BMJ Open Ophthalmology最新文献

Background/aims: To describe the functional outcomes of patients with diabetic macular oedema (DME) non-responsive to bevacizumab switched to ranibizumab or aflibercept over 1 year and the demographic and anatomic predictors of these functional outcomes.

Methods: In a retrospective real-world cohort study, 76 consecutive patients with DME non-responsive to bevacizumab were reviewed at baseline and 12 months after switch to ranibizumab or aflibercept. Visual acuity (VA) and optical coherence tomography features such as central retinal thickness were assessed. Multiple logistic regression was performed to determine predictors for outcomes.

Results: From baseline to 1 year, the overall best-corrected VA improved by LogMAR 0.015±0.19 with no difference between patients who switched to ranibizumab or aflibercept (LogMAR 0.017±0.21 vs LogMAR 0.013±0.17, p=0.92). Ranibizumab patients had more reduction in central subfield thickness (CST) (390.13 µm vs 334.20 µm, p=0.033) than aflibercept patients. Baseline HbA1c (p=0.012) and number of bevacizumab injections (p=0.040) were significantly associated with gain in VA, while change in CST was a strong predictor of VA change (p<0.01). Aflibercept patients were more likely to gain vision after 6 months but not at 12 months.

Conclusions: In a real-world study, improvements in functional outcomes can still be gained after switching anti-vascular endothelial growth factor in bevacizumab non-responders. Both ranibizumab and aflibercept were comparable and effective treatments.

Objective: Report effectiveness of selective laser trabeculoplasty (SLT) and topical medical therapy for treatment initiation and escalation.

Design: Multicentre, retrospective cohort study covering an observation period of 10 years.

Participants: Patients with ocular hypertension or primary open-angle glaucoma initiating intraocular pressure (IOP)-lowering therapy, or escalating from a single topical agent.

Main outcome measures: Kaplan-Meier estimate for duration of treatment success, defined by the time between treatment event to treatment failure, defined as meeting one of the following: a <20% reduction in IOP in comparison to baseline at two consecutive clinic visits; IOP >21 mm Hg at 2 consecutive clinic visits; or subsequent intensification of glaucoma treatment (subsequent increase in medical drops, SLT (re-)treatment, incisional glaucoma therapy).

Results: A total of 4564 eyes (mean baseline IOP 21.8 SD 7.0 mm Hg) of 2708 patients were included. The median time to treatment failure (ie, duration for which treatment success can be expected for 50% of patients) was 1.72 years (95% CI 1.63 to 1.79) following initiation of a topical agent and 1.35 (95% CI 1.13 to 1.73) years after initial SLT.Following escalation in those already on a single topical agent, the median treatment failure time was 1.32 years (95% CI 1.23 to 1.44) for 2 topical agents and 1.53 years (95% CI 1.35 to 2.03) for a single topical agent and SLT.

Conclusion: This retrospective analysis reports the real-world effect of SLT and topical medical therapy on IOP and treatment success following the most common treatment scenarios: initiation of IOP-lowering treatment and intensification from a single topical drop. Due to the non-randomised nature of this study, it is not possible to draw firm conclusions regarding the comparative effectiveness of drop and SLT.

Purpose: To investigate whether corneal changes observed via in vivo confocal microscopy (IVCM) in patients with aniridia-related keratopathy (ARK) reflect clinical severity.

Methods: A cross-sectional, observational study. Patients with congenital aniridia and healthy controls were included. IVCM of the epithelium, anterior stroma and posterior stroma were collected, manually annotated and analysed using the pretrained DINOv2 model as a feature extractor. High-dimensional embeddings were visualised using t-distributed stochastic neighbour embedding (t-SNE) to assess layer-specific clustering. Structural deviations from normal controls were quantified using centroid and Euclidean distance metrics. The cumulative structural changes across corneal layers were then correlated with Ocular Surface Score (OSS), a clinical grading scale for ARK severity.

