Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice.

Introduction: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD. Methods: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-ß-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed. Results: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions. Discussion: The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.

Axial Elongation Trajectories in Chinese Children and Adults With High Myopia.

Importance: Understanding the long-term axial elongation trajectory in high myopia is important to prevent blindness. