Eye

Background/Aims: Neovascular glaucoma (NVG) is an aggressive secondary glaucoma with limited longitudinal data. This study reports the aetiologies, treatments, and longitudinal outcomes in NVG. Methods: Patients with NVG were identified through electronic medical record review. Inclusion required documented rubeosis of the iris and/or anterior chamber angle, intraocular pressure (IOP) [≥]25 mmHg, diagnosis during 2008-2024, and follow-up at Helsinki University Hospital. Baseline data and all follow-up visits were included. Results: Of 919 patients identified, 626 met inclusion criteria, with a median follow-up of 24 months. The estimated NVG incidence was 2.2/100,000/year. The most common aetiology was central retinal vein occlusion (CRVO; 45%), followed by diabetic retinopathy (DR; 14%), central retinal artery occlusion (CRAO; 11%), and ocular ischaemic syndrome (8%). Half of patients had hand motion vision or worse at baseline, with 18% at no light perception (NLP). At 5 years, 13% of patients had Snellen 6/60 vision or better. Visual outcomes differed by aetiology, with median time to NLP ranging from 1.6 (CRAO) to 9.1 (DR) years (log-rank p=0.002). Median baseline IOP was 40 mmHg, decreasing to 21 mmHg by 1 year. Ocular pain fell from 43% at baseline to 11% at last follow-up. Structural eye loss (e.g., enucleation or phthisis) occurred in 3% by 5 years. Conclusion: The estimated incidence was lower than previously reported elsewhere. Unlike other cohorts where DR predominates, CRVO was the most common aetiology, and visual prognosis was strongly aetiology-dependent. Glaucoma drainage device surgery reached 7.6% at 3 years, despite the severity and refractory nature of NVG.

Purpose: To evaluate the safety and exploratory outcomes of a single intravitreal injection of OGX110, a peptide agonist of CXCR3, in eyes with persistent fluid secondary to neovascular age-related macular degeneration (nAMD) despite ongoing anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: This prospective, open-label, sequential dose-escalation phase I study (NCT05904691) enrolled subjects receiving standard-of-care intravitreal anti-VEGF therapy. Subjects received a single intravitreal injection of OGX110 at 0.5 mg, 1.0 mg, or 2.0 mg (n=3 per cohort), 7 to 14 days after the anti-VEGF injection. Results: All nine enrolled subjects completed follow-up through day 56. Two subjects (22%) experienced at least 1 adverse event (AE); all were mild and unrelated to study treatment. Exploratory analyses showed a BCVA change of +1.4 letters following anti-VEGF injection and +4.4 letters from OGX110 baseline to 4 weeks (P < 0.05). Six of 9 subjects gained at least 3 ETDRS letters after OGX110. Anatomic responses were heterogeneous. Four eyes showed a reduction in CRT after anti-VEGF injection that was maintained after OGX110 administration. One additional eye demonstrated a substantial reduction in CRT after OGX110 despite minimal response to anti-VEGF treatment. Conclusions: A single intravitreal injection of OGX110 was well tolerated. Exploratory functional and anatomic findings suggest biologic activity; interpretation is limited by small sample size, open-label design, absence of a concurrent control group, and inter-subject heterogeneity. These results support further study in a controlled trial. Translational Relevance: OGX110 represents a mechanistically distinct investigational approach for nAMD that may warrant further evaluation in eyes with persistent.

Purpose: To evaluate the impact of ''not commonly considered risk factors '' on glaucoma surgical outcomes. Methods: This study included 339 eyes that underwent glaucoma surgery. Surgical procedures included microhook ab-interno trabeculotomy (TLO), Preserflo ab-externo microshunt implantation, trabeculectomy (Trab), and Ahmed Glaucoma Valve (AGV) implantation. In addition to conventional background factors, we examined a set of ''not commonly considered risk factors, '' including very elderly age ([&ge;]85 years), avitreous status, aphakia, use of antithrombotic agents, difficulty attending frequent postoperative visits, small palpebral fissure, corneal endothelial dysfunction, poor vision in the fellow eye, dementia, hearing loss, mental illness, atopic dermatitis, pseudophacodonesis, glaucoma eye drop allergy, and conditions contraindicating {beta}-blocker use. Surgical success was defined as intraocular pressure (IOP) [&le;]21 mmHg, [&ge;]20% reduction from baseline, and no additional glaucoma surgery at 1 year. Logistic regression was performed to identify potential risk factors; significant factors were further evaluated using propensity score matching. Results: Of the 339 cases, surgical success rates were 65% for TLO, 82% for Preserflo, 91% for Trab, and 82% for AGV. Multivariate logistic regression identified two independent predictors of surgical failure: small palpebral fissure (odds ratio 2.52, p < 0.01) and hearing loss (odds ratio 3.94, p = 0.04). Propensity score matching of patients with small versus large palpebral fissures (111 per group) confirmed significantly worse postoperative outcomes in the small-palpebral-fissure group despite balanced baseline characteristics. Conclusion: Small palpebral fissure is an independent and previously unnoticed risk factor for glaucoma surgical failure, affecting both minimally invasive and filtration procedures.

