BMJ Open Ophthalmology最新文献

Introduction: Anti-vascular endothelial growth factor therapy has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). However, some patients face recurrent and persistent disease activity despite ongoing treatment. Faricimab (trade name: Vabysmo) is a recently approved therapy which targets two pathways involved in nAMD. This study aims to assess changes in best-corrected visual acuity (BCVA) and treatment frequency among patients currently treated for nAMD who switch to intravitreal faricimab therapy under a treat-and-extend regimen.

Methods and analysis: The FURGGHORN Study is a prospective, open-label, single-arm, multicentre investigator-initiated clinical trial. 102 patients with nAMD meeting inclusion criteria were recruited from 12 clinical sites across Australia and Singapore. Following 4 monthly loading doses of faricimab, treatment intervals were adjusted according to a regimen developed based on real-world practice patterns and consensus guidelines. The primary endpoint is the change from BCVA at week 52. Secondary endpoints include the proportions of patients at different treatment intervals, changes in central macular thickness and retinal fluid dimensions.

Ethics and dissemination: This study was designed, implemented and reported in accordance with the International Conference on Harmonisation Harmonised Tripartite Guidelines for Good Clinical Practice, with applicable local regulations and with the ethical principles laid down in the Declaration of Helsinki. Ethics approval was obtained from Bellberry Limited (2022-12-1388), St Vincent's Hospital Human Research Ethics Committee (2023/STE01568) and Singhealth Centralized Institutional Review Board (2023-2190). Results will be disseminated at scientific meetings and through peer-reviewed publications.

Trial registration number: ACTRN12623000215628.

Background/aims: The limited availability of corneal donors poses a significant challenge to meeting transplantation demands. Factors such as advanced donor age and prior cataract surgery are known to reduce donor corneal quality, yet a predictive system for resource optimisation is lacking. This study aimed to identify clinical and epidemiological factors affecting donor corneal endothelial cell density (ECD) in an Israeli eye bank, focusing on the impact of short death-to-retrieval time (DRT).

Methods: A retrospective analysis was conducted on 611 donor corneas retrieved at Hadassah Medical Center between 2018 and 2022. Donor age, sex, medical history, cause of death and DRT were evaluated for their association with adequate ECD (defined locally as ≥2400 cells/mm²), using univariate and multivariable analyses.

Results: The study included 611 corneas from 310 donors, with a mean ECD of 2624 cells/mm² (SD 519); 76.3% (n=466) met the local adequacy threshold. The mean donor age was 64.4 years (SD 15.3), and median DRT was 2 hours and 29 minutes. In univariate analysis, lower ECD was associated with advanced age, prior cataract surgery and systemic conditions such as diabetes mellitus, hypertension and ischaemic heart disease. In multivariable analysis, only advanced age (adjusted OR 0.96 per year) and phakic lens status (adjusted OR 14.25) remained significant. A non-significant trend toward higher adequacy was observed in corneas retrieved within 4 hours of death (82.5% vs 75%; p=0.12).

Conclusions: Advanced donor age and prior cataract surgery were the strongest predictors of lower ECD. The potential benefit of shorter DRT on corneal quality warrants further investigation. These findings are subject to limitations, including reliance on a local adequacy threshold (≥2400 cells/mm²) and missing DRT data in part of the cohort.

Objective: Using whole exome sequencing to detect pathogenic genes in families with inherited retinal dystrophy, and also to investigate the effects of CDH23 gene knockdown on the retinal structure of zebrafish.

Methods: In this study, we collected data from a patient diagnosed with retinitis pigmentosa (RP) at Ningxia Eye Hospital in 2022. Comprehensive ophthalmic and systemic examinations were conducted, and peripheral venous blood samples were obtained from the proband and family members. Whole exome sequencing was used to screen for pathogenic gene mutations in the proband, and Sanger validation was performed on the detected likely pathogenic sites. The zebrafish CDH23 gene was knocked down using gene-editing technology. Wild type and CDH23-knockdown zebrafish at 5 days postfertilisation were selected for histological analysis and immunofluorescence staining. This allowed us to preliminarily analyse the effects of CDH23 variants on the structure of the zebrafish eye and retina.

Results: The proband presented with a 20-year history of gradually progressive visual loss with nyctalopia in both eyes, with the best-corrected visual acuity of hand movements in the right eye (OD) and 0.1 in the left eye (OS). Funduscopic examination revealed pale optic discs, atrophic macular regions and large osteoclast-like pigment deposits on the retinal surface, and the retinal vasculature appeared thinner. Electroretinography suggested significant cone-rod dysfunction in both eyes and the pure tone audiometry suggested perfectly normal hearing. Whole exome sequencing revealed that the proband carried compound heterozygous variants in the CDH23 gene: c.2572G>A (p.Val858Ile) and c.8344G>A (p.Asp2782Asn), and Sanger sequencing confirmed that the phenotypically normal parents of the proband carried a heterozygous variant, respectively. Zebrafish knockdown experiments suggested that the gene variant could result in a significant thinning of the retinal photoreceptor layer, a substantial shortening of photoreceptor cell length and a sparse distribution of these cells.

