BMJ Open Ophthalmology最新文献

Background/aims: To examine the association between sociodemographic characteristics and attendance at Hospital Eye Service (HES) referrals from the Diabetic Eye Screening Programme (DESP), in a large, ethnically diverse urban population.

Methods: Retrospective cohort study (4 January 2016-12 August 2019) of people with diabetic retinopathy (DR) referred from an English DESP to a tertiary referral eye hospital. We conducted a multivariable logistic regression with attendance as the primary outcome, controlling for age, sex, ethnicity, Index of Multiple Deprivation, best eye visual acuity and baseline DR grade.

Results: Of 7793 people referred (mean age 64 years, 62.6% male, 13.9% white, 12.5% black, 25.3% South Asian, 6.5% any other Asian background, 19.3% no recorded ethnicity and 20.9% of 'Other' ethnic origin), 69% attended. Compared with white individuals, people of black ethnic origin were similarly likely to attend. South Asians and those of other Asian backgrounds were more likely, and people with 'Other' or missing ethnicity were less likely to attend. Those with higher levels of deprivation, younger (aged 18-45 years) and older (76-90 years) age groups and worse visual acuity were less likely to attend, whereas people identified as having proliferative DR in both eyes were more likely to attend.

Conclusion: Sociodemographic patterns in attendance after referral from the DESP to the HES exist, and these do not appear to explain ethnic differences in more severe sight-threatening DR, suggesting other explanations. More work is needed to understand and reduce inequalities in HES attendance.

Objective: Ocular toxoplasmosis, caused by Toxoplasma gondii, is a significant cause of posterior uveitis and vision impairment globally. Accurate diagnosis is essential to prevent retinal damage and optimise treatment. This study aimed to compare three diagnostic methods funduscopy, serology (ELISA), and PCR in detecting ocular toxoplasmosis in patients at ECWA Eye Hospital, Kano, Nigeria.

Methods and analysis: A total of 264 patients suspected of having ocular toxoplasmosis were enrolled. Funduscopy was performed to identify retinal lesions typical of T. gondii. Serological analysis was conducted using ELISA to detect anti-Toxoplasma IgG antibodies. Additionally, PCR was used to confirm the presence of T. gondii DNA in blood samples. The results from these methods were compared with assess their sensitivity, specificity and diagnostic value.

Results: Funduscopy detected T. gondii in 25.4% (67/264) of the patients, while ELISA showed a higher detection rate of 36.7% (97/264). PCR, the most specific method, confirmed infection in only 3.8% (10/264) of cases, with 60% (6/10) of these being male and 40% (4/10) female. T. gondii detected had 196 base pairs. The study found that ELISA had the highest sensitivity (90.0%) but lower specificity (64.9%), whereas funduscopy showed high specificity (74.4%) but low sensitivity (20.0%). PCR had the highest specificity but a low detection rate, emphasising its role in confirming diagnosis.

Conclusion: Although ELISA and funduscopy detected more positive cases, PCR remains the gold standard for confirming T. gondii infection due to its high specificity. In resource-limited settings like ECWA Eye Hospital, combining serology and PCR offers a practical approach for improving diagnostic accuracy and ensuring timely treatment of ocular toxoplasmosis.

Purpose: To develop an artificial intelligence algorithm to automatically identify the anterior segment structures and assess multiple parameters of primary angle closure disease (PACD) in ultrasound biomicroscopy (UBM) images.

Design: Development and validation of an artificial intelligence algorithm for UBM images.

Methods: 2339 UBM images from 592 subjects were collected for algorithm development. A multitissue segmentation model based on deep learning was developed for automatic identification of anterior segments and localisation of scleral spur. Then, measurement of the typical angle parameters was performed from the predicted results, including angle-opening distance at 500 µm (AOD 500), trabecular-ciliary angle (TCA) and iris area. We then collected 222 UBM images from 45 subjects in two centres for model validation.

