Genome-wide association identifies ATOH7 as a major gene determining human optic disc size.

Optic nerve assessment is important for many blinding diseases, with cup-to-disc ratio (CDR) assessments commonly used in both diagnosis and progression monitoring of glaucoma patients. Optic disc, cup, rim area and CDR measurements all show substantial variation between human populations and high heritability estimates within populations. To identify loci underlying these quantitative traits, we performed a genome-wide association study in two Australian twin cohorts and identified rs3858145, P=6.2x10(-10), near the ATOH7 gene as associated with the mean disc area. ATOH7 is known from studies in model organisms to play a key role in retinal ganglion cell formation. The association with rs3858145 was replicated in a cohort of UK twins, with a meta-analysis of the combined data yielding P=3.4x10(-10). Imputation further increased the evidence for association for several SNPs in and around ATOH7 (P=1.3x10(-10) to 4.3x10(-11), top SNP rs1900004). The meta-analysis also provided suggestive evidence for association for the cup area at rs690037, P=1.5x10(-7), in the gene RFTN1. Direct sequencing of ATOH7 in 12 patients with optic nerve hypoplasia, one of the leading causes of blindness in children, revealed two novel non-synonymous mutations (Arg65Gly, Ala47Thr) which were not found in 90 unrelated controls (combined Fisher's exact P=0.0136). Furthermore, the Arg65Gly variant was found to have very low frequency (0.00066) in an additional set of 672 controls.

Ischaemic stroke subtypes and their genetic basis: a comprehensive meta-analysis of small and large vessel stroke.

BACKGROUND: The extent to which genetic effects on the different subtypes of small (SVD) and large vessel disease (LVD) ischaemic stroke differ remains controversial. METHODS: A comprehensive genetic meta-analysis of all genes investigated by ischaemic stroke subtype was conducted. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association. RESULTS: From the initial search of 526 manuscripts, 5 candidate genes were studied comprising 7,533 cases (LVD 4,181, SVD 3,352) and 9,835 control subjects. There was a preferential association for SVD compared to LVD with ACE/DD (SVD: OR 1.31, 95% CI 0.96-1.79; LVD: OR 1.02, 95% CI 0.82-1.26) and eNOS intron 4 ab polymorphism (SVD: OR 1.41, 95% CI 0.94-2.11; LVD: OR 1.07, 95% CI 0.77-1.49), although statistical significance was not reached. No such preference was observed for MTHFR C677T, ApoE/epsilon4 or PAI-1 4G/5G polymorphism. The overall number of studies and the number of subjects recruited per study in whom stroke subtype was classified were small when compared to previous published work without such phenotype classification. CONCLUSION: Our findings suggest that genetic effects may differ between small and large vessel subtypes, although the evidence base is small.

Anti-VEGF Therapy and the Retina: An Update.

Ocular angiogenesis and macular oedema are major causes of sight loss across the world. Aberrant neovascularisation, which may arise secondary to numerous disease processes, can result in reduced vision as a result of oedema, haemorrhage, and scarring. The development of antivascular endothelial growth factor (anti-VEGF) agents has revolutionised the treatment of retinal vasogenic conditions. These drugs are now commonly employed for the treatment of a plethora of ocular pathologies including choroidal neovascularisation, diabetic macular oedema, and retinal vein occlusion to name a few. In this paper, we will explore the current use of anti-VEGF in a variety of retinal diseases and the impact that these medications have had on visual outcome for patients.

Repeatability of retinal thickness and volume metrics in neovascular age-related macular degeneration using the Topcon 3DOCT-1000.

INTRODUCTION: Optical coherence tomography (OCT) is a commonly used imaging modality that provides detailed cross-sectional retinal images. This has revolutionised management of neovascular age-related macular degeneration. The need for repeated anti-vascular endothelial growth factor injections has led to therapy being delivered using OCT-guided retreatment strategies with both qualitative OCT features of disease activity (e.g. macular fluid) and changes in retinal thickness as triggers for retreatment The purpose of this study is to determine the intra-session repeatability of retinal thickness and volume measurements using the Topcon 3DOCT-1000 spectral-domain optical coherence tomography (SDOCT) device in patients with neovascular age-related macular degeneration (nAMD). This is the largest study to date looking specifically at the Topcon 3DOCT-1000. MATERIALS AND METHODS: Two SDOCT raster scans were performed by the same blinded observer in the same sitting in consecutive patients attending for nAMD treatment as part of standard validation of a new device. Retrospective analysis was undertaken, with retinal thickness and volume measurements automatically calculated by the onboard software for each Early Treatment of Diabetic Retinopathy Study subfield for each scan. Bland-Altman methods of analysis were used to assess repeatability. RESULTS: Data from the 73 patients were analyzed with a mean age of 78 years (standard deviation 8). The 95% coefficient of repeatability (CR) was 64 µm and 0.050 mm 3 for retinal thickness and volume respectively in the central 1 mm macular subfield. The CR did not exceed 85 µm (0.30 mm 3 ) in any subfield. The revised CR for retinal thickness and volume for the subgroup of 37 patients with no segmentation error in the central 1 mm subfield was 53 µm and 0.050 mm 3 respectively. Discussion : We report relatively modest intra-sessional repeatability of SDOCT retinal thickness and volume metrics in patients with nAMD in a clinical setting. Though useful in detecting clinical change from measurement variability in clinical practice, these results suggest the precision of macular thickness measurement does not approach the theoretical resolution of SDOCT.

Randomized Controlled Study of Ocular Lubrication Versus Bandage Contact Lens in the Primary Treatment of Recurrent Corneal Erosion Syndrome.

PURPOSE: To investigate the efficacy of bandage contact lenses (BCLs) in comparison with that of ocular lubricants (OLs) in the initial management of recurrent corneal erosion syndrome. METHODS: A randomized controlled trial of 29 patients with recurrent corneal erosion syndrome presenting to the ophthalmology departments of the Oxford Eye Hospital and the Royal Berkshire Hospital, United Kingdom. The patients were randomized to wear either BCLs (for a 3-month duration, replaced every 30 days) or use OLs (4 times a day, with Lacri-Lube ointment at night for 3 months). The patients were assessed monthly for 4 months, and their symptoms were graded by visual analog scores. The main outcome measure was the complete resolution of symptoms with no noticeable corneal surface abnormality. Patients with a complete resolution were followed up for another 3 months to check for recurrence. RESULTS: Fourteen patients were randomized to the BCL arm, and 15 were randomized to the OL arm. After 3 months, a complete resolution was achieved in 71% of the patients (10/14) with BCLs compared with that achieved in 73% of the patients (11/15) on OLs (P > 0.05). Partial resolution was noted in 7% of the patients with BCLs versus 13% of the patients on OLs. Twenty-one percent of the patients in the BCL group and 13% of the patients in the OL group failed to respond to the treatment. Patients on BCLs had earlier resolution of symptoms, with a mean time of 5 weeks compared with 9 weeks for OLs (P = 0.02). None of the patients with BCLs developed adverse side effects. CONCLUSIONS: BCLs do not increase the likelihood of complete resolution when compared with OLs in the initial management of RCES. However, BCL treatment seems safe, and some patients experience earlier relief from symptoms.