Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9)

Strauss, Rupert W.; Muñoz, Beatriz; Ho, Alexander; Jha, Anamika; Michaelides, Michel; Cideciyan, Artur V.; Audo, Isabelle; Birch, David G.; Hariri, Amir H; Nittala, Muneeswar Gupta; Sadda, Srinivas R; West, Sheila K.; Scholl, Hendrik P. N.

doi:10.1001/jamaophthalmol.2017.4152

Cited by 86 publications

(121 citation statements)

References 32 publications

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“…In the current study, we applied a similar blue light source and a shorter exposure time, but in the pigmented Abca4 −/− mice, which resembled similar phenotypic features of advanced Stargardt disease. Our work also indicates that the fundus AF examination in both SW‐AF and NIR‐AF provides more information for the diagnosis and evaluation of disease progression …”

Section: Discussionmentioning

confidence: 56%

“…Our work also indicates that the fundus AF examination in both SW-AF and NIR-AF provides more information for the diagnosis and evaluation of disease progression. 32,71 Our mouse model reflects the clinical manifestations of advanced Stargardt disease and AMD. Quantitative analysis of RPE nuclei and photoreceptor nuclei indicated that blue light-induced RPE loss preceded the photoreceptor loss in Abca4 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

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Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model

et al. 2020

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Stargardt disease (STGD1), known as inherited retinal dystrophy, is caused by ABCA4 mutations. The pigmented Abca4−/− mouse strain only reflects the early stage of STGD1 since it is devoid of retinal degeneration. This blue light‐illuminated pigmented Abca4−/− mouse model presented retinal pigment epithelium (RPE) and photoreceptor degeneration which was similar to the advanced STGD1 phenotype. In contrast, wild‐type mice showed no RPE degeneration after blue light illumination. In Abca4−/− mice, the acute blue light diminished the mean autofluorescence (AF) intensity in both fundus short‐wavelength autofluorescence (SW‐AF) and near‐infrared autofluorescence (NIR‐AF) modalities correlating with reduced levels of bisretinoid‐fluorophores. Blue light‐induced RPE cellular damage preceded the photoreceptors loss. In late‐stage STGD1‐like patient and blue light‐illuminated Abca4−/− mice, lipofuscin and melanolipofuscin granules were found to contribute to NIR‐AF, indicated by the colocalization of lipofuscin‐AF and NIR‐AF under the fluorescence microscope. In this mouse model, the correlation between in vivo and ex vivo assessments revealed histological characteristics of fundus AF abnormalities. The flecks which are hyper AF in both SW‐AF and NIR‐AF corresponded to the subretinal macrophages fully packed with pigment granules (lipofuscin, melanin, and melanolipofuscin). This mouse model, which has the phenotype of advanced STGD1, is important to understand the histopathology of Stargardt disease.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model

et al. 2020

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“…However, microperimetry is being assessed as a potentially more accurate functional outcome measure for future clinical trials [18]. In ProgStar, anatomic endpoints to assess progression of atrophy through both FAF and OCT are being assessed [19,20].…”

Section: Clinical Presentationmentioning

confidence: 99%

“…It is the most common form of inherited macular degeneration, affecting roughly in 1 in 10,000 people. The age of onset of juvenile and early adult STGD1 is usually [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] years with some cases occurring in older adults (late-adult onset STGD1) [1,2]. These patients develop irreversible vision loss due to atrophy of the macular retinal pigment epithelium (RPE) and loss of photoreceptors, with patients presenting at a younger age having worse visual outcomes compared to those with later onset [1].…”

Section: Introductionmentioning

confidence: 99%

Stargardt macular dystrophy and evolving therapies

Hussain

Ciulla

Berrocal

et al. 2018

Expert Opinion on Biological Therapy

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Stargardt macular dystrophy (STGD1) is a hereditary retinal degeneration that lacks effective treatment options. Gene therapy, stem cell therapy, and pharmacotherapy with visual cycle modulators (VCMs) and complement inhibitors are discussed as potential treatments. Areas covered: Investigational therapies for STGD1 aim to reduce toxic bisretinoids and lipofuscin in the retina and retinal pigment epithelium (RPE). These agents include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Avacincaptad pegol is a C5 complement inhibitor that may reduce inflammation-related RPE damage. Animal models of STGD1 show promising data for these treatments, though proof of efficacy in humans is lacking. Fenretinide and emixustat are VCMs for dry AMD and STGD1 that failed to halt geographic atrophy progression or improve vision in trials for AMD. A1120 prevents retinol transport into RPE and may spare side effects typically seen with VCMs (nyctalopia and chromatopsia). Stem cell transplantation suggests potential biologic plausibility in a phase I/II trial. Gene therapy aims to augment the mutated ABCA4 gene, though results of a phase I/II trial are pending. Expert opinion: Stem cell transplantation, ABCA4 gene therapy, VCMs, and complement inhibitors offer biologically plausible treatment mechanisms for treatment of STGD1. Further trials are warranted to assess efficacy and safety in humans.

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“…The term "definitely decreased AF" (DDAF) was used for areas in which the level of darkness was close to 100% (at least 90%) in reference to the optic nerve head/blood vessels. Regions with levels between 50 and 90% darkness were defined as "questionably decreased AF" (QDAF); in these lesions, the sharpness of the corresponding lesion border defined a lesion either as "well-demarcated QDAF" or "poorly demarcated QDAF" [16][17][18][19].…”

Section: Phenotype Classificationmentioning

confidence: 99%

Clinical and Genetic Characteristics Analysis of Korean Patients with Stargardt Disease Using Targeted Exome Sequencing

et al. 2018

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Purpose: To investigate genetic mutations in Korean patients with Stargardt disease (STGD) using exome sequencing, and to analyze the correlations between genetic mutations and clinical phenotypes. Methods: Peripheral venous blood was obtained from 24 clinically diagnosed Korean STGD patients, followed by extraction of genomic DNAs. Using exome sequencing we investigated gene mutations for the adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) elongation of very-long-chain fatty acids 4 (ELOVL4), and prominin 1 (PROM1), and confirmed gene mutations by the direct sequencing of polymerase chain reaction products. Results: ABCA4 mutations were confirmed in 17 of 24 patients, and 12 novel mutations were identified. ELOVL4 and PROM1 gene mutations were not identified in this study. We also identified 16 previously reported mutations related to STGD1. In patients whose disease symptoms occurred before 20 years of age, visual acuity was poorer and atrophic flecks were more frequently found. In addition, more ABCA4 mutations were found in patients who had choroidal silence or atrophic flecks. Conclusions: Novel ABCA4 gene mutations were found in Korean patients with STGD1. This study will facilitate better understanding of the relationships between ABCA4 gene mutations and clinical symptoms in Korean patients.

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Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9)

Cited by 86 publications

References 32 publications

Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model

Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model

Stargardt macular dystrophy and evolving therapies

Clinical and Genetic Characteristics Analysis of Korean Patients with Stargardt Disease Using Targeted Exome Sequencing

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