Vitamin D and Ocular Diseases: A Systematic Review.

The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a systematic review of recent findings on the association between vitamin D and different ocular diseases, including myopia, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), dry eye syndrome (DES), thyroid eye disease (TED), uveitis, retinoblastoma (RB), cataract, and others, from epidemiological, clinical and basic studies, and briefly discuss vitamin D metabolism in the eye. We searched two research databases for articles examining the association between vitamin D deficiency and different ocular diseases. One hundred and sixty-two studies were found. There is evidence on the association between vitamin D and myopia, AMD, DR, and DES. Overall, 17 out of 27 studies reported an association between vitamin D and AMD, while 48 out of 54 studies reported that vitamin D was associated with DR, and 25 out of 27 studies reported an association between vitamin D and DES. However, the available evidence for the association with other ocular diseases, such as glaucoma, TED, and RB, remains limited.

Epigallocatechin-3-gallate (EGCG) inhibits myofibroblast transformation of human Tenon's fibroblasts.

Myofibroblast transformation of human Tenon's fibroblasts severely challenges the outcome of glaucoma filtration surgery. epigallocatechin-3-gallate (EGCG) is considered as a potential reagent to overcome this issue for its anti-fibrosis effect on various human diseases, but it is unclear on the fibrosis of Tenon's fibroblasts. This study was conducted to investigate the effect of EGCG on TGF-ß1-induced myofibroblast transformation of human Tenon's fibroblasts. The human Tenon's fibroblasts were incubated in the medium containing 10 ng/mL TGF-ß1, and subsequently treated with EGCG or mitomycin C (MMC). The cell proliferation and migration were analyzed. The expression of alpha-smooth muscle actin (α-SMA), type I collagen (Col-I), and p-Smad2/3 were also evaluated. It showed that EGCG and MMC strongly inhibited the elevation in cell number in tissue explants compared to the tissues treated with TGF-ß1 alone. Scratch-Wound assay showed that 48 h after TGF-ß1 induction, only 10% of the wound width remained. But cells treated with EGCG still showed over 93% wound width. Further, EGCG effectively inhibited TGF-ß1-induced expression of α-SMA and Col-I as well as phosphorylation of Smad2/3 in Tenon's fibroblasts. Altogether, we concluded that EGCG suppressed the myofibroblast transformation in Tenon's fibroblasts through inactivating TGF-ß1/Smad signaling. These findings demonstrate that EGCG can be considered as one of the possible antifibrotic reagents for preventing postoperative scarring in glaucoma filtration surgery.

Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis.

PURPOSE: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease. METHODS: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study. RESULTS: Using exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice. CONCLUSION: This study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.

Mutations of RagA GTPase in mTORC1 Pathway Are Associated with Autosomal Dominant Cataracts.

Cataracts are a significant public health problem with no proven methods for prevention. Discovery of novel disease mechanisms to delineate new therapeutic targets is of importance in cataract prevention and therapy. Herein, we report that mutations in the RagA GTPase (RRAGA), a key regulator of the mechanistic rapamycin complex 1 (mTORC1), are associated with autosomal dominant cataracts. We performed whole exome sequencing in a family with autosomal dominant juvenile-onset cataracts, and identified a novel p.Leu60Arg mutation in RRAGA that co-segregated with the disease, after filtering against the dbSNP database, and at least 123,000 control chromosomes from public and in-house exome databases. In a follow-up direct screening of RRAGA in another 22 families and 142 unrelated patients with congenital or juvenile-onset cataracts, RRAGA was found to be mutated in two unrelated patients (p.Leu60Arg and c.-16G>A respectively). Functional studies in human lens epithelial cells revealed that the RRAGA mutations exerted deleterious effects on mTORC1 signaling, including increased relocation of RRAGA to the lysosomes, up-regulated mTORC1 phosphorylation, down-regulated autophagy, altered cell growth or compromised promoter activity. These data indicate that the RRAGA mutations, associated with autosomal dominant cataracts, play a role in the disease by acting through disruption of mTORC1 signaling.

Association of coding and UTR variants in the known regions with wet age-related macular degeneration in Han Chinese population.

