Neurofibromatosis-type 1 (NF1) is a genetic disorder characterized by developing optic pathway gliomas (OPGs) in 15%-20% of patients with higher estimates where consanguinity is prevalent. Clinically, NF1-OPG might be unpredictable with the risk of OPG progression and visual impairment. The optimal time for screening is controversial. We aim to identify the mean/median age at diagnosis of NF1-OPG and its clinical spectrum. A systematic review of PubMed, Web of Science, and Embase databases was conducted for English-language publications from January 1993 to October 2025, exploring the visual screening of OPGs in NF1 patients, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews (PROSPERO ID: CRD420251036244). Inclusion criteria focused on studies reporting the age at OPG diagnosis and visual manifestations in NF1 patients. Data were extracted on demographics, age at NF1 and OPG diagnosis, tumour location (using the Dodge classification), and presenting symptoms. Sixteen studies met the inclusion criteria. Among 4 739 NF1 patients, 818 had OPGs, with prevalence ranging from 4.2% to 46.7%. The age at NF1 diagnosis ranged from 0 to 132 months (mean: 18-38 months), and at OPG diagnosis from 0-240 months (median: 29-58 months). Approximately 58.4% of OPGs were asymptomatic, and 25% were above the age of 5 years. Among symptomatic patients, the most frequent presentations included decreased visual acuity (62%), abnormal optic disc (45%), proptosis (20%), strabismus (12%), and visual field defects (7%). NF1-related OPGs typically present early within 6 years of age. Early ophthalmologic and/or radiologic screening at the time of NF1 diagnosis enhances the detection of silent OPGs.
Actinic Keratosis (AK) is a precancerous lesion related to radiation exposure, leading to malignant transformation (MT). This study aims to assess the epidemiological, clinical and histopathological features of AK in the eyelid to allow early diagnosis and treatment. The McGill University Ocular Pathology & Translational Research Laboratory studied 200 biopsied lesions from 192 patients with a final diagnosis of AK amidst 1993 and 2023. Out of the total, 16 patients and 17 lesions were excluded due to insufficient data about the lesion's location. Samples from 176 patients (183 lesions) were analyzed. The mean age of diagnosis for eyelid AK (EAK) was 73 years old. The co-occurrence of AK and squamous neoplasia within the same specimen was 18.6% for EAK. The typical histopathological variant was the more prevalent representing 53% of all EAK lesions. The most common lesion site in the eyelid was the lower eyelid, constituting for 52.2%. To the best of our knowledge, this is the largest series of patients with EAK. This study emphasizes the importance of early excision with safety margins as a primary choice of treatment due to the risk of co-occurrence of AK and squamous neoplasia.
Optic neuritis is often managed by neuro-ophthalmologists. Neuro-imaging plays an important role in diagnosis. Radiologists can influence care by communicating pertinent findings and recommending next steps. Increasingly, patients have direct access to their reports, which may affect their understanding, anxiety, and interactions with clinicians. This study aimed to characterize the frequency and nature of radiologists' recommendations in magnetic resonance imaging (MRI) reports for optic neuritis. A retrospective chart review. Patients referred to a tertiary neuro-ophthalmology clinic between November 2007 and May 2025 with new-onset optic neuritis and no prior demyelinating disease METHODS: Data on imaging protocols, diagnostic terminology, differential diagnoses, recommendations, and incidental findings were obtained from electronic medical records. We included 219 MRI reports (73.1% female; mean age: 37.4 ± 13.1 years). MRI of the brain and orbit was the most common protocol (73.5%). Signs of demyelination or possible demyelination were noted in 109 cases (49.8%). Overall, recommendations were provided in 16.0% (35/219) to patients, with 20.2% (22/109) of those showing demyelination compared with 2.7% (3/110) without demyelination. The top 3 recommendations were an MRI of the spine (17/22; 77.3%), follow-up imaging (2/22; 9.1%), and follow-up appointment with patient and MRI of orbit (1/22; 4.5% each). Among participating radiologists, recommendations were given to patients in a minority of optic neuritis cases, with MRI of the spine being the most common recommendation. There was a higher likelihood of a recommendation if there were brain changes (20%) compared with no brain changes (3%). These findings highlight variability in reporting practices and support the adoption of standardized language for describing optic nerve abnormalities and appropriate follow-up, reducing unnecessary testing and potential patient anxiety.
