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

Analysis of CYP1B1 sequence alterations in patients with primary open-angle glaucoma of Saudi origin

Khaled K Abu-Amero, Tahira Sultan, Saleh A Al-Obeidan, Altaf A Kondkar Glaucoma Research Chair, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia Abstract: Cytochrome P450 Family 1 Subfamily B Member 1 (CYP1B1; OMIM# 601771) gene encodes one of the cytochrome P450 family of enzymes. CYP1B1 mutations have been associated primarily with primary congenital glaucoma (PCG). Similar studies were reported in juvenile open-angle glaucoma, Rieger’s and Peters anomalies. Reports of likely pathogenic sequence alterations in families affected with adult-onset primary open-angle glaucoma (POAG) triggered this investigation. We screened unrelated POAG cases and healthy controls for mutations in CYP1B1 using automated Sanger sequencing to identify five known polymorphisms and one CYP1B1 mutation (p.G61E) in a heterozygous status. The p.G61E mutation is known to cause PCG in a homozygous or compound heterozygous form, and thus, its presence here in a heterozygous form indicates carrier status. These findings suggest that CYP1B1 may have no major role in the pathogenesis of POAG, at least, in the Saudi population. However, further investigations are needed to validate these findings in a larger cohort. Keywords: CYP1B1, genetics, mutation screening, POAG, Saudi Arabi

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. Methods: A prospective cohort of 120 children presenting with glaucoma to King Abdul Aziz University Hospital (KAUH) was subjected to nonpenetrating deep sclerectomy surgery (NPDS). Eventually, 57 patients had macro perforation and converted to penetrating deep sclerectomy (PDS). Intra-operative mitomycin C (MMC) 0.2mg/ml was used in all patients. Pre- and postintervention glaucoma indices were assessed. Complete success rate (CSR) was identified as achieving an end-point of intraocular pressure <21 without any antiglaucoma medications. Data were analysed to compare pre- and postintervention changes and to compare both procedures. Results: After follow-up of 35.8 (34.5) months, NPDS procedure went smooth in 74 eyes of 63 patients. The complete success rate was 79.7%, whereas the overall success rate was 82.4%. Thirteen cases failed. The probability to survive was 74.6% after the 12th month. The mean intraocular pressure (IOP) went down to 11.53.0mmHg compared to 31.9mmHg preoperatively. Comparing cases with NPDS to those with PDS, the magnitude of IOP reduction (15.8) was higher than that of the PDS (14.8); however, this difference was not statistically significant (p=0.259). Apart from involuntary perforation of trabeculodescemetic window (TDW), neither intra-operative nor early postoperative complications were observed. Conclusions: Deep sclerectomy in childhood glaucoma can effectively reduce the IOP, without the occurrence of serious complications that are commonly seen after trabeculotomy or combined trabeculotomy trabeculectomy

Elevated levels of plasma tumor necrosis factor alpha in patients with pseudoexfoliation glaucoma

Altaf A Kondkar,1 Taif A Azad,1 Faisal A Almobarak,1 Hatem Kalantan,1 Saleh A Al-Obeidan,1 Khaled K Abu-Amero1,2 1Glaucoma Research Chair, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA Background: Tumor necrosis factor alpha (TNF-&alpha;) is a pro-inflammatory cytokine, which plays a role in glaucomatous neurodegeneration. Based on the plausible role of inflammation in the pathogenesis of pseudoexfoliation glaucoma (PEG), we investigated whether there is any relationship between the levels of plasma TNF-&alpha; and PEG or any of its clinical indices in comparison to normal controls.Methods: The study was designed as a retrospective analysis. Plasma samples from 49 PEG patients and 88 non-glaucomatous controls were evaluated for TNF-&alpha; levels using an enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicates on a biochemical/ELISA analyzer.Results: The two study groups were similar in age, sex and systemic disease distribution. The mean TNF-&alpha; concentration was significantly higher in the PEG patients (5.54&plusmn;4.58 pg/mL) than in the control subjects (0.93&plusmn;1.49 pg/mL; 95% confidence interval [CI] =3.50&ndash;5.72; p=0.000). The overall dose&ndash;response trend was significant (&chi;2=57.07, df=2; p=0.000). A moderate positive and significant correlation was seen between TNF-&alpha; level and cup/disc ratio, an important clinical index for PEG. Besides, binary logistic regression analysis showed that the risk of PEG was most significantly affected by TNF-&alpha; level as compared to no association with age and sex. In receiver operating characteristic analysis, the area under the curve was 0.777 (95% CI =0.682&ndash;0.872) and statistically significant (p=0.000).Conclusion: Elevated systemic levels of inflammatory marker, TNF-&alpha;, are associated with PEG and may possibly serve as a biomarker for undiagnosed early glaucoma and/or as a marker for disease progression. Keywords: glaucoma, inflammation, oxidative stress, pseudoexfoliation, TNF-&alpha

Association of increased levels of plasma tumor necrosis factor alpha with primary open-angle glaucoma

Altaf A Kondkar, Tahira Sultan, Faisal A Almobarak, Hatem Kalantan, Saleh A Al-Obeidan, Khaled K Abu-Amero Glaucoma Research Chair, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia Purpose: Retinal ganglion cell (RGC) death is a key feature of glaucoma. Elevated levels of tumor necrosis factor alpha (TNF-&alpha;), a pro-inflammatory cytokine, can induce RGC apoptosis and play a critical role in glaucomatous neurodegeneration. Based on the possible role of inflammation and oxidative stress in the pathogenesis of primary open-angle glaucoma (POAG), we investigated the association between plasma levels of TNF-&alpha; and POAG or its clinical indices in comparison to non-glaucomatous controls. Patients and methods: In a case&ndash;control retrospective cohort of 51 POAG cases and 88 controls, plasma TNF-&alpha; levels were measured using an enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicates on an automated ELISA analyzer. Results: Mean TNF-&alpha; level was significantly elevated in POAG cases (1.88 &plusmn; 2.17 pg/mL) than the controls (0.93 &plusmn; 1.49 pg/mL; p = 0.003). The overall dose&ndash;response trend was significant (&Chi;2 = 6.12, df = 2; p = 0.047). No statistical difference was seen in age, gender and systemic disease distribution. A modest negative and significant correlation was seen between TNF-&alpha; level and number of antiglaucoma medications, an important clinical index of POAG severity. Moreover, logistic regression analysis showed that the risk of POAG was most significantly affected by TNF-&alpha; level and not by age and sex. Conclusion: High systemic level of an inflammatory cytokine, TNF-&alpha;, is associated with POAG; however, its possible use as a biomarker for early glaucoma diagnosis and/or disease severity needs further investigation. Keywords: apoptosis, biomarker, cytokines, ELISA, inflammation, neurodegeneration, oxidative stres