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Stanley Lambertus, Ramon A Huet, Nathalie Martine Bax, Ellen van den Wittenboer, Frans P Cremers, Camiel J F Boon, B Jeroen Klevering, Carel C B Hoyng; The natural progression of early-onset Stargardt disease. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1425.
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To describe the natural progression of early-onset Stargardt disease (STGD1).
We evaluated the medical records of fifty-two STGD1 patients with an age at onset of ≤10 years for history, initial symptoms, visual acuity (VA), ophthalmoscopy, fundus photographs, fundus autofluorescence (FAF), fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). ABCA4 analysis was performed using microarray analysis, multiplex ligation-dependent probe amplification and sequencing.
Mean age at onset was 7 (range 2-10) years. The median time to reach a VA of 0.2, 0.6, 1.0 and 1.4 logMAR was 3, 5, 12 and 23 years respectively. Initial foveal atrophy was reported in 37 (82%) patients at a mean of 1.6 (range, 0-11) years and yellow-white flecks in 46 (90%) patients at a mean of 2.4 (range, 0-15) years. Progression of retinal pigment epithelium (RPE) atrophy was seen on FAF as small diffusely spread spots confluing towards larger lesions and extended to profound chorioretinal atrophy. This was in accordance with RPE-layer signal loss on SD-OCT. A ‘dark choroid’ was reported on FA in 22 patients (69%). One, two, three or four ABCA4 mutations were identified in 7 (16%), 33 (73%), 4 (9%) and 1 (2%) patients respectively. c.768G>T and c.5461-10T>C were present in 24% and 36% respectively.
In light of approaching therapeutic interventions, insight into STGD1 cohorts with comparable phenotypic features is essential, as well as factors underlying clinical variability. Early-onset STGD1 patients demonstrated rapid VA loss. No fundus flecks occurred in some patients and therefore would be probably diagnosed with cone-rod dystrophy (CRD), whereas fundus flecks may appear years after foveal atrophy. As disease progressed, end-stage CRD-like phenotype occurred. As different phenotypes of the ABCA4 spectrum may occur in single patients during the course of early-onset STGD1, it may be preferable to refer to an overlapping definition, e.g. early-onset ABCA4-retinal dystrophy. Nonetheless, early-onset STGD1 belongs to the severe end of retinal phenotypes caused by ABCA4 mutations, where c.5461-10T>C and c.768G>T are most prevalent.
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