BMJ Open Ophthalmology最新文献

Introduction: Annual screening for hydroxychloroquine (HCQ) retinopathy is recommended, and electroretinography (ERG) is considered a gold-standard test, but there are screening shortfalls and standard ERG is burdensome and has limited availability. Newer, portable ERG devices using skin-based electrodes may increase screening capacity but need validation. This study aims to determine initial device accuracies and feasibility of further research.

Methods and analysis: Prospective diagnostic device accuracy and feasibility study comparing novel ERG devices to standard screening tests. Three groups of 35 participants on HCQ, categorised by HCQ retinopathy (definite, possible and no retinopathy), and 35 healthy control participants, recruited by consecutive sampling, will have full field and multifocal ERG index tests, delivered using skin-contact electrodes by two devices-RETEval full-field and UTAS multifocal ERG, both manufactured by LKC Technologies (Gaithersburg, Maryland, USA), compared with spectral-domain optical coherence tomography and autofluorescence reference tests graded by two masked, independent retinal specialists. Eligible HCQ participants will either have diagnosed HCQ retinopathy or be eligible for screening per UK guidelines. Healthy control participants will have no prior HCQ exposure and be of similar age and sex to HCQ participants. Primary outcome is device-specific sensitivity and specificity. Secondary outcomes include the effect of dilation on device outputs, analysis of discriminatory waveforms, device acceptability and recruitment rate. Safety outcomes include adverse and serious adverse events and device events.

Ethics and dissemination: Cambridge East ethics committee gave a favourable opinion (24/EE/0011, 23/02/2024). Results will be published in a peer-reviewed ophthalmology journal.

Trial registration number: ClinicalTrials.gov NCT06035887.

Objective: Age-related macular degeneration (AMD) is one of the leading causes of irreversible visual impairment and blindness in the elderly. As AMD is a multifactorial disease, it is critical to explore useful biomarkers and pathological pathways underlying it. The purpose of this study is to summarise current metabolic profiles and further identify potential metabolic biomarkers and therapeutic targets in AMD, which could facilitate clinical diagnosis and treatment.

Methods and analysis: Relevant metabolomics studies published before 10 December 2021 were generally reviewed from online resources by two investigators. Studies with sufficient information and data were included in this systematic review and repeatedly identified metabolites were extracted. Pathway and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were performed. The public Gene Expression Omnibus (GEO) database was used for coanalysis with differential metabolites to construct a pathway network via MetaboAnalyst V.5.0.

Results: 16 studies were included in our analysis. 24 metabolites were repeatedly detected and regarded as potential biomarkers for AMD. Pathway analysis implied a major role of phenylalanine, tyrosine and tryptophan pathways in AMD pathology. 11 KEGG pathways were enriched, meanwhile, 11 metabolic pathway clusters were identified by coanalysing the differential metabolites and gene profiles using the GEO database.

Conclusion: In this study, we summarised 16 metabolomic studies on AMD, and 24 metabolites were identified as potential biofluid biomarkers. This provided novel insights into the pathogenic mechanisms underlying AMD. Further studies are warranted to validate and expand an effective pattern for AMD diagnosis and treatment.

Background: Very premature infants screened for retinopathy of prematurity (ROP) that do not develop ROP still experience serious visual developmental challenges, and while it is recommended that all children in the UK are offered preschool visual screening, we aimed to explore whether this vulnerable group requires dedicated follow-up.

Methods: We performed a real-world retrospective observational cohort study of children previously screened for ROP in NHS Greater Glasgow and Clyde (Scotland) between 2013 and 2015. We excluded those with any severity of ROP identified during screening. Electronic patient records were searched for preschool orthoptic visual screening (See4School) results and results of referral to the hospital eye service (HES).

Results: 222 children met the inclusion criteria. Their median birth weight was 1200 g and median gestational age was 31 weeks. A total of 111 (50%) of these children had been referred to HES nationally. 103 were referred within the health board where ROP screening took place; of these, 47% (48/103) were referred from the See4School programme, 31% (31/103) from paediatric clinics, 13% (13/103) from primary care and 11% (11/103) from community optometrists. 42 of these 103 referrals (41%) to HES had occurred before the age (3½ years) when children became eligible for See4School screening. At hospital review, 55% (55/99) patients had a glasses prescription issued for refractive error, 22% were estimated to have amblyopia and 30% had a diagnosis of strabismus.

Conclusion: In this non-controlled study we found premature infants that do not develop ROP still face considerable visual morbidity and dedicated follow-up may be warranted.

Objective: This prospective case-control study examined the novel immunoinflammatory markers obtained from blood counts of patients with Graves' orbitopathy (GO), Graves' disease (GD) and healthy subjects.

Methods: Demographic data, white cell count parameters, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), platelet-to-neutrophil ratio (PNR), red cell distribution width (RDW), RDW-to-platelet ratio (RDW/PLT), MPV-to-lymphocyte ratio (MPV/ALC), eosinophil-to-lymphocyte ratio (ELR) and systemic immune-inflammatory index (SII) were evaluated. The European Group on Graves Orbitopathy scale and Clinical Activity Score were used for clinical activity and severity assessment.

