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Danny Siu-Chun Ng,1 Zihan Sun,1 Alvin Lerrmann Young,1,2 Simon Tak-Chuen Ko,3 Jerry Ka-Hing Lok,1 Timothy Yuk-Yau Lai,1 Shameema Sikder,4 Clement C Tham1 1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, 2Department of Ophthalmology, Prince of Wales Hospital, 3Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong, People’s Republic of China; 4Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA Objective: To identify residents’ perceived barriers to learning phacoemulsification surgical procedures and to evaluate whether virtual reality simulation training changed these perceptions. Design: The ophthalmology residents undertook a simulation phacoemulsification course and proficiency assessment on the Eyesi system using the previously validated training modules of intracapsular navigation, anti-tremor, capsulorrhexis, and cracking/chopping. A cross-sectional, multicenter survey on the perceived difficulties in performing phacoemulsification tasks on patients, based on the validated International Council of Ophthalmology’s Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR), using a 5-point Likert scale (1 = least and 5 = most difficulty), was conducted among residents with or without prior simulation training. Mann–Whitney U tests were carried out to compare the mean scores, and multivariate regression analyses were performed to evaluate the association of lower scores with the following potential predictors: 1) higher level trainee, 2) can complete phacoemulsification most of the time (>90%) without supervisor’s intervention, and 3) prior simulation training. Setting: The study was conducted in ophthalmology residency training programs in five regional hospitals in Hong Kong. Results: Of the 22 residents, 19 responded (86.3%), of which 13 (68.4%) had completed simulation training. Nucleus cracking/chopping was ranked highest in difficulty by all respondents followed by capsulorrhexis completion and nucleus rotation/manipulation. Respondents with prior simulation training had significantly lower difficulty scores on these three tasks (nucleus cracking/chopping 3.85 vs 4.75, P = 0.03; capsulorrhexis completion 3.31 vs 4.40, P = 0.02; and nucleus rotation/manipulation 3.00 vs 4.75, P = 0.01). In multivariate analyses, simulation training was significantly associated with lower difficulty scores on these three tasks. Conclusion: Residents who had completed Eyesi simulation training had higher confidence in performing the most difficult tasks perceived during phacoemulsification. Keywords: virtual reality, simulation surgical education, cataract surgery

Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in a further 5,585 PD cases and 5,642 controls. We further refined variant classification using in vitro assays and showed that SMPD1 variants with reduced enzymatic activity display the strongest association (<44% activity, odds ratio (OR) = 2.24, P = 1.25 × 10 -15 ) with PD risk. Moreover, 80.5% of SMPD1 carriers harbored the Asian-specific p.Pro332Arg variant (OR = 2.16; P = 4.47 × 10 -8 ). Our findings highlight the utility of performing exome sequencing in diverse ancestry groups to identify rare protein-altering variants in genes previously unassociated with disease., Competing Interests: Competing interests: Z.G.-O. received consultancy fees from Lysosomal Therapeutics, Idorsia, Prevail Therapeutics, Ono Therapeutics, Denali, Handl Therapeutics, Neuron23, Bial Biotech, Bial, UCB, Capsida, Vanqua Bio, Congruence Therapeutics, Takeda, Jazz Pharmaceuticals, Guidepoint, Lighthouse and Deerfield. R.N.A. received consultation fees from Biogen, Biohaven, Capsida, Gain Therapeutics, Genzyme/Sanofi, Janssen, Servier, SK Biopharmaceuticals, Takeda and Vanqua Bio. Y.X. holds a stock option in NeoCytogen Therapeutics where she is scientific co-founder and Chief Scientific Officer. M.A.N.’s participation in this project was part of a competitive contract awarded to DataTecnica, LLC by the National Institutes of Health to support open science research. M.A.N. also owns stock in Character Bio, Inc. and Neuron23, Inc. The other authors declare no competing interests., (© 2024. The Author(s).)

Background: To investigate the impact of optic disc torsion (ODT), horizontal disc tilt (HDT) angle, and ovality index (OI) on different retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) segments in healthy myopic eyes., Methods: ODT and OI were measured from fundus photographs. HDT angle, peripapillary RNFL, and macular GCIPL were measured by swept-source optical coherence tomography (SS-OCT). The association between optic disc morphology and the RNFL/GCIPL thickness were evaluated, with age and axial length (AL) adjusted., Results: Among 530 healthy myopic eyes of 284 participants (mean age: 41.7 years, mean spherical equivalent: - 7.70 D, and mean AL: 26.6 mm), 335 eyes (63.2%) had temporal disc torsion (temporal group) and 195 eyes (36.8%) had nasal disc torsion (nasal group). For the nasal group, a larger OI was associated with thinner superior-to-superonasal GCIPL (β = - 7.465 to - 6.972, both P = 0.024) and temporal RNFL sectors (β = - 49.596 to - 27.748, P ≤ 0.014). For the temporal group, a larger OI was associated with thinner superior-to-nasal (β = - 50.255 to - 22.093, P ≤ 0.006) and thicker temporal RNFL sectors (β = 29.015 to 56.890, P ≤ 0.003). Additionally, a larger HDT angle was associated with thinner superior-to-nasal RNFL sectors (β = - 0.559 to - 0.242, P ≤ 0.036) and thinner superior-to-superotemporal GCIPL sectors (β = - 0.084 to - 0.069, P ≤ 0.037)., Conclusions: The optic disc tortional direction was associated with the measurement of different RNFL and GCIPL sectors independent of the AL and age. These should be considered when constructing a myopic normative database., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No.: 2021.733). It was conducted in accordance with the principles of the Declaration of Helsinki. All participants have provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Current diagnostic modalities of AD generally focus on detecting the presence of amyloid β and tau protein in the brain (for example, positron emission tomography [PET] and cerebrospinal fluid testing), but these are limited by their high cost, invasiveness, and lack of expertise. Retinal imaging exhibits potential in AD screening and risk stratification, as the retina provides a platform for the optical visualization of the central nervous system in vivo, with vascular and neuronal changes that mirror brain pathology. Given the paradigm shift brought by advances in artificial intelligence and the emergence of disease-modifying therapies, this article aims to summarize