cRORA at M12 with no additional changes at M24. BL AREDS AMD severity scale was 1-4 (72%) and 5-6 (25%) in the Early AMD cohort, and 1-4 (41%) and 5-7 (45%) in the RPD cohort. Two-step progression from BL across AMD scale was seen in 11 % at M12 and 22% at M24 in the Early AMD cohort and 5% and 10% respectively in the RPD cohort. In Control, 6 eyes (13%) developed AMD to scale 1-4 over M24. RPD developed in 5% of Early AMD eyes at M24. Conclusions : The longitudinal analysis of the ARIS cohorts provided a unique opportunity to monitor small changes from the early stages of AMD. Recently established OCT risk factors such as iRORA and HRF were seldom observed in Early AMD and RPD with or without large drusen. Additional research in a larger population is required to understand risk markers in this early stage of the disease. This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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