Within the past few decades, several studies have reported intraocular pressure (IOP)-lowering effects associated with tetrahydrocannabinol (THC) compounds as an alternative or complementary agent to conventional glaucoma therapies. The purpose of this study is to generate pooled estimates on the IOP-lowering effects of THC. This systematic review and meta-analysis article was registered a priori on PROSPERO (CRD420251007916). MEDLINE, EMBASE, and Web of Science were searched for studies reporting IOP reduction following THC administration. Two reviewers independently performed screening, data extraction, and risk of bias assessments. A random-effects meta-analysis of mean differences was performed to estimate the overall pooled peak percentage reduction in IOP following THC administration, stratified by route of THC administration. Five studies were included, consisting of a total of 99 patients and 69 with THC exposure/intervention. Overall, the pooled peak percentage reduction in IOP after THC administration was 14.66% (95% CI: [3.38%, 25.93%]; p < 0.005). By route of THC delivery, the pooled peak percentage reduction in IOP was 33.27% (95% CI: [20.36%, 46.17%]; p < 0.0001) with the IV route. It was 10.65% (95% CI: [-7.60%, 28.89%]) with the oral route and 9.36% (95% CI: [-8.89%, 27.6%]) with the topical route. Four studies reported the peak percentage reduction in IOP after THC and control administration. From these studies, the pooled peak percentage reduction in IOP after THC was 6.88% (95% CI: [-9.56%, 23.33%]; p = 0.41) and nonsignificantly different from control. Our study generated literature-pooled estimates of the overall and route-stratified peak percentage reduction in IOP following THC administration. THC significantly reduced IOP, although comparatively less significant to the control group.
Selective laser trabeculoplasty (SLT) has increasingly been used as a first-line glaucoma treatment. To better understand its impact on the Canadian patient and health care system, a cost-effectiveness analysis was performed to compare SLT against topical eye medications for patients with newly diagnosed open-angle glaucoma. Using a Markov model with a 20-year horizon from a health care payer perspective, the incremental cost-effectiveness ratio (ICER) of treating newly diagnosed mild open-angle glaucoma with SLT and medication was calculated. A discount rate of 1.5% was applied to all costs and health outcomes. Sensitivity and probabilistic analyses were performed to test the uncertainty of the model. The base case analysis indicated that patients who received the SLT treatment had a lower health care system cost of $1,671.48 and a higher quality-adjusted life year of 0.09 per patient compared with the medication treatment. As a result, the SLT treatment dominates medication treatment. The one-way cost-effectiveness sensitivity analysis showed that SLT dominates the medication treatment at all discount rates between 0% and 3%. The largest effects on the ICER value were variations in medication utility of ocular hypertension and mild glaucoma state, and SLT utility of mild glaucoma state, based on the tornado diagram. Probabilistic sensitivity analyses also demonstrated that the SLT treatment dominated the medication treatment. Our model suggests that SLT as the initial treatment strategy for glaucoma patients and investment in SLT could lead to improved clinical outcomes, costs, and resource utilization within the Canadian health care system.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for diabetes, obesity, and cardiovascular risk reduction. However, their ocular safety profile, particularly regarding age-related macular degeneration (AMD), remains uncertain. This systematic review evaluates the association between GLP-1 RA use and the incidence or progression of AMD including both nonexudative and neovascular subtypes. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD420251183938). MEDLINE, Embase, CENTRAL, Web of Science, and PubMed were searched from inception through 2025 for observational studies and randomized trials evaluating AMD outcomes among adults exposed to GLP-1 RAs. Comparators included nonuse, placebo, or alternative metabolic therapies. Risk of bias was assessed using Risk of Bias in Non-Randomized Studies of Interventions and certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Due to heterogeneity of outcome definitions, results were synthesized qualitatively. Eight observational studies encompassing 91 408 to 600 816 participants were included. GLP-1 RA use was associated with a reduced incidence of nonexudative AMD across diabetic and nondiabetic populations, with relative risk reductions varying substantially by population, comparator, and follow-up duration. Findings for neovascular AMD were heterogeneous: most studies reported neutral or protective associations, whereas one population-based cohort of older adults with diabetes observed an increased risk (adjusted hazard ratio 2.21, 95% CI 1.65-2.96), with low absolute event rates. Overall risk of bias was moderate to high, and certainty of evidence for all outcomes was very low. Current evidence does not demonstrate a consistent increase in AMD risk associated with GLP-1 RA therapy and may be associated with a lower incidence of nonexudative AMD, although the certainty of evidence is very low and noncausal explanations cannot be excluded. Prospective studies with standardized endpoints are needed to clarify causal relationships.
