RESUMEN
Achromatopsia (ACHM) is a rare genetic disorder of infantile onset affecting cone photoreceptors. To determine the extent of progressive retinal changes in achromatopsia, we performed a detailed longitudinal phenotyping and genetic characterization of an Italian cohort comprising 21 ACHM patients (17 unrelated families). Molecular genetic testing identified biallelic pathogenic mutations in known ACHM genes, including four novel variants. At baseline, the patients presented a reduced best corrected visual acuity (BCVA), reduced macular sensitivity (MS), normal dark-adapted electroretinogram (ERG) responses and undetectable or severely reduced light-adapted ERG. The longitudinal analysis of 16 patients (mean follow-up: 5.4 ± 1.0 years) showed a significant decline of BCVA (0.012 logMAR/year) and MS (-0.16 dB/year). Light-adapted and flicker ERG responses decreased below noise level in three and two patients, respectively. Only two patients (12.5%) progressed to a worst OCT grading during the follow-up. Our findings corroborate the notion that ACHM is a progressive disease in terms of BCVA, MS and ERG responses, and affects slowly the structural integrity of the retina. These observations can serve towards the development of guidelines for patient selection and intervention timing in forthcoming gene replacement therapies.
Asunto(s)
Defectos de la Visión Cromática/genética , Defectos de la Visión Cromática/patología , Mutación , Adolescente , Adulto , Biomarcadores , Preescolar , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/genética , Canales Catiónicos Regulados por Nucleótidos Cíclicos/genética , Análisis Mutacional de ADN , Proteínas del Ojo/genética , Femenino , Proteínas de Unión al GTP Heterotriméricas/genética , Humanos , Estudios Longitudinales , Masculino , Linaje , Fenotipo , Pronóstico , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
BACKGROUND: To investigate the prevalence of macular abnormalities in patients affected by Usher syndrome (USH), by comparing the clinical findings between two types (i.e., USH1 and USH2). MATERIAL AND METHODS: A retrospective study was performed by reviewing optical coherence tomography (OCT) in 134 USH patients to determine the presence of macular abnormalities, including cystoid macular edema (CME), epiretinal membrane (ERM), vitreo-macular traction syndrome (VMT), and macular hole (MH). RESULTS: Macular abnormalities were observed in 126/268 (47.0%) examined eyes. The most frequent abnormality was ERM observed in 51 eyes (19%), followed by CME observed in 42 eyes (15.7%). Moreover, CME was significantly (p < 0.05) associated with younger age (CME: 30.1 ± 11.1 years; without CME: 36.9 ± 14.9 years), whereas VMT and full thickness MH were associated with older age (p < 0.05). Moreover, a significantly (p < 0.05) decreased best-corrected visual acuity was associated with MH compared to eyes without MH. Finally, CME was more frequent in USH1 compared to USH2. CONCLUSION: Our study, for the first time in the literature, showed the distribution of all macular abnormalities assessed by SD-OCT in a large USH cohort, comparing USH1 and USH2 patients. We observed that ocular abnormalities are highly prevalent in USH patients compared to general population, with ERM and CME being the most common alterations. Based on these findings, OCT screening in USH patients is recommended for early detection of macular changes and early treatment.
Asunto(s)
Membrana Epirretinal/epidemiología , Oftalmopatías/epidemiología , Edema Macular/epidemiología , Perforaciones de la Retina/epidemiología , Síndromes de Usher/epidemiología , Cuerpo Vítreo/patología , Adulto , Anciano , Electrorretinografía , Membrana Epirretinal/diagnóstico por imagen , Oftalmopatías/diagnóstico por imagen , Femenino , Angiografía con Fluoresceína , Humanos , Edema Macular/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Prevalencia , Perforaciones de la Retina/diagnóstico por imagen , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Síndromes de Usher/diagnóstico por imagen , Agudeza Visual , Cuerpo Vítreo/diagnóstico por imagenRESUMEN
PURPOSE: To evaluate differences in the visual phenotype and natural history of Usher syndrome caused by mutations in MYO7A or USH2A, the most commonly affected genes of Usher syndrome Type I (USH1) and Type II (USH2), respectively. METHODS: Eighty-eight patients with a clinical diagnosis of USH1 (26 patients) or USH2 (62 patients) were retrospectively evaluated. Of these, 48 patients had 2 disease-causing mutations in MYO7A (10 USH1 patients), USH2A (33 USH2 patients), and other USH (5 patients) genes. Clinical investigation included best-corrected visual acuity, Goldmann visual field, fundus photography, electroretinography, and audiologic and vestibular assessments. Longitudinal analysis was performed over a median follow-up time of 3.5 years. RESULTS: Patients carrying mutations in MYO7A had a younger age of onset of hearing and visual impairments than those carrying mutations in USH2A, leading to an earlier diagnosis of the disease in the former patients. Longitudinal analysis showed that visual acuity and visual field decreased more rapidly in subjects carrying MYO7A mutations than in those carrying USH2A mutations (mean annual exponential rates of decline of 3.92 vs. 3.44% and of 8.52 vs. 4.97%, respectively), and the former patients reached legal blindness on average 15 years earlier than the latter. CONCLUSION: The current study confirmed a more severe progression of the retinal disease in USH1 patients rather than in USH2 patients. Furthermore, most visual symptoms (i.e., night blindness, visual acuity worsening) occurred at an earlier age in USH1 patients carrying mutations in MYO7A.
