BACKGROUND:Despite an extensive armamentarium, the long-term prognosis of heart failure remains poor, and its pathophysiology is still not fully understood. Microvascular function is impaired early in the development of HF and linked to disease progression. Retinal imaging provides a unique opportunity for fast, non-invasive and affordable detection of early systemic microvascular disease. AIM:To provide a systematic overview of current literature regarding retinal microvascular changes in HF. METHODS:A literature search was performed using MEDLINE, EMBASE, Web of Science and Cochrane Library (Registration number: INPLASY202450114). Studies on retinal microvascular changes, visualized by fundus photography, adaptive optics, optical coherence tomography, scanning laser Doppler flowmetry and dynamic vessel analysis in patients with HF were included. RESULTS:Twenty-four articles were included for qualitative analysis. Compared to healthy controls, patients with HF consistently exhibited reduced flicker light-induced dilation of retinal arterioles and venules, as well as decreased vessel density around the optic nerve head. More limited evidence suggests an increase in arteriolar wall thickness and wall cross-sectional area. Findings supporting other structural changes in the retinal microvessels were inconsistent. The pathophysiology behind retinal vascular abnormalities in HF and their correlation with HF severity remain incompletely understood. Nevertheless, retinal imaging holds promise for identifying individuals at risk of developing HF and predicting prognosis. Overall, analysis of retinal microvascular structure and function could serve as a valid surrogate marker for future interventional studies in HF. CONCLUSION:This review provides a systematic overview on retinal imaging as a promising tool in the prevention, risk stratification and management of HF, and as a surrogate marker in clinical trials.

Microvascular dysfunction is increasingly recognized as an important contributor to ocular and systemic diseases, including diabetic retinopathy, cardiovascular disease, and Alzheimer's disease and related dementias. Elucidating how early microvascular injury contributes to disease pathobiology, and development of sensitive, quantifiable features of microvascular dysfunction, represents a critical frontier for improving risk stratification, enabling earlier diagnosis and guiding targeted interventions. In this context, retinal imaging has emerged as a powerful modality, enabling non-invasive, high-resolution visualization of the microvasculature with color and (ultra)widefield fundus imaging. Rapid technological advances have led to an array of, open-source tools for quantitative extraction of retinal microvascular features. However, progress in this field is hampered by poor comparability between tools, limiting reproducibility and cross-study integration. Differences between tools originate from variations in image processing steps, including vessel segmentation, arteriole-venule classification, optic disc detection, region-of-interest definition, image quality assessment, and the algorithms for metric calculation. In this review we comprehensively compare existing analytical analysis tools for static vessel analyses and delineate how these methodological differences influence the vascular measure quantification. To advance robust, scalable biomarker development, we propose a methodological framework to standardize and harmonize retinal microvascular quantification. This framework can guide future studies in addressing key gaps in literature and in developing imaging biomarkers for clinical use. Critical open questions include whether and when retinal imaging features change during ocular and systemic disease, whether microvascular dysfunction is reversible, how microvascular dysfunction contributes to neurodegeneration, and how central and peripheral retinal microvascular dysfunction differ.

BACKGROUND:To compare the safety and efficacy of trabeculectomy, PRESERFLO MicroShunt (PRESERFLO) and XEN45 Gel Stent (XEN) in patients with open-angle glaucoma (OAG) during the first year. METHODS:A single-centre retrospective case-control study included 384 eyes undergoing standalone glaucoma surgery (2013-2020). Propensity score matching was used to balance baseline covariates. The primary outcome was surgical success at 1 year. Complete success was two-fold defined as an IOP of 6-15 or 6-18 mmHg, without loss of light perception, additional glaucoma surgery or IOP-lowering medication; qualified success allowed medication and/or selective laser trabeculoplasty. Secondary outcomes included IOP, best-corrected visual acuity, medication use and complications/interventions. RESULTS:We included 117 in the trabeculectomy, 82 eyes in the PRESERFLO group and 185 in the XEN group. Complete success was lower after XEN for both IOP criteria (44.0%, IOP 6-18 mmHg and 41.5%, IOP 6-15 mmHg) compared to trabeculectomy (59.8% and 59.3%, respectively; p < 0.05) and PRESERFLO (73.5% and 73.3%, respectively; p < 0.001). All procedures effectively and comparably reduced IOP to 12.3 ± 4.1 mmHg (trabeculectomy), 12.7 ± 3.5 mmHg (PRESERFLO), 13.4 ± 4.3 mmHg (XEN). The proportion of drop-free patients was higher after PRESERFLO (81.0% vs. 58.6% and 56.6%, after trabeculectomy and XEN, respectively). Significant hypotony was uncommon and comparably so. Minor post-operative interventions were more common in trabeculectomy patients compared with PRESERFLO and XEN. CONCLUSION:This study suggests equal success rates for PRESERFLO and trabeculectomy, both outperforming XEN at 1 year, with fewer post-operative interventions for PRESERFLO compared to trabeculectomy. Overall complication rates were comparable across groups.

