EPHA2 Polymorphisms and Age-Related Cataract in India

Objective: We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India. Methods: We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear >= 4, cortical >= 3, posterior sub-capsular (PSC) >= 2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location. Results: 7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p > 0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract. Conclusions: Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians

Associations between cataract and rs3754334.

1<p>defined as any of the following on LOCS III: cortical≥3, PSC≥2, nuclear≥4, dense opacities, operated cataract.</p>2<p>LOCS III: cortical≥3.</p>3<p>LOCS III: posterior subcapsular (PSC)≥2.</p>4<p>LOCS III: nuclear≥4.</p

Associations between cataract and rs7543472.

1<p>defined as any of the following on LOCS III: cortical≥3, PSC≥2, nuclear≥4, dense opacities, operated cataract.</p>2<p>LOCS III: cortical≥3.</p>3<p>LOCS III: posterior subcapsular (PSC)≥2.</p>4<p>LOCS III: nuclear≥4.</p

Distribution of participants by cataract status for those who have at least one of the genotyped SNPs.

1<p>“no cataract” defined as the absence of all of the following on LOCS III: cortical≥3, PSC≥2, nuclear≥4, dense opacities, operated cataract.</p>2<p>defined as any of the following on LOCS III: cortical≥3, PSC≥2, nuclear≥4, dense opacities, operated cataract.</p>3<p>LOCS III: cortical≥3.</p>4<p>LOCS III: posterior subcapsular (PSC)≥2.</p>5<p>LOCS III: nuclear ≥4.</p

Associations between cataract and rs11260867.

1<p>defined as any of the following on LOCS III: cortical≥3, PSC≥2, nuclear≥4, dense opacities, operated cataract.</p>2<p>LOCS III: cortical≥3.</p>3<p>LOCS III: posterior subcapsular (PSC)≥2.</p>4<p>LOCS III: nuclear≥4.</p

EPHA2 genotype distribution by phenotype.

1<p>“no cataract” defined as the absence of all of the following on LOCS III: cortical≥3, PSC≥2, nuclear≥4, dense opacities, operated cataract.</p>2<p>defined as any of the following on LOCS III: cortical≥3, PSC≥2, nuclear≥4, dense opacities, operated cataract.</p>3<p>LOCS III: cortical≥3.</p>4<p>LOCS III: posterior subcapsular (PSC)≥2.</p>5<p>LOCS III: nuclear≥4.</p

Prevalence of Cataract in an Older Population in India: The India Study of Age-related Eye Disease

PURPOSE: To describe the prevalence of cataract in older people in 2 areas of north and south India. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Randomly sampled villages were enumerated to identify people aged ≥ 60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination. METHODS: The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III). MAIN OUTCOME MEASURES: Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥ 4 for nuclear cataract, ≥ 3 for cortical cataract, and ≥ 2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract. RESULTS: The prevalence of unoperated cataract in people aged ≥ 60 was 58% in north India (95% CI, 56-60) and 53% (95% CI, 51-55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46-50) in north India and 38% (95% CI, 37-40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20-23) and 17% (95% CI, 16-19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7-9) and 10.2% (95% CI, 9-11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002). CONCLUSIONS: We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery

Prophylactic biological mesh reinforcement versus standard closure of stoma site (ROCSS): a multicentre, randomised controlled trial

Background: Closure of an abdominal stoma, a common elective operation, is associated with frequent complications; one of the commonest and impactful is incisional hernia formation. We aimed to investigate whether biological mesh (collagen tissue matrix) can safely reduce the incidence of incisional hernias at the stoma closure site. Methods: In this randomised controlled trial (ROCSS) done in 37 hospitals across three European countries (35 UK, one Denmark, one Netherlands), patients aged 18 years or older undergoing elective ileostomy or colostomy closure were randomly assigned using a computer-based algorithm in a 1:1 ratio to either biological mesh reinforcement or closure with sutures alone (control). Training in the novel technique was standardised across hospitals. Patients and outcome assessors were masked to treatment allocation. The primary outcome measure was occurrence of clinically detectable hernia 2 years after randomisation (intention to treat). A sample size of 790 patients was required to identify a 40% reduction (25% to 15%), with 90% power (15% drop-out rate). This study is registered with ClinicalTrials.gov, NCT02238964. Findings: Between Nov 28, 2012, and Nov 11, 2015, of 1286 screened patients, 790 were randomly assigned. 394 (50%) patients were randomly assigned to mesh closure and 396 (50%) to standard closure. In the mesh group, 373 (95%) of 394 patients successfully received mesh and in the control group, three patients received mesh. The clinically detectable hernia rate, the primary outcome, at 2 years was 12% (39 of 323) in the mesh group and 20% (64 of 327) in the control group (adjusted relative risk [RR] 0·62, 95% CI 0·43–0·90; p=0·012). In 455 patients for whom 1 year postoperative CT scans were available, there was a lower radiologically defined hernia rate in mesh versus control groups (20 [9%] of 229 vs 47 [21%] of 226, adjusted RR 0·42, 95% CI 0·26–0·69; p<0·001). There was also a reduction in symptomatic hernia (16%, 52 of 329 vs 19%, 64 of 331; adjusted relative risk 0·83, 0·60–1·16; p=0·29) and surgical reintervention (12%, 42 of 344 vs 16%, 54 of 346: adjusted relative risk 0·78, 0·54–1·13; p=0·19) at 2 years, but this result did not reach statistical significance. No significant differences were seen in wound infection rate, seroma rate, quality of life, pain scores, or serious adverse events. Interpretation: Reinforcement of the abdominal wall with a biological mesh at the time of stoma closure reduced clinically detectable incisional hernia within 24 months of surgery and with an acceptable safety profile. The results of this study support the use of biological mesh in stoma closure site reinforcement to reduce the early formation of incisional hernias. Funding: National Institute for Health Research Research for Patient Benefit and Allergan