Search Results (9)

Background and Objectives: Open-angle glaucoma subtypes share a structural phenotype but differ in pathophysiology: pseudoexfoliative glaucoma (PXG) involves vascular endothelial dysfunction associated with deposition of exfoliative material, whereas normal-tension glaucoma (NTG) reflects primary vascular dysregulation in the absence of elevated intraocular pressure. We characterized subtype-specific OCT angiography (OCTA) profiles obtained from a 3 × 3 mm macular scan and evaluated their discriminatory power for pairwise subtype classification. Materials and Methods: This was a single-center, cross-sectional study of 304 eyes: 198 glaucomatous eyes—primary open-angle glaucoma (POAG, glaucoma simplex in our clinical nomenclature), n = 102; PXG (glaucoma capsulare), n = 68; NTG (glaucoma sine tensio), n = 28—and 106 healthy controls. The Cirrus HD-OCT 5000 AngioPlex 3 × 3 mm OCTA protocol was used to assess vessel density (VD), perfusion density, foveal avascular zone (FAZ) morphology, ganglion cell complex (GCC), and retinal nerve fiber layer (RNFL) thickness. Analyses included Kruskal–Wallis tests with Bonferroni post hoc correction, ROC analysis with DeLong comparison of combined versus structural-only models, multivariate regression, and an exploratory XGBoost classifier with SHAP-based interpretation. Results: VD Inner and Perfusion Inner were lower in PXG (16.37 ± 3.33%; 0.31 ± 0.05) than in POAG (18.73 ± 3.41%; 0.34 ± 0.05; both p < 0.001); Perfusion Inner was also lower than in NTG (p < 0.05). FAZ Area was largest in NTG (0.27 ± 0.11 mm²) and greater than in PXG (0.19 ± 0.08; p < 0.01); FAZ Circularity differed across subtypes (p < 0.001). Combined OCTA–structural models outperformed structural-only models for POAG vs. PXG (DeLong p = 0.002) and for PXG vs. NTG (AUC = 0.770; p = 0.010). Sector-resolved Spearman analysis revealed subtype-specific coupling: in NTG, VD Inner and Perfusion Inner correlated with the inferior RNFL (r = 0.53 and r = 0.52; both p < 0.01); in PXG, coupling shifted nasally (r = 0.41 and r = 0.46; both p < 0.001). The exploratory XGBoost classifier separated glaucoma from controls with an internal cross-validated AUC of 0.975 ± 0.008 (5-fold CV; not externally validated); FAZ Circularity (mean |SHAP| = 0.418) and FAZ Area (0.411) were the top inter-subtype features, supported by case-level SHAP. RNFL avg and average GCC independently predicted MD across subtypes; in PXG, Perfusion Inner also predicted MD (β = −32.78; p = 0.032). Conclusions: In this single-center, cross-sectional cohort, OCTA revealed subtype-associated macular microvascular profiles that are complementary to structural OCT. Reduced vessel and perfusion density characterized PXG, whereas FAZ enlargement and reduced circularity distinguished NTG and PXG. Vascular–structural coupling was nasal-predominant in PXG and inferior-predominant in NTG. Combined multimodal models outperformed structural-only approaches. Macular perfusion additionally predicted MD in PXG. The XGBoost/SHAP analysis is exploratory; prospective and externally validated studies are required before clinical deployment. Full article

