Clinical features and molecular genetics of patients with ABCA4-retinal dystrophies.

PURPOSE: Pathogenic variations in the ABCA4 gene are a leading cause of vision loss in patients with inherited retinal diseases. ABCA4-retinal dystrophies are clinically heterogeneous, presenting with mild to severe degeneration of the retina. The purpose of this study was to clinically and genetically characterize patients with ABCA4-retinal dystrophies in Norway and describe phenotype-genotype associations. METHODS: ABCA4 variants were detected in 111 patients with inherited retinal disease undergoing diagnostic genetic testing over a period of 12 years. In patients where only a single ABCA4 variant was found, whole-gene ABCA4 sequencing was performed and intronic variants were investigated by mRNA analyses in fibroblasts. Medical journals were used to obtain a clinical description and ultrawidefield autofluorescence images were used to analyse retinal degeneration patterns. RESULTS: The genetic diagnostic yield was 89%. The intronic splice variant c.5461-10T>C was the most prevalent disease-causing variant (27%). Whole-gene ABCA4 sequencing detected two novel intronic variants (c.6729+81G>T and c.6817-679C>A) that we showed affected mRNA splicing. Peripheral retinal degeneration was identified in 33% of patients and was associated with genotypes that included severe loss of function variants. By contrast, peripheral degeneration was not found in patients with a disease duration over 20 years and genotypes including p.(Asn1868lle), c.4253+43G>A or p.(Gly1961Glu) in trans with a loss of function variant. CONCLUSION: This study demonstrates the clinical and genetic heterogeneity of ABCA4-retinal dystrophies in Norway. Further, the study presents novel variants and increases our knowledge on phenotype-genotype associations and the presence of peripheral retinal degeneration in ABCA4-retinal dystrophy patients.

Photopic full-field electroretinography and optical coherence tomography in type 1 diabetic retinopathy.

PURPOSE: The purpose of this study was to evaluate the role of photopic full-field electroretinography (ERG) and retinal thickness measurements by spectral-domain optical coherence tomography (SD-OCT) in the assessment of disease severity in type 1 diabetic retinopathy. METHODS: A population-based cohort of 151 patients with type 1 diabetes underwent a complete ophthalmic examination, including photopic full-field ERG and SD-OCT for retinal thickness measurements. Stereoscopic fundus photographs were taken according to the Early Treatment Diabetic Retinopathy Study protocol, and the classification of diabetic retinopathy was based on the International Clinical Diabetic Retinopathy Disease Severity Scale. Associations between photographically determined retinopathy level, b-wave amplitude and peak time of the photopic single-flash and 30-Hz flicker ERG, and central retinal thickness parameters were evaluated. RESULTS: For all ERG measurements, the amplitude decreased and peak time increased with progression of the disease, but these associations lost statistical significance after adjusting for age and excluding laser-treated patients. Mean retinal thickness was significantly associated with the b-wave amplitude of photopic single-flash and 30-Hz flicker responses (r(2) = 0.08, p = 0.006; and r(2) = 0.05, p = 0.025, respectively), but revealed no association with retinopathy level. CONCLUSIONS: Photopic full-field ERG and SD-OCT-derived retinal thickness parameters have limited clinical value in the staging of diabetic retinopathy. However, thinning of the central retina leads to significant functional impairment and may reflect an ongoing neurodegenerative process in the retinal tissue.

Retinopathy and visual impairment in diabetes, impaired glucose tolerance and normal glucose tolerance: the Nord-Trøndelag Health Study (the HUNT study).

PURPOSE: The aim of the study was to describe the prevalence of visual impairment and retinopathy and to investigate risk factors for retinopathy in persons with diabetes, screen-detected diabetes, impaired glucose tolerance and normal glucose tolerance in a subpopulation of the HUNT study. METHODS: We used a sample (n = 163) from a population-based screening survey of hyperglycaemia, undertaken in 2004-2005 in Verdal, Norway. Baseline information was accessible through the second Nord-Trøndelag Health Study (HUNT2), 1995-97. Data collection was made in 2005 and included patient history, refraction, visual acuity, cataract assessment and single-field, nonmydriatic retinal photography. Retinal photographs were graded independently by two graders blinded to patient information. Data were analysed with standard statistical methods, and p < 0.05 was considered significant. RESULTS: In all, 126 (77%) persons participated, 55% were women. The mean (SD) age was 59 (± 14) years. Four (3%) had correctable visual impairment, and none were visually impaired. Retinal photographs were gradable for both eyes in 109 (87%) participants. The prevalence of retinopathy was 11% in persons with known diabetes, 4% in persons with screen-detected diabetes, 3% in persons with impaired glucose tolerance and 10% in persons with normal glucose tolerance. Retinopathy was not associated with known history of diabetes or current glycaemic status. Nonfasting plasma glucose (in 1995-97) was an independent risk factor for retinopathy (in 2005), OR (95% CI) 1.5 (1.01, 2.13), p = 0.046. CONCLUSION: The prevalence of diabetic retinopathy in persons with diabetes in this study was low. Appropriate optical correction and regular eye examination can prevent unnecessary visual impairment in both persons with and without diabetes.