British Journal of Ophthalmology
ISSN / EISSN : 0007-1161 / 1468-2079
Published by: BMJ (10.1136)
Total articles ≅ 24,508
Latest articles in this journal
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2021-319508
Aims To examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia. Methods Our analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data. Results Over 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia. Conclusions AMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2021-319383
Objective Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2. Methods and analysis This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238). Results At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%–7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%–7.8%) after 12 months without treatment. Conclusions Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments. Trial registration number NCT00056836.
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2020-318646
Synopsis A deep-learning-based macular extrafoveal avascular area (EAA) on a 6×6 mm optical coherence tomography (OCT) angiogram is less dependent on the signal strength and shadow artefacts, providing better diagnostic accuracy for diabetic retinopathy (DR) severity than the commercial software measured extrafoveal vessel density (EVD). Aims To compare a deep-learning-based EAA to commercial output EVD in the diagnostic accuracy of determining DR severity levels from 6×6 mm OCT angiography (OCTA) scans. Methods The 6×6 mm macular OCTA scans were acquired on one eye of each participant with a spectral-domain OCTA system. After excluding the central 1 mm diameter circle, the EAA on superficial vascular complex was measured with a deep-learning-based algorithm, and the EVD was obtained with commercial software. Results The study included 34 healthy controls and 118 diabetic patients. EAA and EVD were highly correlated with DR severity (ρ=0.812 and −0.577, respectively, both p<0.001) and visual acuity (r=−0.357 and 0.420, respectively, both p<0.001). EAA had a significantly (p<0.001) higher correlation with DR severity than EVD. With the specificity at 95%, the sensitivities of EAA for differentiating diabetes mellitus (DM), DR and severe DR from control were 80.5%, 92.0% and 100.0%, respectively, significantly higher than those of EVD 11.9% (p=0.001), 13.6% (p<0.001) and 15.8% (p<0.001), respectively. EVD was significantly correlated with signal strength index (SSI) (r=0.607, p<0.001) and shadow area (r=−0.530, p<0.001), but EAA was not (r=−0.044, p=0.805 and r=−0.046, p=0.796, respectively). Adjustment of EVD with SSI and shadow area lowered sensitivities for detection of DM, DR and severe DR. Conclusion Macular EAA on 6×6 mm OCTA measured with a deep learning-based algorithm is less dependent on the signal strength and shadow artefacts, and provides better diagnostic accuracy for DR severity than EVD measured with the instrument-embedded software.
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2021-319618
Aims To predict the vault and the EVO-implantable collamer lens (ICL) size by artificial intelligence (AI) and big data analytics. Methods Six thousand two hundred and ninety-seven eyes implanted with an ICL from 3536 patients were included. The vault values were measured by the anterior segment analyzer (Pentacam HR). Permutation importance and Impurity-based feature importance are used to investigate the importance between the vault and input parameters. Regression models and classification models are applied to predict the vault. The ICL size is set as the target of the prediction, and the vault and the other input features are set as the new inputs for the ICL size prediction. Data were collected from 2015 to 2020. Random Forest, Gradient Boosting and XGBoost were demonstrated satisfying accuracy and mean area under the curve (AUC) scores in vault predicting and ICL sizing. Results In the prediction of the vault, the Random Forest has the best results in the regression model (R2=0.315), then follows the Gradient Boosting (R2=0.291) and XGBoost (R2=0.285). The maximum classification accuracy is 0.828 in Random Forest, and the mean AUC is 0.765. The Random Forest predicts the ICL size with an accuracy of 82.2% and the Gradient Boosting and XGBoost, which are also compatible with 81.5% and 81.8% accuracy, respectively. Conclusions Random Forest, Gradient Boosting and XGBoost models are applicable for vault predicting and ICL sizing. AI may assist ophthalmologists in improving ICL surgery safety, designing surgical strategies, and predicting clinical outcomes.
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2021-319426
Background The associations of geographic atrophy (GA) progression with systemic health status and medication use are unclear. Methods We manually delineated GA in 318 eyes in the Age-Related Eye Disease Study. We calculated GA perimeter-adjusted growth rate as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye (mean follow-up=5.3 years). Patients’ history of systemic health and medications was collected through questionnaires administered at study enrolment. We evaluated the associations between GA perimeter-adjusted growth rate and 27 systemic health factors using univariable and multivariable linear mixed-effects regression models. Results In the univariable model, GA perimeter-adjusted growth rate was associated with GA in the fellow eye at any visit (p=0.002), hypertension history (p=0.03), cholesterol-lowering medication use (p<0.001), beta-blocker use (p=0.02), diuretic use (p<0.001) and thyroid hormone use (p=0.03). Among the six factors, GA in the fellow eye at any visit (p=0.008), cholesterol-lowering medication use (p=0.002), and diuretic use (p<0.001) were independently associated with higher GA perimeter-adjusted growth rate in the multivariable model. GA perimeter-adjusted growth rate was 51.1% higher in patients with versus without cholesterol-lowering medication use history and was 37.8% higher in patients with versus without diuretic use history. Conclusions GA growth rate may be associated with the fellow eye status, cholesterol-lowering medication use, and diuretic use. These possible associations do not infer causal relationships, and future prospective studies are required to investigate the relationships further.
