Improved accuracy of spectral-domain optical coherence tomography and optical coherence tomography angiography for monitoring myopic macular neovascularisation activity.

BACKGROUND/AIMS: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity. METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators. RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01). CONCLUSION: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.

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.

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.

Advances in myopia control strategies for children.

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.

Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-Analysis.

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.

Five-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 4 Report.

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.

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.

Displacement of Submacular Hemorrhage Using Subretinal Cocktail Injection versus Pneumatic Displacement: A Real-World Comparative Study.

INTRODUCTION: The objective of this study was to compare the outcome of submacular hemorrhage (SMH) displacement using pneumatic displacement with intravitreal expansile gas versus pars plana vitrectomy (PPV) with subretinal injection of tissue plasminogen activator (tPA), anti-vascular endothelial growth factor (VEGF) agent, and air as primary surgery. METHODS: Retrospective interventional case series of 63 patients who underwent surgical displacement of SMH secondary to neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) from May 1, 2015, to October 31, 2022. Medical records were reviewed for diagnosis, logMAR visual acuity (VA), central subfield thickness (CST), and postoperative displacement rates and complications up to 12 months after operation. RESULTS: The diagnosis was nAMD in 24 (38.1%) and PCV in 39 (61.9%) eyes. There were 40 (63.5%) eyes in the pneumatic displacement group (38 received C3F8, 2 received SF6) and 23 (36.5%) eyes in the subretinal cocktail injection. Mean baseline VA was 1.46 and 1.62, respectively (p = 0.404). The subretinal injection group had more extensive SMH (p = 0.005), thicker CST (1,006.6 µm vs. 780.2 µm, p = 0.012), and longer interval between symptom and operation (10.65 vs. 5.53 days, p < 0.001). The mean postoperative VA at 6 months was 0.67 and 0.91 (p = 0.180) for pneumatic displacement and subretinal injection groups, respectively, though VA was significantly better in the pneumatic group at 12-month visit (0.64 vs. 1.03, p = 0.040). At least 10 mean change in VA were >10 letters gain in both groups up to 12 months. Postoperative CST reduction was greater (625.1 µm vs. 326.5 µm, p = 0.008) and complete foveal displacement (87.0% vs. 37.5%), p < 0.001, odds ratio [OR] = 11.1) and displacement to arcade or beyond (52.5% vs. 17.5%, p = 0.009, OR = 5.15) were more frequent in the subretinal injection group. Two patients with failed pneumatic displacement were successfully treated with subretinal cocktail injection as a second operation. CONCLUSION: Surgical displacement of SMH leads to clinically meaningful improvement in VA. PPV with subretinal cocktail injection is more effective than pneumatic displacement in displacing SMH with similar safety profile despite longer interval before operation, higher CST, and more extensive SMH at baseline. Retinal surgeons could consider this novel technique in cases with thick and extensive SMH or as a rescue secondary operation in selected cases.

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.

Comparing Half-Dose Photodynamic Therapy with Subthreshold Micropulse Laser for the Treatment of Central Serous Chorioretinopathy.

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.

Cost-Effectiveness Analysis of Myopia Progression Interventions in Children.

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.

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.

Interocular Symmetry in Retinal Nerve Fiber Layer Thickness in Children: The Hong Kong Children Eye Study.

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.

Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes.

Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ([Formula: see text]). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; [Formula: see text]) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

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.

Secondhand smoke exposure and ocular health: A systematic review.

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.

Pathogenesis of myopic choroidal neovascularization: A systematic review and meta-analysis.

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.

Primary open-angle glaucoma risk prediction with ABCA1 and LOC102723944 variants and their genotype-phenotype correlations in southern Chinese population.

Glaucoma is a leading cause of irreversible visual impairment and blindness worldwide. Previous genome-wide association studies have identified caveolin-1 (CAV1), ATP-binding cassette A1 (ABCA1), and forkhead box C1 (FOXC1) loci associated with primary open angle glaucoma (POAG), a major subtype of glaucoma. This study aimed to fine map the association pattern of FOXC1 locus with POAG and determine the correlations of FOXC1, ABCA1, and CAV1 variants with ocular and lipidemic parameters in southern Chinese population. In total, 1291 unrelated Han Chinese subjects were recruited, including 301 high-tension glaucoma (HTG), 126 normal-tension glaucoma (NTG), and 864 control subjects. Twelve variants in FOXC1 locus, and two variants in ABCA1 and CAV1 genes, were genotyped by TaqMan assays. Genetic risk score and genotype-phenotype correlation analyses were conducted. In the FOXC1 locus, LOC102723944 rs6596830, rather than previously reported rs2745572, showed significant association with POAG (P = 8.61 × 10-4, odds ratio (OR) = 0.75) and HTG (P = 3.68 × 10-3, OR = 0.75). ABCA1 rs2487032 was also significantly associated with POAG (P = 3.00 × 10-5, OR = 0.70) and HTG (P = 2.08 × 10-4, OR = 0.70). Joint analysis showed that carriers of homozygous non-protective alleles of ABCA1 rs2487032 and LOC102723944 rs6596830 had 2.99-fold higher risk of POAG (P = 1.27 × 10-3) when compared to those carrying homozygous non-risk alleles. Patients with POAG carrying ABCA1 rs2487032 G allele had higher HDL cholesterol, and those with LOC102723944 rs6596830 A allele had lower LDL. This study revealed individual and joint association of ABCA1 and LOC102723944 variants with POAG in southern Chinese population. Subjects carrying non-protective alleles had increased risk to POAG, and corresponding genotypes would affect the lipid profiles.

Synthesis of Aryl Amides from Acyl-Bunte Salts and Aryl Azides.

In this study, we developed an efficient method for the synthesis of aryl amides from sodium thiosulfate pentahydrate, organic anhydrides, and aryl azides. Sodium thiosulfate may be used as the sulfur source, which reacts with anhydrides to generate acyl-Bunte salt; this salt reacts with aryl azides via the in situ generation of thiocarboxylate. Using our method, we successfully synthesized a key bioactive compound. The advantages of one-pot two-step reactions include operational simplicity, structurally diverse products with favorable yields, use of less toxic odorless reagents, and easy applicability to large-scale operations.