The pattern electroretinogram (PERG) has been investigated as a potential functional biomarker for detecting retinal ganglion cell dysfunction in glaucoma. However, reported diagnostic performance appears to vary across disease stages and recording protocols. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of PERG for glaucoma. PubMed, Embase, and Web of Science were comprehensively searched up to March 2025. Studies assessing PERG accuracy against a clinical reference standard were included. Risk of bias was assessed using QUADAS-2. Data were synthesized using a hierarchical summary receiver operating characteristic model. Subgroup analyses were performed based on disease severity and International Society for Clinical Electrophysiology of Vision-standardized protocols. Sources of heterogeneity were explored through sensitivity analyses. Twenty-one studies involving 1 793 participants (2 580 eyes) were analyzed. Pooled sensitivity and specificity for manifest glaucoma were 0.79 (95% CI: 0.76-0.82) and 0.78 (95% CI: 0.75-0.80), respectively. Diagnostic performance for glaucoma suspects was comparable. The ocular hypertension subgroup exhibited moderate pooled sensitivity (0.54) with considerable heterogeneity. Sensitivity analysis suggested that this variation might stem from the higher sensitivity of the Hemifield protocol compared with standard full-field stimulation. Regarding temporal frequency, transient PERG appeared to demonstrate marginally higher diagnostic estimates than steady-state protocols. Current literature affirms the clinical viability of PERG; however, inconsistent performance metrics in the preperimetric phase suggest that standard full-field configurations may lack the requisite sensitivity to capture incipient localized damage. Preliminary findings suggest that protocol optimization-potentially involving Hemifield stimulation-may offer advantages for detecting early functional loss, warranting further validation in future studies.
To investigate the effect of peripapillary retinoschisis (PPRS) on circumpapillary and macular retinal thickness and its correlation with longitudinal changes in the visual field. A wide-field scan using swept-source optical coherence tomography was performed to measure the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness. The relationship between longitudinal measurements of cpRNFL, mGCIPL thickness, and visual field index (VFI) was assessed using repeated-measures correlation. Pearson correlation analysis was used to evaluate the correlation between the VFI change rate and the change rates of cpRNFL or mGCIPL thickness. A total of 25 eyes were included in the final analysis. The cpRNFL thickness significantly increased with PPRS (P < .001) and decreased after the resolution of PPRS (P < .001), whereas the mGCIPL thickness did not change with PPRS (all P > .05). The longitudinal measurements of cpRNFL thickness did not show a significant correlation with VFI (P = .560), nor did its change rate correlate significantly with the progression rate of VFI (P = .294). In contrast, mGCIPL thickness exhibited a significant correlation with the VFI (P < .001), and its change rate also showed a significant correlation with the progression rate of the VFI (P = .035). The mGCIPL thickness could serve as a reliable marker for assessing progression in glaucomatous eyes with PPRS. Monitoring changes in each parameter across consecutive tests is essential to identifying the most appropriate marker for detecting glaucoma progression, given that structural alterations such as PPRS may occur in glaucomatous eyes.