Results: The GO group showed significantly higher mean MPV (p˂0.001) and MPV/ALC (p=0.03) than the GD group. The PLR (p=0.02), MPV/ALC (p=0.04) and SII (p=0.04) were significantly higher in the GO than healthy group. A significantly higher absolute neutrophil count (p=0.005), NLR (p=0.001), MPV (p=0.001), MPV/ALC (p=0.003), MPV/PLT (p=0.04), RDW (p˂0.001), RDW/PLT (p=0.02) and SII (p=0.01) as well as lower ALC (p=0.01) and PNR (p˂0.001) was observed in the active than inactive GO. Moderate to severe GO group had a significantly higher NLR (p=0.006), PLR (p=0.04), ELR (p=0.006), MPV (p=0.03), MPV/ALC (p=0.002), RDW (p˂0.001), RDW/PLT (p=0.02) and SII (p=0.03) as well as a lower ALC (p=0.01) and PNR (p=0.01) than mild GO.

Conclusions: The MPV/ALC ratio and MPV levels may identify GD patients at risk of GO. The MPV, MPV/ALC, ALC, NLR, PLR, PNR, RDW, RDW/PLT, MPV/PLT and SII may help distinguish the GO activity and severity. However, the study's small sample size and single-centre design may limit the generalisability of the results. Furthermore, the lack of longitudinal follow-up precludes assessing marker evolution over time.

Aim: To evaluate the efficacy of automated machine learning (AutoML) models in detecting fundus diseases using ocular B-scan ultrasound images.

Methods: Ophthalmologists annotated two B-scan ultrasound image datasets to develop three AutoML models-single-label, multi-class single-label and multi-label-on the Vertex artificial intelligence (AI) platform. Performance of these models was compared among themselves and against existing bespoke models for binary classification tasks.

Results: The training set involved 3938 images from 1378 patients, while batch predictions used an additional set of 336 images from 180 patients. The single-label AutoML model, trained on normal and abnormal fundus images, achieved an area under the precision-recall curve (AUPRC) of 0.9943. The multi-class single-label model, focused on single-pathology images, recorded an AUPRC of 0.9617, with performance metrics of these two single-label models proving comparable to those of previously published models. The multi-label model, designed to detect both single and multiple pathologies, posted an AUPRC of 0.9650. Pathology classification AUPRCs for the multi-class single-label model ranged from 0.9277 to 1.0000 and from 0.8780 to 0.9980 for the multi-label model. Batch prediction accuracies ranged from 86.57% to 97.65% for various fundus conditions in the multi-label AutoML model. Statistical analysis demonstrated that the single-label model significantly outperformed the other two models in all evaluated metrics (p<0.05).

Conclusion: AutoML models, developed by clinicians, effectively detected multiple fundus lesions with performance on par with that of deep-learning models crafted by AI specialists. This underscores AutoML's potential to revolutionise ophthalmologic diagnostics, facilitating broader accessibility and application of sophisticated diagnostic technologies.

Aim: To validate the diagnostic performance of a custom 96-micro-organism TaqMan PCR card (iCAM) for microbial keratitis (MK) from a single corneal epithelial sample.

Methods: Patients over the age of 18 referred to Cambridge University Hospital with MK were recruited in this single-site prospective cohort study between September 2021 and January 2023. An ocular-specific, customised microarray card (iCAM) was constructed according to primer and probe nucleotide sequences developed in our department to detect bacteria, viruses, Acanthamoeba and fungi commonly implicated in MK using a single corneal epithelial sample. Part of the corneal epithelial sample was taken for conventional cultures per local protocol, followed by iCAM array. Microbial detection rate and positive predictive value (PPV) were evaluated.

Results: 38 corneal epithelial samples from 32 patients with MK and 4 control samples from healthy participants were obtained from 36 consecutive patients. A causative microbe was isolated in 15/34 samples (44%) using the iCAM test, compared with 15 by conventional methods (44%). iCAM test processing time varied between 6 and 24 hours compared with up to 7 days for conventional tests. Combined, the microbial detection rate was 65%, with the correlation between methods at 62%. The iCAM test could detect all major micro-organism groups with 56% sensitivity and 60% PPV.

Conclusions: The iCAM test can detect bacterial, fungal, viral and protozoan organisms using one corneal epithelial sample. The limitations include small patient cohort size and reduced volume of available corneal epithelial sample when shared between the iCAM PCR test and conventional culture methods utilised in the study. A multicentre trial is being planned to validate the clinical impact of using iCAM test on accuracy of diagnosis, early institution of appropriate antimicrobials and clinical outcomes.

Trial registration number: ISRCTN17422545.

Objective: This study aims to provide updated prevalence estimates of myopia and high myopia among late adolescent men in Seoul, South Korea, and predict future trends up to 2050.

Methods and analysis: This cross-sectional and population-level study includes late adolescent men of the same age who underwent a series of medical examinations at the Seoul Regional Military Manpower Administration between 2013 and 2022. The population with myopia and high myopia was estimated, and the prevalence for 2050 was forecasted. Associated risk factors and ocular disease status of the high myopia population were investigated.