BACKGROUND:Identifying patients with glaucoma who are at risk of rapid disease progression is crucial to preventing vision loss. We aimed to develop and externally validate G-PROG, a deep learning model that predicts 2-5-year glaucoma progression from baseline colour fundus photographs (CFPs). METHODS:G-PROG was trained and validated on data from a single centre (UZ Leuven, Leuven, Belgium); the other datasets (Brussels, Belgium; Liège, Belgium; Tampere, Finland; Mainz, Germany; and Hangzhou, China) served as external test sets. Across six glaucoma departments, we analysed 161 827 fundus images from 127 962 visits (13 913 patients), totalling 128 021 eye-years of follow-up. Progression was defined by the G-RISK slope, calculated via within-eye linear regression on longitudinal G-RISK predictions over follow-up intervals of 2-5 years. G-RISK is a previously validated deep learning model that quantifies glaucomatous optic nerve damage from CFPs. We trained 20 G-PROG configurations with varying inclusion criteria applied to the number of visits, image quality, time between visits, and G-RISK at baseline. Performance was evaluated using the area under the receiver operating characteristic curve (AUC), the coefficient of determination (R2), and explained variance score (EVS). G-RISK slope as a progression biomarker was validated against the visual field mean deviation (MD) slope and average retinal nerve fibre layer thickness (RNFL) slope. FINDINGS:Significant AUC values were obtained in 18 out of 20 model configurations, with internal validation reaching a maximum AUC of 0·98 (95% CI 0·97-1·00) across follow-up intervals (2-5 years). In glaucomatous eyes with a baseline G-RISK exceeding 0·6, the maximum AUC was 0·92 (0·85-0·98). For external validation, the predictions from the eight top-performing configurations (selected based on positive R2 and minimal discrepancy between R2 and EVS in internal validation) were averaged. Maximum AUC values ranged from 0·74 to 0·86 across the five test datasets. G-RISK slope showed significant agreement with established progression markers, with maximum AUCs of 0·82 for MD slope and 1·00 for average RNFL slope. INTERPRETATION:Externally validated across five international cohorts, G-PROG predicts 2-5-year glaucoma progression from baseline CFPs. Prospective evaluation is warranted to assess whether G-PROG can improve risk stratification and resource allocation in glaucoma care. FUNDING:This work was funded and supported by grants from the National Medical Research Council, National Research Foundation Singapore, National Health Innovation Centre Singapore, SingHealth and Duke-NUS, Duke-NUS, the Singapore Eye Research Institute and Nanyang Technological University and the Singapore Eye Research Institute, the Competitive Research Funding of the Pirkanmaa Wellbeing Services County, the LUX-Foundation for Glaucoma Research, state funding for university-level health research at Tampere University Hospital, Wellbeing Services County of Pirkanmaa, the Tampere University Hospital Support Foundation, and the Belgian Ophthalmology Cooperation in Clinical Sciences initiative hosted by the Funds for Research in Ophthalmology.

The relationship between structural and functional damage in glaucoma, the structure-function relationship, forms the cornerstone of disease assessment, monitoring, and prognosis. We provide an updated synthesis of current knowledge on the structure-function relationship, emphasizing recent advances in imaging, analytical methodologies, and artificial intelligence (AI)-driven modelling. We summarize merging evidence from optical coherence tomography (OCT), OCT angiography, and related imaging technologies, highlighting their integration with functional measures such as standard automated perimetry. We also evaluate classical, mechanistic, statistical, and hybrid models that link retinal microstructure and visual function and discusses the role of AI-based approaches in predicting visual field loss and improving clinical interpretation. The structure-function relationship in glaucoma is predominantly nonlinear for currently used clinical metrics, reflecting biological redundancy, psychophysical variability, and measurement constraints with current tools. Stage-dependent changes reveal strong correlations during moderate disease but increasing divergence in early and advanced stages due to floor effects and functional compensation. Emerging frameworks, such as anatomically compensated mapping, multimodal fusion, and deep learning, enhance accuracy and allow individualized structure-function relationship modelling. Data quality, myopia-related anatomical variability, and cross-device harmonization remain key limitations. Integrating multimodal imaging, AI-based harmonization, and longitudinal data will advance structure-function relationship modelling beyond static correlations toward dynamic, personalized biomarkers of neurovascular and neurofunctional health. These developments promise earlier detection, more precise monitoring, and individualized glaucoma management through a deeper mechanistic understanding of the link between retinal structure and visual function.

