Understanding natural language: Potential application of large language models to ophthalmology.

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.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective non-comparative study.

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.

Deep learning-based image quality assessment for optical coherence tomography macular scans: a multicentre study.

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.

Impact of Peripheral Anterior Synechiae on the Outcome of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Primary Angle Closure Glaucoma and Cataract: A Multicenter Observational Study.

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.

Perioperative management of sarcopenia in patients undergoing major surgeries in Singapore: a modified Delphi consensus.

BACKGROUND: Ageing population is a worldwide phenomenon with correspondingly higher proportion of older patients being treated in the hospital setting. Sarcopenia, which increases with age, has serious negative implications on health, hospitalisation, and overall postoperative recovery. There is no mutual consensus on perioperative management of sarcopenia in surgical patients in Singapore. The purpose of this study is to create greater clarity pertaining to the recognition of sarcopenia, the application of assessment criteria of sarcopenia and perioperative management of surgical patients in Singapore. METHODS: A modified Delphi consensus consisting of a panel of experts from Singapore forming a multidisciplinary team, including surgeons, geriatricians, anesthesiologists, physiotherapists, and dieticians. Eight recommendations were proposed by the steering committee. Literature search from MEDLINE, Embase, and Scopus for articles up till June 2023 were performed to support recommendation statements. The expert panel voted on agreement to recommendation statements and graded the level of evidence supporting each statement through surveys to achieve consensus, set at 85% a priori. RESULTS: The panellists underwent two rounds of anonymized, independent voting before reaching consensus for all eight statements. After the first round, seven statements reached consensus, including the corresponding grading for level of evidence. The statement which did not achieve consensus was revised with supporting literature and after the second round of survey, all eight statements and level of evidence reached consensus, completing the Delphi process. These eight statements covered themes to (1) encourage the identification of sarcopenia, (2) guide preoperative, and (3) postoperative management of sarcopenia. CONCLUSION: With the varying approaches in perioperative management, poor understanding of and identification of sarcopenia can result in suboptimal management of sarcopenia in surgical patients. Given the abundance of evidence linking beneficial impact on recovery and postoperative complications with prudent management of sarcopenia, it is imperative and urgent to achieve awareness and consensus.

Genetic association of TIE2 with diabetic retinopathy and diabetic macular edema.

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.

Photokeratitis in Outdoor Event Participants Exposed to UV Radiation Display.

Importance: While UV radiation displays may be used for recreational purposes at outdoor events, unprotected eyes have been reported to have symptoms consistent with photokeratitis. Such symptoms warrant documentation and evaluation in ophthalmic peer reviewed literature. Objective: To describe a case series of photokeratitis associated with a single ultraviolet radiation display at an outdoor event. Design, Setting, and Participants: This case series involved a retrospective record review of 8 patients who presented in public and private health sectors in November 2023 after developing photokeratitis following UV radiation exposure at an outdoor event in Hong Kong on the night of November 4, 2023. Main Outcomes and Measures: Clinical symptoms, signs, and clinical course of patients who were diagnosed acute photokeratitis following exposure to UV radiation. Results: The mean time of UV display exposure for the 8 patients (mean [SD] age, 33.12 [5.19] years; 4 [50%] female) was 3.00 (1.41) hours, and symptoms presented at a mean (SD) 8.88 (8.24) hours after the exposure. None of the patients were wearing spectacles during the exposed period. All patients were affected bilaterally. All patients experienced eye pain, 6 experienced red eye, and 5 experienced tearing and photophobia. Mean (SD) presenting visual acuity was logMAR 0.10 (0.14) (approximate Snellen equivalent, 20/25) for right eyes and 0.06 (0.89) (approximate Snellen equivalent, 20/25) for left eyes. On examination, there were findings of cornea and conjunctival involvement with punctate epithelial erosions and ciliary vasodilation, but none of the patients presented with anterior chamber reaction. Corticosteroids, lubricants, and antibiotics, all provided topically, were prescribed. Five patients were not scheduled for a review, and 3 had follow-up visits, with the length of follow-up ranging from 7 to 10 days. All patients had undergone a complete recovery. Conclusions and Relevance: These findings provide evidence of an association between UV radiation used for recreational purposes and photokeratitis, which may help guide evaluation and management of future cases.

