Search Results (328)

Background/Objectives: To compare the five-year efficacy and safety of the 63 µm (XEN63) vs. 45 µm (XEN45) XEN^® Gel Stent in patients with open-angle glaucoma (OAG). Methods: This retrospective matched (1:1) cohort study included adults with OAG who underwent standalone ab interno implantation of the XEN63 or the XEN45 between 2014 and 2021 at a tertiary referral center in Belgium. The primary outcome was IOP at five years. The secondary outcomes included surgical success, topical medication use, postoperative hypotony, complications and interventions. Results: Thirty eyes of 30 patients (15 XEN63 and 15 XEN45) were analyzed. The baseline characteristics were comparable. At five years, the mean IOP did not differ between the XEN63 and the XEN45 (11.5 vs. 11.0 mmHg; p = 0.54). The XEN63 demonstrated higher complete success rates than the XEN45 for both the IOP < 18 mmHg (10 vs. four eyes; p = 0.016) and <15 mmHg criteria (10 vs. three eyes; p = 0.003). The topical medication use was low and comparable (0.6 vs. 0.9 medications; p = 0.57). The numerical (13 vs. five eyes; p = 0.008) and symptomatic (six vs. two eyes; p = 0.2) hypotony were more frequent after the XEN63 implantation. The two eyes with XEN63 and none with XEN45 experienced clinically significant hypotony. The needling procedures and secondary glaucoma surgeries were more frequent after the XEN45. Conclusions: The XEN63 implantation was associated with higher long-term success rates and also with a higher incidence of early postoperative hypotony. These findings indicate a trade-off between efficacy and safety and suggest that careful patient selection and postoperative management are essential when considering larger lumen subconjunctival drainage devices. Full article

Background: To evaluate the effects of a preservative-free artificial tear formulation containing trehalose, sodium hyaluronate, and N-acetyl-aspartyl-glutamate (NAAGA) on ocular surface parameters and quality of life in patients with primary open-angle glaucoma (POAG) treated with preserved versus preservative-free prostaglandin analogues. Methods: For this prospective, observational clinical study, thirty-eight patients (76 eyes) with POAG receiving stable topical prostaglandin therapy were enrolled and divided into two groups: preserved prostaglandins (Group 1, n = 44) and preservative-free prostaglandins (Group 2, n = 32). All patients received adjunctive preservative-free artificial tears (trehalose, sodium hyaluronate, NAAGA) three times daily for one month. Assessments at baseline (T0) and 1 month (T1) included best-corrected visual acuity (BCVA), intraocular pressure (IOP), contrast sensitivity, Schirmer test, tear break-up time (BUT), Efron grading scale, Ocular Surface Disease Index (OSDI), visual field (VF) indices (Mean Deviation (MD), Pattern Standard Deviation (PSD), Visual Field Index (VFI)), and quality of life (QoL) measured using Visual Analogue Scales (VAS). Results: After 1 month, both groups demonstrated significant improvement in ocular surface parameters. Schirmer test increased by approximately 4–5 mm (p = 0.001 in both groups), and BUT improved by 5 s (p = 0.001 in both groups). OSDI scores significantly decreased (Group 1: –18.5; Group 2: –23; p = 0.001 for both), and Efron grading significantly improved (p = 0.001 in both groups). Artificial tears-related QoL markedly increased in both groups (p = 0.001), while pathology-related QoL remained unchanged. IOP showed a modest but significant reduction in both groups (Group 1 p = 0.011; Group 2 p = 0.003), without intergroup differences. VFI significantly improved in both groups from T0 to T1 (Group 1 p = 0.013; Group 2 p = 0.04). Group 1 also showed an improvement in terms of PSD (p = 0.025). Conclusions: Adjunctive treatment with preservative-free artificial tears containing trehalose, sodium hyaluronate, and NAAGA significantly improved tear film stability VF indexes, ocular surface signs and symptoms, and patient-reported QoL in POAG patients treated with prostaglandins, regardless of preservative status. Routine ocular surface optimization should be considered an integral component of comprehensive glaucoma management. 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: To evaluate the short-term effects of direct selective laser trabeculoplasty (DSLT) on retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG). Methods: This retrospective, single-center study included 45 eyes of 45 patients with OHT or POAG who underwent DSLT at Shaare Zedek Medical Center between February 2024 and February 2025. The primary outcome was the change in RNFL and GCL thickness, as measured by spectral-domain optical coherence tomography (SD-OCT) before and two months after treatment. Secondary outcomes included intraocular pressure (IOP) reduction, corrected distance visual acuity (CDVA), and safety. Only high-quality OCT scans (quality score > 25) were included in the analysis. Results: OCT analysis revealed no statistically significant changes in the inner retinal structure two months post-treatment. The mean RNFL thickness was 77.1 ± 17.2 µm at baseline and 77.4 ± 17.3 µm at follow-up (p = 0.285). The mean GCL thickness remained unchanged (42.4 ± 11.6 µm vs. 42.4 ± 11.3 µm, p = 0.750). CDVA remained stable (0.2 ± 0.4 vs. 0.2 ± 0.4 logMAR; p = 0.351), and no vision-threatening complications were observed. Mean IOP decreased significantly from 19.7 ± 4.0 mmHg at baseline to 16.2 ± 3.5 mmHg at two months (p < 0.001). The mean total laser energy delivered was 196.5 ± 10.2 mJ (range: 176–210 mJ). Conclusions: DSLT was not associated with significant short-term changes in RNFL or GCL thickness, supporting its structural safety in patients with OHT or glaucoma. Further long-term studies are warranted to determine the durability of these findings and the potential neuroprotective effects of DSLT. Full article

