British Journal of Ophthalmology最新文献

Background: Increased pigmentation has been associated with cancer stem-cell-like behaviour and chemoresistance in uveal melanoma (UM) and cutaneous melanoma. Therefore, our present study determines the correlation between pigmentation and cancer stem cell markers in UM patients.

Methods: Expression of PAX3, CD133, ABCG2, TRYP1, TRYP2 and microphthalmia-associated transcription factor (MITF) was assessed by immunohistochemistry along with mRNA expression level of PAX3 using quantitative real-time PCR in 70 prospective UM cases. Kaplan-Meier analysis and Cox-proportional hazards model were used to analyse the correlation of protein expression with clinicopathological parameters and patient outcome.

Results: We found significant expression of PAX3, CD133 and ABCG2 proteins in 28/70 (40%), 34/70 (49%) and 31/70 (44%) cases, respectively. There was a positive correlation between nuclear expression of PAX3 and high-risk clinicopathological parameters such as necrosis and scleral invasion (p<0.01). CD133 and ABCG2 expression were positively correlated with distant metastasis (p=0.03 and 0.01). Immunoexpression of PAX3, CD133 and ABCG2 proteins was positively correlated with MITF. TYRP2 expression correlated with PAX3 and ABCG2 immunoexpression. Tumour pigmentation was not correlated with any of the markers. PAX3 mRNA expression was positively correlated with immunoexpression of CD133 (p<0.01), ABCG2 (p=0.01) and distant metastasis (p<0.01). On Kaplan-Meier survival analysis, reduced metastasis-free survival was observed in patients with tumours showing high CD133 and ABCG2 expression. No significant correlation was observed between tumour pigmentation and overall survival.

Conclusion: Our study highlights the association between PAX3 expression, pigmentation markers such as MITF and TRYP2 and cancer stem-cell markers in UM progression.

Background/aims: There is a paucity in the literature on the presentation, management and outcomes of cases where primary acquired melanosis (PAM) is associated with spill over/contiguous periocular lentigo maligna (LM). We describe experience of such cases at our eyelid and ocular oncology specialist centre.

Methods: We conducted a retrospective consecutive case review of adult patients with PAM and periocular LM between 2005 and 2024 at Moorfields Eye Hospital in London. Demographic data, diagnosis, histology, imaging, treatment, surgical notes, outcomes and follow-up were collected from the electronic patient record.

Results: Of 21 patients identified, 100% were Caucasian, 13 (62%) were women and the average age of diagnosis was 67 years. Grade of PAM atypia was mild in 5 (24%), moderate in 2 (9%) and severe in 14 (67%) patients. 16 (76%) patients developed melanoma (all types) and 12 (57%) patients developed conjunctival melanoma. Of those with PAM with severe atypia, 93% developed melanoma. The average time interval from diagnosis of PAM and LM to melanoma was 72 months. Melanoma recurrence occurred in 7 (44%) and metastases developed in 4 (25%) patients. Four patients died, including two from metastatic melanoma. Average follow-up length was 129 months.

Conclusions: PAM with atypia, particularly severe atypia, when associated with spill over periocular LM, may have significant risk of progression to melanoma. Patients with PAM require careful eyelid examination to identify LM. Management requires multidisciplinary input, urgent biopsy and confocal microscopy if available, lower threshold for treatment and lifelong monitoring.

Aims: Previous studies have suggested an association between retinal artery occlusion (RAO) and ischaemic stroke (IS), both associated with elevated inflammatory factors. However, the role of high-sensitivity C-reactive protein (hs-CRP) in the sequential onset of these two diseases is still unclear. Based on this evidence, we evaluated the association of hs-CRP with RAO and IS.

Methods: We examined hs-CRP from both the large multicentre cohort study UK Biobank and Chinese Retinal Artery Occlusion study. Cox proportional hazard models were used to study the association of hs-CRP with incident RAO and IS during the long-term follow-up in the UK Biobank. Logistic regression analysis was employed to assess the cross-sectional relationship between hs-CRP with RAO and IS in the Chinese cohort. A restricted cubic spline (RCS) approach was employed to evaluate potential non-linear associations of hs-CRP with IS.

Results: After exclusions, the analysis included 459 188 participants from the UK and 338 participants from China. Over a median follow-up of 12.2 years, 136 cases of incident RAO and 3206 cases of incident IS events were recorded in the UK Biobank. After multivariable adjustment, higher hs-CRP (per 10 mg/L) level was associated with increased risks of RAO (HR: 1.34, 95% CI: 1.01 to 1.76) and IS (HR: 1.24, 95% CI: 1.17 to 1.33). RCS analysis revealed a significant non-linear relationship between hs-CRP levels and incident IS (P_non-linear<0.001). Furthermore, RAO patients with higher hs-CRP levels were more likely to be combined with IS (2.81 mg/L vs 10.14 mg/L, p<0.001). In the Chinese cohort, the association between hs-CRP with RAO and IS was further confirmed. Higher hs-CRP (per 1 mg/L) level was associated with increased risks of RAO (OR: 1.43, 95% CI: 1.15 to 1.78) and IS (OR: 1.13, 95% CI: 1.03 to 1.24).

