BMJ Open Ophthalmology最新文献

Objective: To investigate whether being born preterm with very low birth weight (VLBW), lower best-corrected visual acuity (BCVA) or a history of a psychiatric or somatic diagnosis is associated with, or mediates, not having obtained a driver's licence at adult age.

Methods and analysis: Potential predictors of no driver's licence were investigated in participants with a mean age of 36 years and BCVA above the legal limit to drive from the Norwegian University of Science and Technology Low Birth Weight Life Study, Norway, and the Helsinki Study of Very Low Birth Weight Adults, Finland, (VLBW n=119, term-born controls n=149).

Results: Participants with no driver's licence (n=34) had lower BCVA than participants with a driver's licence (mean logarithm of the minimal angle of resolution (SD) -0.03 (0.11) vs -0.101 (0.09), p<0.001. Being born with VLBW and lower BCVA was associated with no driver's licence (OR, 2.5 (95% CI 1.1 to 5.8) and 1.1 per unit (95% CI 1.0 to 1.2), respectively. BCVA was not a mediator of the effect of being born preterm with VLBW.

Conclusion: In a population with good visual acuity, being born preterm with VLBW was a predictor for not having a driver's licence, while lower visual acuity further increased this likelihood. A history of a somatic or psychiatric diagnosis was not associated. These findings should be interpreted with caution due to the relatively small sample size and a non-negligible statistical uncertainty. The causal relationship between being born preterm and not holding a driver's licence remains to be investigated.

Purpose: To develop a cloud-based software for analysing the disc-fovea angle (DFA) in fundus images using the stacking ensemble model and to evaluate the accuracy of the objective DFA assessment between automatic and manual analyses.

Methods: A total of 682 fundus images (573 and 109 images of healthy individuals and patients with cyclotropia, respectively) were included in this retrospective study. For manual DFA analysis, two examiners analysed the DFA using web-based analysis software for the DFA, which was defined as the average value between the two examiners. For automatic DFA analysis, the stacking ensemble model on the cloud web integrated a single-shot multi-box detector to identify the fovea and centre of the optic nerve head, along with a single convolutional neural network combined with five machine learning algorithms.

Results: The DFA did not significantly vary between the automatic (7.25° ± 4.93°) and manual analyses (7.27° ± 5.07°) (p=0.52). The time required to analyse the DFA in a single fundus image was significantly shorter with the automatic analysis (0.430±0.240 s) than with the manual analysis (15.794±1.558 s) (p<0.001).

Conclusion: These findings suggest that automatic analysis using the stacking ensemble model is useful for determining the DFA in clinical settings.

Background/aims: To evaluate the performance of an artificial intelligence (AI) model for detecting and monitoring microbial keratitis (MK) using anterior segment optical coherence tomography (AS-OCT).

Methods: This is a prospective observational study. Patients with clinically suspected MK and healthy participants were included. In addition to routine assessment and treatment with topical fluoroquinolone therapy, patients underwent AS-OCT at each clinic visit. These images were tested on our DeepLabV3 network-based AI model, which aims to diagnose and record changes to infiltrate sizes of MK lesions over time.

Results: The AI model accurately captured MK lesions in 93% of cases (152/163). MK was not detected in scans from healthy eyes, and there were no cases of artefact being falsely detected. The model had a sensitivity of 93% (95% CI 88% to 97%), specificity of 100% (95% CI 88% to 100%), positive predictive value of 100% (95% CI 98% to 100%) and negative predictive value of 73% (95% CI 61% to 83%). Using only the corneal component with masking of the anterior chamber, the AI model showed agreement on change with both observers in 76% (13/18) cases.

Conclusions: This AI framework reliably identified MK lesions using AS-OCT, with high sensitivity and specificity. The framework was able to identify change in most cases compared with corneal specialists.

Objective: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and the primary target of current therapies. When IOP-lowering drugs are insufficient, surgical intervention may be required; however, conjunctival and subconjunctival scarring often limits long-term success. Although intraoperative and postoperative antimetabolite treatments help preserve surgical outcomes, they are associated with ocular side effects. This study investigated the effects of selected anticancer drugs on the proliferation of human Tenon's fibroblasts (HTFs), key mediators of postoperative scarring.

Methods and analysis: Primary HTFs were isolated from explants obtained during glaucoma surgery and characterised by immunofluorescence. The cytotoxic effects of candidate drugs were assessed using the MTT and LDH assays, while HTF migration and proliferation were evaluated by wound-healing assays. Additional cytotoxicity testing was performed on primary human trabecular meshwork cells (HTMCs) to assess ocular safety.