Results: 20 patients with congenital aniridia and six healthy controls were included. t-SNE analysis revealed distinct clusters for normal corneal layers; whereas, ARK samples displayed overlapping clusters, suggestive of blurred structural boundaries. Notably, significant clustering patterns were observed in the anterior stroma, even in cases with mild ARK, underscoring its potential as an early disease marker. Anterior stromal changes were significantly associated with OSS scores (p<0.05), while cumulative structural deviations across all layers demonstrated a stronger correlation with disease severity (p<0.01). The posterior stroma showed relative structural preservation, aligning closely with healthy controls.

Conclusion: DINOv2 is a useful tool for identifying subtle structural changes in corneal layers affected by ARK. The corneal stromal features characterised using IVCM showed strong associations with clinical disease and may serve as structural biomarkers of clinical disease.

Objective: To report insights on proliferative diabetic retinopathy (PDR) risk modification with repeated antivascular endothelial growth factor (VEGF) injections for the treatment of diabetic macular oedema (DMO) in routine care.

Methods and analysis: Multicentre study (27 UK-National Health Service centres) of patients with non-PDR (NPDR) and DMO. Primary outcome was PDR development. Repeated anti-VEGF injections were modelled as time-dependent covariates using Cox regression and weighted cumulative exposure (WCE) adjusting for baseline diabetic retinopathy (DR) grade, age, sex, ethnicity, type of diabetes and deprivation. PDR incidence rates (IRs) were calculated.

Results: We included 2858 DMO anti-VEGF-treated eyes. Anti-VEGF injections showed a protective effect on PDR risk during the most recent 4 weeks from exposure, which rapidly decreased. Mild-NPDR had a lower PDR risk compared with moderate-NPDR (HR 1.99, 95% CI 1.13 to 3.51, p=0.015) and severe-NPDR (HR 4.63, 95% CI 2.55 to 8.41, p<0.001). Patients with type 1 diabetes showed an increased PDR risk when compared with patients with type 2 diabetes (HR 2.08, 95% CI 1.35 to 3.21, p<0.001). And every 5-year increase in age showed a 9% reduction in PDR hazards (p=0.002). The PDR cumulative IR was 4.45 (95% CI 3.89 to 5.09) per 100 person-years.

Conclusions: The WCE method is a valuable modelling strategy for repeated exposures in ophthalmology. Injections are protective against PDR predominantly within the most recent 4 weeks. Based on observed data, we show that age and baseline DR severity are relevant predictors of poor outcomes in patients with DMO treated with anti-VEGF.

Aims: To investigate the shared genetic mechanisms between type 2 diabetes (T2D) and primary open-angle glaucoma (POAG). Using large-scale genome-wide association study (GWAS) data, we performed single nucleotide polymorphism (SNP) level analysis to detect pleiotropic variants and loci, paired eQTL mapping analysis and gene-level analysis to identify candidate pleiotropic genes. In addition, Mendelian randomisation (MR) analysis was performed to assess causal associations.

Materials and methods: We used POAG GWAS data from Finngen (9565 cases and 430 250 controls) and T2D GWAS data from 55 555 European ancestry samples. We used Linkage Disequilibrium SCore (LDSC) regression to assess the genetic association between T2D and POAG and further used PLeiotropic Analysis under the COmposite null hypothesis (PLACO) to identify shared genetic variants between paired traits. Finally, we further used MR analysis to explore the causal association between T2D and POAG at the genetic level.

Results: The LDSC results and MR analysis revealed that the T2D effect was significantly higher than that of the POAG (OR=1.09, 95% CI 1.03 to 1.14, p=1.50×10^-3). The PLACO property analysis determined that the T2D sum POAG shared 178 individual SNPs, separate localisation of 79 individual causes. The five most popular choices are based on the effectiveness of CCND2, SVEP1, ST6GAL1, TCF7L2 and HMGA2. expression quantitative trait loci mapping further revealed 36 genes with regulatory roles in optic nerve-related brain tissues. Functional enrichment analyses indicated that these pleiotropic genes are involved in neurodevelopmental, neuroprotective and metabolic pathways, with tissue-specific enrichment observed in neural, pancreatic, adipose and retinal tissues. It is possible to present the main comorbid mechanisms of T2D and POAG.