Results: The multitissue identification model established in this study reached mean Intersection over Union (IoU) of 0.98, 0.98 and 0.98 on cornea segmentation, iris segmentation and ciliary body segmentation and a mean error distance of 1.07 pixels on scleral spur localisation. Our model got a mean IoU of 0.98, 0.98 and 0.99 on cornea segmentation, iris segmentation and ciliary body segmentation and a mean error distance of 0.49 pixels on scleral spur localisation in open-angle images and received 0.98, 0.98, 0.978 and 1.42 pixels respectively in angle-closure images. The mean differences between automatic and manual measurement of the angle parameters were 3.07 μm of AOD, 3.34 degrees of TCA and 0.05 mm² of iris area.

Conclusions: The automatic method of multitissue identification for PACD eyes developed was feasible, and the automatic measurement of angle parameters was reliable.

Dual inhibition of the angiopoietin (Ang)/Tie and vascular endothelial growth factor (VEGF) signalling pathways in patients with retinal diseases, such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME), may induce greater vascular stability and contribute to increased treatment efficacy and durability compared with treatments that only target the VEGF pathway. Faricimab, a bispecific intravitreal agent that inhibits both VEGF and Ang-2, is the first injectable ophthalmic drug to achieve treatment intervals of up to 16 weeks in Phase 3 studies for nAMD and DME while exhibiting improvements in visual acuity and retinal thickness. Data from real-world studies have supported the safety, visual and anatomic benefits and durability of faricimab, even in patients who were previously treated with other intravitreal agents. These evidence-based expert recommendations from a panel of retina specialists consolidate current evidence with clinical experience for the optimal use of faricimab in patients with nAMD or DME, with a focus on switching from an anti-VEGF agent to faricimab.

Objective: We compared the protein structure and pathogenicity of clinically relevant variants of the COG4 gene with AlphaFold2 (AF2), Alpha Missense (AM), and ThermoMPNN for the first time.

Methods and analysis: The sequences of clinically relevant Cog4 missense variants (one novel identified p.Y714F and three pre-existing p.G512R, p.R729W and p.L769R from Uniprot Q9H9E3) were imported into AF2 for protein structural prediction, and the pathogenicity was estimated using AM and ThermoMPNN. Different pathogenicity metrics were aggregated with principal component analysis (PCA) and further analysed at three levels (amino acid position, substitution and post-translation) based on all possible Cog4 missense variants (n=14 915).

Results: Localised protein structural impact including change of conformation and amino acid polarity, breakage of hydrogen bond and salt-bridge, and formation of alpha-helix were identified among clinically relevant Cog4 variants. The global structural comparison with multidimensional scaling demonstrated variants with similar protein structures (AF2) tended to exhibit similar clinical and biological phenotypes. The Cog4 p.Y714F variant exhibited greater protein structural similarity to mutated Cog4 found in Saul‒Wilson syndrome (p.G512R) and shared similar clinical phenotype (congenital cataract and psychomotor retardation). PCA of included pathogenic metrics demonstrated p.Y714F occurred at a critical position in Cog4 amino acid sequence with disrupted post-translational phosphorylation.

Conclusion: Deep learning algorithms, including AF2, AM and ThermoMPNN, can be useful for evaluating variant of uncertain significance (VUS) by structural and pathogenicity prediction. Despite classified as VUS (American College of Medical Genetics and Genomics criteria: PM1, PP4), the pathogenicity in this Cog4 variant cannot be ruled out and warrants further investigation.

Aims: Compare the prevalence of age-related cataract and the cataract surgical coverage rate between Indigenous and non-Indigenous Australians and explore differences in these estimates across location and time.