and review the current literature to highlight 8 trends in an evolving landscape regarding the role and potential value of retinal imaging in AD screening., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recent advancements in artificial intelligence (AI) herald transformative potentials for reshaping glaucoma clinical management, improving screening efficacy, sharpening diagnosis precision, and refining the detection of disease progression. However, incorporating AI into healthcare usages faces significant hurdles in terms of developing algorithms and putting them into practice. When creating algorithms, issues arise due to the intensive effort required to label data, inconsistent diagnostic standards, and a lack of thorough testing, which often limits the algorithms' widespread applicability. Additionally, the "black box" nature of AI algorithms may cause doctors to be wary or skeptical. When it comes to using these tools, challenges include dealing with lower-quality images in real situations and the systems' limited ability to work well with diverse ethnic groups and different diagnostic equipment. Looking ahead, new developments aim to protect data privacy through federated learning paradigms, improving algorithm generalizability by diversifying input data modalities, and augmenting datasets with synthetic imagery. The integration of smartphones appears promising for using AI algorithms in both clinical and non-clinical settings. Furthermore, bringing in large language models (LLMs) to act as interactive tool in medicine may signify a significant change in how healthcare will be delivered in the future. By navigating through these challenges and leveraging on these as opportunities, the field of glaucoma AI will not only have improved algorithmic accuracy and optimized data integration but also a paradigmatic shift towards enhanced clinical acceptance and a transformative improvement in glaucoma care., (Copyright © 2024. Published by Elsevier Ltd.)

Aims: To develop and externally test deep learning (DL) models for assessing the image quality of three-dimensional (3D) macular scans from Cirrus and Spectralis optical coherence tomography devices., Methods: We retrospectively collected two data sets including 2277 Cirrus 3D scans and 1557 Spectralis 3D scans, respectively, for training (70%), fine-tuning (10%) and internal validation (20%) from electronic medical and research records at The Chinese University of Hong Kong Eye Centre and the Hong Kong Eye Hospital. Scans with various eye diseases (eg, diabetic macular oedema, age-related macular degeneration, polypoidal choroidal vasculopathy and pathological myopia), and scans of normal eyes from adults and children were included. Two graders labelled each 3D scan as gradable or ungradable, according to standardised criteria. We used a 3D version of the residual network (ResNet)-18 for Cirrus 3D scans and a multiple-instance learning pipline with ResNet-18 for Spectralis 3D scans. Two deep learning (DL) models were further tested via three unseen Cirrus data sets from Singapore and five unseen Spectralis data sets from India, Australia and Hong Kong, respectively., Results: In the internal validation, the models achieved the area under curves (AUCs) of 0.930 (0.885-0.976) and 0.906 (0.863-0.948) for assessing the Cirrus 3D scans and Spectralis 3D scans, respectively. In the external testing, the models showed robust performance with AUCs ranging from 0.832 (0.730-0.934) to 0.930 (0.906-0.953) and 0.891 (0.836-0.945) to 0.962 (0.918-1.000), respectively., Conclusions: Our models could be used for filtering out ungradable 3D scans and further incorporated with a disease-detection DL model, allowing a fully automated eye disease detection workflow., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the associations of single-nucleotide polymorphisms (SNPs) in the high-temperature requirement protease A 1 ( HTRA1) gene with myopia., Methods: 25 SNPs in HTRA1 were selected, including 23 haplotype-tagging SNPs, SNP rs2142308 from a previous genome-wide association study (GWAS) of myopia and rs11200638, a SNP strongly associated with age-related macular degeneration (AMD). All SNPs were genotyped in a Hong Kong Chinese cohort of 533 myopia subjects (including 175 high myopia, 189 moderate myopia and 189 mild myopia) and 280 non-myopic controls. The association of individual SNPs were evaluated in overall myopia and different subgroups of myopia using logistic regression., Results: A tagging SNP, rs11200647, was significantly associated with myopia (p=2.17×10 -4 , OR=0.67). Nominal associations were detected for the AMD-associated SNP rs11200638 (p=0.0042, OR=1.37) and tagging SNPs rs12266322 (p=0.0048, OR=0.59) and rs17103569 (p=0.047, OR=1.34). The association of rs11200647 with myopia remained significant after adjusting for rs11200638, rs12266322 and rs17103569. In sub-group analysis, two tagging SNPs, rs11200647 (p=2.24×10 -4 , OR=0.58) and rs12266322 (p=8.31×10 -4 , OR=0.39), showed significant association with moderate myopia. In haplotype association analysis, haplotypes AT (p=1.00×10 -4 , OR=1.77) and haplotype GT (p=0.0019, OR=0.64), defined by rs11200647 and rs66884382, were significantly associated with myopia., Conclusions: This study provided new evidence to support HTRA1 as an associated gene for myopia, especially moderate myopia. The findings suggested that myopia and AMD may have shared genetic components., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate the associations of genetic variants previously linked to axial length (AL) and spherical equivalent refraction (SE) in adults with refractive error and related endophenotypes in children, at baseline and 3-year follow-up., Methods: 15 candidate single-nucleotide polymorphisms (SNPs), selected from previous Genome-Wide Association Studies and meta-analyses, were genotyped in 2819 Chinese children, who had undergone baseline and 3-year follow-up cycloplegic refraction, ocular biometry and ocular health examinations. Linear regression analyses were conducted to assess the associations of the SNPs with baseline measurements and longitudinal changes in SE, spherical power (SPH), AL, corneal radius of curvature (CR) and AL/CR ratio., Results: SNPs ZMAT4 rs7829127, ZMAT4 rs16890057, TOX rs7837791, GRIA4 rs11601239 and RDH5 rs3138142 were associated with SE (β=0.233, p=4.21×10 -4 ; β=0.221, p=7.87×10 -4 ; β=0.106, p=0.0076; β=0.084, p=0.041; β=0.14, p=0.013, respectively) and SPH (β=0.24, p=2.3×10 -4 ; β=0.232, p=3.8×10 -4 ; β=0.088, p=0.025; β=0.086, p=0.034; β=0.14, p=0.012, respectively). Among them, ZMAT4 rs7829127 and rs16890057, were also associated with AL (β=-0.128, p=5.6×10 -4 ; β=-0.128, p=5.21×10 -4 ) and