Preliminary trabeculectomy results using the Moorfields safer surgery technique in Malta

Purpose: To review the results of the Moorfields Safer Surgery System (MSSS) for trabeculectomy, recently introduced in Malta. Methods: Patient files were reviewed from data collected over an 18 month period, from the Maltese national teaching hospital, Mater Dei Hospital. Files of all patients undergoing primary trabeculectomy with a minimum of 12 months follow up data available were reviewed. Primary outcome measure of success was defined as a 30% drop in final post-operative intraocular pressure (IOP) at 1 year. Secondary outcome measure of success was final post-op IOP of less than 21mmHg. Unqualified success was defined as satisfactory IOP without the need of anti-glaucoma medication, while qualified success was defined as satisfactory IOP in those patients requiring anti-glaucoma medication. Results: 43 eyes (mean age = 66.2 yrs ± 11.7) were analysed. The mean pre-operative IOP was 27.0mmHg ± 4.6. Mean post-op IOP at one year was 15.3mmHg ±2.7. Unqualified success for the primary outcome measure was achieved in 64.1% of patients while the qualified success was achieved in 82.1%. Unqualified success for the secondary outcome measure was achieved in 72.7% and a qualified success, of 94.8% was obtained. There was 6.8% failure rate. Conclusions: The results from this first review using the Moorfields safe surgery system for Trabeculectomy surgery in the Maltese islands compares well to the current literature.peer-reviewe

Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping

Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genome-wide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map 1 was divided into 51 LDU windows and additional SNPs were genotyped for six regions (Map 2) that showed preliminary evidence of multi-marker association using composite likelihood. A total of 575 cases and controls selected from the tails of the trait distribution were genotyped for the discovery sample. Malecot model estimates indicate three loci with putative common functional variants centred on MFN1 (180,566 kb; 95% confidence interval 180,505–180, 655 kb), approximately 156 kb upstream from alternate-splicing SOX2OT (182,595 kb; 95% CI 182,533–182,688 kb) and PSARL (184,386 kb; 95% CI 184,356–184,411 kb), with the loci showing modest to strong evidence of association for the Map 2 discovery samples (p<10−7, p<10−10, and p = 0.01, respectively). Using an unselected independent sample of 1,430 individuals, results replicated for the MFN1 (p = 0.006), SOX2OT (p = 0.0002), and PSARL (p = 0.0005) gene regions. MFN1 and PSARL both interact with OPA1 to regulate mitochondrial fusion and the inhibition of mitochondrial-led apoptosis, respectively. That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia

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 = 6.2 × 10−10, 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 = 3.4 × 10−10. Imputation further increased the evidence for association for several SNPs in and around ATOH7 (P = 1.3 × 10−10 to 4.3 × 10−11, top SNP rs1900004). The meta-analysis also provided suggestive evidence for association for the cup area at rs690037, P = 1.5 × 10−7, 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

Common genetic determinants of intraocular pressure and primary open-angle Glaucoma

10.1371/journal.pgen.1002611PLoS Genetics85

A Case of Advanced Glaucoma with Increased Episcleral Venous Pressure in a 17-Year-Old with Eisenmenger Syndrome

Eisenmenger syndrome refers to reversal of shunt and central cyanosis due to pulmonary hypertension induced by congenital heart disease with a large systemic-to-pulmonary shunt. We report a case of a 17-year-old man with Eisenmenger syndrome who presented with gradual deterioration in visual acuity and was diagnosed with advanced secondary open angle glaucoma. There have been reports of patients suffering from thrombosis due to hyperviscosity associated with this syndrome; however, to our knowledge, the association of secondary open angle glaucoma with Eisenmenger syndrome has not yet been documented

Repeated measures of intraocular pressure result in higher heritability and greater power in genetic linkage studies

PURPOSE. To analyze the effect of using one reading, the mean of two readings (from the same eye), or the mean of four readings (two from each eye) on the heritability estimates of intraocular pressure (IOP). This was a cohort study in which 344 pairs of twins, 163 monozygotic (MZ) and 181 dizygotic (DZ), were enrolled. METHODS. IOP was measured using three tonometers: the gold standard Goldmann applanation tonometer (GAT), the Ocular Response Analyzer (ORA; Reichert Buffalo, NY), and the Dynamic Contour Tonometer (DCT, Pascal; Swiss Microtechnology AG, Port, Switzerland). The main outcome measure was the heritability of IOP correlated with the number of measurements. RESULTS. The mean IOPs of all four readings with the three tonometers were: 14.1 ± 2.9 mm Hg for GAT, 15.9 ± 3.2 mm Hg for ORA, and 16.9 ± 2.7 mm Hg for DCT. As the number of readings increased, the calculated heritability (h(2)) of IOP measured using the GAT readings increased from 0.56 for one reading (95% confidence interval [CI], 0.44–0.65) to 0.58 for the mean of two readings (95% CI, 0.46–0.67) to 0.64 for the mean of all four readings (two right and two left; 95% CI, 0.55–0.72). Similar results were seen with the other two instruments. CONCLUSIONS. The results demonstrated that the use of the mean of several readings from both eyes reduced measurement error, yielding a higher heritability estimate. The higher heritability would increase the power to detect linkage in a genome-wide analysis