Conclusion: In this study, we reported the first case of non-syndromic RP resulting from a CDH23 variant, which was demonstrated to cause abnormalities in retinal microstructure by knocking down the CDH23 gene in a zebrafish model.

Polypoidal choroidal vasculopathy (PCV) is characterised by distinctive polypoidal lesions, recurrent serosanguineous retinal pigment detachments and branched neovascular networks. The incidence of PCV is notably higher among Asian populations, leading to inferior clinical outcomes in the absence of intervention. The relationship between PCV and neovascular age-related macular degeneration remains a controversial. The advent of optical coherence tomography (OCT) and OCT angiography (OCTA) technologies has revolutionised our approach to understanding PCV pathogenesis. Innovative OCT and OCTA biomarkers, including double layer sign, the sign of polyps, vessel density, the diameter of choroidal vessels, choroidal vascularity index, and choroidal vortex have emerged as critical imaging parameters for elucidating the pathological intricacies of PCV. Quantitative analysis of the choroid has become an essential adjunct for investigating the mechanisms underlying PCV. This comprehensive review encapsulates the array of quantitative OCT and OCTA biomarkers vital for the diagnosis, prognosis, and clinical management of this complex ocular condition.

Background: Identification of high-risk features is essential for improving treatment outcomes of retinoblastoma. MRI is one of the most used modalities in treatment decision-making; however, its accuracy in detecting extension into different ocular structures is variable. This study aims to evaluate high-risk features in retinoblastoma by comparing MRI with histopathology results.

Methodology: This was a retrospective chart review of patients enrolled in the retinoblastoma programme at the American University of Beirut Medical Center from November 2012 to December 2022. We included enucleated eyes, classified as group D or E per the International Intraocular Retinoblastoma Classification. Data pertaining to high-risk features (including postlaminar optic nerve (ON) and massive choroidal invasion) were collected from preoperative MRI and histopathological examination following enucleation. Data on scleral and anterior segment involvement (not considered high-risk features) were also collected. Morphometric properties were calculated and analysed.

Results: Analysis included 48 eyes from 44 patients. Males constituted 52.1% (n=25) of the sample and females 47.9% (n=23). 58% had unilateral retinoblastoma. The median age at diagnosis was 14.5 months (10-34.5). The median follow-up period from the first visit to data collection was 27.5 months (17.3-49). On tissue examination, 3 patients had postlaminar ON involvement and 11 had massive choroidal involvement. For postlaminar ON involvement, the MRI showed a moderate sensitivity (66.7%) and specificity (71.1%), with a high negative predictive value (NPV) of 96.9% but a low positive predictive value (PPV) of 13.3%. In cases of massive choroidal invasion, MRI demonstrated moderate sensitivity (45.5%) and specificity (75.7%), with a good NPV of 82.4% but a low PPV of 35.7%. Additionally, histopathology identified anterior segment involvement in six cases and scleral involvement in two cases. MRI showed high accuracy in detecting invasion of the anterior chamber (79.2%) and moderate accuracy in detecting invasion of the sclera (62.5%).

Conclusion: MRI showed high levels of variability in detecting high-risk features in advanced retinoblastoma. MRI results ought to be interpreted with caution when making treatment decisions in advanced retinoblastoma. Limitations of our study included a relatively small sample size, retrospective design and possible technical constraints of MRI imaging.

Background: This study aimed to create machine learning (ML) models to predict the long-term uncorrected distance visual acuity (UDVA) in myopic eyes corrected by small incision lenticule extraction (SMILE).

Methods: This was a retrospective cohort study conducted in Zhongshan Ophthalmic Center, Sun Yat-sen University. Participants who underwent SMILE between 2012 and 2016 were invited for the final follow-up examinations in 2019. Medical records and surgical parameter data were collected for analysis. Multicollinearity analysis and feature importance ranking were used to select the most predictive features. The following algorithms were used: least absolute shrinkage and selection operator, random forest, extremely randomised regression trees (extraTrees), gradient boosting machine and extreme gradient boosting. The root mean square error (RMSE) and mean absolute error (MAE) for each ML model were evaluated.

Results: In total, 873 eyes from 440 patients with complete records were included in this study. The long-term UDVA (logarithm of the minimum angle of resolution) distribution at the final follow-up ranged from -0.1760 to 0.7960. The extraTrees model outperformed the other four models, with RMSE and MAE of 0.1162 and 0.0850, respectively. Additionally, some features, including spherical equivalent, lenticular optical zone, added manifest refraction, preoperative corrected distance visual acuity and cap thickness, had moderate-to-strong effects on the average UDVA prediction using the extraTrees model.