Age-related macular degeneration (AMD) is the leading cause worldwide of severe visual impairment among people older than 55 years of age. This study aimed to investigate the genetic association between coding and untranslated region (UTR) variants in previously reported loci and exudative age-related macular degeneration (wet AMD) in a Han Chinese population. Using our previously published whole exome sequencing dataset of 349 wet AMD patients and 1253 controls, we searched for associations between coding and UTR variants of the 72 genes located within the 47 reported wet AMD loci regions. From these, 25 variants in 18 of the 72 genes with P < 10 × 10-3 were selected for the first replication of Sequenom mass-array genotyping in 885 wet AMD subjects and 562 controls. Next, four SNPs were selected for further validation by SNaPshot genotyping in a third Chinese cohort with 456 wet AMD subjects and 211 controls. As a result, we identified two new potential coding and UTR variant SNPs (rs189132250 in BBX located in 3q12.1 and rs144351944 in FILIP1L located in 3q12.1) that showed weak associations with wet AMD in the Han Chinese population. These findings provide new information regarding the coding and UTR variants of the known wet AMD loci in the studied Chinese cohort.

MicroRNA regulation of MDM2-p53 loop in pterygium.

PURPOSE: The pathogenesis of pterygium has been linked to limbal stem cell damage, abnormal apoptosis and cellular proliferation. In this study, we investigated the epigenetic regulation through microRNA expression in the pathogenesis of pterygium. METHODS: Human full-length primary pterygia were microdissected into head and body regions. Specific microRNA and mRNA expression was assayed by TaqMan® real-time quantitative polymerase chain reaction (qPCR). Tissue localization of target microRNAs was performed by LNA-based in situ hybridization. MicroRNA-145 (miR-145) mimics were transfected to primary culture of human pterygial cells, followed by analyses of cell cycle changes, apoptosis, p53 and MDM2 expression using flow cytometry and qPCR. RESULTS: The expression of miR-145 was markedly higher in primary human pterygium than in limbus and conjunctiva. Both miR-143 and miR-145 were predominantly expressed in the basal pterygial epithelium. Oncogene MDM2 expression was abundant in pterygial epithelium and stroma, while the expression pattern was opposite to that of miR-145. Ectopic expression of miR-145 in pterygial cells induced G1 arrest, down-regulated MDM2 and elevated p53 expression. CONCLUSIONS: Our study showed that miR-145 suppressed MDM2 expression, which subsequently influenced the p53-related cell growth pattern in pterygial epithelium. The regulatory miR-145/MDM2-p53 loop can serve as a potential target for treatment of pterygium.

Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing.

PURPOSE: Inherited retinal dystrophy (IRD) is a leading cause of blindness worldwide. Because of extreme genetic heterogeneity, the etiology and genotypic spectrum of IRD have not been clearly defined, and there is limited information on genotype-phenotype correlations. The purpose of this study was to elucidate the mutational spectrum and genotype-phenotype correlations of IRD. METHODS: We developed a targeted panel of 164 known retinal disease genes, 88 candidate genes, and 32 retina-abundant microRNAs, used for exome sequencing. A total of 179 Chinese families with IRD were recruited. RESULTS: In 99 unrelated patients, a total of 124 mutations in known retinal disease genes were identified, including 79 novel mutations (detection rate, 55.3%). Moreover, novel genotype-phenotype correlations were discovered, and phenotypic trends noted. Three cases are reported, including the identification of AHI1 as a novel candidate gene for nonsyndromic retinitis pigmentosa. CONCLUSION: This study revealed novel genotype-phenotype correlations, including a novel candidate gene, and identified 124 genetic defects within a cohort with IRD . The identification of novel genotype-phenotype correlations and the spectrum of mutations greatly enhance the current knowledge of IRD phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments of IRD patients.

The roles of genetic factors in uveitis and their clinical significance.

BACKGROUND: Uveitis is a diverse group of intraocular inflammatory disease and is a significant cause of visual loss worldwide. Recent studies have identified various endogenous immune mechanisms and genetic factors that are involved in the pathogenesis of uveitis. This review provides an overview on the role of genetics in the development and clinical course of uveitis. METHODS: PUBMED was used for literature search, and articles published from 1970 to 2012 that evaluated the genetic associations and mechanisms involved in the development and clinical features of uveitis were included. RESULTS: Studies have demonstrated associations between various genetic factors and the development and clinical course of intraocular inflammatory conditions. Genes involved included genes expressing interleukins, chemokines, chemokine receptors, and tumor necrosis factor and genes involved in complement system, oxidation, and other intracellular molecular pathways. CONCLUSION: Multiple genetic factors play important roles in the pathogenesis of uveitis and may influence the clinical course of uveitis. Further studies to investigate the genetic mechanisms of uveitis might identify additional genetic associations and might have the potential for identifying novel therapeutic targets in the treatment of intraocular inflammation.