Conclusions: Our findings underscore hs-CRP as a robust risk factor for both RAO and IS. Controlling hs-CRP levels might reduce the incidence of RAO and secondary stroke.

Aims: To compare the effect of three-drug regimen (melphalan, topotecan and carboplatin) with two-drug regimen (melphalan and topotecan) on the globe salvage outcomes of retinoblastoma (Rb) with intra-arterial chemotherapy (IAC).

Methods: This study included 83 patients with 87 eyes received two-drug regimen IAC, and 95 patients with 97 eyes received three-drug regimen IAC. Propensity score matching was applied, and 84 matched (42:42) patients (eyes) were analysed. All Rb patients underwent an ophthalmologic examination before IAC using a wide-angle digital fundus camera, which was repeated monthly after the globe salvage management. Progression-free ocular survival (PFOS), relapse rate and local complications were analysed per affected eye. Analysis of overall survival (OS) and systemic complications was based on Rb individuals.

Results: Eyes treated with three-drug regimen IAC presented with higher overall PFOS than those treated with two-drug regimen IAC (p=0.026). Stratified analysis showed PFOS rate in three-drug group was higher than two-drug group among group D eyes (88.5% vs 60.6%, p=0.009). Consistently, among group E eyes, three-drug group correlated with a better PFOS, compared with two-drug group (42.9% vs 23.5%, p=0.002). There did not present with significant differences in OS (p=0.853), relapse rate (p=0.291), incidence of moderate-severe myelosuppression (grade 3-4, p=0.564) or ophthalmic artery obstruction (p=0.998) between these two groups.

Conclusions: Three-drug regimen was a superior IAC management compared with two-drug regiment, with improved progression-free ocular outcome for eyes of advanced retinoblastomas.

Background: We aimed to provide, through the Uveitis in Childhood National Cohort Study, population-based evidence on incidence, distribution and disease characteristics for childhood onset non-infectious uveitis.

Methods: Eligible children and young people (<18 years) were those newly diagnosed with non-infectious uveitis between 1 March 2020 and 28 February 2023. Cases were identified and recruited through passive surveillance across a multicentre network. Descriptive analysis of demographic, socioeconomic and clinical characteristics at diagnosis is reported alongside incidence rates, relative rates by region and sociodemographic patterning.

Results: 468 cases were identified, providing a minimal national disease incidence of 1.89/100 000 (95% CI 1.72 to 2.07). Among the 255 children recruited, anterior uveitis was predominant (76.9%) and 65% of cases were bilateral. Peak incidence was at 11-15 years. Children resident in deprived areas and those from non-White ethnic backgrounds were over-represented (28% and 31% of the cohort). One in seven children (15%) had a diagnosis of juvenile idiopathic arthritis (JIA), and 5% had tubulointerstitial nephritis. Although bilaterally poor vision was uncommon (16.8%), 44.3% had lost some vision in at least one eye.

Conclusions: There is a need to reconsider how best to deliver paediatric rheumatological and eye care that meets the needs of young people, as well as young children, with uveitis. The predominance of non-JIA-related uveitis calls for a shift in focus. There appears to be socioeconomic drivers of disease risk, which are worthy of future exploration and which have implications on the delivery of care for this chronic and blinding disease.

Aims: This study aims to investigate whether denoising diffusion probabilistic models (DDPMs) could generate realistic retinal images, and if they could be used to improve the performance of a deep convolutional neural network (CNN) ensemble for multiple retinal disease classification, which was previously shown to outperform human experts.

Methods: We trained DDPMs to generate retinal fundus images representing diabetic retinopathy, age-related macular degeneration, glaucoma or normal eyes. Eight board-certified ophthalmologists evaluated 96 test images to assess the realism of generated images and classified them based on disease labels. Subsequently, between 100 and 1000 generated images were employed to augment training of deep convolutional ensembles for classifying retinal disease. We measured the accuracy of ophthalmologists in correctly identifying real and generated images. We also measured the classification accuracy, F-score and area under the receiver operating curve of a trained CNN in classifying retinal diseases from a test set of 100 fundus images.

Results: Ophthalmologists exhibited a mean accuracy of 61.1% (range: 51.0%-68.8%) in differentiating real and generated images. Augmenting the training set with 238 generated images in the smallest class statistically significantly improved the F-score and accuracy by 5.3% and 5.8%, respectively (p<0.01) in a retinal disease classification task, compared with a baseline model trained only with real images.