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.

PURPOSE:Evaluate a deep learning model's performance as a pre-referral filter for referable glaucoma using colour fundus photographs. METHODS:Retrospective cohort study. Patients referred for glaucoma evaluation in 2021 were included. Referred glaucoma suspects underwent testing (visual acuity, colour fundus photography, OCT and visual fields) followed by specialist review. Clinician evaluation was classified as accepted for face-to-face visit (further classified as glaucoma diagnosis and clinically suspicious) or discharged. Hypertensive (IOP ≥ 24 mmHg), on IOP-lowering treatment, or patients who had undergone previous glaucoma surgery were excluded as they require glaucoma follow-up regardless. A deep learning model analysed the colour fundus photographs and a simulated referral was considered if the model's output exceeded the manufacturer's recommended threshold (0.73). The model's referral decision was compared against glaucoma experts' glaucoma diagnosis and treatment; performance was measured. RESULTS:A total of 96 patients were included in the study; the mean age was 66.5 (SD: ±15.5) years; around a third of the included participants were male (n = 33; 34.4%). Of these referred patients, 37 were accepted by the glaucoma department (38.5%); 19 were found to have glaucoma (19.8%). A model-led system would have prevented over a third of referrals (36; 37.5%) while not missing any glaucoma cases. The model presented high sensitivity (1.00; 95% CI 0.82-1.00), and reasonable specificity (0.65; 95% CI 0.53-0.75) and positive predictive value (0.41; 95% CI 0.27-0.57). CONCLUSIONS:Glaucoma rate in ophthalmologist-referred patients was low. A deep learning-led system would have accurately referred all patients with glaucoma and reduced unnecessary observations. Current model performance can act as a filter between referring and receiving specialised healthcare.

BACKGROUND/AIMS:Deep learning algorithms have shown promise for glaucoma detection using retinal imaging. The Northern Finland Birth Cohort Eye Study is a randomised prospective cohort designed to evaluate the efficacy and cost-effectiveness of glaucoma screening in a middle-aged population. This study assessed the performance and generalisability of G-RISK, a deep learning model for glaucoma screening from fundus images, in individuals aged 45-49 years with low glaucoma prevalence (1.1%). METHODS:Four screening scenarios were evaluated: detection of (1) glaucoma eyes, (2) glaucoma patients, (3) glaucoma and glaucoma suspect eyes and (4) glaucoma and glaucoma suspect patients. Performance across four photographic modalities was assessed using the area under the receiver operating characteristic curve (AUC), the precision-recall AUC (PR-AUC), and sensitivity at 95% specificity. RESULTS:G-RISK achieved its highest performance when screening for glaucoma eyes using colour fundus photographs, with an AUC of 0.83 (95% CI 0.75 to 0.90), PR-AUC of 0.16 (95% CI 0.05 to 0.28) and sensitivity at 95% specificity of 0.43 (95% CI 0.28 to 0.59). Furthermore, discrimination remained consistent across other modalities (AUC 0.75-0.78). Performance was higher for confirmed glaucoma than combined glaucoma and glaucoma suspect cases (AUC 0.83 vs 0.67). CONCLUSIONS:G-RISK achieved the best results on colour fundus images, while maintaining discrimination across other imaging modalities. Screening metrics were constrained by the relatively young age and low glaucoma prevalence of the cohort. The reduced performance observed when including glaucoma suspects may relate to variability and uncertainty in their clinical definition.