This study aimed to validate administrative data case definitions for identifying individuals with uveitis within health administrative data and to assess case definition performance in different age groups. Among 200,386 eligible patients in a large, province-wide, multisite primary care electronic medical record data repository in Ontario, Canada, 1 020 individuals were selected for medical review based on uveitis-related search terms. After medical record review, 431 cases were identified as having uveitis, in addition to 10,000 nonuveitis cases, which were used to make up the validation reference sample. After the reference standard was linked with administrative data, the performance characteristics (sensitivity and positive predictive value [PPV]) of case definitions using combinations of data sources and time windows were assessed overall, and stratified by age groups. Within the validation sample, the median age of identified uveitis patients was 55 years, with the majority falling within the 26-64 age group. Females represented 59.9% of cases. Family physicians (72.2%) and ophthalmologists (60.6%) were the most common sources of diagnosis documentation, and anterior uveitis was the most prevalent classification (64.0%). At least 1 diagnosis code for uveitis had the highest sensitivity at 74.0% (95% CI: 69.9-78.2) with a PPV of 54.3% (95% CI: 50.2-58.3). PPV increased with more physician diagnosis codes but was accompanied by decreased sensitivity. Case definitions demonstrated variations in sensitivity and PPV across different age groups. This study identified administrative data case definitions for identifying uveitis, with varying sensitivity and PPV for a range of research purposes and data availability.
Inherited optic neuropathies (IONs) cause progressive visual loss and substantially affect quality of life. This updated systematic review aims to synthesize and evaluate evidence on the patient experience of living with IONs, identify currently used assessment tools, and highlight areas for improvement in research and clinical care. We systematically searched MEDLINE, EMBASE, PsycINFO, CINAHL, and Scopus for studies on (i) inherited optic neuropathies; (ii) quality of life or health status; (iii) patient-reported outcome measures; and/or (iv) qualitative research. Inclusion was restricted to peer-reviewed studies. Screening, data extraction, and risk of bias assessment were conducted using Covidence. From 1775 unique records, 5 studies met the inclusion criteria. They evaluated quality-of-life outcomes in patients with Leber hereditary optic neuropathy or autosomal-dominant optic neuropathy across 6 countries. Patient-reported outcome measures used included National Eye Institute Visual Functioning Questionnaire-39, National Eye Institute Visual Functioning Questionnaire-25, Short-Form 12 Health Survey, Beck Depression Inventory, and Pittsburgh Sleep Quality Index. Only one study used qualitative interviews to explore the emotional, social, and financial impacts on patients and families. This updated systematic review builds upon previous work to further characterize the impact of ION on patients living with these conditions and the tools currently used to assess them. We highlight the need for a multifaceted approach to ION management, combining medical treatment with comprehensive psychosocial support to work toward more patient-centred care and improved quality of life for those living with these challenging conditions.
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To evaluate vitrectomy with membrane peeling across the spectrum of myopic traction maculopathy (MTM) and identify prognostic factors for anatomical and functional success. Patients with MTM who underwent vitrectomy and membrane peeling between 2018 and 2023 were included. Percentage reduction in mean foveal thickness (MFT) was used as a marker of anatomical outcome, and visual acuity was the primary outcome. The secondary outcomes were factors associated with anatomical success and visual acuity (VA) improvement. Ninety-four eyes from 84 patients were included. For myopic foveoschisis-only (37 eyes), the anatomical success rate was 95% with a mean of an 8-letter gain. For isolated macular detachment (without macular holes) (15 eyes), 93% achieved retinal reattachment with a mean of a 3.5-line gain. Isolated macular holes (22 eyes) achieved macular hole closure in 73% of cases with a mean of a 7-letter gain. Macular hole retinal detachment (20 eyes) achieved retinal reattachment in 80% of cases and simultaneous macular hole closure in 20%, with a mean of 3-letter gain. Higher preoperative MFT (p < 0.001) and more advanced perpendicular staging (p < 0.001) were associated with greater % MFT reduction. Better preoperative VA (p < 0.001), less advanced tangential staging (p = 0.016), and preoperative phakic status (p = 0.004) were predictive of better postoperative VA. For myopic foveschisis-only, the use of long-acting gas was associated with a postoperative VA that was 3 lines worse (p = 0.04). Vitrectomy with membrane peeling is effective in the management of MTM, especially for myopic foveoschisis-only and isolated macular detachment. Less advanced tangential stages and better preoperative VA are predictive of better postoperative VA.