Results: Under the experimental conditions used, HTF proliferation, rather than migration, was the main driver of wound closure. Among the drugs tested, pemigatinib and sorafenib significantly slowed wound closure. Pemigatinib showed no cytotoxicity in either HTFs or HTMCs, whereas sorafenib induced a moderate (28%) cytotoxic effect in HTMCs.

Conclusions: Pemigatinib and sorafenib, two Food and Drug Administration-approved anticancer agents, effectively reduced HTF proliferation, with pemigatinib showing a more favourable safety profile. These findings identify selective fibroblast growth factor receptor (FGFR) inhibition as a promising strategy for modulating postoperative fibrosis and support further preclinical studies to evaluate the safety and efficacy of FGFR inhibitors as potential adjuncts in glaucoma surgery.

Background/aims: To evaluate the respective roles of systemic vascular vulnerability and local vascular anatomy in the onset of branch retinal vein occlusion (BRVO) by analysing the retinal age gap and arteriovenous crossing patterns.

Methods: This observational study enrolled 202 patients with unilateral BRVO and 100 age-matched, sex-matched and axial length-matched healthy controls. A deep learning model was applied to colour fundus images to estimate the retinal age; the retinal age gap (predicted retinal age minus chronological age) in the fellow eye was used as a surrogate residual marker of systemic vascular vulnerability. At the occlusion site, arteriovenous crossing was classified (arterial vs venous overcrossing) using optical coherence tomography angiography (OCTA).

Results: The mean retinal age gap was 1.8±6.5 years and 0.2±6.0 years in the BRVO and control groups, respectively. Retinal age gap was significantly larger in BRVO eyes than in control eyes (p=0.046). A larger retinal age gap in the fellow eye correlated with younger age at BRVO onset (ρ= -0.350, p<0.001). Among 156 BRVO eyes with OCTA data, venous overcrossing at the occlusion site was more frequent in younger-onset major BRVO (p=0.031), whereas in macular BRVO, onset age did not differ by crossing pattern (p=0.734).

Conclusion: Both systemic vascular vulnerability, reflected by a larger retinal age gap and local anatomical configuration, represented by venous overcrossing, may jointly contribute to BRVO susceptibility, particularly in younger patients. These findings should be interpreted with caution because the retinal age gap is a prediction, using a deep learning model, rather than a direct biological measure.

Objective: Radiotherapy modalities such as iodine-125 (I¹²⁵) and ruthenium-106 (Ru¹⁰⁶) brachytherapy and proton beam radiotherapy (PBR) are well established for the treatment of choroidal melanoma. This study aimed to evaluate the rates of local tumour control, globe retention and visual acuity (VA) outcomes in patients with choroidal melanoma treated with I¹²⁵ or Ru¹⁰⁶ brachytherapy or PBR.

Methods and analysis: A review was conducted of all cases of choroidal melanoma treated with Ru¹⁰⁶ or I¹²⁵ brachytherapy or PBR over a 10-year period. Patient demographics, comorbidities, tumour characteristics, treatment parameters and VA outcomes were analysed. A predictive nomogram was developed to estimate final VA based on baseline clinical, tumour and radiation parameters.

Results: A total of 310 eyes from 310 patients were included, comprising 175 patients (56.5%) treated with Ru¹⁰⁶, 72 (23.2%) treated with I¹²⁵ brachytherapy and 63 (20.3%) treated with PBR. Local tumour control was achieved in 95.8% of cases. The recurrence rates were 4.0%, 4.2% and 4.8% for Ru¹⁰⁶, I¹²⁵ and PBR, respectively. Retention rates were 96.0% for Ru¹⁰⁶, 94.4% for I¹²⁵ and 95.2% for PBR. LogMAR VA of 1.0 or better was maintained in 50.9% of Ru¹⁰⁶patients, 27.8% of I¹²⁵patients and 39.7% of those treated with PBR. Baseline LogMAR VA, tumour volume, radiation dose to the fovea, radiotherapy modality and follow-up duration were significant predictors of final VA and were incorporated into the nomogram.

Conclusions: Each radiotherapy modality demonstrated high rates of local tumour control and globe retention. The predictive nomogram may serve as a practical tool to support individualised visual prognostication and patient counselling in the management of choroidal melanoma.

Objective: To evaluate the safety, tolerability and preliminary efficacy of IBI324, a vascular endothelial growth factor-A/angiopoietin-2 bispecific antibody, in participants with diabetic macular oedema (DME).

