Background: Elevated intraocular pressure in primary open-angle glaucoma (POAG) primarily stems from impaired aqueous humor (AH) outflow dynamics and aberrant extracellular matrix remodeling within the trabecular meshwork. Although uncovering global proteome perturbations is essential, conventional shotgun proteomics fails to resolve the structural states and site-specific proteolytic processing events driving these pathogenic alterations. Methods: Here, we present a site-resolved degradomic and proteomic characterization of AH from POAG patients and cataract control subjects at single-subject resolution ( ; 30 POAG, 36 controls), utilizing an integrated framework of data-independent acquisition (DIA) proteomics and TMTpro™ Zero-based N-terminomics coupled with orthogonal molecular biology validation. Findings: We identified a POAG-specific proteolytic fingerprint defined by the plasmin-dependent cleavage of the fibulin-1c isoform. Biochemical validation confirmed that disruption of this microfibrillar scaffolding axis destabilizes the large latent complex, triggering the pathological solubilization and accumulation of the Latency-Associated Peptide (LAP)–TGF-β precursor in glaucomatous AH. Interpretation: Our multi-dimensional dataset uncovers a finely tuned mechano-proteolytic axis underlying trabecular meshwork failure, establishing plasmin-mediated fibulin-1c processing and TGF-β complex destabilization as potential mechanistic targets for therapeutic intervention in POAG.

OBJECTIVE:To assess the adherence of glaucoma surgical and laser studies to WGA guidelines for reporting glaucoma surgery studies, analyse trends in adherence over time and explore associations between adherence and study characteristics. METHODS:Systematic review (PROSPERO:CRD42023394477) of glaucoma surgical and laser studies published between 2010 and 2023 in PubMed/MEDLINE and EMBASE. Eligible studies included RCTs, non-randomized comparative and prospective observational designs (>100 eyes). Two reviewers independently extracted data across five domains: Methodology, Definition of success, Ethics, Postoperative complications and Statistical reporting. Temporal trends and associations with study features were analysed using linear regression. RESULTS:Two hundred and fifty-six studies were included, 75% of which were published in Q1-Q3 journals. Mean overall adherence was 47% ± 9.2%. Domain-level adherence was highest in Ethics (61% ± 20%), followed by Postoperative complications (50% ± 22%), Statistical reporting (48% ± 18%), Methodology (44% ± 12%) and Definition of success (30% ± 13%). No significant differences (p > 0.06) were observed in overall adherence for studies from Europe, Asia, Oceania or the Middle East. Studies involving cataract surgery for angle-closure disease (est. = -10% [-19%, -2.2%], p = 0.014) and laser trabeculoplasty (est. = -7.1% [-11%, -3.5%], p < 0.001) had lower adherence compared with trabeculectomy, while MIGS studies showed no difference (p = 0.45). Visual field progression was reported in only 3% of studies, while various anatomical outcomes (e.g. bleb morphology) were reported in 0%-24% of studies. CONCLUSION:Current literature shows poor adherence to WGA guidelines across both traditional and newer glaucoma surgeries, reflecting inadequate reporting and outdated recommendations. Evidence-based updates, broader consensus and stronger implementation are needed to ensure standardized and meaningful reporting.

Background/Objectives: Citicoline, also known as CDP-choline, is a nootropic agent currently used in the treatment of glaucoma and is undergoing evaluation as a first-line therapy in a multi-center, international, phase III, randomized clinical trial involving citicoline eyedrops (ClinicalTrials.gov ID: NCT05710198). Numerous clinical and preclinical studies have linked the neuroenhancement and neuroprotective effects of citicoline to its role as a metabolic precursor for structural and functional components of cell membranes (such as phosphatidylcholine and sphingomyelin) and for neurotransmitters (e.g., acetylcholine and dopamine). However, compelling evidence suggests that the molecular mechanisms underlying its cytoprotective activity involve additional as-yet uncharacterized pharmacological actions. Methods: To further elucidate its pharmacology, we investigated the effect of two cytoprotective doses of citicoline (0.1 mM and 1 mM) on the global proteome of neuroblastoma cells using an unbiased shotgun proteomics approach. Results: With over 4000 unique proteins identified and quantified per experimental condition, the proteomics analysis revealed that citicoline, after 6 h of stimulation, induces a profound and robust remodeling of the intracellular proteome compared to untreated cells. Importantly, this effect was observed to significantly diminish by 18 h of stimulation, highlighting its transient nature (data are available via ProteomeXchange with identifier PXD061053). The clustering and rationalization of proteins upregulated by citicoline treatment identified the enrichment of key pathways for mRNA splicing, protein translation, proteostasis balance through the ubiquitin proteasome system (UPS), and mitochondrial metabolism. Conclusions: These proteomics findings introduce previously uncharacterized biological effects of citicoline and foster the working hypothesis that this drug may exert its cytoprotective activity through molecular mechanisms linked to the hormesis principle. These data further support the rationale for its clinical application in neurodegenerative processes and human disorders characterized by proteotoxicity.