Asunto(s)
ADN/genética , Proteínas de la Matriz Extracelular/genética , Mutación , Miosinas/genética , Síndromes de Usher/genética , Agudeza Visual , Campos Visuales , Adolescente , Adulto , Análisis Mutacional de ADN , Progresión de la Enfermedad , Electrorretinografía , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Miosina VIIa , Miosinas/metabolismo , Fenotipo , Retina/diagnóstico por imagen , Retina/fisiopatología , Estudios Retrospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica , Síndromes de Usher/diagnóstico , Síndromes de Usher/fisiopatología , Adulto JovenAsunto(s)
Diabetes Mellitus/epidemiología , Retinopatía Diabética/epidemiología , Vitreorretinopatía Proliferativa/epidemiología , Adolescente , Adulto , Diabetes Mellitus/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Gliburida/uso terapéutico , Humanos , Lactante , Recién Nacido , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: To report on 4 patients affected by Stargardt's disease (STGD) with fundus flavimaculatus (FFM) and ABCA4 gene mutation associated with subretinal fibrosis. METHODS: Four patients with a diagnosis of STGD were clinically examined. All 4 cases underwent a full ophthalmologic evaluation, including best-corrected visual acuity measured by the Snellen visual chart, biomicroscopic examination, fundus examination, fundus photography, electroretinogram, microperimetry, optical coherence tomography and fundus autofluorescence. All patients were subsequently screened for ABCA4 gene mutations, identified by microarray genotyping and confirmed by conventional DNA sequencing of the relevant exons. RESULTS: In all 4 patients, ophthalmologic exam showed areas of subretinal fibrosis in different retinal sectors. In only 1 case, these lesions were correlated to an ocular trauma as confirmed by biomicroscopic examination of the anterior segment that showed a nuclear cataract dislocated to the superior site and vitreous opacities along the lens capsule. The other patients reported a lifestyle characterized by competitive sport activities. The performed instrumental diagnostic investigations confirmed the diagnosis of STGD with FFM in all patients. Moreover, in all 4 affected individuals, mutations in the ABCA4 gene were found. CONCLUSIONS: Patients with the diagnosis of STGD associated with FFM can show atypical fundus findings. We report on 4 patients affected by STGD with ABCA4 gene mutation associated with subretinal fibrosis. Our findings suggest that this phenomenon can be accelerated by ocular trauma and also by ocular microtrauma caused by sport activities, highlighting that lifestyle can play a role in the onset of these lesions.
RESUMEN
BACKGROUND: Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is an autosomal dominant vascular disorder characterized by severe and recurrent nosebleeds, muco-cutaneous telangiectasias, and, in some cases, life-threatening visceral arteriovenous malformations. Ocular abnormalities include conjunctival telangiectasia, arteriovenous fistula, angiectasia, phlebectasia, and angioma. MATERIAL AND METHODS: We describe the ocular abnormalities in 8 patients from a pedigree with hereditary hemorrhagic telangiectasia. This article also reviews and discusses the relevant literature. RESULTS: Five patients (62.5%) had conjunctival telangiectasias and 3 (37.5%) retinal abnormalities, consisting mainly of choriocapillaris atrophy. CONCLUSIONS: To the best of our knowledge, this is the first report describing the occurrence of choriocapillaris atrophy in patients affected by hereditary hemorrhagic telangiectasia and belonging to the same pedigree.