Methods and analysis: This multicentre, open-label, phase 1 dose-escalation clinical trial consisted of a single ascending dose (SAD) stage and a multiple ascending dose (MAD) stage. 24 participants with fovea-involving DME were enrolled. SAD participants received a single intravitreal injection (IVT) of 0.5 mg, 2 mg or 4 mg IBI324 and were followed up until Day 42 post injection. In the MAD stage, six participants each received 3 monthly IVTs of 2 mg or 4 mg IBI324 and were followed up until determined as 'treatment needed' per prespecified criteria or until 24 weeks after first dose. The primary endpoints were incidence of dose-limiting toxicities (DLTs), adverse events (AEs) and changes in vital signs and laboratory test findings.

Results: No DLT, treatment-related AE, AE of special interest or ocular serious AE was reported. Treatment-emergent adverse events (TEAEs), all mild or moderate in severity, were observed in 4 (33.3%) SAD participants and 11 (91.7%) MAD participants. TEAEs of the study eye included intraocular pressure increased, conjunctival haemorrhage, allergic conjunctivitis, posterior capsular opacification and visual acuity decreased. Mean best-corrected visual acuity increase and mean central subfield thickness decrease from baseline in the study eye were observed in all dose groups, accompanied by intraretinal fluid/subretinal fluid improvements. 16 weeks after the last dose, 7 (58.3%) MAD 2 mg and 6 (50.0%) MAD 4 mg participants remained free of 'treatment needed'.

Conclusion: IBI324 was well tolerated with evidence of functional and anatomical improvement in patients with DME.

Trial registration number: NCT05489718.

Objective: The purpose of this study was to describe reports of congenital eye anomalies entered in the international pharmacovigilance database, with a particular focus on medications associated with this type of anomaly.

Methods and analysis: This descriptive, retrospective study selected reports using the adverse reaction term 'congenital eye disorders' and included only those instances where at least one medication was documented as being administered via the transplacental route. Statistical analyses were performed using R software.

Results: We extracted 2923 reports of eye anomalies in children exposed to medications in utero and ultimately selected 676 of these. Congenital anomalies of the eyelids (17.3%), lacrimal apparatus (9.4%) and orbit (1.1%) were the most common. The suspect medications highlighted in this study include teratogenic agents known to pose a risk of triggering eye anomalies such as valproic acid and mycophenolic acid. The list also includes medications with little or no reference in the literature to potential eye anomalies following in utero exposure, such as hydroxychloroquine and ondansetron.

Conclusion: This study provides new data on in utero exposure to medications and congenital eye anomalies that can be severely debilitating. This is a descriptive study, with all the inherent limitations of the pharmacovigilance databases which are used for signal detection. This descriptive study does not allow us to conclude that there is a causal link between exposure to a given medication during pregnancy and congenital eye anomalies and is a basis for future studies using different data sources and/or other methods.

Objective: Biosimilars are helping to reduce the cost burden of treatment and widen patient access to therapies. This multicentre trial compared the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration (nAMD).

Methods and analysis: Patients aged ≥50 years with newly diagnosed nAMD and a best-corrected visual acuity (BCVA) between 20/40 and 20/200 Snellen equivalent were randomised (1:1) to double-masked treatment with 2 mg FYB203 or EU-approved reference aflibercept by intravitreal injection every 4 weeks for three doses (baseline, weeks 4 and 8) then every 8 weeks up to week 48. The primary efficacy endpoint was the change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8 in the study eye. Therapeutic equivalence of FYB203 and reference aflibercept was demonstrated if, depending on the regulatory requirement with respect to the significance level, the two-sided 90.4% and 95.2% CIs were within the predefined equivalence interval of (-3.5 to 3.5) ETDRS letters.

Results: A total of 433 patients received treatment with FYB203 (n=215) or reference aflibercept (n=218). Mean improvement in BCVA from baseline to week 8 was 6.6 ETDRS letters with FYB203 and 5.6 ETDRS letters with reference aflibercept, with an estimated mean treatment difference of 1.0 and the two-sided 90.4% CI (-0.3 to 2.2) and 95.2% CI (-0.6 to 2.5) fully contained within the pre-defined equivalence margins, confirming therapeutic equivalence between FYB203 and reference aflibercept. Safety and immunogenicity profiles were similar between groups.

Conclusion: Although conducted during the COVID-19 pandemic in a potentially vulnerable elderly population and affected by geopolitical disruption in Ukraine, mitigation measures minimised the overall impact of these events. FYB203 demonstrated therapeutic equivalence to reference aflibercept in patients with nAMD, supporting similar clinical performance across all approved indications.

Trial registration number: Clinicaltrials.gov: NCT04522167; EudraCT: 2019-003923-39.