AL/CR ratio (β=-0.014, p=0.0028; β=-0.014, p=0.0034), whereas TOX rs7837791 was associated with AL (β=-0.062, p=0.0058) and GRIA4 11 601 239 with AL/CR ratio (β=-0.0058, p=0.049). Additionally, CD55 rs1652333 and RDH5 rs3138142 were associated with 3-year longitudinal changes in AL (β=0.062, p=0.018; β=-0.079, p=0.029) and CR (β=0.014, p=0.027; β=-0.018, p=0.035)., Conclusion: Among SNPs previously associated with AL and SE in adults, variants in ZMAT4 , TOX and GRIA4 were associated with AL, SE, SPH, and/or AL/CR ratio, while variants in RDH5 and CD55 showed associations with AL and CR changes in children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: To assess the efficacy and safety of retrocorneal membrane interception (RMI)-enhanced penetrating canaloplasty in glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE) with open angle or small peripheral anterior synechiae (PAS)., Methods: A series of 13 patients (13 eyes) with GS-ICE and uncontrolled intraocular pressure (IOP) underwent RMI-enhanced penetrating canaloplasty from March 2019 to October 2020. The patients were followed up at one week, 1 month, 3 months, 6 months, and 12 months, postoperatively. The main outcome measure was surgical success, which was defined as an IOP ≤ 18 mmHg or ≤ 21 mmHg, with glaucoma medications (qualified success), or without glaucoma medications (complete success). Secondary outcome measures were IOP, medication usage, and surgical complications., Results: Among the 13 GS-ICE eyes, 12 (92%) achieved qualified success and 10 (77%) achieved complete success at 12 months postoperatively. The mean IOP decreased from 36.41 ± 8.92 mmHg on 3.0 (IQR 0.5) medications before surgery to 17.09 ± 7.71 mmHg (p = 0.0004) on 0.0 (IQR 0.5) medications (p = 0.0004) at 12 months after surgery. Transient hypotony (38%) and hyphema (38%) were the most common complications., Conclusions: RMI-enhanced penetrating canaloplasty appears effective and safe in treating GS-ICE with open angle or small PAS up to one year of follow up., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population., Methods: A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021., Results: A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation ( P  < 0.0001), a higher male-to-female ratio ( P  = 0.0045) and a higher age of disease onset ( P  = 0.0092). Family history of thyroid disease was more common in TED patients ( P  = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally ( P  < 0.0001), and they have a larger difference in MRD1 ( P  < 0.0001), and extraocular motility ( P  < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients ( P  = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar., Conclusions: Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Prcis: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle closure glaucoma without cataract., Purpose: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle closure glaucoma (PACG) eyes without cataract., Patients and Methods: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6 and 18 mm Hg with at least a 20% reduction compared with baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression., Results: A total of 61 eyes of 50 advanced PACGs were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P =0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P =0.036) reduced success rate., Conclusions: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate (1) the long-term efficacy of low-concentration atropine over 5 years, (2) the proportion of children requiring re-treatment and associated factors, and (3) the efficacy of pro re nata (PRN) re-treatment using 0.05% atropine from years 3 to 5., Design: Randomized, double-masked extended trial., Participants: Children 4 to 12 years of age originally from the Low-Concentration Atropine for Myopia Progression (LAMP) study., Methods: Children 4 to 12 years of age originally from the LAMP study were followed up for 5 years. During the third year, children in each group originally receiving 0.05%, 0.025%, and 0.01% atropine were randomized to continued treatment and treatment cessation. During years 4 and 5, all continued treatment subgroups were switched to 0.05% atropine for continued treatment, whereas all treatment cessation subgroups followed a PRN re-treatment protocol to resume 0.05% atropine for children with myopic progressions of 0.5 diopter (D) or more over 1 year. Generalized estimating equations were used to compare the changes in spherical equivalent (SE) progression and axial length (AL) elongation among groups., Main Outcomes Measures: (1) Changes in SE and AL in different groups over 5 years, (2) the proportion of children who needed re-treatment, and (3) changes in SE and AL in the continued treatment and PRN re-treatment groups from years 3 to 5., Results: Two hundred seventy (82.8%) of 326 children (82.5%) from the third year completed 5 years of follow-up. Over 5 years, the cumulative mean SE progressions were -1.34 ± 1.40 D, -1.97 ± 1.03 D, and -2.34 ± 1.71 D for the continued treatment groups with initial 0.05%, 0.025%, and 0.01% atropine, respectively (P = 0.02). Similar trends were observed in AL elongation (P = 0.01). Among the PRN re-treatment group, 87.9% of children (94/107) needed re-treatment. The proportion of re-treatment across all studied concentrations was similar (P = 0.76). The SE progressions for continued treatment and PRN re-treatment groups from years 3 to 5 were -0.97 ± 0.82 D and -1.00 ± 0.74 D (P = 0.55) and the AL elongations were 0.51 ± 0.34 mm and 0.49 ± 0.32 mm (P = 0.84), respectively., Conclusions: Over 5 years, the continued 0.05% atropine treatment demonstrated good efficacy for myopia control. Most children needed to restart treatment after atropine cessation at year 3. Restarted treatment with 0.05% atropine achieved similar efficacy as continued treatment. Children should be considered for re-treatment if myopia progresses after treatment cessation., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To systematically review and meta-analyze all reported heritability studies of refractive astigmatism (RA), corneal astigmatism (CA) and corneal curvature (CC), and evaluate the existing genetic associations of RA, CA and CC., Design: Systematic review and meta-analysis (PROSPERO ID: CRD42023447370)., Methods: Studies that reported the heritability and genetic associations of RA, CA and/or CC were identified from PubMed, Web of Science and EMBASE (from inception to October 1, 2023). Newcastle-Ottawa Scale criteria was used to assess the risk of bias. Meta-analyses of heritability were conducted using random-effects model for mean difference. All current genetic associations were catalogued according to level