New perspectives in retinal imaging: fundus autofluorescence and age‐related macular degeneration

Abstract

AbstractFundus Autofluorescence (FAF) imaging using confocal scanning laser ophthalmoscopy is a non‐invasive method to to accurately record the topographic distribution of RPE lipofuscin in the human eye in vivo. Excessive lipofuscin accumkulation in the RPE is a common downstream pathogenetic pathway in various complex and monogenetic retinal diseases. Toxic compounds and molecular mechanisms of interference with normal cellular functions have been identified including the dominant fluorophore A2‐E. Alterations in fundus autofluorescence (FAF) appearance in eyes with early and late age‐related macular degeneration (AMD) can be striking. FAF patterns and distribution do not necessarily correlate with the features of interest in color or angiographic images of eyes with early or late AMD. In the prospective, multicenter FAM study distinct patterns of abnormal FAF were identified and classified in the junctional zone of geographic atrophy (GA). Areas of increased FAF outside GA were associated with variable degrees of loss of retinal sensitivity when tested with microperimetry which suggests a functional correlate of lipofuscin accumulation. Increased FAF preceded the development and enlargement of outer retinal atrophy associated with spread of absolute scotoma in eyes with AMD. Longitudinal examinations showed that the abnormal phenotypic FAF patterns serve as novel prognostic determinants which allows to distinguish fast vs. slow progressors. These findings are relevant and now used to design and carry out interventional trials with agents aimed at slowing down spread of atrophy, e.g. using visual cycle modulators to influence lipofuscinogenesis. Hereby FAF imaging also serves as a mean to accurately delineate and measure areas of GA over time in an automated fashion. A phenotype‐genotype correlation was identified for a distinct FAF phenotype subset which was found to represent late‐onset Stargardt macular dystrophy mimicking late‐stage atrophic AMD. New imaging technologies were recently applied including simultaneous recordings of FAF images and high‐resolution, spectral‐domain optical coherence tomography (OCT) which allows to identify morphological correlates of abnormal FAF signals in optical biopsies.