TOPIC:Fast glaucoma progression is generally defined using numerical cut-offs applied to the rate of progression. However, no consensus guidelines exist for standardized thresholds, and multiple methods are used to estimate progression rates. We systematically review how fast progression is defined in the glaucoma literature and quantify heterogeneity in criteria, analytic methods, and structural or functional parameters used across studies. CLINICAL RELEVANCE:Potential heterogeneity in defining fast glaucoma progression may influence reported prevalence, risk factor associations, and interpretation of outcomes across studies. METHODS:A systematic review (PROSPERO: CRD42024502764) was conducted using MEDLINE and Embase to identify studies assessing fast glaucomatous progression based on visual field (VF) examination, optic disc photography, OCT, confocal scanning laser tomography (CSLT), and OCT angiography (OCT-A). Childhood glaucoma was excluded. Two independent reviewers selected eligible studies and extracted complete definitions of fast progression. RESULTS:Of 31 856 records identified, 122 met the eligibility criteria, yielding 88 definitions of fast progression, including 66 unique criteria and 16 analytic methods. The most frequent definition was mean deviation (MD) rate < -1.0 dB/year calculated using ordinary least squares regression (OLSR) (13 studies, 10.7%). Among structural definitions, the most common was global peripapillary retinal nerve fiber layer thickness decay ≥90th percentile of the study sample using OLSR. When analyzed separately, MD rate < -1.0 dB/year was the most commonly used measure (25 studies, 20.5%) and OLSR the most frequent analytic method (79 studies, 64.8%). Visual field testing was used in 103 studies (84.4%), OCT in 25 (20.5%), and CSLT and OCT-A in 1 study each (0.8%). Seven studies (5.7%) combined VF with a structural device (6 with OCT and 1 with CSLT), and 1 study combined OCT and OCT-A. Among VF-based studies, 3 (2.9%) used central testing (10-2), while among OCT-based studies, 4 (16.0%) focused on macular parameters. Mean deviation was the most frequently adopted index (81 studies, 66.3%), followed by peripapillary retinal nerve fiber layer thickness (21 studies, 17.2%). FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CONCLUSIONS:Definitions of fast glaucomatous progression in the literature are predominantly VF-based but vary widely in terms of indices, analytic model, and threshold used. Further research should clarify how different definitions influence fast progressor classification.