To investigate the accuracy of intraocular lens (IOL) calculations for patients with Fuchs' endothelial dystrophy (FED) undergoing Descemet stripping only (DSO) combined with cataract surgery. Retrospective case series METHODS: All FED patients who underwent combined DSO and cataract surgery between August 2020 and January 2023 and met the following criteria were included: guttae in the central 4-5 mm of the cornea, no corneal edema, a clinically healthy peripheral endothelium, and a desired emmetropic target. IOL calculations were made using the Barrett Universal II formula. Eleven eyes were included in the study. The mean age was 68.3 ± 7.9 years. All patients achieved corneal clearance with no observed decompensation. Corrected distance visual acuity improved significantly with sustained improvement at the most recent follow-up (0.59 ± 0.48 vs 0.18 ± 0.16 logMAR; median follow-up 16.5 months). A mean refractive target of -0.64 ± 0.14 D was selected on the basis of prior experience with Descemet membrane endothelial keratoplasty. The mean difference between postoperative MRSE and target refraction was +0.33 ± 0.53 D with a median of +0.18 D. There was no significant change in astigmatism. In select FED patients, DSO combined with cataract surgery can provide significant improvements in vision. In this cohort, combined surgery induced a mean hyperopic shift of 0.33 D. When selecting an IOL power for this population, one should take this into account to achieve optimal visual outcomes.
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Chiari malformation (CM) comprises congenital or acquired hindbrain herniations (>5-mm cerebellar tonsillar descent below the foramen magnum) that disrupt cerebrospinal fluid flow and compress neural structures. While neurological symptoms are well recognized, ophthalmic manifestations, such as papilledema, diplopia, and nystagmus, which are uncommon in the overall CM population but may serve as important diagnostic clues when present, remain undersynthesized. This systematic review summarizes the ophthalmic manifestations of CM to identify symptom patterns, mechanisms, and implications for early diagnosis and interdisciplinary management. EMBASE and MEDLINE databases were searched in June 2024, following PRISMA guidelines. English-language articles describing ophthalmic findings in patients with CM, presented as case study/series, or literature review were included. Thirty-two articles met the inclusion criteria, representing 41 individual patient cases. The most common ophthalmic symptoms were diplopia (37%), decreased visual acuity (22%), and visual field loss (28%). Diplopia often resulted from esotropia secondary to 6th nerve palsy, whereas visual acuity and field loss were secondary to papilledema. Among reported cases, the most frequently reported ophthalmic signs were papilledema (44%), nystagmus (32%), and esotropia (29%). In pediatric patients (n = 15), the symptoms of diplopia occurred in 53% of the cases and the sign of esotropia occurred in 53%; usually from the 6th nerve palsy. Papilledema was reported in 27% of the pediatric cases but was the predominating finding among adults (n = 26). CM demonstrates distinct age-related ophthalmic patterns. In symptomatic patients, targeted neuro-ophthalmic evaluation may aid earlier diagnosis and guide management. Further prospective studies are needed to clarify pathophysiology and optimize interdisciplinary management.