of statistical significance., Results: Pooled heritabilities were moderate for RA (h 2 = 0.46, 95% CI: 0.27-0.65), CA (h 2 = 0.48, 95% CI: 0.38-0.58) and CC (h 2 = 0.64, 95% CI: 0.53-0.76). Subgroup analyses revealed significant differences between analysis methods (CA: P < .01; CC: P = .03) and populations (CA: P < .01; CC: P < .01) in both CA and CC, and between age groups in CA (P < .01). Totally 50 single-nucleotide polymorphisms (SNPs) in 10 genes have been reported with overlapping associations with RA, CA, and/or CC, with BMP3, FMNL2, HERC2, PROX1-AS1, and ZC3H11B associated with RA and CA, FBN1, NHSL1, and PDGFRA with CA and CC, TRAF3IP1 with RA and CC, and CASC15 with RA, CA, and CC., Conclusions: This study confirms moderate heritabilities of RA, CA and CC. Through evaluating overlapping SNPs or genes between these three phenotypes, we prioritized 50 SNPs in 10 genes as candidate variants for further validation. These findings highlight the complex genetic architecture of astigmatism and indicate shared and distinct genetic markers for different astigmatism-related corneal parameters. Future studies in different populations and functional studies evaluating the roles of the involved genes in astigmatism are warranted., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of -17.8%, 95% CI: -29.4%, -6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children., (© 2024. The Author(s).)

Prcis: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae., Purpose: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle closure glaucoma (PACG) and cataract., Patients and Methods: This study included patients diagnosed with PACG and cataracts who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into 3 groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mm Hg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications., Results: Three hundred four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery ( P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the 3 groups ( P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared with 180°≤PAS<270° ( P = 0.044)., Conclusions: PEI+GSL+GT has proven to be an effective treatment for PACG with cataracts over a 1 year period. However, the outcome was not correlated with the preoperative extent of PAS., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To compare and rank the myopia control effects of different light wavelengths in children using a systematic review and Bayesian network meta-analysis (Bayesian NMA)., Methods: The review protocol was registered with PROSPERO. We searched PubMed, EMBASE and MEDLINE for relevant clinical and animal studies published as of 2 February 2023. We included studies comparing red, violet or full-spectrum light with controls. Data extracted included descriptive statistics and study outcomes (axial length (AL) elongation and progression of spherical equivalent (SE) refraction). After quality assessment, estimates of treatment effect outcomes (mean differences (MDs) and 95% CIs) were first pooled for the animal and clinical studies in a traditional meta-analysis. To compare and rank the different light wavelengths, the Bayesian NMA was then conducted for all the included clinical studies (12 studies) and separately for only randomised controlled trials (8 studies). MDs, 95% credible intervals (CrIs) and ranks of the various light wavelengths were estimated in the Bayesian NMA., Results: When all clinical studies were included in the Bayesian NMA (12 studies), only red-light significantly slowed AL elongation, MD (95% CrI), -0.38 mm (-0.59 mm to -0.16 mm)/year and SE refraction progression, 0.72D (0.35D to 1.10D)/year compared with controls. It remained the only significant intervention when effect sizes from only RCTs (eight studies) were separately combined, (-0.28 mm (-0.40 mm to -0.15 mm)/year and 0.57D (0.22D to 0.92D)/year, for AL and SE refraction, respectively)., Conclusion: Myopia control efficacy varied among different wavelengths of light, with red light ranked as the most effective., Prospero Registration Number: Clinical studies: CRD42022368998; animal studies: CRD42022368671., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Deep learning (DL) is promising to detect glaucoma. However, patients' privacy and data security are major concerns when pooling all data for model development. We developed a privacy-preserving DL model using the federated learning (FL) paradigm to detect glaucoma from optical coherence tomography (OCT) images., Methods: This is a multicentre study. The FL paradigm consisted of a 'central server' and seven eye centres in Hong Kong, the USA and Singapore. Each centre first trained a model locally with its own OCT optic disc volumetric dataset and then uploaded its model parameters to the central server. The central server used FedProx algorithm to aggregate all centres' model parameters. Subsequently, the aggregated parameters are redistributed to each centre for its local model optimisation. We experimented with three three-dimensional (3D) networks to evaluate the stabilities of the FL paradigm. Lastly, we tested the FL model on two prospectively collected unseen datasets., Results: We used 9326 volumetric OCT scans from 2785 subjects. The FL model performed consistently well with different networks in 7 centres (accuracies 78.3%-98.5%, 75.9%-97.0%, and 78.3%-97.5%, respectively) and stably in the 2 unseen datasets (accuracies 84.8%-87.7%, 81.3%-84.8%, and 86.0%-87.8%, respectively). The FL model achieved non-inferior performance in classifying glaucoma compared with the traditional model and significantly outperformed the individual models., Conclusion: The 3D FL model could leverage all the datasets and achieve generalisable performance, without data exchange across centres. This study demonstrated an OCT-based FL paradigm for glaucoma identification with ensured patient privacy and data security, charting another course toward the real-world transition of artificial intelligence in ophthalmology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients., Methods: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or flat anterior chamber after initial recovery from treatment., Results: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg ( P <0.001) with 2.9±1.6 medications ( P =0.046) at 1d, and 17.4±6.7 mm Hg ( P <0.001) with 1.3±1.7 medications ( P <0.001) at 12mo. The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo, respectively. A total of 32 (94.1%) eyes achieved initial anatomical success. During follow-up, 2 (5.9%) eyes failed and 8 (23.5%) eyes relapsed, yielding a 12-month anatomical success rate of 64.3%. Complications including anterior synechia (8.82%), choroidal/ciliary detachment (5.88%) and hypopyon (2.94%) were observed within 1wk., Conclusion: LCP is simple, safe, and effective in reforming the anterior chamber in malignant glaucoma., Competing Interests: Conflicts of Interest: Lin HS, None; Xu XP, None; Zheng XL, None; Wang JB, None; Fan SJ, None; Wu ZH, None; Cheng SM, None; Zhao LJ, None; Cai QH, None; Zhang SD, None; Liu SS, None; Lyu AG, None; Zhang Y, None; Chen H, None; Jiang DN, None; Li WL, None; Congdon N, None; Tham CC, None; He MG, None; Liang YB, None., (International Journal of Ophthalmology Press.)