Purpose:To evaluate the effects of 0. 001% glycerophosphoinositol in 0.2% hyaluronate (GPI/HA) vehicle eye drops in patients with glaucoma therapy related-ocular surface disease (GTOSD). Methods:Forty patients diagnosed with GTOSD and receiving GPI/HA or HA 0.2%, underwent ocular surface disease index (OSDI), Symptom Assessment iN Dry Eye (SANDE), National Eye Institute Visual Function Questionnaire (NEI VFQ)-25 questionnaires, and tear matrix metalloproteinase-9 (MMP-9), break-up time (BUT), corneal fluorescein staining (CFS), Schirmer test I (STI), and bulbar conjunctival hyperemia (BCH) determination. Results:After 1 month, GPI/HA eyedrops increased BUT [6 (4-7.25) to 7 (6-8)] and STI [11.5 (8-17.5) to 13.5 (10-18.5)], whereas decreased BCH [2.2 (2.1-2.3) to 2.1 (1.3-2.2)] and CFS [3 (2-4) to 2 (2-3)] (p < 0.001). Questionnaire scores improved from 35 (24.36-46.25) to 33 (20.75-40.52), for SANDE and from 31.5 (20-45) to 28.5 (17.75-40.5), for OSDI (p < 0.001). HA 0.2% eyedrops reduced BCH from 2.75 (2.15-3.20) to 2.25 (1.90-2.30) and CFS from 3.5 (2.75-5) to 2.5 (2-4) (p = 0.014), and increased BUT (p = 0.036). Questionnaire scores improved from 28.95 (20.9-47.6) to 26.86 (19.90-36.41) (p = 0.009) for SANDE, and from 40 (19.5-49) to 29 (19.75-42) (p = 0.005) for OSDI. There were not significant modifications in the MMP-9 immunoassay positivity in either treatment group. Follow-up inter-group comparisons showed better BCH values in GPI/HA, and better NEI VFQ-25 scores in HA 0.2%. Conclusion:Both treatments proved valuable in managing GTOSD, supporting the use of lubricants in this condition. GPI/HA showed a broader pattern of improvement, which should be interpreted cautiously given the observational design and limited inter-group differences.

To investigate the characteristics of referral for glaucoma surgery and compare surgical practices in various European regions in 2025. Data of 300 eyes of 300 consecutive patients undergoing glaucoma surgery were analysed using a standardized questionnaire and compared between geographical regions. Glaucoma specialists from one centre per country provided data on demographics, glaucoma types, intraocular pressure (IOP), visual field and structural metrics, types of surgery and referral timeliness (timely, later than optimal, late). The median (quartiles) age was 72 (64–78) years. Primary open angle glaucoma (52.0 What is new

AIMS:To evaluate how different methods of managing multiple visits within predefined time windows affect intraocular pressure (IOP)-based success rates in glaucoma surgery studies. METHODS:We applied literature-based high IOP failure criteria to two cohorts of 934 and 1760 eyes undergoing trabeculectomy and deep sclerectomy (DS) with median follow-up of 41.4 months and 45.4 months, respectively. Failure was defined by IOP thresholds, loss of light perception, hypotony requiring revision or additional IOP-lowering surgery. Visits were grouped into guideline-based windows and six visit-managing strategies were applied to all visits, mean, lowest, highest, median and closest IOP to the recommended time point. We calculated Kaplan-Meier success rates for each visit-managing strategy. Visual field (VF) analysis was conducted on patients in the trabeculectomy cohort with ≥4 VFs in ≥2 years post-surgery. RESULTS:For the 21 mm Hg threshold, 5-year success was highest with the lowest IOP (trabeculectomy: 54.8%; DS: 74.5%), followed by closest IOP (trabeculectomy: 46.7%; DS: 67.6%), the median (trabeculectomy: 46.9%; DS: 69.1%) and mean IOP (trabeculectomy: 46.3%; DS: 68.6%). Success rates were lower with peak IOP (trabeculectomy: 39.3%; DS: 60.4%) and all visits IOP (trabeculectomy: 38.8%; DS: 61.0%). In the VF subset, eyes classified as failures demonstrated significantly faster mean deviation (MD) progression than those classified as successes although substantial overlap in the distribution of MD rates persisted between groups under every strategy. CONCLUSIONS:Visit-managing strategies influence reported success rates. None of the evaluated approaches achieved a clear separation in VF progression rates, underscoring the inherent limitations of IOP-threshold-based classifications.