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2021-320033
Background/aims Congenital cataracts, which are genetically heterogeneous eye disorders, result in visual loss in childhood around the world. CRYBA1/BA3 serves as an abundant structural protein in the lens, and forms homomers and heteromers to maintain lens transparency. In previous study, we identified a common cataract-causing mutation, βA3-glycine at codon 91 (G91del) (c.271–273delGAG), which deleted a highly conserved G91del and led to perinuclear zonular cataract. In this study, we aimed to explore the underlying pathogenic mechanism of G91del mutation. Methods Protein purification, size-exclusion chromatography, spectroscopy and molecular dynamics simulation assays were used to investigate the effects on the heteromers formation and the protein structural properties of βA3-crystallin caused by G91del mutation. Intracellular βA3-G91del overexpression, MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide) and cell apoptosis were used to investigate the cellular functions of βA3-G91del. Results βA3-crystallin and βB2-crystallin could form heteromers, which have much more stable structures than βA3 homomers. Interestingly, βA3/βB2 heteromers improved their resistance against the thermal stress and the guanidine hydrochloride treatment. However, the pathogenic mutation βA3-G91del destroyed the interaction with βB2, and thereby decreased its structural stability as well as the resistance of thermal or chemical stress. What’s more, the βA3-G91del mutation induced cell apoptosis and escaped from the protection of βB2-crystallin. Conclusions βA3/βB2 heteromers play an indispensable role in maintaining lens transparency, while the βA3-G91del mutation destabilises heteromers formation with βB2-crystallin, impairs cellular viability and induces cellular apoptosis. These all might contribute to cataract development.
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2020-316481
Aims To evaluate the rates of keratoconus progression and associated factors in eyes of children and adolescents. Methods Retrospective, cohort study of individuals ≤18 years old at the time of keratoconus diagnosis and with at least 6 months of follow-up. Corneal tomography was performed using an Orbscan tomographer (Bausch & Lomb, Rochester, New York, USA) to determine whether progression occurred. Tomographic progression of keratoconus was defined as a change in any of the investigated parameters (keratometry values, KMAX, maximum anterior or posterior elevation, central pachymetry, thinnest pachymetry) beyond the limits of repeatability. Results 148 eyes of 106 patients with a mean age of 15.2±2.5 years were studied over a mean follow-up period of 2.9±2.2 years. The overall rate of tomographic progression was 77.0% (114/148 eyes). Eyes that progressed had more advanced disease at presentation with higher anterior curvature (KMAX55.4±6.3 vs 52.2±5.4 dioptres; p<0.01), posterior elevation (108.2±40.9 vs 86.3±35.6 µm; p<0.01) and lower central pachymetry measurements (442.1±56.7 vs 454.4±47.5 µm; p=0.01). Age at presentation, gender, atopy, documented eye rubbing, ethnicity and duration of follow-up were not significantly associated with progression in the multivariate analyses. There was a higher rate of bilateral progression if at least one eye had severe keratoconus (73.9%) compared with no severe keratoconus in either eye (36.8%; p=0.03). Conclusions A high rate of progression was identified in keratoconic eyes of children and adolescents. More advanced disease at initial presentation may increase the risk of further keratoconus progression.
