Diabetic retinopathy in type 1 diabetes patients in Western Norway.

PURPOSE: To describe the prevalence of diabetic retinopathy (DR), associated risk factors and health-related quality of life (HRQoL) in a population-based cohort of patients with type 1 diabetes mellitus (DM1). METHODS: All patients underwent a general and ophthalmic examination including seven-field stereo fundus photography for grading of DR and diabetic macular oedema (DMO). Kaplan-Meier survival analyses were performed to evaluate disease progression in relation to diabetes duration, age and year of diabetes onset. HRQoL and its association with DR were assessed by the Medical Outcomes Study Short Form 36 (SF-36) questionnaire. RESULTS: A total of 237 DM1 patients were included. Mean age at inclusion was 34 years (range, 4-75 years), and mean diabetes duration was 19 years (range, 5 months-63 years). A total of 145 patients (61%) had DR. Sixty-two patients (26%) had mild, 39 (16%) moderate and 13 (5%) severe nonproliferative DR, while 31 (13%) had proliferative DR. The prevalence of DMO was 8%. The most important risk factors predicting severity of DR were diabetes duration (p < 0.0001) and HbA1c level (p < 0.0001). Neuropathy (p = 0.006), nephropathy (p = 0.004) and male gender (p = 0.02) were also significant predictors of DR. Compared to normative SF-36 data, there was a linear trend of decreasing HRQoL with increasing severity of DR that was statistically significant for the four physical dimension scores. CONCLUSION: The prevalence of DR in DM1 was largely within the range of previous reports. Diabetes duration, HbA1c level, neuropathy, nephropathy and male gender were all significant predictors of DR severity. The patients with more severe DR had lower HRQoL.

The intronic ABCA4 c.5461-10T>C variant, frequently seen in patients with Stargardt disease, causes splice defects and reduced ABCA4 protein level.

PURPOSE: Despite being the third most common ABCA4 variant observed in patients with Stargardt disease, the functional effect of the intronic ABCA4 variant c.5461-10T>C is unknown. The purpose of this study was to investigate the molecular effect of this variant. METHODS: Fibroblast samples from patients carrying the ABCA4 variant c.5461-10T>C were analysed by isolating total RNA, followed by real-time polymerase chain reaction (RT-PCR) using specific primers spanning the variant. For detection of ABCA4 protein, fibroblast samples were lysed and analysed by SDS-PAGE followed by immunoblotting using a monoclonal ABCA4 antibody. RESULTS: The ABCA4 variant c.5461-10T>C causes a splicing defect resulting in the reduction of full-length mRNA in fibroblasts from patients and the presence of alternatively spliced mRNAs where exon 39-40 is skipped. A reduced level of full-length ABCA4 protein is observed compared to controls not carrying the variant. CONCLUSIONS: This study describes the functional effect and the molecular mechanism of the pathogenic ABCA4 variant c.5461-10T>C. The variant is functionally important as it leads to splicing defects and a reduced level of ABCA4 protein.

Early panretinal photocoagulation for ERG-verified ischaemic central retinal vein occlusion.

PURPOSE: We have previously shown that photopic cone b-wave implicit time ≥ 35.0 ms in 30 Hz flicker electroretinography (ERG) predicts ocular neovascularization (NV) in central retinal vein occlusion (CRVO). Here, we evaluate the effects of early panretinal photocoagulation (PRP) in patients with ERG-verified ischaemic CRVO. METHODS: Patients with CRVO, admitted to our department between 2000 and 2008, were classified as having ischaemic or non-ischaemic CRVO based on the ERG-results. In a first group of 71 patients, 18 patients had ischaemic CRVO and were assigned to standard treatment that is regular examinations and PRP as soon as NV was found. In a consecutive group of 65 patients, 18 patients with ischaemic CRVO received early PRP. In this group, ERG was performed on average 6 weeks after the first symptoms of CRVO. The patients underwent PRP as soon as possible after the ERG-examination, and the treatment was completed within one to three sessions. RESULTS: Twelve patients in the standard treatment group developed neovascular glaucoma during a mean period of 5 months after the CRVO. In the early treatment group, one patient developed subtle iris rubeosis 7 months after PRP. Otherwise, none of the patients showed any signs of ocular NV, and the intraocular pressure remained within normal range, without the necessity of supplementary medication, during a mean follow-up of 41 months. CONCLUSIONS: This study indicates that ocular NV in patients with CRVO can be predicted by photopic 30 Hz flicker ERG and that early PRP in ERG-verified ischaemic CRVO could be suggested as standard treatment.

Topographical distribution of retinal and optic disc neovascularization in early stages of proliferative diabetic retinopathy.

PURPOSE: We analyzed the topography of proliferative diabetic retinopathy (PDR), and visualized the distribution of neovascularization of the optic disc (NVD) and elsewhere in the retina (NVE). METHODS: The study included 174 eyes of 106 patients with early PDR. Data on the size and location of 391 NVE and 73 NVD were converted into a database of two-dimensional retinal and optic disc charts. The geometric centers of the neovascular lesions were plotted into corresponding areas of the charts, and the topographic distributions of the NVE and NVD were visualized by merging the charts and displaying the number of overlapping lesions on color-coded contour maps. RESULTS: A total of 141 (36%) NVE was located in the temporal and 250 (64%) in the nasal hemisphere (P < 0.0001). The distribution of the NVD in the temporal and nasal half of the optic disc was 46 (63%) and 27 (37%), respectively (P = 0.03). NVE in type 1 diabetes were located significantly farther from the fovea and optic disc, and were more numerous and larger than in type 2 diabetes. The number and diameter of the NVE were also significantly higher when the time from the last examination to the appearance of PDR exceeded 12 months. CONCLUSIONS: The majority of NVE lesions are located inferonasal to the optic disc and along the superior vascular arcades, while NVD have a predilection for the upper temporal disc rim. More extensive PDR is found in patients with type 1 diabetes and those with examination intervals longer than one year.