BACKGROUND/AIMS:To compare the efficacy and safety of a new preservative-free bimatoprost 0.01%/timolol 0.1% fixed combination (BTFC) eye gel with those of bimatoprost 0.03%/timolol 0.5% fixed combination ophthalmic solution (BTFC eye drops) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS:In this phase III, international, multi-centre, randomised, parallel group, investigator-masked study, patients receiving a first-line monotherapy, having insufficiently controlled intraocular pressure (IOP) and requiring dual therapy were randomised to receive either BTFC eye gel or BTFC eye drops once daily for 12 weeks. The primary efficacy endpoint was the change in IOP from baseline to week 12 at 08:00 in the assessed eye. Further efficacy and safety endpoints were assessed as secondary outcomes. RESULTS:The mean±SD change in IOP from baseline to week 12 at 08:00 was -10.96±3.43 mmHg for the BTFC eye gel group and -11.14±3.56 mmHg for the BTFC eye drop group. The least-squares mean difference (BTFC eye gel minus BTFC eye drops) was -0.04±0.24 mmHg (95% CI -0.51 to 0.43 mmHg), with the upper bound of the 95% CI lower than the predefined margin of +1.5 mmHg at week 12 at 08:00. Similar IOP-lowering efficacy was demonstrated at all other timepoints. The safety profile was comparable between the treatment groups. No patients in the BTFC eye gel group discontinued the study due to a treatment-related adverse event compared with 8 (2.9%) patients in the BTFC eye drop group. CONCLUSION:Low-concentration BTFC eye gel can be considered as a safe and effective treatment in the therapeutic management of glaucoma and OHT.

PURPOSE:To compare 12-month effectiveness and safety of 63-μm gelatin microstent (Xen63) versus 45-μm gelatin microstent (Xen45). DESIGN:Multicenter, retrospective cohort study. SUBJECTS:Two hundred eyes of 200 patients (100 in each Xen63 and Xen45 group), with or without phacoemulsification. METHODS:Consecutive patients undergoing 63-μm microstent implantation across 4 countries (Canada, Italy, Austria, and Belgium) were compared with matched controls who underwent 45-μm microstent implantation. MAIN OUTCOME MEASURES:Primary outcome measure was the probability of complete success at 1 year: (1) no 2 consecutive intraocular pressure (IOP) >14 or < 6 mmHg with 2 lines of vision loss and (2) ≥20% reduction from decision IOP, without glaucoma medications or reoperations. Qualified success allowed glaucoma medications and laser trabeculoplasty. Secondary outcomes included success with upper IOP cutoffs of 17 and 21 mmHg, postoperative IOP and medications course, complications, interventions, and reoperations. RESULTS:Complete success favored 63-μm microstent (56.9% vs. 43.9%, P = 0.017), using IOP cutoff of 14 mmHg. The 45-μm microstent was associated with an increased hazard of failure compared with the 63-μm microstent (hazard ratio, 1.9; 95% confidence interval, 1.2-3.0). Complete success using IOP cutoffs of 17 and 21 mmHg in the 63- versus 45-μm group was 60.1% versus 53.9% (P = 0.156) and 60.1% versus 55.0% (P = 0.243), respectively. Qualified success was not significantly different between the 2 groups using any IOP threshold (P > 0.05). At 12 months, the 63-μm group had significantly lower IOP (mean, 14.6 ± 7.6 vs. 15.8 ± 6.1 mmHg; P = 0.021) and medication count (0.6 ± 1.1 vs. 1.1 ± 1.5; P = 0.024). Postoperative needling was performed in 16.0% and 18.0% of 63- and 45-μm microstent-implanted eyes, respectively. Incidence of early postoperative choroidal effusion was higher in the 63-μm group (25.0% vs. 6.0%; P < 0.001). Interventions (62.0% vs. 59.0%) and reoperations (21.0% vs. 15.0%) were comparable between the groups (P > 0.050). CONCLUSIONS:Xen63 demonstrated superior IOP-lowering effectiveness compared with its 45-μm variant in patients requiring more robust IOP targets. Xen63-implanted eyes experienced a higher incidence of early postoperative choroidal effusion, the majority of which were transient. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background/objectives: The efficacy and safety of the XEN45 gel stent implant in patients with glaucoma have been amply demonstrated. XEN63 is a new device that has been developed with a larger bore. This multicenter, observational, retrospective study assessed the efficacy and safety of XEN63 in patients with glaucoma. Methods: Medical records from six participating centers were screened to identify patients meeting the inclusion criteria. The primary outcome was mean IOP at 6 months after surgery. Results: The study included 114 eyes from 102 patients (XEN63 alone: 68 eyes, and XEN63 + Phaco: 46 eyes); 92% of patients had primary open-angle glaucoma. Baseline IOP for all patients was a median of 23.0 mmHg (IQR: 18.5-27.5 mmHg), which decreased significantly on day one post-surgery to 7.0 mmHg (IQR: 4.5-9.5 mmHg) and gradually stabilized at around 13.5 mmHg (IQR: 10.5-16.5 mmHg) by 6 months with no significant differences between groups at 6 months. The number of ocular hypertensive medications (OHMs) reduced significantly from a baseline median of 2.7 ± 1.1 to 0.5 ± 1.0 at 6 months in the entire cohort. The XEN63 alone group showed a significantly lower need for OHMs at 3 and 6 months. The surgical success rate was comparable between the two groups (54.4% vs. 47.8%, p = 0.05, XEN63 alone and XEN63 + Phaco). There was no statistically significant difference in survival outcomes between the XEN63 (0.59, 95% CI: 0.49-0.73) and XEN63 + Phaco groups (0.55, 95% CI: 0.42-0.72) (p = 0.89). Conclusions: In the largest study with XEN63 to date, the device appears to significantly decrease the IOP and the OHMs. Simultaneous XEN63 implant and phacoemulsification showed similar outcomes compared to XEN63 alone.