Background: Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide, characterized by progressive optic nerve degeneration and marked molecular heterogeneity. Increasing evidence indicates that metabolic dysregulation and immune remodeling contribute to POAG pathogenesis; however, the underlying regulatory networks and reliable diagnostic biomarkers remain incompletely defined. Methods: Bulk transcriptomic and single-cell RNA sequencing (scRNA-seq) datasets of trabecular meshwork tissues were retrieved from Gene Expression Omnibus (GEO). Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify disease-associated modules. A machine learning framework was applied to construct classification models. Estimated immune-cell fractions were assessed using CIBERSORT, followed by pathway and transcription factor analyses. Single-cell analysis was conducted to examine the cell type-specific expression patterns. Results: A total of 195 differentially expressed genes were identified between POAG and control samples. WGCNA revealed a lactylation-related module strongly correlated with disease status. Machine learning identified S100A2 and S100A14 as candidate diagnostic biomarkers with consistent classification performance across datasets. Immune infiltration analysis suggested alterations in the immune microenvironment in POAG. Single-cell data showed that the model genes exhibited sparse but non-uniform expression across cell populations. Conclusions: This integrative analysis prioritizes S100A2 and S100A14 as candidate diagnostic biomarkers for POAG and indicates potential associations with immune-metabolic regulatory mechanisms. Full article

Background: In this study, we aimed to evaluate and compare the diagnostic performance of peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell–inner plexiform layer (GCIPL) thickness, and GCIPL asymmetry parameters in differentiating healthy eyes from primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG), and secondary open-angle glaucoma (SOAG). Methods: This retrospective study included 204 eyes of 204 patients categorized into four groups: healthy controls (n = 46), PACG (n = 53), POAG (n = 58), and SOAG (n = 47). All participants underwent spectral-domain optical coherence tomography (OCT). Peripapillary RNFL thickness, sectoral and average GCIPL thickness, and GCIPL-derived asymmetry ratios were analyzed. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Results: Diagnostic accuracy varied according to glaucoma subtype. In distinguishing POAG from healthy controls, the average RNFL thickness (area under the ROC curve [AUC] = 0.82) demonstrated the highest diagnostic performance, followed by the superotemporal, inferotemporal, and average GCIPL thickness parameters. In contrast, no parameter reached an AUC of ≥0.80 in the PACG or SOAG comparisons. GCIPL asymmetry ratios exhibited limited discriminative ability across most analyses. Subtype differentiation was modest; POAG versus SOAG comparisons yielded AUC values up to 0.66, whereas PACG versus SOAG comparisons demonstrated minimal discrimination (AUC range: 0.47–0.63). Conclusions: Peripapillary RNFL and localized temporal GCIPL thickness measurements provide the highest diagnostic accuracy for identifying POAG. Diagnostic performance is reduced in PACG and SOAG, and the OCT parameters show limited ability to differentiate between glaucoma subtypes. GCIPL asymmetry indices do not enhance diagnostic discrimination beyond direct thickness measurements. Full article