Most glaucoma genetic data derive from European and East Asian cohorts, leaving high-consanguinity Middle Eastern populations under-characterized. This review synthesizes 33 Saudi-specific genetic studies (2014–2024, >9000 participants) to define a population-level glaucoma genetic architecture that diverges substantially from global models and carries direct precision medicine implications. Three findings distinguish the Saudi landscape. First, CYP1B1 functions as the dominant causal gene across both primary congenital glaucoma (PCG) and juvenile-onset open-angle glaucoma (JOAG), accounting for 76–86% of cases, with two founder alleles, p.G61E (penetrance 87.7%) and p.R469W (penetrance 93%), driving severe, early-onset phenotypes. Critically, MYOC and LTBP2, the primary JOAG genes in other populations, carry no pathogenic variants in Saudi cohorts, rendering standard multi-ethnic gene panels inadequate for this population. Second, adult-onset glaucoma follows a distinct polygenic architecture where APOE ε2 confers a near five-fold risk for primary angle-closure glaucoma (OR = 4.82), an effect absent or inconsistent in global datasets, and NOS3 variants associate with primary open-angle glaucoma specifically in men, a sex-stratified signal unreported outside Saudi cohorts. The MTHFR T/T genotype, common in European and Asian POAG patients, is entirely absent locally, indicating population-specific allelic distributions that alter folate-metabolism-related optic nerve susceptibility. Third, ACVR1 rs12997 associates across POAG, PACG, and pseudoexfoliation glaucoma (PXG), positioning BMP/TGF-β signaling as a shared mechanistic pathway spanning multiple subtypes. These findings argue for Saudi-specific genetic panels, CYP1B1-centered cascade testing in consanguineous families, and polygenic risk models incorporating local allele frequencies rather than globally derived weights. Full article

Background/Objectives: This study aims to evaluate the long-term efficacy and safety of ab interno techniques using minimally invasive glaucoma surgery (MIGS), specifically XEN gel stent implantation, by evaluating its 2-year outcomes in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). Methods: This retrospective single-center study consecutively included 31 eyes of 31 patients with POAG or PXG who underwent XEN gel stent implantation. Patients were followed for 24 months, with assessments at multiple time points. Success was defined as achieving an IOP of less than 14 mmHg and a reduction of more than 20% from preoperative IOP without additional glaucoma surgery. Bleb morphology was evaluated using anterior segment optical coherence tomography (AS-OCT) and slit-lamp photographs. Postoperative interventions and complications were also recorded. Results: At 24 months, complete success and qualified success rates were 35.5% (11/31) and 51.6% (16/31), respectively. There was no difference in surgical success rates at 2 years based on the tip location (intraconjunctiva, intratenon, and uviform) on the 1st postoperative day. Patients with high sparse wall on AS-OCT imaging or avascular bleb morphology via slit-lamp photography at 6 months postoperatively had higher complete success rates at 2 years than those without (p = 0.007, p = 0.009, respectively). Patients with avascular bleb types at 6 months postoperatively had higher qualified success rates at 2 years compared with the vascular types (p = 0.038). Needling was performed in 32.3% of eyes, with secondary surgical procedures required in 16.1% of eyes. The most common adverse event was hypotony, occurring in 67.7% of eyes on the 1st postoperative day but resolving within 6 months. Conclusions: The ab interno XEN gel stent is an effective and minimally invasive option for managing POAG and PXG, with long-term success predicted by the AS-OCT assessment of bleb morphology at 6 months. Proactive postoperative management, emphasizing early intervention and monitoring, is crucial for maintaining optimal outcomes. Full article

Objective: This study aimed to investigate the structural, vascular, and biochemical alterations in patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PXG) and to evaluate the associations between serum biomarkers, the retinal nerve fiber layer (RNFL), choroidal thickness (CT), and vessel density (VD) in these groups. Methods: All subjects underwent spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) to assess RNFL thickness, CT, and VD. Serum levels of inflammatory and oxidative stress biomarkers—including malondialdehyde (MDA), glutathione (GSH), interleukin-6 (IL-6), nitric oxide (NO), inducible NO synthase (iNOS), galectin-3, and SCUBE-1—were analyzed, and regression and ROC curve analyses were performed to evaluate predictive value and diagnostic performance. Results: A total of 80 patients were included and are listed as follows: 25 controls, 30 with PES, and 25 with PXG. There were no significant differences among groups in terms of age or gender. RNFL thickness, CT, and VD were significantly reduced in the PXG group compared to the PES and control groups (p < 0.001). PXG patients showed the most pronounced reductions in both peripapillary and macular CT, as well as superficial and deep VD. Serum iNOS, SCUBE-1, galectin-3, and MDA levels were significantly elevated in PXG, while GSH levels were lower (p < 0.001); NO levels showed no significant differences. In the PES and PXG groups, several ocular parameters correlated significantly with serum biomarkers, particularly iNOS, MDA, and GSH. Regression analysis in PXG patients identified iNOS and MDA as significant predictors of RNFL thickness and VD. ROC analysis demonstrated that MDA and GSH exhibited the highest diagnostic accuracy among the tested biomarkers for distinguishing PXG patients from controls. Conclusions: PXG is associated with significant structural, vascular, and biochemical alterations, including reduced RNFL thickness, choroidal thinning, and decreased VD. Altered serum levels of MDA and GSH were significantly associated with these ocular changes and demonstrated the highest diagnostic accuracy among the biomarkers evaluated. These findings support their potential utility as non-invasive biomarkers for distinguishing PXG from PES and healthy controls and for monitoring disease progression. Full article

