Impact of genetic loci identified in genome-wide association studies on diabetic retinopathy in Chinese patients with type 2 diabetes

© 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.PURPOSE. Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes (T2DM). Genome-wide association studies (GWAS) had identified novel DRsusceptibility genetic variants in various populations. We examined the associations of these DR-associated single nucleotide polymorphisms (SNPs) with severe DR in a Chinese T2DM cohort. METHODS. Cross-sectional case-control studies on sight-threatening DR (STDR) and proliferative DR (PDR) were performed. We genotyped 38 SNPs showing top association signals with DR in previous GWAS in 567 STDR cases, including 309 with PDR and 1490 non-DR controls. Multiple logistic regression models with adjustment for conventional risk factors, including age, sex, duration of diabetes, and presence of hypertension, were employed. RESULTS. The strongest association was found at INSR rs2115386, an intronic SNP of INSR: Padjusted = 9.13 × 10-4 (odds ratio [OR],1.28; 95% confidence interval [95%CI], 1.11-1.48) for STDR, and Padjusted = 1.12 × 10-4 (OR [95%CI],1.44 [1.20-1.74]) for PDR. rs599019 located downstream of COLEC12 (Padjusted = 0.019; OR [95%CI],1.19 [1.03-1.38]) and rs4462262 located at an intergenic region between ZWINT and MRPS35P3 (Padjusted = 0.041; OR [95%CI],1.38[1.01-1.89]) also were significantly associated with STDR, but not with PDR alone. On the other hand, MYT1L-LOC729897 rs10199521 (Padjusted = 0.022; OR [95%CI],1.25 [1.03-1.51]) and API5 rs899036 (Padjusted = 0.049; OR [95%CI],1.36 [1.00-1.85]) showed significant independent associations only with PDR. Similar results were obtained when hemoglobin A1c also was included in the adjustment models. CONCLUSIONS. We demonstrated the significant and independent associations of several GWAS-identified SNPs with DR in Chinese T2DM patients with severe DR. The findings on INSR rs2115386 are supportive of the role of insulin resistance, or the compensatory hyperinsulinemia, in the pathogenesis of DR.Link_to_subscribed_fulltex

Prospective study on the efficacy of treating normal tension glaucoma with a single session of selective laser trabeculoplasty

PURPOSE: The purpose of this study was to investigate the efficacy of selective laser trabeculoplasty (SLT) in the treatment of normal tension glaucoma (NTG). METHODS: This prospective cohort study recruited consecutive cases of NTG on antiglaucoma medication. Cases were excluded for previous glaucoma surgery or laser. All patients underwent a 1-month washout of medication followed by a mean baseline intraocular pressure (IOP) measured at 9 AM, 1 PM, and 5 PM. A 30% reduction from baseline was set as the target IOP. A single session of SLT was performed to 360 degrees of the trabecular meshwork. IOP phasing was repeated at 1 month after SLT and medication was resumed to achieve the target IOP. Patients were followed up to 6 months after SLT. RESULTS: In 83 eyes of 46 subjects, the mean prestudy IOP was 14.2 ± 3.1 mm Hg when on 1.5 ± 0.9 antiglaucoma medication. The mean baseline IOP without medication was 16.1 ± 2.2 mm Hg. The mean SLT shots applied was 187.8 ± 27.5 using a mean energy of 1.0 ± 0.07 mJ. At 1-month post-SLT, the IOP was 12.7 ± 2.0 mm Hg (21.6% IOP reduction) from baseline without medication (P<0.05). The 6-month IOP was 11.4 ± 1.6 mm Hg when on 1.1± 1.0 medications, representing a 19.7% reduction from prestudy IOP, a 29.6% reduction from baseline IOP, and a 26.7% reduction in antiglaucoma medication (all P< 0.05). A higher baseline IOP was correlated with greater IOP reduction with SLT (r=0.3, P=0.009). CONCLUSIONS: A single session of SLT for NTG achieved an additional 20% reduction in IOP with 27% less medication at 6 months compared with prestudy levels while maintaining a 30% reduction from baseline IOP.Link_to_subscribed_fulltex