Background/Objectives: To characterize sectoral corneal thickness (CT) profiles in eyes with primary open-angle glaucoma (POAG) compared with healthy eyes and to evaluate potential associations between CT, retinal nerve fiber layer (RNFL) thickness, and optic disc rim area (RA). Methods: In this cross-sectional study, 192 participants (91 with POAG and 101 controls) contributed 297 eyes (145 glaucoma eyes and 152 control eyes). All participants underwent comprehensive ophthalmological examination and spectral-domain optical coherence tomography (OCT; Optovue Solix, Fremont, CA, USA) to obtain peripapillary RNFL measurements, optic disc rim area, and corneal pachymetry maps across five sectors (central, superior, inferior, temporal, and nasal). Repeated-measures correlation analyses were used to assess within-subject associations between CT and RA, and generalized estimating equation (GEE) models were applied to evaluate independent associations between CT, glaucoma status, disease severity, and RNFL thickness while adjusting for relevant covariates. Results: Eyes with POAG exhibited significantly thinner corneas across all sectors compared with controls (all p < 0.05), with the greatest differences observed in the superior (median 607.0 μm vs. 640.0 μm, p < 0.001) and temporal (562.0 μm vs. 579.5 μm, p < 0.001) regions. Average RNFL thickness and rim area were also significantly reduced in glaucoma eyes (all p < 0.001). However, no independent associations between sectoral CT and RNFL thickness or RA were observed after adjustment for multiple comparisons. Although nominal associations between thinner inferotemporal CT and reduced RNFL thickness were observed in unadjusted analyses, these did not remain statistically significant after false discovery rate correction. In multivariable GEE models, glaucoma diagnosis and greater disease severity were consistently associated with reduced RNFL thickness (β range: −11.0 to −42.2 μm; all p < 0.001), whereas CT was not independently associated with RNFL thickness (all adjusted p > 0.07). Conclusions: Sectoral corneal thickness is significantly reduced in eyes with POAG but does not independently correlate with RNFL thickness or optic disc rim area after adjustment for confounding factors. These findings support the concept that corneal thinning reflects structural and biomechanical susceptibility to glaucoma rather than serving as a marker of established neuroretinal damage severity. Further longitudinal studies incorporating comprehensive biomechanical assessments are warranted to clarify the role of corneal structure in glaucoma pathophysiology. Full article

Background/Objectives: Optical coherence tomography-angiography (OCT-A) is a non-invasive method of visualizing the capillary system. As vascular dysregulation impacts glaucoma pathogenesis, the aim of this study was to evaluate APSified-BMO-based-peripapillary vessel density (VD) in patients with ocular hypertension (OHT), pre-perimetric-open-angle glaucoma, as well as primary (POAG) and secondary (SOAG) open-angle glaucoma in comparison to healthy controls using OCT-A. Methods: The present study included 180 eyes from 115 patients of the Erlangen Glaucoma Registry, divided into 35 eyes with OHT, 16 pre-perimetric-OAG eyes, 64 OAG eyes—which were subdivided into 37 POAG and 27 SOAG eyes—and 65 healthy controls. All subjects underwent measurements of the retinal nerve fiber layer (RNFL), inner nuclear layer (INL), retinal ganglion cell (RGC) layer, and Bruch membrane opening–minimum rim width (BMO-MRW). APSified-BMO-based-peripapillary vessel density (VD) was visualized by using OCT-A and quantified using the Erlangen Angio Tool. Results: Mean APSified-BMO-based peripapillary VD showed a significant correlation with age (p < 0.0001). Considering the age effect, mean APSified-BMO-based peripapillary VD of OAG was significantly lower compared to healthy eyes (p < 0.0001) and OHT (p = 0.016). Subgroup analysis yielded a significant difference in mean APSified-BMO-based peripapillary VD between controls and POAG (p = 0.001) and SOAG (p = 0.018), respectively. In addition, a significant difference was observed between OHT and POAG patients (p = 0.036). No significant differences were observed between the OHT, pre-perimetric-OAG, and healthy eyes, respectively. Conclusions: As peripapillary VD was significantly decreased in glaucoma patients compared to controls, the data might suggest that peripapillary VD might be useful for monitoring glaucoma progress. Full article