Etiology including epigenetic defects of retinoblastoma.

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.

Cross-sectional survey of health literacy among health science students in Singapore.

Background: Health literacy proficiency is essential for health care professionals to provide quality patient care. There is limited research exploring health literacy proficiency among undergraduate health science students. Objectives: To determine health literacy among health science students in Singapore using the electronic Health Literacy Questionnaire (HLQ). Design: A cross-sectional survey using purposive sampling was conducted among undergraduate health science students. Methodology: This study hypothesises that health literacy is influenced by gender, and it increases with the level of health science education, attributed to the increased exposure to the health care system and health care education as undergraduates progress through the years of study. Eligible students from the 4-year entry-level programmes of diagnostic radiography, dietetics, occupational therapy, physiotherapy, radiation therapy and speech and language therapy, aged from 21 to 50, were invited. Exclusion criteria were students who were no longer studying due to dropping out or having immediately graduated from these programmes and students in the accelerated programmes whose studies would be completed in less than 4 years. Results: In total, 111 respondents (72 females and 37 males) completed surveys (response rate, 7.7%) returned from physiotherapy (n = 69), occupational therapy (n = 25), diagnostic radiography (n = 12) and dietetics (n = 5), with nil from radiation therapy and speech and language therapy. All participants were English literate. Female participants demonstrated higher HLQ with a mean total score of 30.67 (standard deviation (SD) = 0.61) versus male participants 29.83 (SD = 0.53). Year 2, 3 and 4 students generally scored higher than Year 1 across all nine HLQ scales. Overall, dietetics students had the highest total score on the HLQ, while the diagnostic radiography students had the lowest scores for all the nine HLQ scales. Conclusion: This study established the health literacy level of health science students in Singapore. Gender and years of study influenced health literacy levels, supporting the hypothesis.

Background: Health care professionals need to understand health information well to provide good patient care. There is little research on how well health science students understand health information. Objectives: This study aims to determine how well health science students in Singapore understand health information using a questionnaire known as the Health Literacy Questionnaire (HLQ). Design: The study surveyed health science students. Methodology: The study explored if the understanding of health information is influenced by gender and increases with more years of health science education. This is because students get more exposure to the health care system and education as they continue their studies. Students from various health science programmes aged 21 to 50 were invited to participate. Students who had dropped out or just graduated and were in accelerated programmes were excluded. Results: The survey was completed by 111 students (72 females and 37 males) from physiotherapy, occupational therapy, diagnostic radiography and dietetics. No students from radiation therapy and speech and language therapy participated. All participants could read and write in English. Female participants scored higher on the questionnaire than male participants. Students scored higher in their second, third and fourth years than in their first year of study. Dietetics students scored the highest overall, while diagnostic radiography scored the lowest. Conclusion: This study reported the level of understanding of health information among health science students in Singapore. The level of understanding was influenced by gender and years of study. Key messages: • Establishing the health literacy level of health science students in Singapore is important.• Senior students tend to have better health literacy compared with junior students.• Navigating the health care system and obtaining support from health care providers are areas where students can benefit from health literacy education.• Educational materials should be optimised to address potential health literacy deficits and ensure high literacy levels upon graduation.

Survey on the level of health information understanding among the health science students in Singapore.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

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.

Genetic associations of central serous chorioretinopathy subtypes, neovascular age-related macular degeneration, and polypoidal choroidal vasculopathy.

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.

Effects of firsthand tobacco smoking on retinal vessel caliber: a systematic review and meta-analysis.

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 15th 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.