Background Dry eye disease (DED) is a multifactorial condition marked by tear film instability and ocular inflammation, causing symptoms like grittiness and blurred vision. The global prevalence of Dry eye disease among pregnant women ranges from 27.4% to 89.3% and in Africa it ranges between 20% and 50%. Hormonal changes, advanced maternal age, late pregnancy and prolonged screen time play an important part in its development. Methodology A hospital-based cross-sectional study among 380 pregnant women. Systematic sampling technique was used for recruitment at the antenatal clinic in Mnazi Mmoja Hospital in Dar es Salaam. Clinical dry eye tests were performed along with the administration of a symptom questionnaire that included demographic characteristics and the OSDI tool where OSDI >13 is the threshold for diagnosis of DED. Data were analyzed using Stata version 17.0 and Modified Poisson analyses identified factors associated with dry eye disease, with statistical significance set at p-value<0.05. Results A total of 380 pregnant women were recruited and analyzed with the mean age 31.7{+/-}6.7, 196 (51.6%) were aged 31-46 years. Most were married 273 (71.8%) and 211 (55.5%) had completed secondary education. Dry eye disease (DED) prevalence was 53.2% (48.8%-58.2%). Among those with DED (n=202), 112 (55%) had mild symptoms, 26 (13%) moderate, and 64 (32%) severe. The most common DED subtype was unclassified 72 (35.6%), followed by mixed (67, 33.2%), evaporative 50 (24.8%), and aqueous deficient 13 (6.4%). Significant associations with DED were: advanced gestation age (aPR=2.18 (1.550-3.072), p<0.001), being a housewife (aPR=1.48(1.179-1.857), p=0.001), use of visual display terminals (aPR=1.36(1.219-1.845), p=0.048), working in low humidity (aPR=2.62(1.698-4.045), p=0.001), and working in air-conditioned rooms (aPR=2.40(1.685-3.415), p=0.001). Secondary education was protective against DED (aPR = 0.668 (0.466-0.958), p = 0.028). Conclusion Approximately half of pregnant women have DED, with unclassified DED being the predominant subtype. Late gestation age, occupation, extended screen time, and working environment are significantly associated factors. It is essential to integrate DED screening into antenatal care and establish standardized protocols on DED management. Also, it is essential to promote lifestyle modifications such as reduction of screen time and avoiding dry environments.

Purpose: To evaluate the incidence and baseline predictors of intraocular pressure (IOP)-lowering treatment following detection of referable glaucoma by teleretinal screening. Design: Retrospective cohort study. Methods: Participants were derived from a safety-net teleretinal diabetic retinopathy screening program (2013-2024). Participants included individuals who screened positive for referable glaucoma (cup-to-disc ratio [CDR] [&ge;]0.6 or CDR asymmetry [&ge;]0.2) and completed in-office diagnostic evaluation. The primary outcome was initiation of IOP-lowering treatment (medication, laser, or surgery) and the secondary outcome was intervention with surgery. Cumulative incidence functions were estimated, accounting for loss to follow-up. Fine-Gray models were used to identify baseline screening predictors to risk stratify each outcome. Glaucoma diagnosis was approximated using diagnostic codes and chart review. Results: 2,367 participants were included. The cumulative incidence of treatment was 19.6% (95% CI: 18.0-21.2) at Year 1 and 45.1% (42.1-48.1) at Year 8. Early treatment occurred primarily in glaucoma cases, whereas treatment accumulated longitudinally in glaucoma suspects, reaching 36.5% (31.6-41.5) by Year 8. Surgery was less common (8-year incidence: 5.3%). Baseline screening data predicted treatment and surgery, enabling risk stratification. At Year 8, cumulative incidence differed substantially between high- and low-risk groups (treatment: 59.9% vs. 31.2%; surgery: 9.7% vs. 1.0%). Older age (sub-distribution hazard ratio [SHR] 1.03 per year, p<0.001), Black race (SHR 1.50, p<0.001), and personal history of glaucoma (SHR 1.90, p<0.001) were associated with treatment; Asian race was protective (0.71, p=0.03). Older age (SHR 1.06, p<0.001), worse visual acuity (SHR 5.11 per logMAR unit, p<0.001), and screening at a hospital-based site (SHR 2.46, p=0.003) were associated with surgical treatment. Conclusion: Nearly half of safety-net diabetic patients screening positive for referable glaucoma initiated IOP-lowering treatment over 8 years, while few received surgery. Baseline screening characteristics enabled risk stratification of treatment and surgery. These findings address an evidence gap about longitudinal consequences of screening and suggest that its impact extends beyond detection of prevalent glaucoma to include identification of high-risk glaucoma suspects who warrant ongoing surveillance.