Methods: The Joanna Briggs Institute guidance for systematic reviews of prevalence studies was followed. A systematic search of Medline, Embase, Web of Science and grey literature from database inception to June 2022 was performed. All studies reporting cataract prevalence in Australian populations were included. Pooled prevalence estimates were derived using meta-analyses with a random-effects model. Nine studies enrolling 36 302 participants were included. Most studies only reported the prevalence of cataract causing vision loss (visual acuity<6/12) or blindness (visual acuity<6/60), restricting our meta-analysis to these definitions.

Results: Cataract causing unilateral vision loss was common in both Indigenous and non-Indigenous adults (3.5% and 3.6%, p=0.891). Indigenous adults had a higher prevalence of bilateral vision loss (3.6% vs 1.1%, p=0.011) and bilateral blindness (0.385% vs 0.001%, p=0.002) than non-Indigenous adults. Cataract surgical coverage was lower in Indigenous (68.0%; 95% CI, 55.9 to 79.0) than non-Indigenous (88.4%; 95% CI, 79.9 to 94.8) adults (p=0.004). No differences in bilateral vision loss, blindness or surgical coverage were found between rural and urban subgroups or between studies conducted before and after the year 2000.

Conclusions: Cataract causes vision loss in a substantial number of adults living in urban and rural Australia. Policies to improve diagnosis and surgery rates should be prioritised, particularly for Indigenous Australians who experience a disproportionate burden of advanced cataract and reduced access to surgery.

Prospero registration number: CRD42022340197.

Purpose: To quantify the effect of cataract surgery on cornea shape.

Methods: Patients undergoing cataract surgery with standardised 2.75 mm surgical incisions at 110 degrees with a side port at 50 degrees were included. Repeat biometric measurements were taken before surgery and at 6 weeks on both operated and unoperated fellow eyes. Data were transformed into Long's formalism for analysis. Device-specific measurement error was determined. The main outcome measure was the change in keratometry taking into account the change in keratometry of the unoperated fellow eye. Secondary outcome measures included the variability introduced due to location of the incision.

Results: 132 patients were included. The mean change in keratometry of the operated eye was -0.23@111/+0.21@21 (95% CI -1.43@122/+0.04@32 to +1.04@135/+0.30@45). The flattening effect of the surgical incision was greater and more variable than the steepening effect (p<0.01), particularly if the incision was in the flat meridian. Coupling, defined as ratio of the keratometric change in the preoperative meridians of K2 and K1, varied from 0.91 (SD 2.31) for eyes with an incision in the steep meridian, 0.75 (SD 1.81) for an incision in the flat meridian to 0.28 (SD 2.06) when the incision was made in a neutral meridian.

Conclusion: Cataract surgery has a slightly greater flattening than steepening effect on corneal shape. Although the effects are very small and variable with incomplete coupling, it is preferable to place the incision in the steep meridian. Greater emphasis, however, should be placed on eye-specific factors, such as biometry, or patient-related factors to optimise refractive outcomes.

Aim: There remain limited therapies to treat thyroid eye disease (TED) orbital fibrosis, highlighting the urgency to develop novel targets. Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts are important pathogenetic factor of TED. Endoplasmic reticulum (ER) stress may play a role in TED pathogenesis since it has been linked to liver, kidney, heart and lung fibrotic remodelling. We would evaluate the role of thioredoxin domain containing 5 (TXNDC5), a fibroblast-enriched ER protein, in TGF-β1-induced myofibroblast transdifferentiation from TED orbital fibroblasts.

Methods: Orbital fibroblasts from patients with TED were treated with TGF-β1 to investigate ER stress-relative gene expression especially for TXNDC5. To determine if TXNDC5 is involved in TGF-β1-induced fibrosis, we transfected TED orbital fibroblasts by lentivirus with a small hairpin RNA of pLKO-TXNDC5 gene (shTXNDC5) to knockdown TXNDC5 protein expression levels. After transfection of shTXNDC5 in TED orbital fibroblast followed by TGF-β1 treatment, we analysed TGF-β1-induced fibrosis protein expression.