Primary open angle glaucoma (POAG) is one of the leading causes of irreversible blindness and is associated with dysfunction of the trabecular meshwork (TM), a three-dimensional (3D) structure that regulates aqueous humor outflow and, consequently, intraocular pressure (IOP). IOP is the only modifiable factor for glaucoma. Outflow facility is the inverse of aqueous humor outflow resistance caused by the presence of the TM and adjacent tissues, and reflects the TM’s central role in IOP control, representing the most physiologically relevant measure of human trabecular meshwork (HTM) function. Therefore, development of ex vivo systems to study outflow facility and IOP regulation is critical for advancing glaucoma research. We present a comprehensive review of bioengineering approaches to generation of 3D HTM models using synthetic, natural, and hybrid hydrogels, micro- and nanofabricated synthetic substrates or porous scaffolds, and microfluidic devices. These 3D HTM systems have been designed to capture key features such as topography, stiffness, and fluid flow in the conventional outflow pathway. In particular, we highlight HTM models that recapitulate IOP regulation and allow measurement of outflow facility, which directly reflect pressure-dependent outflow resistance in dynamic HTM physiology and glaucoma pathophysiology. By integrating these bioengineering approaches with emerging stem cell technologies, this review offers an evidence-based landscape overview and framework for designing next-generation 3D human-relevant TM models for outflow physiological studies and IOP-modulating drug discovery. Full article

Background: To evaluate the effects of preoperative topical ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, on Schlemm’s canal (SC) morphology in patients with primary open-angle glaucoma (POAG). Methods: This study included 95 SC specimens obtained during trabeculectomy from 95 patients with POAG. Based on preoperative treatment, patients were divided into two groups: ripasudil (−) group (n = 68) receiving four topical medications [FP receptor agonist, β-blocker, carbonic anhydrase inhibitor (CAI), and α₂ agonist], and ripasudil (+) group (n = 27) receiving the same four medications plus ripasudil. SC morphology parameters were assessed in thrombomodulin (TBM)-stained sections, including length parameters [TBM-positive/negative and opened/closed SC lengths] and area parameters [TBM-positive/negative and opened SC areas]. Between-group comparisons were performed using unpaired t-tests, and multiple regression analysis was conducted to adjust for age, gender, preoperative intraocular pressure (IOP), and oral CAI use. Results: The ripasudil (+) group had significantly longer total SC length (TSC: 302.5 µm) than the ripasudil (−) group (273.0 µm, p = 0.023). Among area parameters, the ripasudil (+) group showed significantly larger opened SC area (OSC-A: 2689 µm² vs. 1881 µm², p = 0.008) and TBM-negative opened SC area (NOSC-A: 716 µm² vs. 305 µm², p = 0.001), whereas TBM-positive opened SC area (POSC-A) was not significantly different between groups (2001 µm² vs. 1575 µm², p = 0.096). After multivariate adjustment, ripasudil use remained significantly associated with longer TSC (p = 0.011) and larger OSC-A (p = 0.014) and NOSC-A (p = 0.001). Conclusions: Preoperative use of topical ripasudil was associated with preservation of SC lumen morphology, particularly in regions lacking SC endothelium. These findings provide a theoretical basis for therapeutic strategies employing ROCK inhibitors to maintain SC morphology and function. Full article

Background: The impact of cataract surgery on anterior segment structures in subjects affected by primary open-angle glaucoma (POAG) remains incompletely understood. The aim of this study was to characterize changes in anterior segment parameters after cataract surgery in POAG subjects compared with non-glaucoma subjects (control). Methods: A prospective comparative study was conducted, including patients scheduled for cataract surgery who underwent a comprehensive ophthalmic examination before and after surgery using anterior segment optical coherence tomography (OCT). Longitudinal changes and between-group comparisons were analyzed. Results: The results demonstrated a significant enlargement of the anterior chamber and iridocorneal angles after surgery in both groups (p < 0.05), with no significant differences between POAG and control eyes (p > 0.05). Several preoperative parameters, particularly angle-related metrics, were correlated with postoperative anatomical changes, suggesting their potential role as predictors of anterior segment variation (R > 0.50; p < 0.05). Conclusions: In conclusion, this study provides a detailed characterization of anterior segment changes in POAG subjects following cataract surgery, demonstrating anterior chamber enlargement comparable to that observed in non-glaucoma eyes, which may assist clinicians in the management of glaucoma. Full article