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.

Bilateral retinal nerve fiber layer thickness reduction in a 9-year-old myopic boy suffering from unilateral optic neuritis: A case report.

BACKGROUND: In this paper, we present a 9-year-old boy who demonstrates a complex interplay between myopia progression, axial length (AL) extension, and retinal nerve fiber layer (RNFL) thickness loss in both eyes. Additionally, concurrent optic neuritis has directly impacted RNFL thickness in his right eye, and its potential indirect influence on RNFL and macular ganglion cell layer (mGCL) thickness in his left eye is also noteworthy. CASE SUMMARY: A 9-year-old boy with bilateral myopia presented with diminished vision and pain in his right eye due to optic neuritis, while his left eye showed pseudopapilledema. Steroid therapy improved his vision in the right eye, and 16-mo follow-up revealed recovery without recurrence despite myopia progression. Follow-up optical coherence tomography conducted 16 mo later revealed a notable thinning of the RNFL in both eyes, especially along with a reduction in mGCL thickness in the left eye. This intricate interaction between optic neuritis, myopia, and retinal changes underscores the need for comprehensive management, highlighting potential long-term visual implications in young patients. CONCLUSION: The progression of myopia and AL extension led to the loss of RNFL thickness in both eyes in a 9-year-old boy. Concurrently, optic neuritis directly affected RNFL thickness in his right eye and may indirectly play a role in the thickness of RNFL and mGCL in his left eye.

Prevalence of myopia and uncorrected myopia among 721 032 schoolchildren in a city-wide vision screening in southern China: the Shantou Myopia Study.

AIMS: To explore the prevalence and risk factors for myopia and uncorrected myopia in schoolchildren in southern China. METHODS: The government-led Shantou Myopia Study was conducted from September 2020 to June 2021. Non-cycloplegic refraction was performed. Uncorrected visual acuity (UCVA) was measured along with presenting visual acuity if participants wore spectacles. Spherical equivalent refraction (SER) is defined as the spherical dioptres added to half of the cylindrical dioptres. Myopia is defined as SER <-0.50 dioptre with UCVA of <20/20 in at least one eye. RESULTS: This study enrolled 724 828 schoolchildren (77.8% of all schoolchildren in Shantou) from 901 schools. Data from 721 032 schoolchildren (99.5%) were analysed (mean age 11.53±3.13 years, 6-20 years, 373 230 boys and 347 802 girls). Among them, 373 459 (51.8%) had myopia: 37.1% of 465 696 children in primary schools, 75.4% of 170 164 children in junior high schools and 84.8% of 85 172 children in senior high schools. The prevalence of myopia increases non-linearly with age. Older age, female and urban living environment were independently associated with myopia prevalence and myopic SER. Among the 373 459 children with myopia, 60.0% had no refractive correction: 74.9%, 53.9% and 35.5% in primary, junior high and senior high schools, respectively. CONCLUSION: The overall prevalence of myopia among schoolchildren in Shantou was 51.8%, higher than the national average in China. The proportion of uncorrected myopia is high, especially in primary schools. Our results indicate the need for public education on eye care among schoolchildren even in a municipal city.

Treatment outcomes and their determinants of IgG4-related ophthalmic disease: a territory-wide cohort study.