Précis: The relationship between structural and hemodynamic parameters in patients with primary open angle glaucoma is strongest in the temporal region of the optic nerve. Purpose: To investigate the relationship between radial peripapillary capillary (RPC) vessel density (VD) and retinal nerve fiber layer (RNFL) thickness in quadrants and sectors of the optic nerve head (ONH) in patients with and without primary open angle glaucoma (POAG). Methods: In a cross-sectional prospective analysis, 191 subjects (80 early-stage POAG; 111 non-glaucomatous controls) were assessed for RNFL thickness and RPC VD in each quadrant [superior (S), inferior (I), nasal (N) and temporal (T)] and sector [inferior-temporal (IT), temporo-inferior (TI), temporo-superior (TS), superior-temporal (ST), inferior-nasal (IN), naso-inferior (NI), naso-superior (NS), and superior-nasal (SN) sectors] of the ONH via optical coherence tomography angiography (OCTA, Avanti, Optovue). Pearson correlations were used to test for associations between measurements, with P<0.05 considered statistically significant. Results: Significantly stronger positive correlations were found between RPC VD and RNFL thickness in the S, I, and T quadrants in POAG patients compared to non-glaucomatous controls (all P<0.05). The temporal quadrant in POAG patients displayed the largest difference in correlation compared to controls. A stronger positive correlation was also found between RPC VD and RNFL thickness in the temporal sectors of the ONH in POAG patients compared to controls, with the largest difference in the TS sector (all P<0.05). Conclusion: Early-stage POAG patients have a stronger relationship between RPC VD and RNFL in the temporal regions of the ONH compared to non-glaucomatous controls, with the TS sector demonstrating the largest difference between groups. Temporal sector VD loss may represent an early-stage biomarker for vascular-linked POAG disease.

Glaucoma is a chronic optic neuropathy and is the second cause of irreversible blindness worldwide. Although the pathogenesis of the disease is not fully understood, the death of retinal ganglion cells and degeneration of the optic nerve are likely promoted by a combination of local and systemic factors. Growing attention has been paid to nonintraocular pressure risk factors, including mechanisms of inflammation and neuroinflammation. Phenotypical and molecular alterations of circulating immune cells, in particular, lymphocyte subsets, have been documented in murine models of glaucoma and in human subjects. Very recently, oxygen consumption rate and nicotinamide adenine dinucleotide levels of human peripheral blood mononuclear cells (PBMC) have been proposed as biomarkers of disease progression, thus suggesting that immune cells of glaucoma subjects present severe molecular and metabolic alterations. In this framework, this pilot study aimed to be the first to characterize global proteome perturbations of PBMC of patients with primary open-angle glaucoma (POAG) compared to nonglaucomatous controls (control) by shotgun proteomics. The approach identified >4,500 proteins and a total of 435 differentially expressed proteins between POAG and control subjects. Clustering and rationalization of proteomic data sets and immunodetection of selected proteins by Western blotting highlighted significant alterations of immune system compartments (i.e., complement factors, regulators of immune functions, and lymphocyte activation) and pathways serving key roles for immune system such as proteolysis (i.e., matrix metalloproteinases and their inhibitors), autophagy (i.e., beclin-1 and LC3B), cell proliferation (Bcl2), mitochondrial (i.e., sirtuin), and energetic/redox metabolism (i.e., NADK). Based on these findings, this proteomic study suggests that circulating immune cells suffer from heterogeneous alterations of central pathways involved in cell metabolism and homeostasis. Larger, properly designed studies are required to confirm specifically how immune cellular alterations may be involved in the pathogenesis of both neuroinflammation and glaucomatous disease.