Results: Over the 10-year period, the prevalence of myopia and high myopia among late adolescent men in Seoul was 70.67% and 20.29%, respectively. Between 2013 and 2022, the prevalence of the myopia and high myopia has increased significantly (p<0.001 and 0.006, respectively). The annual growth rate for the prevalence of myopia and high myopia was 0.61% and 0.33%, respectively. Regression analyses predicted that by 2050, myopia and high myopia prevalence will reach 90.90% and 31.26% by linear regression, and 90.75% and 31.17% by non-linear regression, respectively. Risk factor analysis identified that a high education level was associated with a higher prevalence of high myopia. Retinal detachment was significantly more common among those with high myopia, while retinal dystrophy was less common.

Conclusion: This study highlights a concerning trend of increasing myopia and high myopia prevalence, which is likely to reach 90.90% and 31.26% by 2050, with significant future burden for public health and society.

Purpose: To compare the anatomical and functional outcomes of pars plana vitrectomy (PPV) alone versus PPV with the addition of a scleral buckle in treating inferior rhegmatogenous retinal detachments (RRDs).

Methods: Comparative, retrospective cohort study including patients who were diagnosed with primary inferior RRD, defined as RRD with one or more retinal tears located between 4 and 8 hours, and divided into two treatment groups. Group 1 patients were treated with PPV and gas tamponade alone, whereas group 2 patients were treated with PPV, gas tamponade and the addition of an encirclement band. Demographic and clinical features were collected, and surgical outcomes of both groups were analysed. A univariable logistic regression model evaluated the factors influencing surgical success.

Results: A total of 161 eyes were included in the study. The average age at diagnosis was 64.1 years. There was a male predominance (66.5%), and most patients had macula-off detachments (54%). Group 1 included 75 eyes (43.1%), whereas group 2 included 86 eyes (56.9%). Baseline best-corrected visual acuity was 1.00 logMAR, improving to 0.62 logMAR at the last visit (p=0.003). No significant difference in primary success rate was observed between the two groups (86.0% with encirclement band vs 80.0% without; p=0.3). The mean follow-up period was 29 weeks (SD 39).

Conclusions: PPV alone may be as effective as PPV with an encirclement band when treating inferior RRDs. The choice of tamponade does not appear to significantly influence anatomical success, and short-acting gas can be considered sufficient for favourable outcomes.

Background/aims: Staffing represents the most significant cost to the National Health Service, and ophthalmology is its largest outpatient specialty. Value-based healthcare (VBH) focuses on care processes. Innovative models include a shift towards 'virtual' glaucoma services. We used VBH costing methodology to quantify personnel costs of virtual and face-to-face (F2F) glaucoma clinics.

Methods: Virtual and F2F clinics were process-mapped to produce step-by-step pathways of patients in each setting. Real-world timings were then audited, and time-driven activity-based costing was used to calculate the personnel cost-per-patient for both settings.

Results: Data were captured from 24 consecutive virtual glaucoma patients and 42 consecutive patients across two F2F clinics. The capacity cost rates in £/min were £0.24 for technicians and £1.16 for consultants. The average time taken to acquire clinical data in the virtual pathway was 39 min per patient (95% CI 36 to 43, range 27-61) with 14 min (95% CI 13 to 14, range 12-20) for their remote consultant review. The estimated personnel costs associated with a single virtual glaucoma clinic visit totalled £25.60 (95% CI £23.72 to £33.52). The average time taken to be seen in the F2F clinic was 50 min (95% CI 42 to 59 min, range 12-123 min) with a personnel cost of £31.08 (95% CI £19.70-£42.43).

Conclusion: Staff costs associated with visits to the consultant-delivered virtual and F2F glaucoma clinics were similar (p value=0.14), supporting virtual clinics to provide service capacity. The main limitations were that our study involved a single site, small sample size and did not consider the severity of glaucoma.

Objective: The transparency of the cornea is determined by the extracellular matrix, which is secreted by corneal stromal keratocytes (CSKs). Human-induced pluripotent stem cell (hiPSC)-derived keratocytes (hiPSC-CSKs) can be used in cell-based therapy for treating corneal blindness. Our goal was to develop an effective small molecule-based technique for differentiating hiPSCs into keratocytes.

Methods and analysis: hiPSCs were cultured in chemically defined medium, and embryoid bodies (EBs) were generated; these EBs were induced into CSKs using keratocyte-differentiated medium. The expression of keratocyte-specific markers was assessed using quantitative RT-PCR, immunostaining and Western blotting.

Results: We found that the expression of genes encoding keratocyte markers, including aldehyde dehydrogenase 1 family member A1 (ALDH1A1), lumican and keratocan, was upregulated. Immunostaining showed positive staining for ALDH1A1 and keratocan in the hiPSC-CSK samples. Similarly, western blot analysis indicated that ALDH1A1 and keratocan expression levels were significantly greater in the hiPSC-CSKs than in the control cells. In addition, hiPSC-CSKs were not transformed into fibroblasts or myofibroblasts.

Conclusion: We established an innovative and effective method to generate CSKs via the EB-based differentiation of hiPSCs, which might be employed for cell-based therapy of corneal stromal opacities.