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2021-319632
Background To assess prevalence and associated factors of changes in the ophthalmoscopic optic disc size and shape. Methods The case–control study included all highly myopic eyes (myopic refractive error ≤−6.0 diopters) and a randomly selected group of non-highly myopic eyes, examined in the population-based Beijing Eye Study 2001 and 2011. Results The study included 89 highly myopic eyes (age:65.0±9.8 years) and 86 non-highly myopic eyes. Reduction in ophthalmoscopic disc size (prevalence, high myopia: 30 (33.7%) eyes; non-high myopia: 7 (8.1%) eyes) was associated with non-circular gamma zone enlargement (OR: 19.4; 95% CI: 6.7 to 56.6; p<0.001) and disc-fovea line elongation (OR: 2.80;95% CI: 1.12 to 6.98; p=0.03). Disc size reduction was correlated with a disc diameter shortening in direction of the widest gamma zone enlargement (correlation coefficient r=34; p=0.01). The perpendicular disc diameter remained mostly unchanged, resulting in an ovalisation of the ophthalmoscopic disc shape. Enlargement of the ophthalmoscopic disc size (prevalence, high myopia: 22 (24.7%) eyes; non-high myopia: 4 (4.7%) eyes) was associated with circular gamma zone enlargement (4.99; 95% CI: 1.95 to 12.8; p=0.001) and high myopia (OR: 4.29; 95% CI: 1.34 to 13.8; p=0.01). Conclusions Myopic axial elongation may lead first to a Bruch’s membrane (BM) opening (BMO) shift into the foveal direction leading to BM overhanging into the nasal intrapapillary compartment, development and enlargement of gamma zone at the temporal disc side, reduction in the ophthalmoscopically visible disc area and ovalisation of the ophthalmoscopic disc shape. In a second step, an axial elongation-associated BMO enlargement may lead to a circular gamma zone increase and, due to the retraction of BM at the nasal disc border, to an enlargement of the ophthalmoscopically visible optic disc.
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2021-318880
Background To explore the outcomes and mechanisms of intraocular pressure (IOP) control using low-dose transscleral cyclophotocoagulation (LDTSCP) followed by phacoemulsification in patients with prolonged acute primary angle closure (APAC). Methods Patients with prolonged APAC refractory to all other treatment modalities were prospectively recruited, and underwent LDTSCP (10 shots, 2 s duration, 120° treatment with the energy starting at 1500 mW and titrated to the level with audible burst but not exceeding 2000 mW) and anterior chamber paracentesis 1 week prior to phacoemulsification with intraocular lens implantation and viscogoniosynechiolysis. Postoperative IOP, vision, anatomic changes on anterior segment optical coherence tomography and complications were recorded. Results Twenty eyes with prolonged APAC were recruited. Median follow-up was 12 months (range 9–18), at which point the vision in all eyes had improved and IOP was ≤17 mm Hg on no antiglaucoma medications. Following LDTSCP at postoperative day (POD) 1, IOP decreased in all eyes to a median 15 mm Hg (range: 6–28 mm Hg). Post-LDTSCP supraciliary effusion (SCE) occurred in 90% of eyes on POD1 or POD7 and ciliary body defect (CBD) was detected in 30% of eyes and resolved in all cases by postoperative month 1. Lower post-LDTSCP IOP was associated with more number of bursts (r=−0.558, p=0.011) and higher grade of SCE (r=−0.877, p<0.001), but not with total energy (p=0.240). Eyes with CBD (p=0.018) and a higher number of bursts (r=0.657, p=0.002) had higher grade SCE. Conclusions LDTSCP-induced SCE may explain the post-LDTSCP IOP reduction seen in eyes with prolonged APAC. LDTSCP instead of traditional more extensive treatment, was sufficient to provide a relatively safe and effective bridge therapy prior to phacoemulsification. Trial registration number Chinese Clinical Trials Registry (ChiCTR1900023567).
British Journal of Ophthalmology; https://doi.org/10.1136/bjophthalmol-2021-319863
Synopsis/precis We investigated the relationship between contrast sensitivity (CS) and vision-related quality of life (VR-QOL) in patients with central retinal vein occlusion following ranibizumab intravitreal injection; CS showed a stronger association with VR-QOL than visual acuity. Background/aims To investigate the relationship between CS, VR-QOL and optical coherence tomography (OCT) findings in patients with cystoid macular oedema secondary to central retinal vein occlusion (CRVO-CMO) following intravitreal injection of ranibizumab. Methods This was a multicentre, open-label, single-arm, prospective study. The study included 23 patients with CRVO-CMO who were followed up for 12 months after treatment. The best-corrected visual acuity (BCVA), letter contrast sensitivity (LCS) and OCT images were obtained every month. For VR-QOL assessment, the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was administered to the patients before treatment and at 3, 6 and 12 months following treatment. Results The LCS and VFQ-25 composite score improved significantly from baseline to 12 months following treatment. The multiple regression analysis revealed that the LCS of the affected eye and BCVA of the fellow eye were related to the VFQ-25 composite score following treatment. The LCS improvement showed a significant correlation with the improvement in the VFQ-25 composite score, whereas the BCVA improvement was not correlated with the improvement in the VFQ-25 composite score. Stepwise multiple regression analyses revealed that, at the time of macular oedema resolution, the distance between the external limiting membrane and retinal pigment epithelium (ELM-RPE) and average ganglion cell-inner plexiform layer (GCIPL) thickness were associated with LCS. Conclusion CS had a stronger association with VR-QOL than with BCVA in patients with CRVO-CMO. With the resolution of macular oedema, CS was associated with ELM-RPE thickness and average GCIPL thickness.