Objective: To assess the feasibility and acceptability of VISON-ACT, a standalone, mobile app psychosocial intervention for psychological distress in individuals with primary open-angle glaucoma (POAG). Design: Single-arm pilot. Participants: Patients (N=28) with a diagnosis of POAG, self-reporting at least mild (>3) distress on the 4-item Patient Health Questionnaire, were recruited from the Duke Eye Center between April 2025-December 2025. Methods: Patients (n=28) were consented and completed a baseline (A1) self-report assessment. VISION-ACT was comprised of 6 weekly modules. Follow-up self-report assessments occurred at post- (A2) and 1-month post-intervention (A3) and included measures of psychological distress, vision and health-related quality of life, psychological flexibility, disease acceptance, self-efficacy for symptom management, mindfulness, and social support. Participants were invited to complete an exit interview at 1-month post-intervention to gather qualitative feedback on the VISION-ACT protocol. Descriptive statistics were used to assess feasibility and acceptability metrics and patterns of pre-post change on patient reported outcomes were explored with linear mixed mdels using R Statistical Software. Main Outcome Measures: Feasibility (target accrual (n=25) in 12 months, <20% attrition at post-intervention); Acceptability (>75% reporting use of VISION-ACT skills or ideas at post-intervention, >80% reporting M>3.00/4.00 at post-intervention on the Client Satisfaction Questionnaire); Psychological Distress (Hospital Anxiety and Depression Scale [HADS], Subjective Units of Distress Scale [SUDS]). Results: VISION-ACT was highly feasible; accrual target was surpassed (N=28) in 6 months, and attrition was low (3.85%) at post-intervention (A2). Acceptability was strong with 100% of participants reporting use of VISION-ACT skills or ideas at A2 and M=3.27/4.00 intervention satisfaction. Adherence was remarkable with 88.5% of participants completing all six VISION-ACT modules. Pre-post change patterns were in the expected direction for psychological distress (HADS A1 M=13.88, A2 M=11.21; SUDS A1 M=35.54, A2 M=26.46) and all other patient-reported outcomes across baseline, post- and 1-month post-intervention assessments. Data on participant perspectives highlighted valuable aspects of VISION-ACT, and areas for refinement. Conclusions: Robust feasibility and acceptability data seen here provide support a fully-powered, randomized trial to evaluate the efficacy of VISION-ACT for reducing psychological distress and improving related patient-reported and clinical outcomes.

Purpose: To characterize peripheral immune alterations in treated birdshot uveitis (BU) patients using high-dimensional mass cytometry and multiplex serology. Design: Cohort study. Subjects: 36 BU patients on immunomodulatory treatment (IMT) and 31 healthy controls (HCs). Methods: Detailed ophthalmologic examinations were performed, and peripheral blood and serum samples were collected for immune profiling using mass cytometry and multiplex cytokine analysis. Main Outcome Measures: Imaging-based indicators of ocular inflammation; peripheral immune cell frequencies; serum cytokine levels. Results: Compared to HCs, BU patients showed increased frequencies of Th17, CD146+ T cells, intermediate effector/central memory T cells co-expressing CXCR3 and CCR4, CD56dim NK cells and elevated IL-18 levels. Patients were clinically stratified by an expert ophthalmologist into three disease activity groups: Inactive, Active (comprising combinations of surface retina, deep retina and choroid activity) and Burned-out. Inactive patients harbored more quiescent effector T cells, e.g. Tim-3+ Tc17-Tc22 intermediates and more CD8+ TSCM, potentially representing a resting pool of autoimmune T cells. Active patients exhibited increased in vivo activation of relevant T cells, with stronger HLA-DR, CD38 or PD-1 expression, and highest levels of CD56dim NK cells. Immune profiles were also linked to treatment subgroups: csDMARDs (conventional synthetic disease-modifying antirheumatic drugs) were associated with higher CD56bright NK frequencies, and absence of therapy showed elevated PD-1/SLAMF7 Tc17+1 and PD-1CD57 CD8 TEMRA cells. IL-6R blockade (tocilizumab) resulted in loss of IL-6R T-cells accompanied by increased SLAMF7 T cells, due to epitope masking. Conclusions: Peripheral CyTOF profiling anchored to thorough clinical stratification revealed disease activity-associated immune signatures and therapy-associated imprints in BU.

