BMJ Open Ophthalmology最新文献

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.

Objective: To assess the prevalence of symptoms associated with Charles-Bonnet syndrome (CBS) in adult patients with inherited retinal disease (IRD) and explore patient perspectives and need for support.

Methods and analysis: This was a prospective single-centre cross-sectional service evaluation and improvement project that involved adult patients with a clinical diagnosis of IRD under the care of the specialist IRD service at a tertiary NHS healthcare provider in the UK. Information was gathered from a survey questionnaire completed by participants remotely or at a hospital appointment and electronic patient records.

Results: There were 103 surveys returned of which 94 were suitable for inclusion in the analysis. Visual hallucinations were reported by 18.6% of patients overall. Patients with visual acuity worse than 0.3 logMAR made up 76% of those reporting CBS symptoms.Of the patients who experienced visual hallucinations, 59% reported that their visual hallucinations had no effect on them, while 29% reported a negative effect, with 12% not commenting; only 12% said that they require further support.

Conclusion: CBS symptoms were reported by almost one in six patients in our IRD practice.Only a small proportion of patients included in this survey felt that they required additional support, but they did express that being informed early on of an explanation for their visual hallucinations was helpful.The limitations of our study are the small number of patients included in the survey, the lack of external validation of the questionnaire used, the risk of selection bias and the two different methods/phases of data collection used.

Aims: To evaluate the efficacy of myopia control by spectacle lenses in a real-world study.

Methods: This is a longitudinal, retrospective, comparative, observational, real-world study of the French Myopia Cohort. Records of prescriptions for optical correction, gender and age were collected from 1500 opticians between 2020 and 2023. The study cohort consisted of myopic children aged 4 to 15 years who were assigned to three groups: two control groups wearing single vision lenses (SVL) and one intervention group wearing myopia control spectacles (MCS); either defocus incorporated multiple segments (DIMS, n=1786) or highly aspheric lenses (HAL, n=585). The first SVL group was matched to the MCS group for age, sex and initial refractive error (first matching), and the second SVL group was matched for the same criteria and myopia progression during the first 6 months of follow-up (second matching).The difference in myopia progression was calculated between SVL groups and the MCS group. DIMS and HAL were also compared for myopia progression.

Results: A total of 2542 children (mean age of 9.5 years and mean spherical equivalent of -2.3 D at baseline) were included in each of the three groups. The mean progression rates for MCS were by +0.59 D (95% CI +0.57 to +0.62D; p<0.001) after the first matching and by +0.30 D (95% CI +0.28 to +0.32D; p<0.001) after the second matching, in comparison to the SVL groups. Children wearing HAL spectacles showed slightly less myopia progression (difference in progression = +0.14 D, 95% CI = +0.10 to +0.18, p<0.001) compared with the DIMS group.

Conclusions: Although there are some limitations, including its retrospective design, the lack of lifestyle and environmental data and the use of SE rather than axial length, this study showed that in a real-world setting, both DIMS and HAL spectacles demonstrated efficacy in reducing myopia progression. While a statistically significant lower myopia progression rate was observed in the HAL group, this difference was not clinically meaningful. This study also showed that DIMS and HAL reduce myopia progression among younger children aged 4 to 6 years.

Background: Orbital malignant tumours seriously affect the quality of life of patients; however, there is currently no quality-of-life questionnaire for patients with orbital malignant tumours.

Objective: To develop and evaluate a quality-of-life questionnaire for patients with orbital malignant tumours.

Methods: A pool of items was generated through a literature search, expert meeting and patient interview. Pre-survey and scale evaluation were performed, the quality-of-life questionnaire for patients with orbital malignant tumours (QLQ-OT) was modified, and the scale was evaluated by measuring the quality of life of 46 patients with orbital tumours.

Results: The effective rate of QLQ-OT was 97.4%, the Cronbach's alpha coefficient was >0.6, and the test-retest reliability Intraclass Correlation Coefficient was >0.7, suggesting good internal consistency and test-retest reliability. The Pearson correlation coefficients were >0.8 between individual domain scores; > 0.6 between items and their own domains in the QLQ-OT; and >0.6 between domains and their corresponding domains in Quality of Life Center Questionnaire, thereby indicating good content, convergent and criterion-related validity. Ten principal components (the initial eigenvalues >1) were abstracted from 38 items of the general by factor analysis, accounting for 81.0% of cumulative variance.

Conclusions: QLQ-OT has good compliance, reliability, validity and responsiveness and can be used to measure the quality of life of patients with orbital malignant tumours.