Large language models (LLMs), a natural language processing technology based on deep learning, are currently in the spotlight. These models closely mimic natural language comprehension and generation. Their evolution has undergone several waves of innovation similar to convolutional neural networks. The transformer architecture advancement in generative artificial intelligence marks a monumental leap beyond early-stage pattern recognition via supervised learning. With the expansion of parameters and training data (terabytes), LLMs unveil remarkable human interactivity, encompassing capabilities such as memory retention and comprehension. These advances make LLMs particularly well-suited for roles in healthcare communication between medical practitioners and patients. In this comprehensive review, we discuss the trajectory of LLMs and their potential implications for clinicians and patients. For clinicians, LLMs can be used for automated medical documentation, and given better inputs and extensive validation, LLMs may be able to autonomously diagnose and treat in the future. For patient care, LLMs can be used for triage suggestions, summarization of medical documents, explanation of a patient's condition, and customizing patient education materials tailored to their comprehension level. The limitations of LLMs and possible solutions for real-world use are also presented. Given the rapid advancements in this area, this review attempts to briefly cover many roles that LLMs may play in the ophthalmic space, with a focus on improving the quality of healthcare delivery., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Myopia has long been a global threat to public health. Timely interventions are likely to reduce the risk of vision-threatening complications. There are both established and rapidly evolving therapeutic approaches to slow myopia progression and/or delay its onset. The effective methods for slowing myopia progression include atropine eye-drops, defocus incorporated multiple segments (DIMS) spectacle lenses, spectacle lenses with highly aspherical lenslets target (HALT), diffusion optics technology (DOT) spectacle lenses, red light therapy (RLT), multifocal soft contact lenses and orthokeratology. Among these, 0.05% atropine, HALT lenses, RLT and +3.00 peripheral addition soft contact lenses yield over 60% reduction in myopia progression, whereas DIMS, DOT and MiSight contact lenses demonstrate at least 50% myopia control efficacy. 0.05% atropine demonstrates a more optimal balance of efficacy and safety than 0.01%. The efficacy of 0.01% atropine has not been consistent and requires further validation across diverse ethnicities. Combining atropine 0.01% with orthokeratology or DIMS spectacles yields better outcomes than using these interventions as monotherapies. Increased outdoor time is an effective public health strategy for myopia prevention while recent studies suggest that 0.05% low-concentration atropine and RLT therapy have promising potential as clinical myopia prevention interventions for high-risk groups. Myopia control spectacle lenses, being the least invasive, are safe for long-term use. However, when considering other approaches, it is essential to ensure proper instruction and regular follow-ups to maintain safety and monitor any potential complications. Ultimately, significant advances have been made in myopia control strategies, many of which have shown meaningful clinical outcomes. However, regular use and adequate safety monitoring over extended durations are imperative to foster confidence that can only come from extensive clinical experience., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the associations of the TIE2 gene with diabetic retinopathy (DR) and diabetic macular edema (DME)., Methods: This study included a Chinese cohort of 285 non-proliferative DR patients and 433 healthy controls. The DR patients were classified further into those with or without DME. Thirty haplotype-tagging single-nucleotide polymorphisms (SNPs) in TIE2 were genotyped using TaqMan technology. Associations of DR and subtypes were analyzed by logistic regression adjusted for age and sex. Stratification association analysis by sex was performed., Results: TIE2 rs625767 showed a nominal but consistent association with DR [odds ratio (OR) = 0.71, P = 0.005] and subtypes (DR without DME: OR = 0.69, P = 0.016; DME: OR = 0.73, P = 0.045). SNP rs652010 was consistently associated with overall DR (OR = 0.74, P = 0.011) and DR without DME (OR = 0.70, P = 0.016), but not with DME. Moreover, SNPs rs669441, rs10967760, rs549099 and rs639225 showed associations with overall DR, whilst rs17761403, rs664461 and rs1413825 with DR without DME. In stratification analysis, three SNPs, rs625767 (OR = 0.62, P = 0.005), rs669441 (OR = 0.63, P = 0.006) and rs652010 (OR = 0.64, P = 0.007), were associated with DR in females, but not in males. Moreover, one haplotype T-T defined by rs625767 and rs669441 was significantly associated with DR in females only., Conclusions: This study revealed TIE2 as a susceptibility gene for DR and DME in Chinese, with a sex-specific association in females. Further validation should be warranted., Competing Interests: Conflict of interest The authors declare no conflict of interest including any financial, personal, or other relationships with other people or organizations that might influence or be perceived to influence their work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Effects of genetic variants on primary angle-closure disease remained uncertain., Objective: To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression., Data Sources: Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen., Study Selection: Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression., Data Extraction and Synthesis: PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics., Main Outcomes and Measures: SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized., Results: Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease-associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified., Conclusions and Relevance: This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.