Objectives: Amblyopia is a pediatric visual disorder traditionally treated by patching the fellow eye, though many patients retain residual amblyopia post-treatment. Increasing evidence suggests that visual plasticity allows treat-ment beyond the classical therapeutic window. AMBER evaluated the efficacy of binocular serious games in virtual reality (VR) in residual amblyopia. Methods and Analysis: The monocentric, prospective, randomized, crossover trial (reported as case series) includ-ed 14 anisometropic, strabismic, or mixed residual amblyopia patients (6-35 years; 5 children, 9 adults). Participants underwent two 2-month intervention phases: optical correction (standard care) and standard care plus VR games (2.5 h/week), each with a 2-month follow-up. Best-corrected visual acuity (BCVA), stereoacuity, and reading speed were assessed (5 timepoints) using the Sloan and Landolt charts, the Titmus, TNO, Lang II, Asteroid, and Mnread tests. Compliance and adverse events (AE) were recorded. Results: VR training improved BCVA in 10 amblyopic eyes (Landolt and Sloan), with more pronounced effects in anisometropic patients. Six patients showed improved stereoacuity (Titmus; 4x mixed, 1x anisometropic, 1x stra-bismic amblyopia), persistent only in children (1x strabismic, 1x mixed amblyopia). Four improvements were ob-served with TNO (1x), Lang II (1x), Asteroid (0x), and MNread (1x). Despite positive trends, when comparing re-sults of individual patients, between both eyes, and with standard treatment, consistency of improvements cannot be conclusively demonstrated. One non-severe AE (dizziness) was reported. Conclusions: Following individual cases, VR training improved BCVA and stereoacuity, particularly in children and patients with high compliance. However, considering the cohort as a whole, consistency of effects has to be confirmed in larger groups. Thus, the methodologically sophisticated AMBER study revealed differences in VR treatment efficacy between amblyopia types, children/adults, endpoints and tests, offering precious data for the design of meaningful future studies. It shows that neurovisual plasticity gauged by VR-games offers safe, engaging treatment options for residual amblyopia.

Purpose: To quantify the binocular integrated visual field (IVF) loss patterns with archetypal (AT) analysis and their associations with patients' Quality of Life (QoL). Design: Retrospective study. Participants: Over 125,000 patients from three datasets from Massachusetts Eye and Ear and Glaucoma Research Network Consortium. Methods: We used: (1) the Glaucoma Research Network excluding the Massachusetts Eye and Ear subset for the binocular archetypal model training (77, 270 IVFs from 77 270 patients), (2) Massachusetts Eye and Ear dataset for demographic correlation analysis (47,965 IVFs from 47,965 patients), and (3) the MEE Quality of Life Survey dataset for QoL correlation analysis (75 IVFs from 75 patients). The whole study was restricted to the most recent VF measurements from each subject and binocular VFs were constructed by the integrated visual field method, which was taking the higher sensitivity at each test location. We first applied archetypal analysis to cluster 24-2 binocular VFs into archetypal patterns. The total number of patterns was determined by the Bayes factor. Pearson's correlations analyzed the associations between patients demographic information, binocular VF patterns and QoL scores, and the coefficients were set to 0 if p-values corrected by multiple comparisons < 0.05. Main Outcome Measures: A binocular VF archetypal patterns and its relationships with demographic divergences and QoL. Results: We identified 17 binocular VF loss patterns. Patterns with major vision impairment (AT10, AT12, AT13, AT14, and AT17) were more common in older patients, while Black or African Americans exhibited a broader spectrum of visual loss, notably AT5 and AT12, compared to Asian and White counterparts. 81 MEE patients with QoL survey data was analyzed to investigate the impact of demographic and vision-related variables on QoL. Older age and female gender were significantly associated with lower QoL. Binocular central vision loss (AT 5) and total vision loss (AT 12) had a significantly greater impact on QoL than binocular peripheral vision loss (AT 2, AT 5, AT 16). Conclusions: Individuals with central or total vision loss, as well as certain demographic groups, experience a significantly greater impact on quality of life. The quantifications of binocular VF loss patterns by archetypal analysis may help better understand glaucoma's impact on patients' quality of life.

Objective: To define CSC genetic architecture and identify implicated ocular tissues, cell types, genes, and circulating proteins. Data Sources: Genome-wide data were assembled from FinnGen, All of Us, Mass General Brigham Biobank, Million Veteran Program, and a Dutch chronic CSC cohort. Serum protein quantitative trait loci, human single-cell ocular atlases, and UK Biobank macular optical coherence tomography (OCT) imaging were used for downstream analyses. Study Selection: Five European-ancestry cohorts with genome-wide data and cohort-specific CSC case-control definitions were included, comprising 2,584 cases and 1,044,455 controls. Variants present in at least 2 cohorts were meta-analyzed. Data Extraction and Synthesis: Cohort-level GWASs were adjusted for age, age squared, sex, genotyping array or batch, and 10 genetic principal components, then combined using fixed-effects inverse-variance meta-analysis. Post-GWAS analyses included gene prioritization, colocalization, Mendelian randomization, single-cell disease-relevance scoring, and testing of a CSC genetic risk score in UK Biobank OCT images. Main Outcome(s) and Measure(s): Genome-wide significant CSC loci, effector genes and proteins, tissue and cell-type enrichment, and CSC-relevant OCT abnormalities. Results: Across 11,068,938 variants, 10 loci reached genome-wide significance (P < 5e-8), including 3 novel loci near TGFB1, LINC00551, and LOC105375630 and 7 replicated loci near CFH, CD46, NOTCH4, PREX1, PTPRB, GATA5, and TNFRSF10A. Integrative analyses prioritized 10 candidate effector genes. Colocalization and Mendelian randomization implicated circulating TNFRSF10A, TGFB1, and CASP10 levels. Single-cell analyses localized genetic risk to sclera (P = 2.0e-4) and vascular endothelial cells (P = 4.0e-4), with fibroblast enrichment. In UK Biobank, OCT abnormalities were more frequent in the top vs bottom 1% of CSC genetic risk (18 of 109 [16.5%] vs 8 of 134 [6.0%]; odds ratio, 4.05; 95% CI, 1.65-10.87; P = .002). Conclusions and Relevance: In this GWAS meta-analysis, CSC susceptibility localized predominantly to scleral and vascular biology rather than primary retinal pigment epithelial dysfunction. These findings support CSC as a sclerovascular disorder and nominate complement regulation, endothelial signaling, and extracellular matrix pathways for future study.