Background and Objectives: The search for less invasive and more effective methods in the surgical treatment of glaucoma continues. For advanced glaucoma, all surgical options carry a high risk of complications and vision loss. The aim of this study was to evaluate the outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) surgery in advanced glaucoma. Materials and Methods: In this retrospective study, advanced open-angle glaucoma (OAG) patients were followed up on the 1st day, 1st week, and 1st month, then monthly for 6 months and then every 3 months after GATT surgery. Outcomes at 6 and 24 months were analyzed to evaluate early and long-term surgical success. Surgical success was defined as a ≥20% intraocular pressure (IOP) reduction from baseline, final IOP ≤21 mmHg, and no need for additional glaucoma surgery. Pre- and postoperative measurements included IOP, retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT), peripapillary vessel density (VD) via optical coherence tomography angiography, and visual field (VF) tests. Results: Among 44 advanced glaucoma patients (61.4% pseudoexfoliative glaucoma), surgical success was 81.8% at 6 months and 76.5% at 24 months. Mean IOP decreased from 26.9 ± 10.4 mmHg preoperatively to 13.8 ± 8.3 mmHg at 3 months (40.36% reduction, p < 0.001) and 13.9 ± 4.0 mmHg at final follow-up (42.12% reduction, p < 0.001). Disease progression was absent in 66% of patients. BCVA initially declined (0.61 ± 0.36 to 0.41 ± 0.33 logMAR at 3 months, p = 0.011) but returned to baseline (0.59 ± 0.35 logMAR at final follow-up, p = 1.00). Glaucoma medications decreased by 66.2%, and peripapillary VD remained stable (p > 0.05). The most common complication was mild hyphema (34.1%), which resolved without intervention; only one patient (2.3%) experienced vision-threatening complications (wipe-out phenomenon in degenerative myopia). Conclusions: GATT is a safe and effective alternative to trabeculectomy for advanced glaucoma, achieving significant IOP reduction with stable VD and low rates of serious complications. This study provides novel insights by offering long-term (24-month) follow-up data, evaluating peripapillary VD stability, and specifically assessing GATT outcomes in an advanced glaucoma cohort. However, caution is advised in patients with additional ocular pathologies. Full article

Objectives: To investigate whether phakia affects the outcome of XEN-45 gel stent implantation in the treatment of pseudoexfoliative glaucoma (PXG). Methods: A retrospective, comparative cohort study of 30 phakic and 55 pseudophakic PXG patients who received the XEN-45 gel stent at a tertiary centre. The primary outcome measure was two-year success defined as a ≥20% lowering of intraocular pressure (IOP) and a target IOP of 6–21 mmHg. Success was complete without and qualified irrespective of antiglaucoma medication use. Further glaucoma surgery other than needling was regarded as a failure. The secondary outcome measures included changes in IOP, revision and complication rates. Results: The complete two-year success rates were 70% and 59% in the phakic and pseudophakic groups, respectively (p = 0.75, log-rank test), and the qualified rates were 80% and 72%, respectively (p = 0.89). The median IOP reduction from baseline was 54% in phakic, and 46% in pseudophakic eyes. While needling rates were similar, the incidence of early incisional bleb revisions was significantly higher in the phakic eyes (13% vs. 0% within 3 months; p = 0.0098, chi-square). Increasing after a year, significantly more pseudophakic eyes failed due to secondary glaucoma surgery (16% vs. 0%; p = 0.0191). Conclusions: The XEN-45 gel stent offers equally effective IOP control for both phakic and pseudophakic patients. However, the onset of bleb revisions and the necessity for secondary glaucoma surgery differed significantly between the groups. Full article