BACKGROUND: Oral corticosteroid remains the first-line treatment of IgG4-related ophthalmic disease, but steroid-dependence is common and serious. Factors associated with steroid dependence and relapse have to be further explored. STUDY POPULATION: A city-wide, biopsy-proven, Chinese cohort. METHODS: Retrospective, masked review of medical records, orbital images and histopathology reports. RESULTS: There were 101 patients with at least 24-month follow-up. Up to 82% (82/101) received oral corticosteroid as first-line treatments, and 7 of them received also concomitant steroid-sparing agents (SSA)/biological agents as primary treatment. There was 61% (50/82) of patients required long-term corticosteroid (alone=23, with SSA=27) after 1.9±0.7 (range 1-5) relapses. When compared with the 21% (17/82) of patients who tapered corticosteroid successfully for 24 months, steroid dependence was associated with elevated baseline serum IgG4 level (94% vs 65%, p<0.01) and Mikulicz syndrome (46% vs 18%, p<0.05). Up to 13% (11/82) of patients tolerated residual disease after tapering off corticosteroid. There was 17% (17/101) of patients did not require any medications after biopsies. They were more likely to have debulking surgeries (71% vs 40%, p<0.05), discrete orbital lesions (65% vs 26%, p<0.05), normal baseline serum IgG4 level (24% vs 6%, p<0.05) and no Mikulicz syndrome (94% vs 61%, p<0.05). CONCLUSION: In this cohort, 60% of patients required long-term maintenance oral corticosteroid. Elevated pretreatment serum IgG4 level and Mikulicz syndrome were associated with steroid dependence. Debulking surgery is an alternative for a subgroup of patients with discrete orbital lesions, normal baseline IgG4 level and no Mikulicz syndrome.

Complement factor H and interleukin gene polymorphisms in patients with non-infectious intermediate and posterior uveitis.

OBJECTIVE: To investigate the associations of complement factor H (CFH), KIAA1109, and interleukin-27 (IL-27) gene polymorphisms in patients with non-infectious intermediate and posterior uveitis. METHODS: The study cohort consisted of a total of 95 Chinese non-infectious uveitis patients, including 38 patients with intermediate uveitis (IU), 38 patients with Vogt-Koyanagi-Harada disease (VKH), and 19 patients with Behçet's disease and 308 healthy controls. The genotypes of CFH-rs800292, KIAA1109-rs4505848, and IL27-rs4788084 were determined using TaqMan single nucleotide polymorphism genotyping assays. RESULTS: The frequency of carriers of G allele for CFH-rs800292 was significantly higher in patients with non-infectious intermediate and posterior uveitis than in controls (GG/AG versus AA; p=0.02). No significant association was found between uveitis and both KIAA1109-rs4505848 and IL27-rs4788084. In stratified analysis by gender, the frequency of carriers with G allele for KIAA1109-rs4505848 was significantly higher in male uveitis patients than in male controls (GG/AG versus AA; p=0.034). There was no significant difference in allelic and genotypic frequencies for CFH-rs800292 and IL27-rs4788084 in either male or female groups. In addition, higher frequency of KIAA1109-rs4505848 G allele was found in Behçet's disease patients compared with controls and IU patients (p=0.01 and p=0.003, respectively). CONCLUSIONS: Our results demonstrated that CFH-rs800292 and KIAA1109-rs4505848 are associated with non-infectious intermediate and posterior uveitis. Moreover, gender susceptibility for uveitis might be involved in the KIAA1109 gene and the KIAA1109-rs4505848 polymorphism might be associated with the development of Behçet's disease.

Longitudinal change of peripapillary vessel density and retinal nerve fibre layer thickness in normal tension and primary angle closure glaucoma.

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.

Myopia Genetics and Heredity.

Myopia is the most common eye condition leading to visual impairment and is greatly influenced by genetics. Over the last two decades, more than 400 associated gene loci have been mapped for myopia and refractive errors via family linkage analyses, candidate gene studies, genome-wide association studies (GWAS), and next-generation sequencing (NGS). Lifestyle factors, such as excessive near work and short outdoor time, are the primary external factors affecting myopia onset and progression. Notably, besides becoming a global health issue, myopia is more prevalent and severe among East Asians than among Caucasians, especially individuals of Chinese, Japanese, and Korean ancestry. Myopia, especially high myopia, can be serious in consequences. The etiology of high myopia is complex. Prediction for progression of myopia to high myopia can help with prevention and early interventions. Prediction models are thus warranted for risk stratification. There have been vigorous investigations on molecular genetics and lifestyle factors to establish polygenic risk estimations for myopia. However, genes causing myopia have to be identified in order to shed light on pathogenesis and pathway mechanisms. This report aims to examine current evidence regarding (1) the genetic architecture of myopia; (2) currently associated myopia loci identified from the OMIM database, genetic association studies, and NGS studies; (3) gene-environment interactions; and (4) the prediction of myopia via polygenic risk scores (PRSs). The report also discusses various perspectives on myopia genetics and heredity.