Abstract Purpose:Comparison of ocular parameters (ACD, AL, LT, VL, CCT, ASD, LC, LT/ACD) in preterm infants with retinopathy after treatment, those with spontaneous regression, and those without retinopathy, at postmenstrual (ages of 0 (40 weeks), 3 , and 6 months. Methods: Cross-sectional study. This research involved 297 premature infants assigned to three groups based on fundus results and intravitreal injection therapy: an ROP post-injection group, an ROP spontaneous regression group, and a non-ROP group. Axial length (AL), anterior chamber depth (ACD), l e n s t h i c kn e s s (LT), and vitreous length (VL) were assessed in all three groups using a corneal thickness meter at po st menstrual age s (PMA) of 0, 3, and 6 months. Derived parameters--ASD ((ACD + LT), LC ((ACD + LT/2), and LT/ACD--were subsequently calculated. A one-way ANOVA analysis revealed statistically significant differences in these ocular parameters among the groups (P < 0.05). Results: Significant differences e m e r g e d in anterior chamber depth (ACD) and l e n st h i c k n e s s ( LT) between the ROP post-injection group, ROP spontaneous regression group, and non-ROP group at 0, 3, and 6 (months postmenstrual age (PMA). At 0 months PMA: ACD(F=4.33, P=0.014), LT (F=5.45, P=0.005). At 3 months PMA: ACD (F=17.20, P<0.01), LT(F=15.23, P<0.01). At 6 months PMA: ACD (F=17.89, P<0.01), LT (F=17.21, P<0.01). Central corneal thickness (CCT) also differed significantly among the three groups at 0 months PMA(P <0 .0 1 ). All ocular parameters correlated significantly with Postmenstrual Age, with CCT and LT showing a negative correlation. Before 6 months PMA, axial length (AL) and vitreous length (VL) increased significantly, and ACD deepened significantly across all groups (P <0 .05 ). However , LT exhibited no significant change within the ROP group (post-injection group P=0.4; spontaneous regression group P=0 .33). No significant differences existed in any ocular parameters between the ROP post-injection group and the ROP spontaneous regression group (P>0.05). Conclusions: Before 6 months of postmenstrual age (PMA), axial length (AL), vitreous length (VL), and anterior chamber depth (ACD) were increased between the ROP group and non-ROP group; lens thickness (LT) remained unchanged in the ROP group but increased in the non-ROP group. The injection group and the spontaneous regression group showed no significant differences. The primary factors influencing anterior segment development were birth weight (BW), gestational age (GA), and postmenstrual age (PMA).

Background: Refractive errors are the leading cause of preventable visual impairment worldwide, yet data from isolated Indigenous populations remain virtually absent from the global literature. The Yanomami, one of the largest Indigenous peoples in the Americas with recent and limited contact with non-Indigenous society, have no prior epidemiological data on refractive errors. Methods: A cross-sectional observational study was conducted in 2024 at the Yanomami Indigenous Health House, Boa Vista, Roraima, Brazil. A total of 158 self-identified Yanomami individuals aged 5 years or older were examined by an ophthalmologist. Refractive status was classified according to International Myopia Institute criteria. Results: Emmetropia was observed in 67.7% of participants, with a marked age-related decline from 100% in children aged 5 to 9 years to 38.6% in those aged 40 to 59 years. Myopia was present in 16.5% of participants, all low myopia; it was absent in children under 10 years and no high myopia was identified. Astigmatism affected 24.1% of participants and hyperopia 13.3%. Presbyopia was identified in 25.9%. Overall, 25.3% of participants presented with reduced visual acuity attributable to uncorrected refractive error, of whom 67.5% improved to normal or near-normal acuity (p < 0.001). Conclusions: This is the first characterisation of the Yanomami refractive profile, revealing a distinct myopia pattern shaped by high outdoor exposure and minimal near-work demands. Despite this, refractive correction remains effectively inaccessible to this population, leaving preventable visual impairment unaddressed and reflecting a profound health inequity. Corrective lens provision represents a high-impact, scalable intervention for this underserved community.

