Satya Maripi

Introduction

Stargardt disease is an autosomal recessive condition characterised by a mutation in the adenosine binding cassette transporter 4 (ABCA 4) gene, which is pivotal in the normal physiological metabolism of vitamin A. This loss of function of the ABCA 4 gene results in damage to the retinal cells from vitamin A dimers which are not metabolised normally and causes a build-up of lipofuscin within the retinal pigment epithelium (RPE) of the retina (1, 2). Stargardt disease is one of the most common causes of macular dystrophy in young adults, the prevalence of Stargardt disease within the western world is approximated to be 1-10 per 100,000 (3).  

Symptoms and Signs

It is important to note, due to the range of heterogenicity of the mutation in ABCA 4 gene, there is a large degree of variation in the clinical manifestation of Stargardt disease, However, the most common form presentation is with painless bilateral central vision loss, with other associated symptoms ranging from central scotoma, impaired dark adaptation and impaired colour vision. The onset of the disease has two peak incidences, either in childhood or early adulthood (1).

Investigations

Ophthalmic investigations should include (2) (4):

• Slit lamp and/or indirect ophthalmoscopy – can be used to detect changes in the fundus; notably mottled pigmentation, fundal flecks and bullseye maculopathy. It is important to note fundal changes may be absent in the early stages of the disease
• Fluorescein angiography – non-invasive method to examine the RPE, can be used to detect the abnormal accumulation of lipofuscin
• Electroretinograms (ERG) – important for detection of photoreceptor dysfunction and impaired dark adaptation
• Optical coherence tomography (OCT) – used in conjunction with ERG, high resolution study of the retina. Used in the staging of Stargardt disease especially
• Genetic testing – novel microarray technique with a detection rate between 65 to 75%

Treatment

There is no curable option current presently for Stargardt disease, the options are limited to be mainly supportive and aim to slow disease progression. The mainstay of supportive management is for avoidance of light exposure (due to the impaired vitamin A metabolism), therefore avoidance of direct sunlight exposure and UV blocking sunglasses are highly recommended. In addition, vitamin A supplementation has shown to accelerate disease progression, and hence should also be avoided (4).

Conclusion

Stargardt disease is a genetic condition characterised by a mutation in the ABCA4 gene resulting in progressive macular dystrophy in young adults with the main symptomatic presentation being progressive loss of central vision. There are currently no definitive therapeutic measures

References

1. Kohli P. Stargardt disease – statpearls – NCBI bookshelf [Internet]. 2023 [cited 2023 Aug 16]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK587351/
2. Tanna P, Strauss RW, Fujinami K, Michaelides M. Stargardt disease: Clinical features, molecular genetics, animal models and therapeutic options. British Journal of Ophthalmology. 2016;101(1):25–30. doi:10.1136/bjophthalmol-2016-308823
3. Spiteri Cornish K, Ho J, Downes S, Scott NW, Bainbridge J, Lois N. The epidemiology of stargardt disease in the United Kingdom. Ophthalmology Retina. 2017;1(6):508–13. doi:10.1016/j.oret.2017.03.001
4. Cremers FPM, Lee W, Collin RWJ, Allikmets R. Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations. Progress in Retinal and Eye Research. 2020;79:100861. doi:10.1016/j.preteyeres.2020.100861