Glaucomatous optic neuropathy (GON), affecting an estimated 64.3 million people globally, causes irreversible vision loss when not detected early. Traditional diagnosis requires time-consuming ophthalmic examinations by specialists. Recent deep learning models for automating GON detection from colour fundus photographs (CFP) have shown promise but often suffer from limited generalizability across different ethnicities, disease groups and examination settings. To address these limitations, we introduce GONet, a robust deep learning model developed using seven independent datasets, including over 119 000 CFPs with gold-standard annotations and from patients of diverse geographic backgrounds. GONet consists of a DINOv2 pre-trained self-supervised vision transformer fine-tuned using a multisource domain strategy. GONet demonstrated high out-of-distribution generalizability, with an AUC of 0.88-0.99 in target domains. GONet performance was similar or superior to state-of-the-art works and the cup-to-disc ratio, by up to 18.4%. GONet is available via Lirot.ai (www.aimlab-technion.com/lirot-ai). We also contribute a new dataset consisting of 747 CFPs with GON labels as open access, available at https://doi.org/10.13026/pdxv-m215.

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

Background/Objectives: Although advances in understanding glaucoma have been made, early detection remains challenging due to the asymptomatic nature of the disease. The Metabolomics In Surgical Ophthalmological Patients (MISO) study previously demonstrated that aqueous humor (AH) metabolomics can distinguish glaucoma patients from controls. We aimed to determine if the metabolic profile of AH has predictive power for overall survival and glaucoma progression after surgery. Methods: Glaucoma patients (n = 34) were retrospectively analyzed and classified into progression categories based on surgical and medical interventions and assessed for survival. Results: Glutamine and α-ketoglutarate were significantly associated with glaucoma progression, while N-acetylglutamate, lysine, and creatine correlated with mortality. These metabolites are linked to excitotoxicity, mitochondrial dysfunction, and oxidative stress, highlighting their potential role in glaucoma pathophysiology. Conclusions: These results suggest that metabolomic profiling of AH could provide valuable biomarkers for predicting surgical outcomes and overall survival, paving the way for individualized therapeutic approaches. Further studies are required to confirm these findings before they can be integrated into clinical practice.

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.

Glaucoma, a leading cause of irreversible blindness, is primarily managed by lowering intraocular pressure, yet treatment remains limited by poor adherence, ocular surface toxicity, and systemic adverse effects. This review focuses specifically on treatment simplification strategies in topical glaucoma therapy, exploring the paradigm shift towards a "Less is better" approach in glaucoma care, with particular emphasis on the use of preservative -free formulations, lower active ingredient concentrations, and fixed combinations. These approaches aim to improve treatment tolerability, adherence, and clinical outcomes while minimizing toxicity, complexity, and environmental burden. Although barriers such as higher costs and limited long-term data remain, this new approach represents a patient-centred, sustainable, and clinically effective model for the future of glaucoma management.

Purpose:To evaluate the efficacy and safety of preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01%) compared with BAK-preserved bimatoprost ophthalmic solution 0.01% (PB 0.01%) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods:In two international Phase III, randomized, investigator-masked trials, 951 patients with OAG or OHT and controlled intraocular pressure (IOP) at screening were randomized following washout to receive PFB 0.01% (n=468) or PB 0.01% (n=483) daily for 84 days. The primary endpoint was the mean IOP change from baseline at Weeks 6, and 12 at 8 am, 10 am, and 4 pm. Safety was assessed by monitoring adverse events (AEs), conjunctival hyperemia, corneal fluorescein staining, ocular tolerance, and patient reported symptoms. Results:PFB 0.01% and PB 0.01% demonstrated similar IOP reductions at all time points (31-35% vs. 32-36%, respectively). Across the 12-week treatment period, between-group differences in IOP lowering were <1.0 mm Hg at all time points. A trend toward fewer patients reporting treatment-related ocular AEs was observed in the PFB 0.01% group compared with the PB 0.01% group (23.8% vs. 27.6%, respectively). Most common events included conjunctival hyperemia and eye irritation. There was a numerical trend in favor of PFB 0.01% in terms of presence of conjunctival hyperemia and CFS at Week 6 and Week 12. Conclusion:This pooled analysis of nearly 1000 patients confirmed the efficacy and safety outcomes observed in the individual Phase III pivotal studies, supporting the clinical use of preservative-free bimatoprost 0.01% in the management of glaucoma and OHT.