Purpose: To compare the anatomic and functional outcomes of half-dose photodynamic therapy (PDT) and yellow 577-nm subthreshold micropulse laser (SMLT) in treating patients with chronic central serous chorioretinopathy (CSCR)., Design: Prospective, double-masked, randomized, controlled clinical trial., Participants: Patients with chronic CSCR confirmed by clinical features and multimodal imaging., Methods: Eligible patients were randomized (1:1) to receive half-dose PDT or SMLT. The same treatment was repeated if persistent subretinal fluid (SRF) was observed. Treatment responses were evaluated 1 month after treatment and every 3 months until the end point at 12 months., Main Outcome Measures: The primary outcome measure was the complete resolution of SRF on OCT scan at month 12. Secondary outcomes included the changes in best-corrected visual acuity (BCVA), central macular thickness (CMT) as measured by OCT, retinal sensitivity as measured by microperimetry, and vision-related quality of life using the National Eye Institute 25-Item Visual Function Questionnaire., Results: Between April 2017 and October 2020, 68 patients were recruited. At 1 month after treatment, SRF resolved in 8 (24.2%) of 33 patients receiving SMLT and in 20 (58.8%) of 34 patients receiving half-dose PDT. This increased to 23 (82.1%) of 28 patients in the SMLT group and 30 (90.9%) of 33 patients in the half-dose PDT group at 12 months of follow-up. Kaplan-Meier survival curves showed significantly faster resolution of SRF in the half-dose PDT group than the SMLT group (P = 0.016). Both groups showed significant improvement in BCVA (-0.12 ± 0.21, P = 0.005 for SMLT; -0.13 ± 0.12, P < 0.001 for half-dose PDT), CMT (-154.2 ± 105.6, P < 0.001 for SMLT; -140.8 ± 94.0, P < 0.001 for half-dose PDT), and retinal sensitivity (5.70 ± 5.02, P < 0.001 for SMLT; 6.05 ± 3.83, P < 0.001 for half-dose PDT) at 12 months compared with baseline. There was no significant difference between the 2 treatment groups at each time point in all investigations except BCVA at 3 months (P = 0.03)., Conclusions: When comparing half-dose PDT to subthreshold SMLT, this study has shown both treatments to be viable options, with half-dose PDT achieving faster anatomic success and functional improvement., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Retinoblastoma (RB), originating from the developing retina, is an aggressive intraocular malignant neoplasm in childhood. Biallelic loss of RB1 is conventionally considered a prerequisite for initiating RB development in most RB cases. Additional genetic mutations arising from genome instability following RB1 mutations are proposed to be required to promote RB development. Recent advancements in high throughput sequencing technologies allow a deeper and more comprehensive understanding of the etiology of RB that additional genetic alterations following RB1 biallelic loss are rare, yet epigenetic changes driven by RB1 loss emerge as a critical contributor promoting RB tumorigenesis. Multiple epigenetic regulators have been found to be dysregulated and to contribute to RB development, including noncoding RNAs, DNA methylations, RNA modifications, chromatin conformations, and histone modifications. A full understanding of the roles of genetic and epigenetic alterations in RB formation is crucial in facilitating the translation of these findings into effective treatment strategies for RB. In this review, we summarize current knowledge concerning genetic defects and epigenetic dysregulations in RB, aiming to help understand their links and roles in RB tumorigenesis., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To review the effects of firsthand tobacco smoking on central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) of firsthand tobacco smokers., Methods: We performed a search on EMBASE and PubMed for studies up to 15 th July 2022. Two independent reviewers selected studies with baseline data of CRAE and CRVE of current smokers, nonsmokers, and former smokers. Initial search identified 893 studies, of which 10 were included in the meta-analysis. Two independent reviewers extracted data from the included studies. The quality of studies was assessed by the Newcastle-Ottawa Scale., Results: In this meta-analysis, 7431 nonsmokers, 2448 current smokers and 5786 former smokers, as well as 7404 nonsmokers, 2430 current smokers and 5763 former smokers were included in CRAE and CRVE analysis respectively. Nonsmokers had narrower CRVE (Weighted mean difference [WMD], -12.15; 95% CI, -17.33 - -6.96) and CRAE (WMD, -4.77; 95% CI, -7.96 - -1.57) than current smokers, and narrower CRVE (WMD, -3.08; 95% CI, -6.06 - -0.11) than former smokers. Current smokers had wider CRVE (WMD, 10.42; 95% CI, 7.80 - 13.04) and CRAE (WMD, 7.05; 95% CI, 6.65 - 7.46) than former smokers. Subgroup analysis and sensitivity analysis were performed., Conclusion: Firsthand tobacco smoking resulted in wider CRAE and CRVE in current and former smokers, particularly in CRVE, and such changes may not be reversible after smoking cessation. Therefore, retinal vessel caliber may reflect the effects of firsthand tobacco smoking and be used to estimate the risk of cardiovascular diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Euthyroid Graves' ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients., Methods: A cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging., Results: Between 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05)., Conclusion: EGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO. (249 words)., (© 2024. The Author(s).)

