Stargardt disease is the most common juvenile macular dystrophy and a common cause of central vision loss in adults younger than 50 years. The visual acuity in Stargardt disease typically ranges from 20/50 to 20/200.
The classic Stargardt phenotype is characterized by a juvenile-onset foveal atrophy surrounded by discrete, yellowish, round or pisciform flecks at the level of the RPE (Fig 13-11A). If the flecks are widely scattered throughout the fundus with central sparing, the condition, which used to be referred to as fundus flavimaculatus, is now known to result from mutations in the same genes and can be present in families with the classic Stargardt phenotype. On fluorescein angiography, 80% or more of patients with Stargardt disease have a “dark choroid,” or, in other words, blocking of choroidal fluorescence that highlights the retinal circulation (Fig 13-11B). Fundus autofluorescence imaging is a more reliable means of demonstrating elevated background autofluorescence and characteristic findings, including peripapillary sparing of the RPE changes, central macular hypoautofluorescence, and, over time, an outward expanding pattern of hyperautofluorescent flecks, which leave hypoautofluorescent areas in their wake. Full-field ERGs are not diagnostic for this condition; however, individuals with significantly abnormal responses generally have more severe and progressive disease.
Figure 13-11 Stargardt disease. A, Color fundus photograph shows paramacular yellowish flecks and “beaten-bronze” central macular atrophy. B, Fluorescein angiography image of the same eye shows a dark choroid, hyperfluorescence associated with flecks, and bull’s-eye pattern of macular transmission defect.
(Courtesy of Mark W. Johnson, MD.)
The age of onset and presentation of the clinical features in Stargardt disease varies, sometimes even among individuals within the same family. The condition is usually slowly progressive with the accumulation of lipofuscin-like material in the RPE (Fig 13-12). Once the central vision is involved, the loss of visual acuity can be relatively rapid, over months to a few years, and then plateaus. However, if the central fovea area is spared, it is not unusual for a patient to be unaware that they are affected until adulthood. In later stages, atrophic maculopathy, with or without lipofuscin flecks and panretinal degeneration, can be observed.
Figure 13-12 Scanning electron micrograph of the RPE in Stargardt disease. The flecks represent regions of RPE cells engorged with abnormal lipofuscin-like material.
(From Eagle RC Jr, Lucier AC, Bernardino VB Jr, Yanoff M. Retinal pigment epithelial abnormalities in fundus flavimaculatus: a light and electron microscopic study. Ophthalmology. 1980;87(12):1189–1200.)
The majority of cases of Stargardt disease are autosomal recessive and are due to mutations in the ABCA4 gene. However, autosomal dominant transmission patterns can result from mutations in other genes, most notably PRPH2. The ABCA4 gene encodes an adenosine triphosphate (ATP)-binding cassette (ABC) transporter protein expressed by rod outer segments and RPE. See Table 13-1 for a list of additional genetic causes. Based on animal models of ABCA4-related disease, vitamin A supplementation accelerates the accumulation of lipofuscin pigments in the RPE and, in conjunction with blue light, also accelerates retinal cell death. Drug therapies to reduce lipofuscin accumulation, gene therapies, and stem cell treatments are currently undergoing clinical trials.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.