Background: Glaucoma is a neurodegenerative disease and the second leading cause of irreversible blindness in developed countries. It is characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve axons, leading to permanent vision impairment. Although elevated intraocular pressure (IOP) is the main recognized risk factor, recent evidence suggests that ocular and gut microbiota may play a significant role in the onset and progression of glaucoma. Objectives: This study aimed to characterize ocular and gut microbiota alterations in patients with different types of glaucoma. Methods: Five searches were conducted between June and September 2025 using selected keywords. A total of 121 articles were identified, of which 14 met the inclusion criteria following the PRISMA 2020 guidelines. Results: Findings indicate a Mendelian genetic predisposition influencing microbiota composition associated with glaucoma development. Patients treated with benzalkonium chloride (BAK) showed increased Gram-negative and Alphaproteobacteria on the ocular surface, along with enhanced lipopolysaccharide synthesis. Compared with controls, glaucoma patients exhibited reduced Corynebacterium mastiditis and Actinobacteria and increased Firmicutes, Proteobacteria, and Verrucomicrobiota. Dysbiosis was more pronounced in patients with concurrent dry eye disease, characterized by higher Gram-negative taxa and pro-inflammatory microbial activity. Conclusions: Significant differences in ocular and gut microbiota were observed between glaucoma patients and controls, as well as among glaucoma subtypes such as pseudoexfoliation and primary open-angle glaucoma. Age-related dysbiosis and epigenetic factors appear to contribute to disease development. Microbiota profiling may offer new opportunities for improved prediction, management, and treatment of glaucoma. Full article

Background: Minimally invasive glaucoma surgery, often performed with phacoemulsification (PHACO-MIGS), for the management of primary open angle glaucoma (POAG), has good clinical outcomes and safety profiles. However, few studies have comprehensively evaluated the impact of PHACO-MIGS on patients’ quality of life (QoL). We determined the post-operative effectiveness of PHACO-MIGS on glaucoma-specific QoL domains in mild–moderate POAG patients. Methods: In this prospective study, adults aged ≥ 21 years with mild–moderate POAG in one eye scheduled for PHACO-MIGS at the Singapore National Eye Centre were administered a digital patient-reported outcome measure (PROM) that utilizes computerized adaptive testing (CAT) to precisely estimate glaucoma-specific QoL across 12 different domains (GlauCAT^TM), pre-surgery and at 6 months post-surgery. The 12 domains included the following: Visual Symptoms (VSs), Ocular Comfort Symptoms (OSs), Emotional (EM), Activity Limitation (AL), Driving (DV), Lighting (LT), Mobility (MB), Treatment Convenience (TCV), Concerns (CNs), Social (SC), General Convenience (GCV), and Economic (EC). Clinical variables collected included intraocular pressure (IOP), better eye visual acuity (VA), visual field deficit (VFD) and number of glaucoma drops prescribed. Linear mixed models were utilized to determine the within-group changes in each domain, adjusted for relevant clinical, treatment and sociodemographic variables. Results: Of the 83 patients (mean age ± SD: 70.84 ± 6.70 years; 65.1% male; 90.4% Chinese), 61 (73.5%) underwent PHACO-MIGS with Hydrus^® Microstent, and 22 (26.5%) with iStent^® inject. Mean (SD) improvements in VA and IOP were observed post-surgery (0.11 [0.15] LogMAR units and 1.35 [4.20] mmHg, respectively), while VFD and the average number of anti-glaucoma medications prescribed decreased by 0.90 (2.97) dB and 1.30 (0.11) drops (all p < 0.05). Compared to pre-operative scores, four GlauCAT^TM domains [VSs (13.04%, p < 0.001; ES: 0.84), OSs (6.42%, p < 0.001; ES: 0.52), CNs (7.53%, p = 0.002; ES: 0.51), and GCV (6.34%, p = 0.004; ES: 0.45)] showed significant improvements post-surgery. The improvements across these four domains were driven primarily by a reduction in IOP and improvements in VA. Conclusions: Using a novel and AI-driven QoL PROM, we found significant post-operative improvements in Visual and Ocular Comfort Symptoms, Convenience, and Concerns in patients with POAG undergoing combined PHACO-MIGS, driven by improvements in IOP and VA post-surgery. Full article