Conclusions: Latent diffusion models generated highly realistic retinal images, as validated by human experts. Adding generated images to the training set improved performance of a CNN ensemble without requiring additional real patient data.

Aims: To investigate the associations between a healthy lifestyle score and retinal neurovascular health, and explore whether lower inflammation levels mediate these associations.

Methods: This study is based on the UK Biobank. The healthy lifestyle score ranged from 0 to 6 and comprised physical activity, diet, sleep duration, smoking status, alcohol consumption and bodyweight. Outcomes included retinal diseases (age-related macular degeneration (AMD) and retinal vascular occlusion (RVO)) from hospital admission records (378 648 participants), retinal vascular metrics from retinal photography (32 226 participants) and retinal neural metrics from optical coherence tomography (42 557 participants). An INFLA-score was used to characterise inflammation levels.

Results: Participants with better healthy life score (scored from 5 to 6) were associated with a 29% lower risk of AMD, 25% lower risk of RVO, 2% increase in artery-to-vein ratio (AVR), 0.22 µm increase in central retinal artery equivalent, 0.36 µm decrease in central retinal vein equivalent (CRVE), 0.004 increase in fractal dimension, 0.38 µm increase in retinal nerve fibre layer, 0.69 µm increase in ganglion cell-inner plexiform layer (GCIPL) and 0.35 µm increase in photoreceptor segment (PS) compared with those with worst lifestyle score (scored from 0 to 1) (all p_trend<0.01). In addition, INFLA-score partially mediated the associations between healthy lifestyle score and increased risk of AMD (mediated proportion (MP): 14.8%), higher AVR (MP: 12.76%), narrower CRVE (MP: 24.49%), thicker GCIPL (MP: 4.97%) and thicker PS (MP: 26.86%).

Conclusion: Great adherence to a healthier lifestyle was associated with better retinal health in a dose-response manner. Lower inflammation partially mediated the association between a healthy lifestyle score and retinal health.

Purpose: To examine the associations of commonly-used serum lipid measures (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG)) with glaucoma.

Methods: This prospective cohort study included 400 229 participants from the UK Biobank. Cox regression and restricted cubic spline models and polygenic risk scores were employed to investigate the associations between serum lipids and glaucoma.

Results: Over a mean follow-up of 14.44 years, 6868 (1.72%) participants developed glaucoma. Multivariate Cox regression revealed that higher levels of HDL-C were associated with an increased risk of glaucoma (HR for 1-SD increase in HDL-C 1.05, 95% CI 1.02 to 1.08, p=0.001), while elevated levels of LDL-C (HR 0.96, 95% CI 0.94 to 0.99, p=0.005), TC (HR 0.97, 95% CI 0.94 to 1.00, p=0.037) and TG (HR 0.96, 95% CI 0.94 to 0.99, p=0.008) were all associated with reduced risk. The analysis examining the associations between polygenic risk score of serum lipids and glaucoma showed per 1-SD increment of HDL-C genetic risk was associated with a 5% greater hazard of glaucoma (HR 1.05, 95% CI 1.00 to 1.11, p=0.031). However, the polygenic risk score of LDL-C, TC, and TG did not show a significant association with glaucoma.

Conclusions: Elevated HDL-C is associated with an increased risk of glaucoma, while elevated LDL-C, TC, and TG levels are associated with a lower risk of glaucoma. This study enhances our understanding of the association between lipid profile and glaucoma and warrants further investigation of lipid-focused treatments in glaucoma management.

Background: Implementing lipid control in patients with diabetes is regarded as a potential strategy for halting the advancement of diabetic retinopathy (DR). This study seeks to use Mendelian randomisation (MR) to assess the causal relationship between lipid traits and lipid-lowering drug targets and full-course DR (background DR, severe non-proliferative DR (NPDR) and proliferative DR (PDR)).

Methods: A two-sample MR and drug target MR to decipher the causal effects of lipid traits and lipid-lowering drug targets on full-course DR, including background DR, severe NPDR and PDR, was conducted in the study. Genetic variants associated with lipid traits and genes encoding the protein targets of lipid-lowering drugs were extracted from the Global Lipids Genetics Consortium and UK Biobank. Summary-level data of full-course DR are obtained from FinnGen.

Results: No significant causal relationship was found between lipid traits and full-course DR. However, in drug target MR analysis, peroxisome proliferator-activated receptor gamma (PPARG) enhancement was associated with lower risks of background DR (OR=0.12, p=0.005) and PDR (OR=0.25, p=0.006). Additionally, mediation MR analysis showed that lowering fasting insulin (p=0.015) and HbA1c (p=0.005) levels mediated most of the association between PPARG and full-course DR.

Conclusions: This study reveals PPARG may be a promising drug target for full-course DR. The activation of PPARG could reduce the risk of full-course DR, especially background DR and PDR. The mechanism of the PPARG agonists' protection of full-course DR may be dependent on the glucose-lowering effect.