Purpose Considering that myopia is associated with thinning of the ocular coats, this study investigated the inter-relationship of retinal, choroidal and scleral thickness in foveal regions in Indian high myopes. Methods A total of 23 high myopes (spherical equivalent refraction [&le;]-6.00D) aged 16 to 35 years underwent posterior segment imaging with swept-source optical coherence tomography. The retinal, choroidal and scleral thickness was determined using semi-automated custom-designed software at sub-foveal regions. Axial length was determined using Lenstar LS 900 non-contact biometer. Results The mean plus-or-minus sign SD axial length was 30.17 plus-or-minus sign 2.23 mm, sub-foveal retinal thickness was 245 plus-or-minus sign 28 lower case Greek mum, sub-foveal choroidal thickness was 82 plus-or-minus sign 46 lower case Greek mum, and sub-foveal scleral thickness was 254 plus-or-minus sign 68 lower case Greek mum. The choroid was significantly thinner compared to the retina and sclera (p<0.001). With a 1 mm increase in axial length, there was no significant variation in sub-foveal retinal (increased by 0.86 lower case Greek mum) and scleral thickness (decreased by 4.31 lower case Greek mum, p[&ge;]0.05), but sub-foveal choroidal thickness decreased by 10.35 lower case Greek mum (p=0.02). For a 1D decrease in spherical equivalent refraction, the choroidal thickness reduced significantly (decreased by 5.88 lower case Greek mum, p<0.001), while there was no significant variation in retinal (decreased by 0.68 lower case Greek mum, p=0.55) and scleral thickness (increased by 0.13 mum, p=0.98). The association of the sub-foveal retinal, choroidal, and scleral thickness was weak and was not significant in high myopes (p[&ge;]0.10). Conclusions With increasing axial length and severity of myopia in high myopes, compared to scleral and retinal thickness, the choroidal thickness alone decreased significantly. Our findings indicate that the changes in the choroid do not necessarily reflect the changes in retinal and scleral thickness and highlight the importance of the choroid as a marker for axial elongation even in high myopes.

Purpose To investigate the relative efficacy of nine distinct visual field (VF) denoising artificial intelligence (AI) methods and a pathology-aware AI strategy to discourage over-correction of glaucomatous defects. Design Retrospective study. Participants 87,940 paired visual field (VF) and optical coherence tomography (OCT) samples from a tertiary academic center. Methods Denoising models were trained on a separate VF-only dataset and evaluated on an independent structure-function dataset of paired VF-OCT samples. We implemented and evaluated nine distinct VF denoising strategies representing three broad categories: baseline measurements, self-supervised and image restoration models (including Noise2Noise, Noise2Void, and NAFNet), and latent variable compression-based models (autoencoders and variational autoencoders). All models were designed to reconstruct VF sensitivity maps. We then predicted retinal nerve fiber layer thickness (RNFLT) maps from the denoised VFs using a fixed, independently trained VF-to-RNFLT prediction model. Main Outcome Measures Predicted VF and RNFLT maps and resultant evaluation metrics. Results The raw VF baseline achieved a global R2 of 0.5468 and MAE of 16.83 um. Restoration-based models maintained or slightly improved concordance, with the pathology-aware NAFNet achieving the highest global R2 of 0.5485 and a comparable MAE of 16.82 um. In contrast, compression-based models degraded concordance, with CNN-VAE showing a significant reduction (R2 approximately 0.50). In severe glaucoma, concordance decreased across all methods; however, compression architectures exhibited disproportionately greater degradation compared with restoration-based approaches. Conclusions We present a comparative benchmark of AI-based VF denoising strategies paired with structure-function evaluation. While restoration-based models can reduce variability without loss of biological signal, latent compression risks attenuating clinically meaningful defects. Visually smoother fields are not necessarily more biologically accurate.

Purpose: Psychological distress is highly prevalent in glaucoma and is associated with worse adherence, reduced quality of life, and faster disease progression. However, distress is rarely assessed in ophthalmology settings due to time, workflow, and staffing constraints. We evaluated two artificial intelligence (AI)-based screening strategies, designed to efficiently identify distressed primary open angle glaucoma (POAG) patients during routine care, aiming to achieve effective, resource conscious, low burden clinical screening. Design: Hybrid retrospective cohort and prospective cross-sectional study. Participants: The retrospective cohort included >3,000 POAG patients from the Duke Ophthalmic Registry. Prospective validation was conducted in a separate 300 POAG patient cohort who completed patient-reported distress screening. Methods: Using retrospective data, a neural network model was trained to predict an electronic health record (EHR)-derived computable phenotype of distress ("silver standard"). Prospective validation used the 8-item Patient Health Questionnaire (PHQ-8) as the "gold standard." Three screening strategies were compared against PHQ-8: (1) universal PHQ-2 screening (two-item screener administered to all patients), (2) AI-only screening (fully automated EHR-based screener), and (3) sequential screening, (only patients flagged as high risk by AI screener completed the PHQ-2). Performance metrics included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and screening burden. Main Outcome Measures: Sensitivity; specificity; PPV; NPV; accuracy; proportion of patients requiring secondary screening (screening burden). Results: Distress prevalence was 17% (PHQ-8 > 6). Universal PHQ-2 screening (> 0) achieved high sensitivity (0.96) but lower specificity (0.73) and PPV (0.41), while requiring screening of all patients. The AI-assisted sequential approach substantially reduced screening burden while maintaining strong diagnostic performance. By administering PHQ-2 to ~25% of patients, sequential screening achieved sensitivity 0.64, specificity 0.93, PPV 0.64, NPV 0.93, and accuracy 0.88, representing a ~50% increase in PPV compared to PHQ-2 alone. AI-only screening reduced burden further but did not achieve comparable sensitivity or predictive performance. Conclusions: AI-assisted sequential screening enables scalable, resource efficient identification of psychological distress in glaucoma care, substantially reducing screening burden while preserving clinically meaningful performance. This framework offers a practical pathway for integrating distress screening into routine ophthalmology workflows and improving the identification and referral of at-risk patients.