Systemic Involvement in Immunoglobulin G4-Related Ophthalmic Disease.

BACKGROUND: Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and the clinical, serological and radiological associations of a cohort of Chinese patients. METHODS: A territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports. RESULTS: A total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001). CONCLUSIONS: 95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD.

Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation.

Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.

Influence of secondhand smoke exposure on the retinal vasculature of children in Hong Kong.

BACKGROUND: A recent prospective demonstrated that cardiovascular risk factors in early childhood were associated with later cardiovascular events. However, the impact of secondhand smoke (SHS) on children is unclear. The aims of this study is to determine the effects of SHS exposure on the retinal vasculature of children. METHODS: This is a population-based cross-sectional study of children aged 6 to 8 years. All participants received comprehensive ophthalmic examinations and retinal photography. Data on SHS exposure was derived from a validated questionnaire. A validated deep-learning system was used to automatically estimate retinal arteriolar and venular calibers from retinal photographs. Associations of quantitative retinal vessel caliber values with SHS exposure, number of smokers in the household, and total number of cigarettes smoked were determined by analyses of covariance (ANCOVA) after adjusting for potential confounders. Test of trend was determined by treating categorical risk factors as continuous ordinal variables. RESULTS: Here we show children exposed to SHS have wider retinal arteriolar (CRAE 152.1 µm vs. 151.3 µm, p < 0.001) and venular (CRVE 216.7 µm vs. 215.5 µm, p < 0.001) calibers compared to those in smoke-free homes, after adjustment for different factors. Wider arteriolar and venular calibers are also associated with increasing number of smokers in the family (p trend < 0.001) and more cigarettes smoked among family smokers (p trend<0.001). CONCLUSIONS: Exposure to SHS at home is associated with changes in retinal vasculature among children. This reinforces the adverse effect of secondhand smoking around children though further research incorporating comprehensive assessment of potential confounders is necessary.

Exposure to secondhand smoke can be harmful, particularly for our heart and lung health as adults. However, the impact of secondhand smoke on children is less clear. Here, we looked at the effects of secondhand smoke exposure on vessels within children's eyes. The health of these vessels is a potential indicator of overall eye health and is also associated with cardiovascular disease. Pictures were taken of children's eyes and analyzed using a computer program. We looked at the association between vessel measurements in the eye and how much secondhand smoke the children are exposed to. We observed differences in the vessels in children exposed to secondhand smoke, compared to those from smoke-free homes. These findings indicate that secondhand smoke may affect the health of children's eyes and highlight the need to promote smoke-free home environments.

Presumed Silicone Oil Droplets After Intravitreal Pegcetacoplan Injections.

Importance: Recently, intravitreal pegcetacoplan became the first drug to gain US Food and Drug Administration approval for the treatment of geographic atrophy associated with nonexudative age-related macular degeneration, but the administration of this medication may be associated with unanticipated posttreatment complications. Objective: To assess the prevalence of presumed silicone oil droplets in the vitreous cavity after intravitreal injection of pegcetacoplan. Design, Setting, and Participants: This case series study involved a retrospective record review of all 55 patients treated with intravitreal pegcetacoplan, 0.1 mL in 150-mg/mL solution, between March 24 and June 5, 2023, at a single specialty retina practice. All injections were done using needles from the kit supplied by Apellis Pharmaceuticals on a 1-mL McKesson Luer lock syringe. Main Outcomes and Measures: The presence or absence of presumed silicone bubbles detected during dilated biomicroscopic fundus examination and/or on color fundus photographs, the presence or absence of symptoms, change in visual acuity, and/or increase in intraocular pressure. Results: A total of 62 intravitreal pegcetacoplan injections were given to 55 patients (mean [SD] age, 83.8 [7.8] years; 33 women [60%]) from March 24 to June 5, 2023. Of the 55 patients, 16 (29%; mean [SD] age, 83.8 [7.4] years; 9 women [56%]) had presumed intravitreal silicone droplets discovered 2 to 4 weeks after treatment, 3 of which were documented on color fundus photographs. Of the 16 patients, 14 (88%) were symptomatic for new floaters that they described as persistent, while 2 (13%) were asymptomatic. There were no signs of inflammation or infection, no increases in intraocular pressure, and no changes in visual acuity for all 16 patients. Conclusions and Relevance: A substantial percentage of patients had symptomatic floaters from presumed intravitreal silicone oil droplets after injections of pegcetacoplan using a McKesson 1-mL Luer lock syringe. These findings support consideration of informing patients of this potential adverse effect, avoiding use of the McKesson syringe, and considering use of silicone-free syringes for pegcetacoplan injections.