Purpose: To compare the rates of peripapillary vessel density (pVD) loss and retinal nerve fibre layer (RNFL) thinning in normal tension glaucoma (NTG) and primary angle closure glaucoma (PACG)., Methods: Baseline age and severity-matched NTG and PACG eyes (75 eyes of 60 patients for each subtype) were observed longitudinally. All participants' RNFL thickness were measured by optical coherence tomography (OCT); pVD were measured by swept-source OCT-angiography (OCT-A) and quantified by a customised MATLAB program. The rate of pVD loss and RNFL thinning were estimated by linear mixed-effects models., Results: NTG eyes had significant pVD loss in all sectors (p≤0.05) while PACG eyes' pVD loss was borderline significant in the global region (p=0.05). Significant RNFL thinning was detected in the inferotemporal and superonasal regions of both groups, and the superotemporal region in the NTG group (all p≤0.02). NTG had faster rate of pVD loss in the global (difference (95% CI) -1.08 (-1.90 to -0.27) %/year), temporal (-1.57 (-2.91 to -0.23) %/year) and superotemporal (-1.46 (-2.65 to -0.26) %/year) regions than PACG (all p ≤ 0.02), without significant difference of the rate of RNFL thinning. A lower baseline mean deviation (MD) was associated with a faster rate of global pVD loss, while a lower baseline pVD was associated with a slower rate of global pVD loss in multivariable analyses (both p≤0.04)., Conclusions: NTG had more extensive and faster rate of pVD loss than PACG. Baseline global pVD and MD were independently associated with the rate of pVD loss in NTG., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to explore the influence of the interaction between parental myopia and lifestyle on myopia among school-age children., Design: Cross-sectional study., Setting: This study used data from the Tianjin Child and Adolescent Research of Eye between August and October 2022., Participants: A total of 49 035 participants between 6 and 18 years of age were eligible for this study., Primary and Secondary Outcome Measures: The primary outcome was the interaction between eye-healthy lifestyle and parental myopia on myopia. Parental myopia and eye-healthy lifestyle were ascertained by a Child and Adolescent Behavior Questionnaire. The lifestyle risk score (LRS) of eye health was calculated based on beta-coefficient in the backward regression model. The interaction between LRS and parental myopia was analysed by multivariate logistic regression. The predictive value of different predicted models was estimated using receiver operating characteristic curves. Multiple linear regression was used to evaluate the associations of lifestyle risk factors and parental myopia with spherical equivalent refraction, which were defined as the secondary outcomes., Results: A total of 31 839 participants aged 6-18 years were included, and the myopia prevalence was 55.46%. Eye-healthy lifestyle and parental myopia were significantly associated with myopia, as was interaction. The predictive value for LRS & parental myopia was 0.714 (95% CI: 0.709 to 0.720), which was higher than LRS (0.693, 95% CI: 0.687 to 0.699) and parental myopia (0.710, 95% CI: 0.704 to 0.716) separately., Conclusions: High-risk lifestyles of myopia and parental myopia were significantly associated with a higher risk of myopia, and the combination had the strongest effect. For children, lifestyle adjustment should be prioritised in preventing myopia, especially for those with parental myopia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts., Design: Multicenter, randomized controlled, non-inferiority trial., Methods: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications., Results: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group., Conclusions: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life., Competing Interests: Declaration of Competing Interest None reported., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the genetic associations of different subtypes of central serous chorioretinopathy (CSCR), neovascular age-related macular degeneration (nAMD), and polypoidal choroidal vasculopathy (PCV)., Design: A case-control genetic association study., Methods: This study enrolled 217 CSCR, 341 nAMD, 288 PCV patients, and 1380 controls. The CSCR patients were classified into those with focal or diffuse leakage, with or without pigment epithelial detachment (PED), and with or without macular neovascularization (MNV). Associations between 11 variants from 8 genes, ADAMTS9, ANGPT2, ARMS2, CFH, NR3C2, PGF, TNFRSF10A and VIPR2, and diseases/subtypes were analyzed by logistic regression analysis adjusted for age and sex, and inter-phenotype comparison by heterogeneity test., Results: The CFH rs800292-A conferred a protective effect for CSCR with MNV (OR=0.44, P = 0.002) and a risk effect for CSCR without MNV (OR=1.31, P = 0.023). CSCR patients carrying rs800292-G had a 3.23-fold of increased risk towards developing secondary MNV (P = 1.45 ×10 -4 ). CFH rs3753394, rs800292 and rs1329428 showed similar effects among CSCR with MNV, nAMD and PCV, but opposite effects on CSCR without MNV. TNFRSF10A rs13278062-T was associated with overall CSCR but not with CSCR subtypes, nAMD or PCV. Moreover, CFH and ARMS2 SNPs showed heterogeneous effects in CSCR without MNV against CSCR with MNV, nAMD and PCV., Conclusions: Genetic associations of CSCR with MNV resembled nAMD and PCV compared to CSCR without MNV, indicating differential genetic effects on neovascularization and choroidopathy. Further investigation of the functional roles of CFH, ARMS2, and TNFRSF10A in CSCR, nAMD and PCV should help elucidate the mechanisms of these maculopathies., Competing Interests: Declaration of Competing Interest No conflicting relationship exists for any author., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients., Design: Cross-sectional, matched case-control comparison study., Methods: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings., Results: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001)., Conclusions: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The aim of this work is to determine the interocular differences in peripapillary retinal nerve fiber layer (p-RNFL) thickness and its associations among school children in Hong Kong., Methods: We conducted a population-based study including 4034 children aged 6-8 years from the Hong Kong Children Eye Study (HKCES). All participants received comprehensive ocular examinations where p-RNFL thickness was measured using spectral-domain optical coherence tomography (SD-OCT). The degree of symmetry between both eyes was analyzed and represented by intraclass correlation coefficient (ICC) values. Multivariable linear regression analysis was used to investigate the associations between ocular and systemic factors with p-RNFL thickness difference., Results: The study included 4034 children with a mean age of 7.61 ± 0.98 years. The mean global p-RNFL thickness was 106.60 ± 9.41 μm in right eyes and 105.99 ± 9.30 μm in left eyes. The ICC for global p-RNFL difference was 0.866 (95% CI 0.858-0.873, p < 0.001). The symmetry displayed the largest values in nasal inferior quadrant with the ICC value of 0.736 (95% CI 0.721-0.749); and the smallest degree of symmetry was found to be in the superior temporal quadrant with the ICC value of 0.567 (95% CI 0.546-0.588). Axial length (AL) difference was found to have more pronounced correlation to interocular symmetry in p-RNFL thickness with the coefficient of 0.514 (p < 0.001)., Conclusions: Normal variation in interocular symmetry exists in children. Our results can contribute to the establishment of a standard reference for interocular differences in OCT parameters in children. The interocular differences in AL should be considered in the interpretation of RNFL symmetry, in terms of identifying children at risk of developing glaucoma or other ocular disorders., (© 2023. The Author(s).)