Background: Glaucoma is a chronic neurodegenerative disorder characterized by the selective vulnerability of retinal ganglion cells (RGCs), in which mitochondrial dysfunction, redox imbalance, and impaired bioenergetic signaling play central pathogenetic roles. Mitochondrial homeostasis in RGCs critically depends on maintaining intracellular NAD⁺ pools, which support oxidative phosphorylation, sirtuin-mediated deacetylation, and antioxidant gene expression. Nicotinamide riboside (NR), a potent NAD⁺ precursor, and berberine (BBR), an AMPK activator derived from Berberis aristata, have recently emerged as synergistic modulators of mitochondrial metabolism and oxidative stress resistance. Methods: This study retrospectively assessed clinical outcomes associated with combined nutraceutical supplementation of nicotinamide riboside (NR) and berberine (BBR) in patients with primary open-angle glaucoma undergoing stable topical hypotensive therapy. We have included a narrative review in the current literature regarding NAD⁺ biology, AMPK–sirtuin signaling, and oxidative stress responses in retinal ganglion cell (RGC) degeneration. Due to the absence of comparator groups receiving only NR or only berberine in this retrospective cohort, the combined supplementation has been regarded as a biologically complementary strategy, and the potential for synergistic efficacy remains a subject for further investigation. Results: Translationally, a retrospective clinical cohort receiving combined NR and BBR supplementation showed functional stabilization of the visual field and structural preservation of the retinal nerve fiber layer over a six-month follow-up, in line with the proposed mitochondrial protective mechanisms. Conclusions: The clinical trends identified in this retrospective cohort have substantiated the translational significance of NR + BBR supplementation as a potential adjunctive approach in glaucoma management. NAD⁺ repletion and engagement of the AMPK–SIRT–NRF2 pathway may enhance mitochondrial resilience in RGCs. Collectively, these findings offer initial clinical evidence advocating for additional controlled studies on NR + berberine supplementation, while mechanistic interpretations have been derived from the existing literature and are hypothesis-generating. Full article

Background and Objectives: Primary open-angle glaucoma (POAG) is one of the leading ocular diseases leading to irreversible blindness and is often asymptomatic until advanced cases. While intraocular pressure reduction remains the cornerstone of treatment, neuroprotective strategies targeting retinal ganglion cell metabolism are actively investigated. Niacinamide (nicotinamide, vitamin B3), a precursor of NAD+, has shown neuroprotective potential in preclinical models. This exploratory study evaluated the short-term functional, structural, and electrophysiological effects of oral niacinamide supplementation in POAG. Materials and Methods: In this interventional study, patients with POAG received oral niacinamide 500 mg daily for six months. Visual field (VF) global and localized sensitivity (Mean Deviation [MD], Pattern Standard Deviation [PSD]), Optic Coherence Tomography (OCT)-derived peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC), and Visual evoked potentials (VEP) latency parameters (P2 1.4 Hz, P100 1°, and P100 15′) were assessed at baseline and at six months. Because both eyes from some participants were included, primary longitudinal inference was based on clustered analyses using generalized estimating equations and linear mixed-effects models to account for inter-eye correlation. Eye-level paired analyses were used for exploratory comparison. Change–change relationships across modalities were explored using Spearman correlation. Results: After accounting for inter-eye correlation, no statistically significant change in MD was detected (mean ΔMD +0.43 dB; GEE p = 0.099; LME p = 0.101), and PSD remained stable. RNFL thickness showed a small decrease (−1.26 µm; GEE p = 0.046), while GCC did not change significantly. VEP P100 latencies remained stable, whereas P2 latency showed a small increase (+3.9 ms; GEE p = 0.039). Correlation analysis revealed a moderate association between changes in GCC and MD (ρ = 0.44), suggesting concordance between macular structural stability and global visual field performance. Conclusions: When inter-eye correlation is appropriately accounted for, six months of niacinamide supplementation in POAG is associated with overall functional, structural, and electrophysiological stability, without evidence of clinically meaningful improvement or progression. These findings support short-term safety and highlight the importance of clustered analytical approaches and macular-centered biomarkers in future glaucoma neuroprotection trials. Full article