Cost-effectiveness of virtual reality and wet laboratory cataract surgery simulation.

PURPOSE: To evaluate the cost-effectiveness of phacoemulsification simulation training in virtual reality simulator and wet laboratory on operating theater performance. METHODS: Residents were randomized to a combination of virtual reality and wet laboratory phacoemulsification or wet laboratory phacoemulsification. A reference control group consisted of trainees who had wet laboratory training without phacoemulsification. All trainees were assessed on operating theater performance in 3 sequential cataract patients. International Council of Ophthalmology Surgical Competency Assessment Rubric-phacoemulsification (ICO OSCAR phaco) scores by 2 masked independent graders and cost data were used to determine the incremental cost-effectiveness ratio (ICER). A decision model was constructed to indicate the most cost-effective simulation training strategy based on the willingness to pay (WTP) per ICO OSCAR phaco score gained. RESULTS: Twenty-two trainees who performed phacoemulsification in 66 patients were analyzed. Trainees who had additional virtual reality simulation achieved higher mean ICO OSCAR phaco scores compared with trainees who had wet laboratory phacoemulsification and control (49.5 ± standard deviation [SD] 9.8 vs 39.0 ± 15.8 vs 32.5 ± 12.1, P < .001). Compared with the control group, ICER per ICO OSCAR phaco of wet laboratory phacoemulsification was $13,473 for capital cost and $2209 for recurring cost. Compared with wet laboratory phacoemulsification, ICER per ICO OSCAR phaco of additional virtual reality simulator training was US $23,778 for capital cost and $1879 for recurring cost. The threshold WTP values per ICO OSCAR phaco score for combined virtual reality simulator and wet laboratory phacoemulsification to be most cost-effective was $22,500 for capital cost and $1850 for recurring cost. CONCLUSIONS: Combining virtual reality simulator with wet laboratory phacoemulsification training is effective for skills transfer in the operating theater. Despite of the high capital cost of virtual reality simulator, its relatively low recurring cost is more favorable toward cost-effectiveness.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

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.

The role of EZH2 in ocular diseases: a narrative review.

EZH2, acting as a catalytic subunit of PRC2 to catalyze lysine 27 in histone H3, induces the suppression of gene expression. EZH2 can regulate cell proliferation and differentiation of retinal progenitors, which are required for physiological retinal development. Meanwhile, an abnormal level of EZH2 has been observed in ocular tumors and other pathological tissues. This review summarizes the current knowledge on EZH2 in retinal development and ocular diseases, including inherited retinal diseases, ocular tumors, corneal injury, cataract, glaucoma, diabetic retinopathy and age-related retinal degeneration. We highlight the potential of targeting EZH2 as a precision therapeutic target in ocular diseases.

EZH2 is a protein that helps to regulate the activity of genes in cells. It works as a part of a complex called PRC2 to control a chemical group called lysine 27 in histone H3 and then inhibit the expression of genes. EZH2 is important for the normal development of the retina. Abnormal levels of EZH2 are associated with various eye diseases. This review summarizes the role of EZH2 in different ocular diseases and the potential mechanisms. Targeting EZH2 may be a novel way to treat or prevent ocular diseases.