Thicker Retinal Nerve Fiber Layer with Age among Schoolchildren: The Hong Kong Children Eye Study.

This study aims to investigate the effect of age on the peripapillary retinal nerve fiber layer (p-RNFL) thickness among schoolchildren. A total of 4034 children aged 6-8 years old received comprehensive ophthalmological examinations. p-RNFL thickness was measured from a circular scan (⌀ = 3.4 mm) captured using spectral-domain optical coherence tomography (SD-OCT). Associations between p-RNFL thickness with ocular and systemic factors were determined by multivariate linear regression after adjusting potential confounders using generalized estimating equations (GEE). The mean global p-RNFL thickness was 106.60 ± 9.41 µm (range: 72 to 171 µm) in the right eyes, 105.99 ± 9.30 µm (range: 76 to 163 µm) in the left eyes, and 106.29 ± 9.36 µm (range: 72 to 171 µm) across both eyes. Age was positively correlated with p-RNFL after adjusting for axial length (AL) and confounding factors (ß = 0.509; p = 0.001). Upon multivariable analysis, AL was positively associated with temporal p-RNFL thickness (ß = 3.186, p < 0.001) but negatively with non-temporal p-RNFL thickness (ß = (10.003, -2.294), p < 0.001). Sectoral p-RNFL was the thickest in the inferior temporal region (155.12 ± 19.42 µm, range 68 to 271 µm), followed by the superior temporal region (154.67 ± 19.99 µm, range 32 to 177 µm). To conclude, p-RNFL increased significantly with older age among children 6 to 8 years old in a converse trend compared to adults. Our results provide a reference for interpreting OCT information in children and suggest that stable p-RNFL thickness may not indicate a stable disease status in pediatric patients due to the age effects.

Near work, screen time, outdoor time and myopia in schoolchildren in the Sunflower Myopia AEEC Consortium.

PURPOSE: To examine the association between near work, screen time including TV and outdoor time with myopia in children from the Sunflower Myopia Asian Eye Epidemiology Consortium (AEEC). METHODS: We analysed AEEC cross-sectional data (12 241 children) on risk factors (near work, screen time including TV and outdoor time) and myopia of six population-based studies (China, Hong Kong and Singapore). Cycloplegic refraction and axial length (AL) measurements were included. Risk factors were determined using questionnaires. Data were pooled from each study, and multivariable regression analysis was performed to evaluate the associations between risks factors and myopia, spherical equivalent (SE) and AL. RESULTS: Among the included children, 52.1% were boys, 98.1% were Chinese and 69.7% lived in urban areas. Mean±standard deviation (SD) for age was 8.8 ± 2.9 years, for SE was -0.14 ± 1.8 D and for AL was 23.3 ± 1.1 mm. Myopia prevalence was 30.6%. In multivariate analysis, more reading and writing (OR = 1.17; 95% CI, 1.11-1.24), more total near work (OR = 1.05; 95% CI, 1.02-1.09) and less outdoor time (OR = 0.82, 95% CI, 0.75-0.88) were associated with myopia (p's < 0.05). These factors were similarly associated with SE and AL (p's < 0.05), except for total near work and AL (p = 0.15). Screen time including TV was not significantly associated with myopia (p = 0.49), SE (p = 0.49) or AL (p = 0.83). CONCLUSION: In this study, increased reading and writing and decreased outdoor time were associated with myopia. Screen time may be a surrogate factor of near work or outdoor time, but further research is needed to assess its role as an independent risk factor for myopia.

Myopia incidence and lifestyle changes among school children during the COVID-19 pandemic: a population-based prospective study.