This study investigated the association between apolipoprotein E (APOE) gene polymorphisms (rs429358 and rs7412) and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) in a Saudi cohort. Genotyping of 437 DNA samples (251 controls, 92 PACG, 94 PXG) was conducted using PCR-based Sanger sequencing. The results showed no significant differences in the allele and genotype frequencies of rs429358 and rs7412 between the PACG/PXG cases and controls. Haplotype analysis revealed ε3 as predominant, followed by ε4 and ε2 alleles, with no significant variance in PACG/PXG. However, APOE genotype analysis indicated a significant association between ε2-carriers and PACG (odds ratio = 4.82, 95% CI 1.52–15.26, p = 0.007), whereas no notable association was observed with PXG. Logistic regression confirmed ε2-carriers as a significant predictor for PACG (p = 0.008), while age emerged as significant for PXG (p < 0.001). These findings suggest a potential role of ε2-carriers in PACG risk within the Saudi cohort. Further validation and larger-scale investigations are essential to elucidate the precise role of APOE in PACG pathogenesis and progression. Full article

Purpose: To compare the differences between eyes with pseudoexfoliative glaucoma (PXG) when they are divided into two groups (hypertensive PXG and normotensive PXG) according to the intraocular pressure (IOP). Methods: This is a retrospective study. Data from 86 hypertensive PXG eyes and 80 normotensive PXG eyes were included. Hypertensive PXG was defined as PXG with IOP ≥ 22 mmHg, and normotensive PXG was defined as with IOP ≤ 21 mmHg). Central corneal thickness (CCT) was measured by ultrasound pachymetry. Lamina cribrosa thickness (LT) was evaluated using swept-source optical coherence tomography. Results: No significant differences were observed between hypertensive and normotensive PXG in terms of age, gender, axial length, hypertension, or diabetes. Normotensive PXG eyes had thinner CCT than hypertensive PXG eyes (p = 0.02). To compare LT, a sub-analysis was performed after matching age, VF MD and retinal nerve fiber layer thickness. The normotensive PXG group (n = 32) demonstrated significantly thinner LT compared with the hypertensive PXG group (n = 32) at similar ages and levels of glaucoma severity (p < 0.001). Conclusions: Eyes with normotensive PXG demonstrated thinner CCT and LT compared with those with hypertensive PXG, suggesting structural vulnerability to glaucoma. Full article

We investigated the association between DICER1 (rs3742330) and DROSHA (rs10719) polymorphisms and pseudoexfoliation glaucoma (PXG) and related clinical phenotypes in a Saudi cohort. In a retrospective case-control study, TaqMan real-time, PCR-based genotyping was performed in 340 participants with 246 controls and 94 PXG cases. The minor (G) allele frequency of rs3742330 in PXG (0.03) was significantly different from that in the controls (0.08) and protective against PXG (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.16–0.92), p = 0.017). Similarly, the rs3742330 genotypes showed a significant protective association with PXG in dominant (p = 0.019, OR = 0.38, 95% CI = 0.15–0.92), over-dominant (p = 0.024, OR = 0.39, 95% CI = 0.16–0.95), and log-additive models (p = 0.017, OR = 0.38, 95% CI = 0.16–0.92). However, none remained significant after an adjustment for age, sex, and multiple testing. Rs10719 in DROSHA did not show any significant allelic or genotype association with PXG. However, a protective effect of the GA haplotype in DICER1 and DROSHA and PXG (p = 0.034) was observed. Both polymorphisms showed no significant effect on intraocular pressure and the cup–disk ratio. In conclusion, we report a significant genetic association between variant rs3742330 in DICER1, a gene involved in miRNA biogenesis, and PXG. Further investigation in a larger group of patients of different ethnicities and functional studies are warranted to replicate and validate its potential role in PXG. Full article