Conclusions: Our study provides new insights into the aetiology and pathogenesis of T2D and POAG at the genetic level.

Background/aims: Acanthamoeba keratitis is a rare, severe corneal infection. Until the recent approval of polihexanide (PHMB) 0.08% by the European Medicines Agency, there were no licensed medical therapies and current treatments relied on off-label or compounded products. The purpose of this study is to estimate the relative efficacy of PHMB 0.08% compared with current treatments.

Methods: A patient-level indirect treatment comparison (ITC) compared data from a pivotal trial of PHMB 0.08% and a retrospective real-world study of current treatments: (1) any anti-amoebic treatment (AAT), (2) PHMB 0.02% plus a diamidine (propamidine or hexamidine) 0.1% and (3) chlorhexidine (CXL) 0.02% alone or in combination with a diamidine. The primary outcome was the clinical resolution rate (CRR) without surgery within 12 months. ITCs were implemented using propensity scoring analysis with overlap weighting and adjustment for covariates (age, sex, disease stage, treatment delay, prior use of corticosteroid or antiviral).

Results: The CRR was 84.8% for PHMB 0.08% (n=66), 43.6% for any AAT (n=227), 55.0% for PHMB 0.02% plus a diamidine (n=111) and 40.0% for CXL 0.02% with or without a diamidine (n=35). In the unweighted analysis, the absolute difference (95% CI) in favour of PHMB 0.08% was 41.2% (28.8%, 51.2%; p<0.001) compared with any AAT, 29.9% (14.5%, 42.1%; p<0.001) compared with PHMB 0.02% plus a diamidine and 44.8% (23.9%, 62.3%; p<0.001) compared with CXL 0.02% with or without a diamidine. Similar results were observed in the weighted analyses.

Conclusions: These results suggest that PHMB 0.08% when delivered with the recommended protocol is significantly more effective than currently used treatments in achieving clinical resolution without surgery. The study limitations include differences in recruitment periods, diagnostic criteria and drug delivery methodology, as well as limitations of the ITC adjustment measures which can lead to residual confounding.

Objective: To evaluate the frequencies of input parameters in cost-effectiveness analyses (CEA) within ophthalmology, particularly in willingness-to-pay (WTP), and to assess trends over time in studies conducted in the United States.

Methods and analysis: A cross-sectional analysis of CEAs from the Tufts Medical Center CEA Registry spanning 1993 to 2022 was conducted, including all studies evaluating diseases of the eye and adnexa. The primary outcomes measured included trends in WTP thresholds, funding sources, types of interventions and disease classifications.

Results: A total of 82 US-based CEAs met the inclusion criteria. All studies assessed outcomes in quality-adjusted life years (QALYs). WTP thresholds of US$50 000 (41%) and US$100 000 (39%) were most frequently reported, with US$150 000 emerging in 9% of studies since 2019. Discounting at 3.0% for costs and QALYs was universally applied. Government (33%), nonprofit (29%) and pharmaceutical (17%) funding predominated. Pharmaceutical-funded studies often employed higher WTP thresholds of US$100 000 (29%) and US$150 000 (29%). The most common intervention types were surgical (40%) and pharmaceutical (40%), whereas diseases of the choroid and retina (43%) were most frequently studied. Healthcare perspectives (17 studies) were more commonly reported than societal perspectives (6 studies).

Conclusions: US-based ophthalmology CEAs commonly use US$50 000-$100 000 WTP thresholds and a 3.0% discount rate, with higher thresholds emerging recently. Public and nonprofit funding predominates, focusing on retinal diseases and surgical or pharmaceutical interventions. Reassessing fixed WTP thresholds and incorporating societal perspectives could improve CEAs' relevance, ensuring alignment with evolving economic and healthcare landscapes.

Background/aims: To determine whether retinopathy of prematurity (ROP) screening is initiated on time according to current South African (SA) guidelines, that is, before the onset of stage 3 and type 1 ROP.