To describe the 3-year clinical outcomes of PRESERFLO MicroShunt (PMS) implantation in eyes with uncontrolled glaucoma and previous failed trabeculectomy. A retrospective, single-centre observational cohort study. Seventy-four eyes with glaucoma that had at least 1 failed trabeculectomy and no other previous surgeries for glaucoma. All consecutive eyes undergoing PMS implantation after failed trabeculectomy were included. Clinical data were collected at baseline and scheduled postoperative visits. Primary outcome measures were intraocular pressure (IOP), number of glaucoma medications, and surgical success, defined as an IOP reduction ≥20% (criterion 1) or ≥30% (criterion 2) from baseline, with postoperative IOP <18 mm Hg and no need for additional glaucoma filtering surgery. Complete success was defined as achieving target IOP without medications and qualified success as achieving target IOP with medications. The median follow-up was 36 months. Mean baseline IOP was 23.0 ± 5.7 mm Hg on 3.0 ± 0.7 medications. At 3 years, mean IOP decreased to 12.1 ± 3.5 mm Hg (-46.1%; mean reduction -10.6 mm Hg; 95% CI, -12.1 to -8.3; P < 0.001) with 0.8 ± 1.3 medications; 51.4% of eyes were medication-free. Using criterion 1, overall success was 68.6% (51.5% complete); using criterion 2, overall success was 62.9% (51.5% complete). No eye required additional glaucoma-filtering surgery. Complications occurred in 44.6% of eyes, most of which were mild and self-resolving; 5.9% required surgical intervention. PMS implantation resulted in sustained IOP reduction, reduced medication burden, and an acceptable safety profile over 3 years in eyes with previous failed trabeculectomy. Further prospective studies with longer follow-up are warranted.
To compare the effectiveness and safety of micropulse (MP-CPC) and continuous-wave cyclophotocoagulation (CW-CPC). A retrospective, comparative cohort study. Patients with all types of glaucoma and severity having received MP-CPC or CW-CPC between 2017 and 2021 followed for 2 years. Complete success is defined as intraocular pressure (IOP) of 6-21 mm Hg and IOP reduction from baseline of 30% or higher with no additional glaucoma medications. Qualified success includes those with additional glaucoma medications. Safety outcomes include vision loss, visual field (VF), optical coherence tomography (OCT), CPC retreatment, additional glaucoma surgeries, and adverse events. 118 eyes and 114 eyes underwent CW-CPC and MP-CPC, respectively. There was a trend toward better survival in CW-CPC throughout the 24 months, notably at 6 and 18 months (p < 0.04). CW-CPC required significantly less glaucoma medication throughout the follow-up than MP-CPC (p = 0.049). Safety outcomes showed no difference in significant vision loss or change in VF and OCT. Ocular inflammation was more common in the CW-CPC group (33.1% vs 18.4%; p = 0.01), but similar rates of hypotony were observed in both groups (12% vs 9.6%; p = 0.73). The MP-CPC group needed additional incisional glaucoma surgeries sooner than the CW-CPC group (6.7 months vs 10.8 months; p = 0.002). CW-CPC demonstrated better IOP control with less use of glaucoma drops than MP-CPC. Early retreatment was more common and occurred sooner in the MP-CPC group. Ocular inflammation was more common with CW-CPC, but overall safety parameters were comparable between the 2 groups.
Visual field testing is essential for monitoring field defects, but traditional devices are bulky and resource intensive. This study evaluated the agreement and usability of the RetinaLogik RVF100 virtual reality perimetry device compared with the Humphrey visual field analyzer (HVF) among Filipino adults. A comparative cross-sectional study. Participants were Filipino adults presenting to 2 major eye centres in the Philippines from January to October 2024. A total of 46 participants (76 eyes) were included. Participants were categorized as normal, glaucoma, or other diagnoses (e.g., optic neuritis, ocular hypertension). Both devices tested visual fields using the 30-2 grid, measuring mean deviation (MD), pattern standard deviation (PSD), fixation losses (FL), false positives (FP), false negatives, and test duration. Agreement was assessed using Bland-Altman analysis and Pearson correlation. Pointwise analyses with heatmap visualizations were also used. Usability was evaluated using a postexamination Likert-scale questionnaire. RVF100 demonstrated strong agreement with HVF (MD: r = 0.979, PSD: r = 0.837; p < .0001). The Bland-Altman analysis showed a mean difference in sensitivity of -1.06 decibels (dB) (95% CI: -4.2 to 2 dB). RVF100 had shorter test durations (5.41 vs 6.96 min; p < 0.001), fewer FL (1.79% vs 5.59%; p < 0.001), and slightly higher FP rates (3.44% vs 1.92%; p < 0.001). Usability results showed 90% preferred RVF100 over HVF for comfort (86.4%) and engagement (95.3%). RVF100 is a comparable alternative to HVF, offering comparable accuracy with improved patient comfort. Further research is warranted to assess its efficacy in detecting early and advanced disease stages and in broader populations.
