April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
The natural progression of early-onset Stargardt disease
Author Affiliations & Notes
  • Stanley Lambertus
    Ophthalmology, Radboud university medical center, Nijmegen, Netherlands
  • Ramon A Huet
    Ophthalmology, Radboud university medical center, Nijmegen, Netherlands
  • Nathalie Martine Bax
    Ophthalmology, Radboud university medical center, Nijmegen, Netherlands
  • Ellen van den Wittenboer
    Ophthalmology, Radboud university medical center, Nijmegen, Netherlands
  • Frans P Cremers
    Human Genetics, Radboud university medical center, Nijmegen, Netherlands
  • Camiel J F Boon
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • B Jeroen Klevering
    Ophthalmology, Radboud university medical center, Nijmegen, Netherlands
  • Carel C B Hoyng
    Ophthalmology, Radboud university medical center, Nijmegen, Netherlands
  • Footnotes
    Commercial Relationships Stanley Lambertus, None; Ramon Huet, None; Nathalie Bax, None; Ellen van den Wittenboer, None; Frans Cremers, None; Camiel Boon, None; B Klevering, None; Carel Hoyng, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1425. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To describe the natural progression of early-onset Stargardt disease (STGD1).

 
Methods
 

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.

 
Results
 

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.

 
Conclusions
 

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.

 
 
Progression of atrophy in early-onset STGD1: (A1,2,3) initial foveal atrophy, (B1,2,3) parafoveal diffuse spread spots, (C1,2,3) confluing into larger lesions, (D1,2,3) extension beyond the vascular arcades, (E1,2,3) profound chorioretinal atrophy with loss of peripapillary sparing.
 
Progression of atrophy in early-onset STGD1: (A1,2,3) initial foveal atrophy, (B1,2,3) parafoveal diffuse spread spots, (C1,2,3) confluing into larger lesions, (D1,2,3) extension beyond the vascular arcades, (E1,2,3) profound chorioretinal atrophy with loss of peripapillary sparing.
 
Keywords: 696 retinal degenerations: hereditary • 539 genetics • 550 imaging/image analysis: clinical  
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