Conclusion: Long-term UDVA in myopic eyes corrected by SMILE can be effectively predicted using ML technologies, particularly the extraTrees model. However, more features and samples for the prediction model need to be explored to improve accuracy. Otherwise, there was a limitation in this research that sphere and cylinder refraction were treated as independent variables. But, the proportion of astigmatism to spherical refraction is relatively low, less than 1/5. Consequently, this does not lead to the incorrectness of our results, but they are weakened by this.

Background/aims: This study aimed to investigate the outcomes of intravitreal faricimab (IVF) injection for neovascular age-related macular degeneration (nAMD) and their relationships with clinical findings.

Methods: At 14 sites, we retrospectively examined the 6-month treatment outcomes of 186 eyes that underwent IVF for treatment-naïve nAMD or nAMD previously treated except for >3 months before the baseline.

Results: Visual acuity and central retinal thickness (CRT) significantly improved at 1, 3 and 6 months after treatment (p<0.001, respectively). At 3 or 6 months, 151 eyes (81.2%) exhibited dry macula. The dry macula rate in the treatment-naïve group (85.7%) was significantly higher than the previously treated group (71.7%, p=0.022). Eyes with pretreatment submacular haemorrhage (SMH) had a significantly higher rate of dry macula (93.9%) than those without (78.4%, p=0.048). Eyes with pretreatment subretinal fluid had good final visual acuity, but poor visual acuity was observed in those with intraretinal fluid (IRF), subretinal hyper-reflective material (SHRM), SMH or hard exudates. However, a similar tendency was also observed at baseline. CRT improvement was good in the eyes with pretreatment IRF, pigment epithelial detachment, SHRM and SMH, although these eyes had higher CRT at the baseline.

Conclusion: IVF treatment for nAMD was associated with improvements in visual acuity and CRT over 6 months. Eyes presenting with SMH showed a higher rate of achieving a dry macula. This result indicates that faricimab may be useful in treating patients with nAMD and SMH. Given the retrospective, non-randomised design, however, these findings should be interpreted cautiously and viewed as hypothesis-generating rather than definitive.

Objectives: This study aimed to evaluate the suitability of the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) for measuring vision-related quality of life (VRQoL) in patients with Leber hereditary optic neuropathy receiving lenadogene nolparvovec gene therapy in three Phase III randomised controlled clinical trials.

Methods: VRQoL was assessed using the NEI-VFQ-25 at baseline (n=174) and 2 years after treatment (n=152). All participants received lenadogene nolparvovec in at least one eye. The scoring structure of the original NEI-VFQ-25 was evaluated for fit to the Rasch model, and a post hoc revision was created and psychometrically reevaluated. Stacked analysis was conducted to compare Rasch-revised scores at baseline and 2 years after treatment.

Results: The original NEI-VFQ-25 exhibited multiple issues including limitations in response functioning and scale dimensionality. These issues were rectified by revising the NEI-VFQ25 into two separate unidimensional scales measuring 'Vision-related Activity Limitation' (VAL) and 'Socioemotional Functioning' (SEF). Participants' mean VAL score at baseline on a Rasch-transformed 0-100 scale was 46.1 (11.7), improving to 48.4 (13.7) after treatment (F(1, 324) = 2.67, p=0.103). On the SEF scale, there was a significant difference 2 years after treatment, with participants improving from a mean score of 40.1 (14.1) at baseline to 49.6 (17.6) (F(1, 324) = 29.1, p<0.001).

Conclusions: The scoring structure of the original NEI-VFQ-25 has limitations that undermine its psychometric validity as a measure of VRQoL. Using the Rasch-revised NEI-VFQ-25, we determined that improvement in VRQoL after treatment with lenadogene nolparvovec was driven predominantly by an improvement in socioemotional functioning.

Purpose: The Clinical Activity Score (CAS) is widely used to assess thyroid eye disease (TED) activity but can vary based on the evaluator's expertise. We developed and externally validated Glandy CAS, a machine learning (ML)-assisted system for detecting active TED (CAS ≥3) using digital facial images. This clinical trial aimed to gain approval from the Korea Ministry of Food and Drug Safety (KMFDS) for this Software as a Medical Device (SaMD).

Methods: This is a clinical trial based on the retrospective cohort. Glandy CAS analysed 756 photos of patients with TED, classifying them as having active or inactive TED. Its diagnostic performance was compared with that of three general ophthalmologists (less than 5 years of experience), using the F1 score. The reference CAS was determined by an oculoplastic specialist.

Results: Active TED was detected in 207 of 756 patients. Glandy CAS achieved a sensitivity of 87.9%, specificity of 95.8% and an F1 score of 0.88. In comparison, general ophthalmologists had a sensitivity of 60.4%, specificity of 83.0% and an F1 score of 0.57. Glandy CAS predicted CAS within 1 point of the reference score in 82.3% of cases, with a mean absolute error of 0.83.

Conclusions: Glandy CAS, an ML-assisted system for detecting active TED using facial images, showed high accuracy and outperformed general ophthalmologists. This system can consistently and accurately assess disease activity, facilitating early detection and timely treatment of active TED. Based on this clinical trial, the SaMD received KMFDS approval (Product Licence No., 24-93).