Essam A. Osman

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR) = 1.22; P = 5.33 × 10−12), rs3753841 in COL11A1 (per-allele OR = 1.20; P = 9.22 × 10−10) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR = 1.50; P = 3.29 × 10−9). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

ABCC5, a Gene That Influences the Anterior Chamber Depth, Is Associated with Primary Angle Closure Glaucoma

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = −0.045 mm, P = 8.17×10−9). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06–1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45×10−9; 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Association of Mn-SOD Mutation (c.47T > C) with Various POAG Clinical Indices

Abstract Background: To investigate whether the c.47T > C mutation in the manganese superoxide dismutase gene (Mn-SOD) is a risk factor for primary open angle glaucoma (POAG) in the Saudi population. Materials and Methods: A cohort of 226 unrelated POAG patients and 403 unrelated control subjects from Saudi Arabia were genotyped for a single nucleotide polymorphism (SNP; rs4880; c.47T > C) utilizing Taq-Man® assay ID: C_8709053_10. The association between mutant genotypes and various clinical indices important for POAG was also investigated. Results: Among cases, the prevalence of the wildtype genotype (T/T) was 22.1% (50/226), while the heterozygous mutated genotype (T/C) was 50.9% (115/226) and the homozygous mutant genotype (C/C) was 27% (61/226). There were no statistically significant differences between cases and controls in terms of the genotype distribution on both heterozygous mutant (p = 0.916) and homozygous mutant (p = 0.988) genotypes. POAG patients with the mutant genotypes had slightly higher intraocular pressure (IOP) than controls. Additionally, patients with T/C genotype had slight elevation of the cup/disc ratio than the normal group. Additionally, the age at onset of disease showed an increasing trend with severity of mutation where it increases across groups T/T, T/C, and C/C being at [48.9 (±16.3), 51.4 (±12.2), and 56.5 (±13.9)] respectively and a p value of 0.028 for the C/C genotype. Conclusions: This mutation could be associated with various clinical indices important for POAG. If similar findings were found in other populations and larger cohorts, then this SNP may be used as a marker for assessing the severity of the disease.

Efficacy and safety of deep sclerectomy in childhood glaucoma in Saudi Arabia.

Purpose:  To evaluate the efficacy and safety of deep sclerectomy in childhood glaucoma.

The profile of glaucoma in a Tertiary Ophthalmic University Center in Riyadh, Saudi Arabia

PURPOSE To report the pattern of glaucoma among Saudi patients who were presented to King Abdul Aziz University Hospital (KAUH). METHODS All glaucoma or glaucoma suspect patients who were presented to KAUH from 2006 to 2008 were included; medical files of all patients were retrieved and evaluated through standardized international guidelines. Collected data included: age, sex, laterality, intraocular pressure, and cup/disk ratio. Prevalence of different glaucoma types (including 95% CI) was calculated, ANOVA and post hoc tests were applied to evaluate the difference in indices across different types. RESULTS A total of 2296 eyes of 1236 patients were included. Primary angle closure glaucoma (PACG) was the predominant type (46.6%) followed by primary angle closure (PAC) (17.2%), then primary open angle glaucoma (POAG) (12.8%), and secondary glaucoma (13%). Other types including (normal tension glaucoma (5.9%), childhood glaucoma (2.6%), and juvenile glaucoma (1.9%)) were also present but of lower prevalence. CONCLUSION Primary angle closure glaucoma was the predominant form of glaucoma followed by PAC, and POAG suggesting that the pattern in Saudi Arabia could be quite different from that reported for primary glaucomas in the Western literature. In addition, pseudoexfoliation was the most common form of secondary open and closed angle glaucoma. These results indicate the need for a national intervention program for early detection and referral of glaucoma cases in order to prevent significant visual loss. There is also a need for a community based assessment to determine the prevalence of glaucoma as a baseline for future intervention.

Association of total antioxidants level with glaucoma type and severity

Objectives: To compare the mean total antioxidant status (TAS) among 3 glaucoma types, namely: pseudoexfoliation glaucoma (PEG), primary open angle glaucoma (POAG), and primary angle closure glaucoma (PACG), and study its potential association with various clinical glaucoma-parameters. Methods: In this case-control study, plasma samples were obtained between September 2013 and October 2014 from 340 glaucoma patients (PEG [n=54]; POAG [n=147]; PACG [n=139]), and 351 controls of matching age, gender, ethnicity, and 5 different systemic co-morbidities from King Abdulaziz University Hospital, Riyadh, Saudi Arabia. The TAS in all samples was determined by a colorimetric-based assay. Results: The mean±standard deviation of TAS was significantly lower among cases: 0.77±0.32 than controls: 1.1±0.22, p<0.0001. Moreover, the TAS levels were significantly different across the 3 types of glaucoma: 0.86±0.24 in PEG, 0.47±0.32 in POAG, and 0.98±0.41 in PACG (all p<0.0001). In addition, there was a significant correlation between TAS and age at onset (Pearson correlation coefficient [R] 0.17, p<0.0001), cup/disc ratio (R: -0.13, p=0.004), and number of anti-glaucoma medications (R: -0.16, p=0.001). Conclusion: Our findings provide evidence that plasma TAS levels are decreased in patients with glaucoma, more so in POAG and PEG than PACG, supporting the hypothesis that decreased antioxidative defense and/or increased oxidative stress may have a critical role in the pathogenesis of glaucoma.