Purpose:Reporting of open-label extension data following a Phase III, randomized study examining treatment outcomes with preservative-free latanoprost eye drop cationic emulsion and preserved latanoprost in patients with open-angle glaucoma (OAG)/ocular hypertension (OHT). Patients and Methods:OAG/OHT patients were randomized 1:1 to receive preservative-free latanoprost 0.005% eye drop emulsion or preserved latanoprost 0.005% for 12 weeks. Patients entering the extension study received open-label preservative-free latanoprost eye drop emulsion from Week 12 through Month 15. Endpoints included mean (standard deviation [SD]) change from baseline (Day 1, post-washout) in peak (9:00 AM ± 1 hour) intraocular pressure (IOP), corneal fluorescein staining (CFS; modified Oxford Grade Scale) score, ocular surface disease (OSD) symptom score and adverse event (AE) reporting. Results:Respective mean (SD) peak (9:00 AM) IOP reductions from baseline at Week 12, and Months 6, 9 and 15 were 8.9 (3.0), 8.9 (3.0), 9.0 (2.7) and 8.7 (2.3) mmHg for preservative-free latanoprost eye drop emulsion users (N=70) and 7.8 (2.6), 8.3 (2.6), 8.1 (2.7) and 7.6 (2.8) mmHg for patients switching from preserved latanoprost at Week 12 (N=66). Between-group differences for the change in IOP were statistically significant at Week 12 (-1.06; nominal p=0.029). Mean CFS and OSD symptoms scores were reduced in both groups through Month 15. No serious treatment-related AEs were reported during the study period. Conclusion:Open-label preservative-free latanoprost eye drop emulsion treatment provided dual benefit of sustained IOP-lowering efficacy and improvements in OSD signs and symptoms over the 15-month study period. No serious treatment-related AEs were reported throughout the study period.

Background/Objectives: To evaluate the efficacy and safety of preservative-free latanoprost eye drop emulsion in reducing intraocular pressure (IOP) versus preserved latanoprost in open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: A Phase III non-inferiority study randomised patients with OAG/OHT 1:1 to receive preservative-free latanoprost eye drop emulsion or preserved latanoprost. The primary efficacy endpoint was change from baseline in peak (9:00 A.M. +/- 1 h) and trough (4:00 P.M. +/- 1 h) IOP at Week 12 (non-inferiority margin: 95% confidence interval for treatment difference of <= 1.5 mmHg). Key secondary endpoints were change from baseline in corneal fluorescein staining (CFS) score and in ocular surface disease (OSD) average symptom score at Week 12 (in patients with baseline CFS >= 1 or OSD score > 0, respectively). Results: Non-inferiority criteria for IOP-lowering were met. Least square (LS) mean (standard error [SE]) IOP change from baseline with preservative-free latanoprost eye drop emulsion (N = 193) versus preserved latanoprost (N = 193) at Week 12 was -8.8 (0.3) mmHg versus -8.2 (0.3) mmHg at peak (difference: -0.6 mmHg; nominal p = 0.023); -8.6 (0.2) mmHg versus -8.1 (0.3) mmHg at trough (difference: -0.5 mmHg; p = 0.080). LS mean change in CFS (SE) was -0.7 (0.07) with preservative-free latanoprost eye drop emulsion and -0.4 (0.08) with preserved latanoprost (nominal p < 0.001). LS mean change in OSD symptom score was -0.3 (0.1) with preservative-free latanoprost eye drop emulsion and -0.2 (0.1) with preserved latanoprost (nominal p = 0.090). Conclusions: Preservative-free latanoprost eye drop emulsion demonstrated non-inferior IOP-lowering efficacy compared with preserved latanoprost, and improved signs and symptoms of OSD.