To determine whether nonglaucomatous retinal nerve fibre layer (RNFL) defects independently predict incident cerebral infarction or coronary heart disease. Retrospective, observational cohort study. A total of 80,996 adults from a health screening cohort (2011-2022) with gradable serial fundus photographs. Individuals with pre-existing ocular or vascular disease were excluded. RNFL defects were classified as glaucomatous or nonglaucomatous based on predefined imaging criteria. Multivariable logistic regression identified independent predictors. To ensure temporal validity, participants with prior stroke or coronary heart disease were excluded. A 1:3 propensity score-matched analysis compared outcomes between individuals with nonglaucomatous RNFL defects and matched controls. Vascular events were tracked through 2024. Of 80,996 individuals, 787 had nonglaucomatous RNFL defects, 1,328 had glaucomatous defects, and 78,881 served as controls. Male sex (odds ratio [OR] 1.33), hypertension (OR 2.77), diabetes (OR 1.68), reduced eGFR, and younger age were independently associated with nonglaucomatous RNFL defects (all p < .05). In the matched cohort (747 vs 2,241), incident vascular events occurred in 7.5% of those with nonglaucomatous RNFL defects versus 0.6% in controls (OR 9.11; 95% CI: 5.37-15.48; p < .001). Nonglaucomatous RNFL defects are strong independent predictors of future cerebral infarction or coronary heart disease. Routine fundus photography may provide systemic vascular risk insight beyond ophthalmic evaluation.
The progression of glaucoma despite adequate intraocular pressure (IOP) control highlights the need for neuroprotective and neuroregenerative therapies. Preclinical studies suggest insulin promotes retinal ganglion cell survival and regeneration, but its safety in higher concentrations (100 and 500 units/mL), administered topically, has been poorly characterized in humans. We aim to assess the safety and tolerability of these two concentrations of insulin eye drops in patients with open-angle glaucoma (OAG). A phase I, randomized, double-blind, placebo-controlled, single-centre clinical trial. Patients with mild to moderate OAG were randomized 2:2:1 to receive once-daily topical insulin U-100, U-500, or placebo in 1 eye for 5 days, with follow-up visits at 1, 3, and 6 months. The primary safety outcomes include glycemia, serum potassium, ocular adverse events (AEs), and ocular tolerability scores. Secondary outcomes included IOP, best-corrected visual acuity (BCVA), retinal nerve fibre layer thickness, ganglion cell complex, visual field, and OCT angiography. Eighteen open-angle glaucoma patients were enrolled (mean age: 66.2 ± 10.1 years). No serious AEs related to insulin were observed. One asymptomatic, transient near-hypoglycemia event occurred in a fasting participant (3.9 mmol/L), with no recurrence after dietary adjustment. No significant changes were found in serum potassium, IOP, BCVA, visual fields, or OCT. Ocular symptoms in the insulin groups were limited to transient, mild burning sensation upon application. One participant experienced cystoid macular edema at 3 months, which was attributed to pre-existing ocular pathology. Topical insulin at 100 and 500 units/mL concentrations was well tolerated in patients for short-term use and did not result in significant systemic or ocular toxicity.