Valentina Di Iorio1, Ada Orrico1, Gabriella Esposito2, Paolo Melillo1, Settimio Rossi1, Sandro Sbordone1, Alberto Auricchio3,4, Francesco Testa1, Francesca Simonelli1. 1. Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. 2. Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy and CEINGE - Advanced Biotechnologies, Naples, Italy. 3. Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy. 4. Medical Genetics, Department of Advanced Biomedicine, University of Naples Federico II, Naples, Italy.
Abstract
PURPOSE: To investigate the natural history of Stargardt disease over a multiyear follow-up. METHODS: We reviewed medical records of Stargardt disease patients, with clinical diagnosis of Stargardt disease at a single institution, which was also supported by molecular diagnosis. All patients underwent best-corrected visual acuity, fundus photography, optical coherence tomography, and full-field electroretinography. RESULTS: The study cohort consisted of 157 Stargardt disease patients aged 30.4 ± 1.1 years. Longitudinal analysis (mean follow-up: 3 years) showed a significant worsening of best-corrected visual acuity at an average rate of 1.5 Early Treatment Diabetic Retinopathy Study letters/year (P < 0.001), an enlargement of retinal pigment epithelium lesion area by optical coherence tomography at an average linear rate of 0.10 mm/year (P < 0.001), and a thinning of central macular thickness at a mean rate of -1.42 μm/year (P < 0.001). Survival analysis showed that patients with 2 alleles harboring likely-null variants, on average, reached most severe disease stage, i.e., legal blindness, alteration in both dark-adapted and light-adapted electroretinographic responses, and retinal pigment epithelium lesion area larger than 2.5 mm significantly earlier than patients with at least one allele harboring a missense variant. CONCLUSION: The current longitudinal study showed a significant genotype-phenotype correlation characterization, because patients harboring 2 likely-null alleles reach a severe disease stage about 10 years earlier than patients with at least one missense allele.
PURPOSE: To investigate the natural history of Stargardt disease over a multiyear follow-up. METHODS: We reviewed medical records of Stargardt diseasepatients, with clinical diagnosis of Stargardt disease at a single institution, which was also supported by molecular diagnosis. All patients underwent best-corrected visual acuity, fundus photography, optical coherence tomography, and full-field electroretinography. RESULTS: The study cohort consisted of 157 Stargardt diseasepatients aged 30.4 ± 1.1 years. Longitudinal analysis (mean follow-up: 3 years) showed a significant worsening of best-corrected visual acuity at an average rate of 1.5 Early Treatment Diabetic Retinopathy Study letters/year (P < 0.001), an enlargement of retinal pigment epithelium lesion area by optical coherence tomography at an average linear rate of 0.10 mm/year (P < 0.001), and a thinning of central macular thickness at a mean rate of -1.42 μm/year (P < 0.001). Survival analysis showed that patients with 2 alleles harboring likely-null variants, on average, reached most severe disease stage, i.e., legal blindness, alteration in both dark-adapted and light-adapted electroretinographic responses, and retinal pigment epithelium lesion area larger than 2.5 mm significantly earlier than patients with at least one allele harboring a missense variant. CONCLUSION: The current longitudinal study showed a significant genotype-phenotype correlation characterization, because patients harboring 2 likely-null alleles reach a severe disease stage about 10 years earlier than patients with at least one missense allele.
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