Decreased Total Antioxidants in Patients with Primary Open Angle Glaucoma

Abstract Purpose: To evaluate total antioxidant status (TAS) in the plasma of primary open angle glaucoma (POAG) patients and to compare it to that of the control group. Additionally, we aim to investigate the association of various POAG clinical indices with TAS level. Materials and Methods: Plasma samples were obtained from 139 POAG patients and 148 glaucoma- free controls of matching age, sex, and ethnicity. TAS in all samples was determined by spectrophotometric and enzyme-linked immunosorbent assay methods. We studied the possible association of the TAS level with various clinical indices relevant to POAG. Results: The mean (±SD) total antioxidant (TAS) value was lower among patients: 0.47 (±0.32), than controls: 0.97 (±0.43) and this difference was statistically significant (p < 0.0001). TAS concentration was not significantly associated neither with the level of intraocular pressure, nor with number of anti-glaucoma medications (p = 0.532 and 0.084 respectively). However, TAS level shows a trend towards reduction with increased severity of glaucoma presented in a reversed significant association with cup/disc ratio (p = 0.043). Conclusions: Our findings provide evidence that TAS decreases in the plasma of POAG patients and that it may play a role in POAG pathogenesis. Association of TAS level with increased cup-to-disc ratio highlights TAS potential role as a predictive-marker for POAG-severity.

Full preoperative panretinal photocoagulation improves the outcome of trabeculectomy with mitomycin C for neovascular glaucoma.

Purpose To investigate the efficacy of full panretinal photocoagulation (PRP) followed by trabeculectomy with mitomycin C (MMC) in the management of eyes with neovascular glaucoma (NVG). Methods This study is based on 30 consecutive eyes of 27 patients with NVG who underwent full PRP followed by trabeculectomy with MMC. NVG was secondary to proliferative diabetic retinopathy (23 eyes) and central retinal vein occlusion (7 eyes). Kaplan-Meier survival analysis of the surgical outcome was performed. Operative success was defined as an intraocular pressure (IOP) of ≤21 mmHg without medical therapy. Results Kaplan-Meier cumulative success rates at the 6-, 12-, and 24-month intervals were 86.5%, 74.7%, and 57.6%, respectively. Pseudophakia was the only identified significant risk factor for failure (p=0.0138; Fisher exact test). Additional surgical procedures were performed in 8 (26.6%) eyes. The mean IOP decreased from 41.0±10.2 mmHg to 18.2±9.2 mmHg (p<0.001; Wilcoxon signed rank test). The number of anti-glaucoma medications was reduced from 3.1±0.5 preoperatively to 0.3±0.7 postoperatively (p<0.001; Wilcoxon signed rank test). Twenty-four (80%) eyes were classified as surgical success after a mean follow-up period of 17.3±22.1 months. Twenty-two (73.3%) eyes had improved vision or retained preoperative vision. Conclusions Full PRP followed by trabeculectomy with MMC can effectively reduce the elevated IOP associated with NVG. Presence of pseudophakia is a significant negative predictor of surgical outcome.

Lack of association between LOXL1 gene polymorphisms and primary open angle glaucoma in the Saudi Arabian population.

Purpose: To investigate whether major single nucleotide polymorphisms (SNPs) in the LOXL1 gene associated with pseudoexfoliation glaucoma are associated with primary open angle glaucoma (POAG) in the Saudi Arabian population. Methods: The regions of the LOXL1 gene associated with pseudoexfoliation glaucoma, encompassing the three common SNPs, (rs1048661, rs3825942 and rs2165241), were sequenced in a Saudi Arabian dataset consisting of 96 POAG cases and 101 healthy controls. Results: The allele frequency of the G exfoliation risk allele for SNP rs1048661 in POAG cases and controls was 0.75 and 0.76 (p = 0.886), respectively and the allele frequency difference was not statistically significant (p = 0.866). There was no statistically significant difference in the genotypes between patients and controls (p = 0.261 and 0.156 for genotypes G/G and G/T respectively). As for SNP rs3825942, the frequency of the “G” allele in the POAG patients was comparable to that in the controls (p = 0.477) and there was no statistically significant difference in genotype G/G and A/G frequency in the study groups. As for SNP rs2165241, the “T” allele frequency in the POAG patients (0.46) was slightly higher than the frequency in controls (0.39), but this difference was not statistically significant (p = 0.176). Conclusion: The Saudi Arabian POAG population, similar to all other populations studied to date, demonstrates no association with SNPs associated with pseudoexfoliation glaucoma.

Long-term Evaluation of Efficacy and Safety of Deep Sclerectomy in Uveitic Glaucoma

Abstract Purpose: To assess long-term efficacy and safety of deep sclerectomy (DS) in uveitic glaucoma. Patients and methods: Thirty-three consecutive eyes (21 patients) with uveitic glaucoma underwent DS with mitomycin C and implant. Goniopuncture (GP) was done for uncontrolled postoperative intraocular pressure (IOP). Results: Mean (±SD) follow-up was 33.2 (±19.8) months. IOP was reduced from a mean preoperative value of 37.2 to postoperative value of 14.7 mmHg (p < 0.0001). Complete success was achieved in 24/33 eyes (72.7%); qualified success was obtained in 7/33 eyes (21.2%). Neodymium:YAG GP was performed in 12 eyes. Postoperative complications included cataract progression in 9 eyes, transient hypotony in 6 eyes, shallow choroidal effusions in 4 eyes, hypotony with persistent maculopathy in 1 eye, hyphema in 1 eye, and decompression retinopathy in 1 eye. Conclusion: DS is safe and effective in patients with uveitic open-angle glaucoma. However, laser goniopuncture is frequently needed to improve the outcome.