Results: We measured increased TXNDC5 gene and protein expression in primary TED orbital fibroblasts. TXNDC5 protein levels were increased in TED orbital fibroblasts under TGF-β1 stimulation (2.5, 5, 10 and 20 ng/mL). Moreover, TXNDC5 knockdown of attenuated TGFβ1 (5 ng/mL)-induced myofibroblast transdifferentiation and extracellular matrix protein upregulation whereas increasing TXNDC5 expression by a recombinant protein of TXNDC5 (rhTXNDC5) addition increased alpha smooth muscle actin, fibronectin and connective tissue growth factor protein expression.

Conclusion: In conclusion, targeting TXNDC5 may be a novel therapeutic approach against TGF-β1-induced myofibroblast transdifferentiation in TED orbital fibroblasts.

Objective: Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness in preterm infants with low birth weight. The efficacy and safety of prophylactic agents, including vitamin A, propranolol and lipids, in reducing ROP incidence remain unclear. This systematic review and meta-analysis evaluated the effectiveness and safety of these agents in preventing ROP.

Methods and analysis: A systematic search was conducted in Embase, MEDLINE and CENTRAL databases. Eight randomised controlled trials involving 1101 preterm infants were included. We assessed the incidence of ROP at any stage, severe ROP, adverse events and mortality. Subgroup analyses were performed for each prophylactic agent. Data were pooled using the inverse variance weighting method and reported as risk ratios (RRs) with 95% CI.

Results: No significant reduction in ROP incidence at any stage was found in the intervention groups compared with placebo (RR=0.83; 95% CI= (0.69 to 1.00); p=0.05; I²=0%). Lipids significantly reduced severe ROP incidence (RR=0.48; 95% CI= (0.28 to 0.80); p=0.005), while vitamin A (RR=1.14; 95% CI= (0.51 to 2.54); p=0.75) and propranolol (RR=0.69; 95% CI= (0.29 to 1.65); p=0.41) did not. There were no significant differences in adverse events (RR=0.83; 95% CI= (0.59 to 1.17); p=0.28) or mortality (RR=0.93; 95% CI= (0.67 to 1.30); p=0.68) across all groups.

Conclusion: Lipids show promise in reducing severe ROP in preterm infants, while vitamin A and propranolol were not effective. Further research is needed to confirm these findings and explore the potential role of lipids in clinical practice.

Aims: To assess the feasibility of a study protocol for a randomised controlled trial of zoledronic acid (ZA) as adjuvant therapy for neovascular age-related macular degeneration (nAMD).

Methods: In this 1-year, randomised, double-blinded, placebo-controlled pilot study, nAMD patients were allocated 1:1 to receive intravenous ZA 5 mg or placebo at baseline and after 6 months in addition to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy following a treat-and-extend regimen. Bevacizumab was the first-line anti-VEGF drug, but eyes with refractory nAMD were switched to aflibercept. The primary outcome was mean change in best-corrected visual acuity (BCVA).

Results: 40 participants enrolled in the study, with 20 allocated to each treatment group. 38 participants received both study infusions, and all participants completed the final assessment. Mean (SD) change in BCVA was 7.5 (9.5) letters in the ZA group and -0.5 (11.5) letters in the control group; the between-group difference was 8.0 letters (95% CI: 1.5 to 15.0 letters). There were no between-group differences in mean change in central retinal thickness, refractory nAMD proportion or mean number of injections.

Conclusion: It is feasible to conduct a randomised controlled trial of ZA as adjuvant therapy for nAMD in terms of recruitment and adherence to the pilot study protocol. We found a possible visual benefit of ZA that is worth further investigation. To clarify the relationship between ZA and the need for intravitreal injections, we recommend amending the protocol by omitting switching of the anti-VEGF drug. Due to the limited sample size of the pilot study, the estimates of treatment effect are not meant to be confirmatory and should be interpreted with caution.

Trial registration number: 2019-001492-37 (EudraCT), 04304755 (NCT).