Francesco Oddone

Purpose To investigate the characteristics of referral for glaucoma surgery and compare surgical practices in various European regions in 2025. Methods 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). Results The median (quartiles) age was 72 (64–78) years. Primary open angle glaucoma (52.0%) and pseudoexfoliative glaucoma (23.0%) were the most common glaucoma types. Median disease duration was 75 (28–144) months, preoperative IOP 22 (18–28) mmHg, mean deviation − 14.47 (− 21.60 to − 7.85) dB, and retinal nerve fibre layer thickness 60 (50–75) µm. Trabeculectomy (38.3%), minimally invasive bleb forming surgeries (28.3%), and drainage devices (11.3%) were the predominant procedures; 18.7% of the surgeries were combined with phacoemulsification. More severe disease was associated with filtering or drainage device surgery (p < 0.001). Referral was timely in 34.7%, later than optimal in 35.7%, and late in 29.7%. Late referrals were associated with higher IOP, more advanced MD, and thinner RNFL (p < 0.001). Regional differences were significant for common glaucoma types (p = 0.013) and surgical choice (p < 0.0001). Late and later-than-optimal referrals ranged between 22% and 38.3%, and 30.0% and 41.7% between the regions, respectively. The proportion of timely referrals in the East European region (20%) was significantly lower than that in the South and West European (approximately 40%) and North European (31.7%) regions (p = 0.019). Conclusions Marked differences exist in Europe in glaucoma referral timeliness and surgical practice. Late referral remains frequent and associated with advanced structural and functional damage in Europe.

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.

Objectives: To evaluate the changes in retinal function and neural conduction along the visual pathways after 12 months of treatment with Citicoline oral solution in patients with open-angle glaucoma (OAG). Methods: In this randomized, prospective, double-blind study, 29 OAG patients were enrolled. Fifteen patients (Citicoline Group, 15 eyes) received Citicoline oral solution (Neurotidine^®, 500 mg/day), and 14 patients (Placebo Group, 14 eyes) received placebo for 12 months. Visual field (VF), pattern electroretinogram (PERG), visual evoked potentials (VEP), and Retinocortical Time (RCT) were assessed at baseline and after 6 and 12 months. Brain Diffusion Tensor Imaging (DTI)-Magnetic Resonance Imaging (MRI) was performed at baseline and at 12 months. Results: PERG, VEP, and RCT baseline values were comparable between groups (p > 0.01) at baseline. After 12 months of Citicoline treatment, significant (p < 0.01) increases in PERG P50–N95 and VEP N75-P100 amplitudes, and significant shortening of PERG P50, VEP P100 implicit times and RCT were observed. VEP implicit times shortening significantly correlated with the changes in VF Mean Deviation, and RCT shortening was associated with changes in DTI-MRI metrics in the lateral geniculate nucleus and on optic radiations, without reaching the level of significance. No significant changes were found in the Placebo Group. Conclusions: In OAG, Citicoline oral solution enhances retinal function likely through neuromodulation processes and changes post-retinal visual pathway connectivity. This could explain the improvement of visual field defects.

Background/Objectives: Reversibility of glaucomatous optic-disc cupping, following intraocular pressure (IOP) reduction, represents a fascinating structural response observed in both pediatric and adult patients. This review summarizes evidence on its mechanisms, diagnostic evaluation, and clinical significance. Methods: A comprehensive review of experimental, clinical, and imaging-based studies investigating optic-disc cupping reversibility was conducted. Findings were categorized by patient population, imaging technique, and follow-up duration. Results: Experimental models established a strong correlation between IOP reduction and optic-disc structural recovery. Pediatric glaucoma demonstrated the greatest reversibility due to enhanced ocular tissue elasticity, whereas adult cases showed limited yet measurable structural changes after sustained IOP lowering. Imaging modalities, including confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography (SD-OCT), consistently confirmed quantitative disc-shape changes correlated with pressure reduction. Conclusions: Although optic-disc cupping reversal reflects biomechanical and glial remodeling rather than true neuronal recovery, it remains an important biomarker of successful IOP control. Advanced imaging provides valuable insights into optic-nerve-head (ONH) biomechanics and may improve glaucoma management.

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.

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.

Introduction In order to better understand comorbidity rates and the associated risk of death in patients with glaucoma we retrospective analyzed two groups of subjects aged 50 years and above residing in Lombardy Region (Northern Italy) following them from January 1, 2017 to February 1, 2020 (just before the COVID-19 pandemic started in Italy). The two groups were all subjects with incident glaucoma in 2017 and a 3:1 random sample stratified by age and sex of subjects without glaucoma. Main outcome was overall survival. Other outcomes were incidence of cardiovascular diseases (heart attack, stroke, and peripheral arterial disease). Methods All data were taken from Lombardy Region administrative database and therefore the presence of glaucoma was ascertained using antiglaucoma drug prescriptions, being hospitalized or undergoing an intervention for glaucoma, and having a glaucoma exemption for healthcare co-payments. Results The study identified 14,138 incident cases of glaucoma and selected 42,414 subjects without glaucoma. The number of deaths was higher among glaucoma subjects (11.6%) compared to those without glaucoma (10.5%). The death hazard ratio (HR) for glaucoma subjects compared to controls was 1.07 (95% CI 1.01–1.14, p = 0.015) in the adjusted model. Similarly incidence of stroke was higher in glaucoma compared to non-glaucoma subjects (HR 1.10, 95% CI 1.01–1.20), while the incidence of heart attack and peripheral arterial disease during the follow-up period was similar in the two groups. HRs varied by age classes for death and peripheral arterial disease. Individuals with glaucoma showed higher comorbidity rates compared to those without glaucoma, particularly in diabetes mellitus (16.7% vs. 11.0%) and hypertension (62.2% vs. 58.1%). Conclusions Our results show an increased risk of mortality in subjects with glaucoma compared to those without glaucoma, with age being a significant factor influencing outcomes. These findings suggest the importance of monitoring and managing comorbidities in individuals with newly incident glaucoma to potentially improve their overall health outcomes and quality of life.