Purpose: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG)., Design: Cross-sectional multicenter study., Participants: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included., Methods: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database., Main Outcomes Measures: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG., Results: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all)., Conclusions: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. All rights reserved.)

The toxicology of secondhand smoke (SHS), along with the harm of its exposure to human health, has been generally acknowledged; however, specific evidence is lacking on the association between SHS exposure and ocular health. In this systematic review (PROSPERO registration number: CRD42022247992), we included 55 original articles published by 12 May 2023, which dealt with SHS exposure and ocular disorders, such as eye irritation, conjunctivitis, dry eye diseases, uveitis, myopia, astigmatism, contact lens discomfort, age-related macular degeneration, glaucoma, and thyroid eye disease that addressed the ocular neurovascular structures of the macular, retinal nerve fiber layer, choroid, and corneal biomechanical parameters. We found compelling correlational evidence for eye irritation, conjunctivitis, and dry eye symptoms-supporting that SHS exposure was positively associated with inflammatory and allergic changes in the eyes. Yet, evidence about the associations between SHS exposure and other ocular disorders, structures, and parameters is still limited or controversial. Given the limitations of existing literature, more investigations with high quality and rigorous design are warranted to elucidate the potentially harmful effects of SHS exposure on ocular health., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. This study was supported in part by the General Research Fund (GRF), Research Grants Council, Hong Kong (14111515 and 14103419 [JCY]); the Collaborative Research Fund (C7149–20 G [JCY]); the Health and Medical Research Fund (HMRF), Hong Kong (5160836 [LJC] and 07180826 [XJZ]), and the Direct Grants of the Chinese University of Hong Kong (4054193 [LJC], 4054121, 4054199, and 178662514 [JCY], and 4054634 [XJZ]); the Innovation and Technology Fund (7010590 [JCY]); the UBS Optimus Foundation Grant 8984 (JCY); the Centaline Myopia Fund [JCY]; the National Natural Science Foundation of China (8217040098 [JCY]); the CUHK Jockey Club Children’s Eye Care Programme, and the CUHK Jockey Club Myopia Prevention Programme. The sponsor or funding organization had no role in the design or conduct of this research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown and has not been compared., Objective: To determine cost-effective options for controlling myopia progression in children., Design, Setting, and Participants: In this cost-effectiveness analysis, a Markov model was designed to compare the cost-effectiveness of interventions for controlling myopia progression over 5 years from a societal perspective in a simulated hypothetical cohort of patients aged 10 years with myopia. Myopia interventions considered included atropine eye drops, 0.05% and 0.01%, defocus incorporated multiple segment spectacles, outdoor activity, soft contact lenses (daily disposable and multifocal), rigid gas-permeable contact lenses, progressive addition lenses, bifocal spectacle lenses, orthokeratology, highly aspherical lenslets (HALs), and red light therapy; all interventions were compared with single-vision lenses. Deterministic and probabilistic sensitivity analysis determined the association of model uncertainties with the cost-effectiveness. Costs were obtained from the charges of the Hospital Authority of Hong Kong and The Chinese University of Hong Kong Eye Center., Main Outcome and Measures: The mean costs (in US dollars) per child included the cost of hospital visits, medications, and optical lenses. The outcomes of effectiveness were the annual spherical equivalent refraction (SER) and axial length (AL) reductions. Incremental cost-effectiveness ratios (ICERs) were calculated for each strategy relative to single-vision lenses over a time horizon of 5 years., Results: Outdoor activity, atropine (0.05%), red light therapy, HALs, and orthokeratology were cost-effective. The ICER of atropine, 0.05%, was US $220/SER reduction; red light therapy, US $846/SER reduction; and HALs, US $448/SER reduction. Outdoor activity yielded a savings of US $5/SER reduction and US $8/AL reduction. Orthokeratology resulted in an ICER of US $2376/AL reduction., Conclusions and Relevance: These findings suggest that atropine eye drops, 0.05%, and outdoor activity are cost-effective for controlling myopia progression in children. Though more expensive, red light therapy, HALs, and orthokeratology may also be cost-effective. The use of these interventions may help to control myopia in a cost-effective way.

Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV., Competing Interests: Declaration of Competing Interest No conflicts of interest exist for any of the authors., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: The authors have no conflicts of interest to disclose.