BACKGROUND/AIMS:Minimally invasive glaucoma surgery (MIGS) procedures are commonly combined with phacoemulsification to provide additional intraocular pressure (IOP) and/or topical medication reduction in patients with mild-to-moderate glaucoma. This study compared the 1-year efficacy and safety of excimer laser trabeculostomy (ELIOS) versus trabecular micro-bypass stenting (iStent inject and iStent inject W), both performed in combination with cataract surgery. METHODS:This multicentre retrospective cohort study included patients undergoing combined phacoemulsification with either ELIOS (Phaco-ELIOS) or iStent implantation (Phaco-iStent) at three European centres between 2020 and 2025. The primary endpoint was IOP at 12 months postoperatively. Secondary endpoints included longitudinal IOP and medication use, surgical success, adverse events and the need for secondary glaucoma surgery. Longitudinal outcomes were analysed using multiple imputation. RESULTS:A total of 343 eyes were included (164 Phaco-ELIOS and 179 Phaco-iStent), with 1-year follow-up available in 70%. Mean IOP decreased by 21.6% for Phaco-ELIOS and 20.7% for Phaco-iStent and remained stable through 12 months (p=0.74). Both procedures were associated with a similar reduction in postoperative topical glaucoma medications (0.56 vs 0.41; p=0.2). With Phaco-ELIOS, a higher proportion of eyes achieved medication reduction (46.4% vs 31.3%; p=0.02). Rates of adverse events and secondary glaucoma surgery were low and comparable in both groups. CONCLUSION:Phaco-ELIOS and Phaco-iStent provided comparable 1-year IOP reduction and overall safety. Phaco-ELIOS showed a greater number of patients with topical medication reduction, supporting its role as an effective combined MIGS option in patients undergoing cataract surgery.

IntroductionEpithelial inclusion cysts of the iris are a rare complication following ocular surgery or trauma and typically exhibit a more aggressive course than other types of iris cysts. Their management remains challenging due to their tendency for rapid growth, which can lead to obscuration of the visual axis, elevated intraocular pressure, corneal decompensation, and secondary glaucoma or uveitis. Particularly in pediatric and young adult patients, the high proliferative capacity of epithelial cells increases the risk of recurrence. Current treatment modalities, including Nd:YAG laser cyst disruption, sclerosing agent irrigation, and complete surgical excision, are associated with high recurrence rates.MethodsIn this retrospective case series we describe two patients with a recurrent iris cyst resulting from a trauma in childhood, and successfully managed with glaucoma drainage devices (Baerveldt tube and PAUL tube) to provide continuous cyst fluid drainage.ResultsIn both cases, implantation of the drainage device effectively controlled the progression of the cyst and maintained its position outside the visual axis. The pediatric patient developed a scleral perforation at the surgical site one year postoperatively, following additional mechanical trauma from ocular rubbing; this complication was successfully managed with surgical repair, resulting in a favorable outcome. In the second case, the patient experienced a transient postoperative diplopia, which resolved spontaneously without further intervention.ConclusionThese cases illustrate the potentially promising role of glaucoma drainage devices as a new treatment strategy for recurrent iris cysts, particularly after multiple prior resections or when conventional therapies have failed.

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.

Alzheimer’s disease (AD) pathology is increasingly recognized to manifest in the retina, offering a non-invasive window for early biomarker discovery. This proof-of-concept study investigated whether multimodal retinal imaging—hyperspectral imaging (HSI), optical coherence tomography (OCT), and color fundus photography (CFP)—can differentiate individuals with and without cerebral amyloid-beta (Aβ) pathology in 40 participants with PET-confirmed Aβ status (17 Aβ+, cognitively normal or with mild cognitive impairment; 23 Aβ− cognitively normal controls). HSI-derived gray-level co-occurrence matrix (GLCM) texture, OCT-derived ganglion cell–inner plexiform layer (GC-IPL) thickness, and CFP-derived vascular biomarkers (VBMs) were extracted, and logistic regression with leave-one-out cross-validation assessed classification performance per modality, alone and combined; the cohort was supplemented with AD dementia patients for an exploratory cross-sectional comparison across disease-stage groups. HSI showed nominally lower GLCM correlation at 466 nm in Aβ+ participants, most pronounced in the inferior macula (AUC = 0.72). GC-IPL thickness showed a similar inferior-predominant regional pattern. Combining HSI and GC-IPL features yielded the best performance (AUC = 0.84; sensitivity = 0.82; specificity = 0.78), although this improvement over the unimodal models did not reach statistical significance, whereas vascular biomarkers contributed minimally. In an exploratory cross-sectional comparison across AD stage groups drawn from two cohorts, HSI features showed a non-monotonic pattern, decreasing in early Aβ+ stages and rising again in dementia. These findings provide preliminary evidence of complementary information between HSI and OCT for detecting retinal biomarkers of early-stage AD, supporting multimodal retinal imaging as a scalable screening approach warranting validation in larger, longitudinal cohorts.

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.