Methods: A prospective study of preterm infants screened at five neonatal units between 1 May 2022 and 31 January 2023 in Cape Town, SA. Data on all infants screened with a birth weight <1250 g or gestational age (GA) <32 weeks were extracted from the ROP South African (ROPSA) register, including postnatal age (PNA) and postmenstrual age (PMA) at first screening.

Results: A total of 696 infants were included, 58.9% (n=410) of whom had an early ultrasound (EUS) for GA estimation. Overall, 220 (31.6%) infants developed ROP, 20 (2.9%) had stage 3 or type 1 and 7 (1.0%) required treatment. Screening was initiated on time according to SA criteria in 549 (78.9%) infants, none of whom had stage 3 or type 1 ROP at first screening. Stage 3 and type 1 ROP were first detected at PNA and PMA of 6.3 and 33.1 and 8.9 and 35.9 weeks, respectively. Most infants (319, 45.8%) were screened according to PNA only, and 78.9% of the 185 infants screened only once did not attend subsequent examinations.

Conclusion: Screening started on time in most infants and prior to the development of severe ROP. Due to the limited availability of EUS in our region and to promote complete screening, we recommend that screening be initiated using PNA alone at 4-6 weeks or prior to discharge, whichever is earliest. The low proportion of infants with stage 3 and type 1 ROP is a limitation in our study. Therefore, recommendations may not be generalisable to South African regions where neonatal care results in a higher proportion of infants developing type 1 ROP.

Purpose: To assess retinal and choroidal changes following rapid mydriasis in healthy adults.

Methods: Seventy-one volunteers (71 right eyes) participated in a prospective randomised controlled trial. They were divided into two groups: tropicamide (n=36) and a mixture (tropicamide:phenylephrine=1:1, n=35) groups. Ophthalmic examinations included visual acuity, intraocular pressure and axial length measurements. Ultra-widefield swept-source optical coherence tomography angiography was used to assess retinal and choroidal parameters before and after mydriasis. This technique covers a 24×20 mm² area, allowing for non-invasive, simultaneous structural and haemodynamic assessment of retinal and choroidal regions.

Results: Both central (tropicamide: 33.3%; mixture: 22.22%) and mid-peripheral (tropicamide: 28.47%; mixture: 36.81%) retinas thickened slightly postmydriasis (p<0.05, false discovery rate (FDR) corrected). Specifically, thickening primarily occurred in the temporal (tropicamide: 25.61%; mixture: 34.31%) and inferior (tropicamide: 50.00%; mixture: 35.29%) mid-peripheral regions. Outer retinal layer thickening correlated positively with overall retinal thickness in both groups (tropicamide: r=0.71, p<0.001; mixture: r=0.74, p<0.001). Choroidal stroma volume increased in 18 regions post-tropicamide treatment and in two regions postmixture treatment (p<0.05, FDR corrected). However, no significant differences were found in retinal vascular density, choroidal thickness, vascular density or matrix between the two groups premydriatic and postmydriatic administration (p>0.05, FDR corrected).

Conclusions: Rapid mydriasis causes slight retinal thickening, the slight change in the outer layer, particularly in the temporal and inferior regions. There were no significant changes in the choroid parameters following mydriasis, except for choroidal stroma volume. The limitation of this study was the small sample size and the absence of a control group.

Geographic atrophy (GA) is a form of advanced age-related macular degeneration (AMD) affecting approximately 1 million people in the USA and 5 million globally. In this review, retinal imaging techniques used for diagnosis and monitoring progression of GA in AMD, and the risk factors associated with the development and progression of GA are summarised. To familiarise clinicians with common phenotypes of patients with GA, the clinical and imaging features that may lead to rapid progression of GA in various phenotypes are highlighted. With the recent US Food and Drug Administration approval of new GA treatments that reduce lesion growth, understanding the risk of progression to GA and factors contributing to GA growth may aid in patient selection and guide patient-level management and treatment.