Inherited Retinal Disease in a Young Patient

A 17-year-old female patient presented for a comprehensive eye examination with a chief complaint of blurred central vision, greater OS than OD, that had been present for as long as she could remember. Her ocular history was significant for myopia, for which she wore spectacles, while her medical history, family history, and review of systems were all normal.

EXAMINATION

BCVA measured 20/30 OD and 20/60 OS. Color vision, pupillary responses, extraocular motility, and anterior segment examination were all within normal limits. Stereoacuity was reduced, while IOP measured 12 mm Hg OD and 11 mm Hg OS.

Dilated fundus examination OD revealed a crescent-shaped pigmented lesion inferior to the fovea with several smaller pigmentary lesions extending toward the optic nerve. Examination of the left eye showed a large centrally located pigmented lesion involving the macula. Macular OCT revealed disruption of the outer retinal architecture consistent with macular dystrophy (Figure).

Comparison with color fundus photography obtained 4 years earlier suggested interval progression of her macular dystrophy, particularly in the left eye. Although subtle, the increase in retinal pigment epithelial (RPE) alteration and enlargement of the affected area supported the diagnosis of a progressive retinal disorder rather than a stable congenital lesion.

DIAGNOSIS

Given these findings, the differential diagnoses included Stargardt disease, Best disease, and choroidal rupture. Based on the patient’s age, lifelong reduction in central vision, bilateral macular involvement, and multimodal imaging findings, Stargardt disease was diagnosed.

DISCUSSION

Stargardt disease is the most common inherited macular dystrophy, with an estimated prevalence of approximately one in 8,000 to 10,000 individuals. Most cases are inherited in an autosomal recessive pattern and result from pathogenic variants in the ABCA4 gene.¹ ABCA4 dysfunction leads to accumulation of toxic bisretinoids, within the RPE, ultimately causing RPE and photoreceptor degeneration.

Patients typically develop progressive bilateral central vision loss, often accompanied by central scotomas, dyschromatopsia, photophobia, and difficulty with dark adaptation. Clinical findings include macular RPE changes and characteristic yellow-white pisciform flecks, although the fundus may appear relatively normal early in the disease. Fundus autofluorescence and OCT can help identify lipofuscin accumulation, RPE atrophy, and outer retinal loss.²

Stargardt disease demonstrates considerable phenotypic variability, and progression may differ substantially among patients. Earlier disease onset is generally associated with faster progression and a poorer visual prognosis, while later-onset disease may follow a slower course with greater preservation of central vision.³

MANAGEMENT

Therapeutic options for Stargardt disease remain investigational, with clinical trials exploring pharmacologic, cellular, and genetic approaches.⁴ Pharmacologic therapies primarily aim to reduce the accumulation of toxic vitamin A byproducts and lipofuscin. Agents such as ALK-001 (gildeuretinol), a deuterated form of vitamin A, and tinlarebant have shown promise in slowing retinal atrophy. Stem cell therapies using human embryonic stem cell-derived RPE cells have demonstrated acceptable safety and evidence of cell survival, although meaningful visual improvement remains uncertain. Genetic therapies seek to address the underlying ABCA4 defect through gene supplementation, RNA-based therapies, and gene editing. While the large size of the ABCA4 gene presents challenges for conventional viral delivery, newer technologies may help overcome this limitation.

Until these therapies become widely available, careful longitudinal monitoring and appropriate referral to a retina specialist remain among the most valuable interventions we can provide.⁵ Referral to a retina specialist is valuable for confirming the diagnosis, excluding other macular disorders, establishing a retinal baseline, and providing access to specialized testing, genetic counseling, and emerging clinical trials. As investigational pharmacologic, gene, and stem cell therapies continue to evolve, establishing a relationship with a retina specialist may also facilitate access to future treatment opportunities. Ongoing care can then be coordinated between the optometrist and retina specialist.

CASE OUTCOME

While establishing the diagnosis was critical, it was equally as important to provide our patient with thoughtful, empathetic counseling, so she could navigate the uncertainty of her prognosis. We took time to acknowledge the uncertainty and emotional impact of being diagnosed with a progressive retinal condition at a young age. We explained that Stargardt disease primarily affects central vision, which may eventually make activities such as reading, recognizing faces, and driving more difficult, but that the condition rarely results in complete blindness. We focused on what vision she was likely to retain, emphasizing that peripheral vision is typically preserved and can continue to provide functional vision for mobility and independence even if central vision declines. We were careful not to give her a predetermined timeline, as progression varies considerably among patients. Finally, we discussed low-vision resources, continued monitoring, and the encouraging advances in pharmacologic, gene, and stem cell therapies currently under investigation. Our goal was to be realistic about what she may face, while focusing equally on the vision, independence, and opportunities she can reasonably expect to continue to have.

Additionally, the patient was referred to a retina specialist for genetic testing and further evaluation. Unfortunately, she has not yet undergone genetic testing because she does not have medical insurance to cover it. As a result, a definitive molecular diagnosis has not yet been established. Annual monitoring was recommended, along with continued efforts to obtain genetic testing.