A 52-year-old Hispanic female presented complaining of reduced acuity in both eyes, more so in her right eye than her left. She also felt as though her vision was cloudy and smoky. She had presented to another eye doctor several times with her near vision complaints. That doctor described her eyes as very interesting.
Her medical history was unremarkable, and she took no medications.
Best-corrected visual acuity at this visit was 20/50 O.D. and 20/25 O.S. Motility testing was normal, but confrontation fields showed generalized constriction O.U. Pupils were equally round and reactive with no afferent pupillary defect. Her anterior segment exam was unremarkable. IOP measured 24mm Hg O.D. and 27mm Hg O.S.
Dilated fundus exam revealed moderate cupping in both optic nerves, with a cup-to-disc ratio of approximately 0.70. Other changes could be seen throughout the fundus O.U. (figures 1 and 2). We ordered fluorescein angiography for this patient (figures 3 and 4).
1, 2. Fundus photos (O.D. left, O.S. right) show extensive atrophy of the RPE throughout the posterior pole.
Take the Retina Quiz
1. Based on the pattern around the macula, which diagnosis would you initially suspect?
a. Retinitis pigmentosa.
b. Stargardts macular dystrophy.
c. Choroideremia.
d. Cone dystrophy.
2. What is the significant finding on the fluorescein angiogram?
3, 4. Fluorescein angiogram (O.D. top, O.S. bottom) shows hyper- and hypofluorescence. Note the fluorescein change in the peripheral retina of the left eye, nasally.
a. Staining of the macula.
b. Quiet choroid.
c. Bulls-eye pattern of hypo- and hyperfluorescence in the macula.
d. Cystoid macular edema.
3. Given the overall fundus appearance and fluorescein angiography, what is the correct diagnosis?
a. Retinitis pigmentosa.
b. Stargardts macular dystrophy.
c. Choroideremia.
d. Cone dystrophy.
4. What additional test would help confirm the diagnosis?
a. Electroretinogram.
b. Visual field.
c. Visual evoked potential.
d. Ocular coherence tomography.
5. What is the etiology of this condition?
a. Genetic defect affecting chromosome 1p.
b. Lipofuscin storage disease.
c. Genetic defect affecting chromosome 11q.
d. Both a and b are correct.
For answers, click here.
Discussion
The fundus appearance in this patient is very striking. There is an obvious bulls-eye pattern around the macula in each eye. Also, a large circumferential ring of atrophy of the retinal pigment epithelium can be seen along the arcades; the atrophy extends 360 around the posterior pole.
Based on this presentation, our differential diagnosis included a cone dystrophy, retinitis pigmentosa (RP) and Stargardts macular dystrophy (SMD). The bulls-eye maculopathy originally made us suspect cone dystrophy. An electroretinogram (ERG) and fluorescein angiography would help confirm the diagnosis.
We were surprised that the ERG was essentially normal. There was a normal b-wave amplitude on the rod ERG, normal a- and b-wave amplitudes on the mixed rod-cone ERG and only a slightly delayed amplitude on the cone ERG. These results ruled out cone dystrophy or RP, so the likely diagnosis is SMD.
Fluorescein angiography confirmed the diagnosis. The angiogram shows hypo- and hyperfluorescence that corresponds to the bulls-eye pattern around the macula. A diffuse pattern of hyperfluorescence throughout the posterior pole and along the arcades corresponds to the circumferential ring of RPE atrophy seen on the clinical exam and in the color photos.
We were surprised to see this amount of hyperfluorescence on the fluorescein angiogram when we suspected SMD, though we really should not have been. SMD is a lipofuscin storage disease, so the hallmark finding on fluorescein angiography is a silent, or quiet, choroid. That seems to be missing in this patient.
Or, is it? Look carefully outside the arcades and outside the hyperfluorescent ring in the macula. The choroid is indeed very dark and silent, as we would expect with Stargardts. The RPE atrophy masks this, but it is there if we look past the hyperfluorescence.
Stargardts macular disease is autosomal recessive and is the most common inherited macular dystrophy. (There is a dominant form of the disease, although this is extremely rare.) Genetic linkage studies have mapped the gene responsible for SMD to chromosome 1p. It has been identified as STG1. The gene is a photoreceptor-specific gene called ABCA4. An autosomal dominant form of Stargardts has also been identified and is linked to chromosome 6 (STGD3) and 4p (STGD4).
The hallmark findings of SMD are the classic beaten metal appearance of the macula and yellow-white flecks that can be present throughout the fundus. These flecks often appear pisciform (fish-like) or in a triradiate pattern. Realize that these findings can vary among patients. The fundus sometimes can appear normal, with an absence of yellow flecks and a normal-looking macula, or there can be widespread RPE atrophy, as in our patient.
In all instances of autosomal-recessive SMD, however, the quiet choroid will always be present. On examination this can give the fundus a deep reddish, or vermilion, color. This is subtle and can be overlooked, but is explained by the lipofuscin that is stored within the RPE. This is also the reason for the dramatic quiet choroid that is seen on the fluorescein angiography.
Patients with SMD typically present with vision loss in their teens or early adulthood. Most patients will have less than 20/200 acuity in at least one eye by the time they are in their 40s.
It is unusual that our patient has maintained good vision for so long. She obviously has had the disease most of her life, as evidenced by the amount of atrophy in the macula and midperipheral retina. Unfortunately, she has developed glaucoma, which may increase her risk for developing poor vision and loss of her peripheral field.
Her cloudy vision is likely the result of both her glaucoma and the SMD. A visual field showed constriction of the midperipheral field and a dense ring scotoma that corresponded to the area of peripheral RPE atrophy. Fortunately, her central vision has remained pretty good. We continue to follow her closely.