Purpose It is important for clinicians to identify patients with glaucoma at higher risk of poor adherence to topical therapy at an early stage to prescribe alternative treatments. An expert-based set of statements was developed to assist clinicians in the early identification of patients at high risk of low adherence and subsequent poorer clinical outcomes.Methods A two-step strategy was used. First, statements were developed by a panel of experts using data from a literature search as a starting point. Second, we measured agreement with the statements in a representative group of ophthalmologists managing patients affected by glaucoma.Results A total of 18 statements and consensus was reached for all. The available evidence and clinical experience have identified some subpopulations at high risk of poor adherence. These include young individuals with competing interests, being frequently away from home, multiple comorbidities and particularly when they affect joint function of the hands or cognitive abilities, being asymptomatic, and being poorly informed about the severity of the disease. The unavailability of caregivers and living alone seems to be relevant factors, particularly in older and more frail patients.Conclusion Taken together our results allow us to profile patients with glaucoma who will be more likely to show poor adherence to topical treatments. Moreover, the consensus statements can be used to identify patients who are unsuitable for topical drops and who would benefit more from alternative treatments.

Mitochondrial dysfunction and oxidative stress have been suggested as potential contributors to the initiation and progression of primary open-angle glaucoma (POAG). Nicotinamide and pyruvate are important in the human body for maintaining metabolic function and preserving cytoskeletal structures. Both substances show an age-dependent decline in humans which may contribute to metabolic dysfunction and POAG vulnerability. Pilot works suggest their consumption may help prevent retinal ganglion cell deterioration under elevated intraocular pressure (IOP) and oxidative stress. Currently, there are no approved POAG treatments to mitigate risks from non-IOP drivers of disease, including oxidative stress. The purpose of this review is to summarize and critically evaluate interventional studies that have investigated nicotinamide and pyruvate supplementation in attempts to treat metabolic dysfunction in POAG patients. A review of the relevant literature from October 1979 to November 2025 was performed using related search terminologies through PubMed, ClinicalTrials.gov, and Google Scholar, and by reference cross-matching of all related articles. Current pilot data suggests that supplementation with nicotinamide and pyruvate demonstrates certain aspects of retinal neuroprotection and produces short-term improvements in visual function. However, much of the existing work has been conducted in animal models, and human study data are severely limited in scope and duration. Several clinical trials are registered as being in progress that aim to determine the chronic effects of nicotinamide and pyruvate in humans. Long-term longitudinal investigations with significantly larger and diverse sample sizes tied to functional and structural outcomes are needed for the safety and potential clinical utility of nicotinamide and pyruvate for POAG.

Purpose: We aimed to analyze the effects of age on human tear film (TF) using a novel nanometer resolution TF imaging device (Tear Film Imager, TFI, AdOM, Israel). Methods: 44 healthy adult subjects (≥18 years of age) without ocular or systemic diseases or prior eye treatments with ages spanning seven decades were enrolled in this prospective cross-sectional study. Subjects underwent a comprehensive ophthalmic examination and completed the Ocular Surface Disease Index questionnaire (OSDI). All study participants underwent TF imaging using the TFI, including assessment of muco-aqueous layer thickness (MALT), lipid-layer thickness (LLT), inter-blink interval, and lipid map uniformity. Associations between TFI parameters and age were tested using linear regression (accounting for multiple eyes). Results: A total of 80 eyes (44 subjects) were imaged: 19 eyes from 10 subjects in the 3rd decade of life (aged 20–29); 10 eyes from 5 subjects in the 4th decade of life (aged 30–39); 5 eyes from 3 subjects in the 5th decade of life (40–49); 12 eyes from 7 subjects in the 6th decade of life (50–59), 19 eyes from 11 subjects in the 7th decade of life (60–69); 11 eyes from 6 subjects in the 8th decade of life (70–79); and 4 eyes from 2 subjects in the 9th decade of life (80–89). With increasing age, MALT significantly decreased (p = 0.024), and LLT significantly increased (p = 0.001). No statistically significant linear age effects were found for the other TFI parameters (p > 0.05) or the OSDI scores of study participants of different ages (p = 0.786). Conclusions: Quantitative TF biomarkers varied significantly with advancing age in healthy individuals, highlighting the importance of accounting for age in TF assessments.