Quiz
1) What is the correct diagnosis for this patient?
a) Age-related macular degeneration.
b) Familial/cuticular drusen.
c) Stargardt's disease/fundus flavimaculatus
d) Cone dystrophy.

2) Describe the significant fluorescein staining pattern in this patient?
a) Marked hyperfluorescence of the drusen.
b) Blockage of the background choroidal fluorescence.
c) Hyperfluorescence of the macula in a "bull's eye" pattern.
d) Increased hyperfluorescence in the macula from choroidal neovascular membrane.

3) What is the etiology for this condition?
a) Age-related degenerative process.
b) Lipofuscin storage disease.
c) Congenital loss of cone receptors.

4) What is the best long-term management for this patient?
a) Low-vision services.
b) Electrodiagnostic testing.
c) Submit blood sample for genetic testing.
d) All of the above.

Discussion
The clinical picture could be easily mistaken for AMD. However, a diagnosis of macular degeneration in a black patient is uncommon and should always make you suspicious. Macular degeneration associated with choroidal neovascular membranes in a black patient is even rarer. This patient actually has Stargardt's disease or fundus flavimaculatus (SD/FFM). Because SD/FFM is a lipofuscin storage disease, the fluorescein pattern shows blockage of the background choroidal fluorescence resulting in a "quiet" choroid. That is exactly what the fluorescein staining pattern in this patient showed. In addition, there was scattered hyperfluorescence in the macula from atrophy of the RPE.

Stargardt's disease is an autosomal recessive disorder that is present in about one in 10,000 people.1 It is the most common inherited macular dystrophy. The age of presentation typically is in the teens to early 20s. What makes this patient particularly interesting is the late age at which he became symptomatic.

The clinical findings in SD/FFM vary among patients. The macula can appear normal or show atrophic RPE changes that can resemble the classic "beaten bronze" appearance. Yellow-white flecks may also appear throughout the fundus. They vary in size and are irregular in shape, often described as pisciform (fish-like) or having a tri-radiate pattern. Over time the flecks can disappear, resulting in RPE/ choriocapillaris atrophy, and new ones may appear. The flecks increase in number as the disease progresses.
Patients may present with any combination of these findings. They may have macular atrophy with or without scattered yellow-white flecks, or may present with flecks in the absence of macular atrophy. In the late stages of the disease the clinical signs and symptoms can mimic retinitis pigmentosa. As the patient ages, you can mistake the clinical presentation for the late stages of macular degeneration.

The fundus in SD/FFM patients has been described as vermilion or deep red in color due to an increase in lipofuscin stored within the RPE resulting in loss of choroidal detail. When examining a patient you suspect may have SD/FFM, try to visualize the choroidal detail. If the choroidal detail is easy to see, the likelihood of SD/FFM is low. If, however, you don't see any choroidal detail, your suspicion for SD/FFM would increase.

The most significant breakthrough in SD/FFM is identifying the gene responsible for the disease, which has been localized to chromosome 1p. Unlike retinitis pigmentosa, for which more than 40 different genes have been postulated as a cause, only one abnormal gene causes SD/FFM.

Today there is no treatment for SD/FFM, but advances in cellular and genetic testing may ultimately make this the first inherited macular dystrophy treatable with genetic therapy.

In many academic settings, patients with confirmed SD/FFM are entered into a Stargardt's disease registry and their blood samples are sent to one of three sites in the United States for genetic confirmation: Massachusetts Eye and Ear Infirmary, Baylor College of Medicine in Houston and the University of Iowa.