Purpose: To predict retinal nerve fiber layer thickness (RNFLT) norms from fundus images. Methods: We selected 18,000 OCT scans and visual fields (VF) from the Massachusetts Eye and Ear Glaucoma Service. A U-Net-based deep learning model was developed to predict RNFLT norms from OCT en face fundus images. A total of 10,000 OCT scans with normal VFs (mean deviation [MD] [&ge;] -1 dB, glaucoma hemifield test within normal limits, and pattern standard deviation probability > 5%) tested within 30 days were used for training, while the remaining 8,000 OCT scans (mean VF MD: 3.3 +/- 4.9 dB), including 2,419 scans with normal VFs, were used for evaluation. Structure-function correlations between RNFLT maps and VFs were assessed using linear regression and VGG-16 across original RNFLT maps, deviation maps, and their combination. Performance was evaluated using correlation coefficients, mean absolute error (MAE), and R-squared. Results: Predicted RNFLT norm maps showed agreement with baseline RNFLT maps in eyes with normal VFs (R-squared = 0.81 +/- 0.13). RNFLT deviation maps correlated more strongly with VF MD than original RNFLT maps (R = 0.42 vs. 0.19, p < 0.01). In deep learning-based VF prediction, combining original and deviation maps achieved the best performance (MAE = 3.31 dB, R-squared = 0.39), outperforming the model (p < 0.05) using original RNFLT maps alone (MAE = 3.36 dB, R-squared = 0.35). Conclusions: Deep learning can estimate individualized RNFLT norms and improve structure-function assessment in glaucoma. Translational Relevance: Personalized RNFLT norm prediction may improve detection of glaucomatous damage.

Purpose: To develop and evaluate a deep learning model that predicts optical coherence tomography (OCT)-equivalent retinal nerve fiber layer thickness (RNFLT) maps directly from color fundus photographs and to assess their diagnostic value for glaucoma detection. Design: Retrospective model development and evaluation study. Participants: 15,031 paired fundus photographs and spectral-domain OCT scans collected at Massachusetts Eye and Ear between 2011 and 2022. Methods: Paired fundus and OCT images were used to train a U-Net-based model to predict pixel-wise RNFLT maps with artifact-corrected supervision. Diagnostic performance was evaluated across single-modality models (fundus photos only, real RNFLT maps, predicted RNFLT maps) and multimodal fusion models (fundus + predicted RNFLT maps). Stratified analyses examined model performance across glaucoma severity and demographic subgroups. Glaucoma was defined based on standard criteria applied to Humphrey 24-2 visual field testing. Main Outcome Measures: Mean absolute error (MAE) and structural similarity index (SSIM) for RNFLT map prediction. Area under the ROC curve (AUC) and accuracy for glaucoma detection. Results: RNFLT map prediction achieved a MAE = 15.4 m and a SSIM = 0.65, measured against artifact-corrected RNFLT maps derived from OCT. For glaucoma detection, the predicted RNFLT-only classifier outperformed the fundus-only classifier (AUC 0.889 vs 0.883, p < 0.005; Accuracy 82.0% vs 78.0%), but performed worse than the real-RNFLT-only classifier (AUC 0.889 vs 0.903, p < 0.005). Multimodal fusion of fundus images with predicted RNFLT maps improved performance, achieving an AUC of 0.909, outperforming all single-modality inputs (p < 0.005 vs fundus-only, predicted-RNFLT-only, and real-RNFLT-only). Performance gains between the fundus-only and the multimodal classifier were greater in early-stage glaucoma compared to severe cases: accuracy increased from 55.3% to 64.0% in mild cases, from 71.5% to 80.4% in moderate cases, and from 90.0% to 94.6% in severe cases. Conclusions: Predicted RNFLT maps derived from fundus photographs provide quantitative, OCT-like structural information and improve glaucoma detection. Unlike prior work that predicted only summary RNFLT values, our model generates full RNFLT maps that better support glaucoma classification than fundus images alone. This approach offers a scalable pathway for early glaucoma screening and expands diagnostic access in resource-limited settings.

