Saleh A. Al-Obeidan

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.

Incidence, management, and visual outcomes of buttonholed laser in situ keratomileusis flaps

PURPOSE: To describe the incidence, management, and visual outcomes of buttonholed laser in situ keratomileusis (LASIK) flaps. SETTING: Private practice, Riyadh, Saudi Arabia. METHODS: This retrospective review identified eyes that developed buttonholed flaps during LASIK. Preoperative, intraoperative, and postoperative data were obtained to identify factors predictive of this complication. RESULTS: Of 4250 primary LASIK procedures, 17 eyes (0.4%) with buttonholed flaps were identified. Buttonholes occurred with the Hansatome microkeratome in 64.7% of eyes and with the Moria microkeratome in 35.3% of eyes, the incidence of buttonholed flaps was 0.62% and 0.19%, respectively (P = .03). Laser ablation was performed at the same time as buttonhole formation in 8 eyes (47.1%) and was aborted in the other eyes. Retreatment was performed in 10 eyes (58.8%); of retreated eyes, 6 had repeat LASIK and 3 had surface ablation. The final spherical equivalent refraction was −0.38 diopter ± 0.79 (SD). Two eyes had a final loss of more than 2 lines of best corrected visual acuity (BCVA). The mean loss of BCVA lines was 0.72 in eyes that had complete LASIK, 0.62 in eyes that had aborted LASIK followed by retreatment with repeat LASIK, and 0.80 in eyes that had aborted LASIK followed by retreatment with surface ablation. CONCLUSIONS: Buttonholed flaps occurred more frequently in the second of 2 consecutively treated eyes. Microkeratomes that produce a larger diameter flap were more likely to produce flap buttonholes. The least loss of BCVA was achieved when LASIK was aborted and then repeated after refractive stability.

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.

Cytokine and CXC chemokine expression patterns in aqueous humor of patients with presumed tuberculous uveitis.

Aqueous humor (AH) samples from 14 patients with presumed tuberculous uveitis (PTU), and 30 control patients were assayed for the proinflammatory cytokines interleukin IL-4, IL-12, IL-15, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, the immunosuppressive cytokine IL-10, and the chemokines GRO-α/CXCL1, IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and SDF-1/CXCL12 with the use of a multiplex assay. Among cytokines, IL-4 and IL-12 were not detected. IL-15, IL-17, IFN-γ, TNF-α and IL-10 levels in AH were significantly higher in patients than in controls (p<0.001; p=0.004; p<0.001; p<0.001; p<0.001, respectively). Among chemokines, SDF-1 levels did not differ significantly between patients and controls, whereas GRO-α, IL-8, MIG and IP-10 levels were significantly higher in patients than in controls (p=0.001; p<0.001; p<0.001; p<0.001, respectively). Mean GRO-α levels in AH of PTU patients were 6-fold higher than IL-8 levels and mean IP-10 levels were 15-fold higher than MIG levels. Clinical disease activity correlated significantly with the levels of IL-15, IFN-γ, TNF-α and IP-10. Logistic regression analysis demonstrated a significant positive association between PTU and high levels of IFN-γ, IL-8, MIG and IP-10. These data suggest that both T helper (Th) Th(1) and Th(17) cells are involved in PTU and that the cytokine profile is polarized toward a Th(1) response. GRO-α and IP-10 might be involved in neutrophil and activated T lymphocyte chemoattraction in PTU, respectively.

Retinal periphlebitis resembling frosted branch angiitis with nonperfused central retinal vein occlusion

Purpose To report the unusual association between severe retinal periphlebitis resembling frosted branch angiitis and nonperfused central retinal vein occlusion (CRVO). Methods Observational case reports. Results Patient 1 was a 28-year-old man who presented with extensive sheathing involving all retinal veins in one eye followed by nonperfused CRVO. Twenty-seven months after initial presentation, he developed perfused CRVO in the other eye followed by periphlebitis that progressed into nonperfused CRVO. Patient 2 was a 47-year-old man who presented with unilateral severe retinal periphlebitis associated with nonperfused CRVO. Despite systemic administration of corticosteroid therapy, rubeosis iridis developed in both patients and neovascular glaucoma developed in Patient 1 despite full panretinal photocoagulation. Extensive systemic workup and coagulation studies were unremarkable except for the presence of antiphospholipid antibodies in both patients and elevated plasma homocysteine level in Patient 2. Conclusions Severe retinal periphlebitis complicated by nonperfused CRVO is associated with poor visual outcome despite appropriate medical and surgical treatment.

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.

Comparison of central corneal thickness measurements using Pentacam and ultrasonic pachymetry in post-LASIK eyes for myopia.

Purpose To compare central corneal thickness (CCT) measurements obtained using the Pentacam Scheimpflug system with those obtained using DGH ultrasound pachymetry (UP) in post-laser in situ keratomileusis (LASIK) eyes for myopia. Methods In a prospective study, measurement agreement was assessed in 143 eyes of 72 post-LASIK patients using both the Pentacam and UP at the Eye Consultants Center in Riyadh, Saudi Arabia. Results The mean CCT was 522±42.2 μm with the Oculus Pentacam and 516.2±40.6 μm with UP. The Bland-Altman plot showed that the mean ± SD for the differences between the 2 devices was 5.8±13.6 μm, with 95% confidence interval limits ranging from −20.9 μm to 32.6 μm. A test of statistical significance indicated that the mean differences of 5.8±13.6 μm differed significantly from zero (p<0.001; Wilcoxon signed-rank test), thus indicating that the Pentacam measurements tended to overestimate CCT compared with UP. Analysis of regression showed a high correlation between the values obtained with both devices (r=0.947, p<0.001). Conclusions In post-LASIK myopic eyes, although a high correlation has been shown between Pentacam and UP measurements, Pentacam tends to overestimate CCT compared to UP. Pentacam probably cannot be used interchangeably with UP in post-LASIK eyes for myopia.

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.