Prevalence, Natural Course, and Prognostic Role of Refractile Drusen in Age-Related Macular Degeneration.

Purpose To report prevalence, clinical characteristics, and prognostic significance of refractile drusen in eyes with intermediate age-related macular degeneration (AMD). Methods Presence of refractile drusen by color fundus photography (CFP), corresponding findings by multimodal imaging, and longitudinal changes with annual examinations for up to 4 years were analyzed within a prospective natural history study of 98 eyes with non-late AMD of 98 patients (Age-Related Eye Disease Study [AREDS] stages 3 and 4). Results A total of 115 refractile drusen were detected at baseline in 20 eyes (20.4%). Refractile drusen typically showed hyperreflectivity by infrared (80.9%) and blue (93.9%) reflectance imaging, appearing more distinct when compared to CFP. Laminar intense hyperreflectivity of Bruch's membrane was detected in 31 lesions by spectral-domain optical coherence tomography and was strongly related to atrophy development (23 out of 31 lesions). Presence of refractile drusen at baseline was overall associated with later development of geographic atrophy (GA) (9/20 eyes versus 6/78 eyes, P < 0.001). Spontaneous regression without evident atrophy occurred in seven lesions. Conclusions Refractile drusen are a relative common phenotype in intermediate AMD and appear to confer risk for the development of late AMD. While not all lesions develop late AMD and regression may also occur, distinct subphenotypes as identified by multimodal imaging may not only be visible earlier but also be topographically associated with the risk for GA development. Recognizing the characteristic pattern on multimodal imaging would inform physicians for identification of the lesion and its clinical history.