Introduction: Early exposure to otolaryngology (ENT) procedural skills in undergraduate medical education is limited by patient safety concerns, restricted clinical opportunities, and the cost of commercial simulators. As a result, essential ENT skills are often underrepresented in structured, hands-on curricula for medical students. Methods: We developed a low-cost, multistation ENT simulation curriculum consisting of five reproducible task trainers: ear examination and otologic procedures, mirror laryngoscopy, rigid and flexible endoscopic navigation, introductory mastoid drilling, and emergency cricothyrotomy. The curriculum was delivered as a 2-hour, faculty-led workshop during a third-year medical student otolaryngology rotation. Learners rotated through stations in small groups. Pre- and post-workshop surveys assessed self-reported anatomical familiarity, procedural confidence, and educational value using a 5-point Likert scale, with additional qualitative feedback collected. Results: All participants completed pre- and post-workshop evaluations. Learners demonstrated increased confidence across all assessed anatomical and procedural domains, including otoscopy, endoscopy, mirror laryngoscopy, mastoid drilling orientation, and cricothyroid membrane identification. Educational value ratings were high across all stations, with mean scores ranging from 4.33 to 5.00. Qualitative feedback emphasized the realism, accessibility, and benefit of hands-on practice in a low-stakes learning environment. Conclusion: This low-cost, multistation ENT simulation curriculum provides a feasible and reproducible approach for introducing foundational otolaryngology skills to medical students. The structured format and affordable models support early procedural exposure and may enhance learner preparedness prior to supervised clinical encounters, particularly in settings with limited simulation resources.

Breast cancer was the leading cause of cancer-related mortality among women worldwide in 2022. In Kenya, more than a quarter of breast cancer patients have the aggressive Human Epidermal Growth Factor Receptor 2 positive subtype. Trastuzumab is recommended for its treatment, but high costs have limited access. This study evaluated the cost-effectiveness and affordability of trastuzumab-based regimens to inform their adoption and use in Kenya. A cost-utility analysis was conducted from the healthcare payer perspective over a lifetime horizon. Five trastuzumab-based regimens of varying durations (9-week, 6-month, 9-month, 12-month, and 24-month) were compared with chemotherapy alone. Direct medical costs were estimated using a bottom-up micro-ingredient approach. All costs were reported in 2022 USD. A cohort Markov state-transition model with a monthly cycle length was used to estimate the costs and outcomes for an open hypothetical cohort. Scenario, deterministic sensitivity and probabilistic sensitivity analyses were conducted. A budget impact analysis estimated the financial implications of each regimen. The 9-week regimen had the lowest incremental cost-effectiveness ratio (ICER) of USD 3,230 per QALY, while the remaining regimens had ICERs ranging from USD 4,046 to 9,846 per QALY. The findings were most sensitive to the price and quantity utilized per cycle of trastuzumab. A reimbursement cap of KES 40,000 per cycle reduced ICERs by up to 61%. Over five years, the 9-week regimen would account for 1.2% of the projected insurers budget, whereas the current recommended 12-month regimen would consume 2.82%. Although none of the regimens were cost-effective at Kenyas WTP threshold (USD 1054.80), the 9-week regimen may still be considered by policymakers given its greater affordability. Further cost reductions can be achieved through negotiating lower drug prices, improving access to biosimilars, and implementing vial sharing.

Background Early onset obesity in children, almost always accompanied by significant health complications, may be driven by rare genetic variants that influence appetite, metabolism, and nutrient absorption. Traditional treatment approaches are usually insufficient for those with monogenic obesity of this type. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, and related drugs such as melanocortin 4 receptor agonists, have emerged as promising first-line treatments for severe obesity. There is no established protocol or pathway in England for identifying children with monogenic obesity who could benefit from these and similar treatments Methods We undertook early economic modelling to examine the cost-effectiveness, from a health service perspective, of implementing a new pharmacotherapeutic care pathway for the identification and treatment of monogenic obesity in children. We modelled a hypothetical population of children with hyperphagia and body mass index (BMI) three standard deviations above mean values for age and sex. We evaluated the clinical decision to initiate the pathway using a decision tree model with patient quality-adjusted life years (QALYs) and NHS healthcare costs 12 months from an initial clinic visit as outcomes, and calculated incremental cost effectiveness ratios and a cost-effectiveness acceptability curve. Results Both costs and QALYs were higher under further investigation (GBP3,247 and 0.47 QALYs) compared to no further investigation (GBP1,589 and 0.24 QALYs). The incremental cost-effectiveness ratio in the base case was GBP7,133 per QALY. Further examination of these children was therefore likely to be cost effective in this model. Conclusion A decision-tree model suggested that further investigation of severely obese children potentially eligible for treatment with semaglutide is likely to be cost-effective for the NHS. However, this result is associated with uncertainty arising from a lack of evidence for many key model parameters.