BACKGROUND: The impacts of social restrictions for COVID-19 on children's vision and lifestyle remain unknown. AIMS: To investigate myopia incidence, spherical equivalent refraction (SER) and lifestyle changes among schoolchildren during the COVID-19 pandemic. METHODS: Two separate longitudinal cohorts of children aged 6-8 years in Hong Kong were included. The COVID-19 cohort was recruited at the beginning of the COVID-19 outbreak, whereas the pre-COVID-19 cohort was recruited before the COVID-19 pandemic. All children received ocular examinations, and answered a standardised questionnaire relating to their lifestyle, including time spent on outdoor activities and near work, both at baseline and at follow-up visits. RESULTS: A total of 1793 subjects were recruited, of whom 709 children comprised the COVID-19 cohort with 7.89±2.30 months of follow-up, and 1084 children comprised the pre-COVID-19 cohort with 37.54±3.12 months of follow-up. The overall incidence was 19.44% in the COVID-19 cohort, and 36.57% in pre-COVID-19 cohort. During the COVID-19 pandemic, the change in SER and axial length was -0.50±0.51 D and 0.29±0.35 mm, respectively; the time spent on outdoor activities decreased from 1.27±1.12 to 0.41±0.90 hours/day (p<0.001), while screen time increased from 2.45±2.32 to 6.89±4.42 hours/day (p<0.001). CONCLUSIONS: We showed a potential increase in myopia incidence, significant decrease in outdoor time and increase in screen time among schoolchildren in Hong Kong during the COVID-19 pandemic. Our results serve to warn eye care professionals, and also policy makers, educators and parents, that collective efforts are needed to prevent childhood myopia-a potential public health crisis as a result of COVID-19.

CFH 184G as a genetic risk marker for anterior uveitis in Chinese females.

OBJECTIVE: To investigate the association of three single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), KIAA1109, and interleukin-27 (IL-27) genes in patients with anterior uveitis (AU). METHODS: A case-control study was performed in 98 Chinese AU patients and 308 healthy controls. Three SNPs including CFH-rs800292, KIAA1109-rs4505848, and IL27-rs4788084 were detected using TaqMan SNP Genotyping Assays. Analyses were also stratified according to gender, clinical features and human leukocyte antigen (HLA)-B27 status of the patients. RESULTS: No significant association was found between all three SNPs and AU. However, when stratified by gender, there were significant increases in the frequency of the CFH-rs800292 184G allele and GG homozygosity in female patients compared with control subjects (p=0.003 and p=0.009, respectively). Similar association was not detected in males. No significant association was found between AU and KIAA1109-rs4505848 or IL27-rs4788084 even stratified by gender. There was no significant difference in genotypes of AU patients stratified by various clinical features. Subgroup analyses showed that all three SNPs (rs800292, rs4505848, and rs4788084) were not associated with AU in HLA-B27-positive patients, neither in HLA-B27-negative patients. CONCLUSIONS: Our results showed an association between AU and CFH polymorphism in Chinese female patients but not in males, indicating gender-specific genetic differences in CFH. Gender should be considered in genetic studies of anterior uveitis even extending to other immunologic diseases.

In vitro compatibility study of cephalosporin with intraocular irrigating solutions and intracameral medications.

BACKGROUND: To study the compatibility of cephalosporins with intraocular irrigating solutions and intracameral medications commonly used in cataract surgery. DESIGN: The was an in vitro experiment conducted in the Research Laboratory of the Department of Microbiology, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. SAMPLES: Three cephalosporins--cefazolin, cefuroxime and ceftazidime--were separately diluted and mixed with irrigating solutions and intracameral medications to form 192 samples and 12 control solutions. METHODS: The cephalosporins were dissolved in normal saline and further diluted to the concentration of 1 mg in 0.1 mL with normal saline, Ringer's solution, balanced salt solution and fortified balanced salt solutions. These were mixed with balanced salt solutions or fortified balanced salt solutions, with adrenaline, acetylcholine or carbachol and kept at 37°C for 2 h. The concentrations of free cephalosporins were measured with rapid high-performance liquid chromatography at baseline (0 h) and at 2 h. MAIN OUTCOME MEASURES: Free concentrations of cephalosporins at 2 h were compared with mean baseline (0 h) value. A difference of 3 standard deviations or more was considered statistically significant. RESULTS: At 2 h there was a significant drop in the cefuroxime concentration in preparations in which cefuroxime was diluted with normal saline (P < 0.01). In all preparations, the final concentrations of cephalosporins were higher than the minimal inhibitory concentrations (MIC(90)) for microbials commonly isolated from the external eye. CONCLUSION: Cefazolin, cefuroxime and ceftazidime were compatible with irrigating solutions and intracameral medications commonly used in cataract surgery.