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Girl with progressively worsening vision
Retinal lesions were observed upon examination.
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A 7-year-old white girl was referred to the retina service at the New England Eye Center for evaluation and management of decreasing vision. Developmentally, the girl had previously been doing well, excelling in school and exhibiting good coordination. According to the parents, however, she seemed to be having more difficulties in school over the past 3 months, with the teachers remarking on her lack of progress with reading. She appeared to prefer using her left eye more so than her right. The patient’s ocular history was otherwise unremarkable, without prior evidence of strabismus or amblyopia. The parents noted that she was treated the previous summer for Lyme disease with a course of amoxicillin. She had no other medical history of significance, and her immunizations were up to date.
 Isabel Balderas |  Tom Hsu, MD |
Examination
On examination, the patient’s best corrected visual acuity by Snellen chart was 20/100 in the right eye and 20/80 in the left eye. IOP by applanation was 8 mm Hg bilaterally. Pupils were equally reactive without an afferent pupillary defect. Visual fields by confrontation were intact. On slit lamp examination, the anterior chambers of both eyes were quiet. Her dilated funduscopic exam showed slightly yellow discrete lesions in the macular region (Figures 1a and 1b). The retinal lesions were more apparent in a red-free photograph of the left eye (Figure 2) and in an oral fluorescein angiogram (Figures 3a, 3b and 3c).
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| Figures 1a, 1b. Color fundus photographs of the eyes. Notice the slightly yellow discrete lesions in the macular region. | Figure 2. Red-free photograph of the left eye. The retinal lesions are more apparent. | |
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| Figures 3a, 3b and 3c. Oral fluorescein angiograms of the left eye. The patient’s right eye (not shown) demonstrates similar findings. Images: Hsu T, Duker JS | ||
What is your diagnosis?
Retinal fleck lesions
The funduscopic retinal changes in this young girl, although somewhat subtle, point us in a clear direction for classification of her disease. While the differential diagnosis for a child who presents with a gradual onset of progressive visual loss may be rather varied, the retinal fleck lesions allow us to approach the diagnosis in a systematic fashion.
Differential diagnosis
Some retinal disorders to consider include Best’s vitelliform dystrophy, a condition typically characterized by the formation of a central “egg-yolk” lesion in the macula. In its later stages, the lesion breaks up into smaller components and may be seen as flecks within the retina. However, this process tends to occur over decades, and the patient should still have been in the pre- or vitelliform stage of the disease at her age, and therefore, her vision should have been relatively good. Fundus albipunctatus is another condition in which prominent retinal fleck lesions exist. This disease falls under the category of congenital stationary night blindness, with a nonprogressive nature of visual disturbance. In addition, in patients with this disorder, nyctalopia is a distinguishing feature, along with dense, prominent fleck lesions that typically spare the macula. With dark adaptation, these patients tend to have improved vision.
Similarly, fundus punctata albescens is a disorder whereby fine yellow-white dots are present in the retina, more prominently at the equator. Fundus punctata albescens can be classified as a variant of retinitis pigmentosa, with many shared clinical features. In fundus punctata albescens, the classic bone spicule pigmentation, arterial attenuation and waxy disc pallor are often seen in advanced stages of the disease. This is a progressive disorder, and visual loss can be expected to continue with time. There are several other disorders, such as dominant drusen or fleck retina of Kandori, that present with retinal fleck lesions. However, the presentations of these other disorders do not come close to fitting the clinical profile of this girl. Of note, disorders such as cone dystrophy and chloroquine toxicity can often present with subtle retinal pigment epithelium changes and demonstrate a characteristic “bulls-eye” appearance on funduscopic examination. These diseases, again, do not fit the clinical picture of our patient.
Piecing together the critical elements of this case, we see that this is a problem of progressive bilateral visual loss in a young patient, without profound night blindness. Retinal findings include yellowish flecks scattered throughout the macula and periphery. The optic discs and vessels appear normal. In the fluorescein angiogram, there is a bulls-eye pattern of signals surrounding the macula, along with other hyperintense punctate signals throughout the retina. Overall, the choroid takes on a dark and silent appearance. All of this information points to a diagnosis of Stargardt’s disease, or fundus flavimaculatus.
Discussion
Initially described in 1908 by Dr. Stargardt, this disorder is the most common inherited juvenile macular dystrophy. The inheritance pattern of this dystrophy is overwhelmingly autosomal recessive, although a small but significant population is autosomal dominant. Recently, linkage of the ABCA4 gene – a gene encoding for an ATP-binding cassette transporter – has been made to correlate with the development of Stargardt’s disease. Functionally, this gene encodes for a protein associated with the transport of toxic lipofuscin fragments in the photoreceptors, and the impact of mutations in this gene is beginning to manifest themselves throughout a broad range of retinal disorders, including age-related macular degeneration.
From a pathological standpoint, the disease is thought to be mediated by an accumulation of lipofuscin and related products within the retinal pigment epithelial cell. As these products build up, they cause eventual dysfunction and death of the photoreceptor. Incidentally, it is this accumulation of the lipofuscin that blocks transmission of the fluorescein signal, resulting in the dark choroid. The punctate areas of hyperintense signals are thought to be “window defects” through the accumulated lipofuscin and do not correlate spatially with the yellow flecks seen in the retina.
With regards to clinical course, patients typical complain of gradual visual decline in both eyes, with most patients remaining at a residual visual acuity of around 20/400 or better. Peripheral vision is usually not affected grossly, and most patients learn to do well with eccentric fixation. Color vision can be strongly affected later in the disease, along with difficulties in adapting to different lighting situations. However, night vision is typically preserved. In general, patients with Stargardt’s disease benefit greatly from low-vision aids, and most are capable of remaining fully functional throughout the course of their lifetime.
For more information:
- Tom Hsu, MD, and Jay S. Duker, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.
- Edited by Isabel Balderas, MD, and Tom Hsu, MD. Drs. Balderas and Hsu can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Balderas and Hsu have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.
References:
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