Background: Fundus flavimaculatus (Stargardt disease) is a group of inherited macular dystrophies in which central vision usually decreases in the first two decades of life. Previous histopathologic studies used light, scanning, and transmission electron microscopy to characterize the retinal pigment epithelium (RPE) in fundus flavimaculatus. The authors describe in detail the pathologic changes in the neurosensory retina, including use of specific immunocytochemical markers.
Methods: The eyes of a patient with fundus flavimaculatus were processed using Medcast and JB-4 plastic for light and electron microscopy, and cryomicrotomy and LR-white resin for immunocytochemistry.
Results: Changes in the RPE occurred in a peripheral/central gradient and included increased lipofuscin content and cell loss toward the macula. The changes in the retina paralleled those in the RPE, including accumulation of lipofuscin in photoreceptor inner segments, loss of photoreceptors, and reactive Müller cell hypertrophy. Immunocytochemistry using rod- and cone-specific markers showed abnormal photoreceptor morphology but qualitatively normal immunoreactivity, and there was strong reactivity for glial fibrillary acid protein in reactive Müller cells. Labeling for cellular retinaldehyde-binding protein was qualitatively normal in Müller cells, but was reduced in RPE cells that were engorged with lipofuscin.
Conclusions: The histopathologic changes in the retina correlate with clinical progression of the disease process. Although abnormal lipofuscin metabolism has been implicated in the loss of vision in fundus flavimaculatus and other macular diseases, the mechanism is not understood. Based on the authors' observations and a review of recent literature on lipofuscin, the authors propose that all-trans-retinol dehydrogenase, a photoreceptor outer segment enzyme, may be defective in fundus flavimaculatus.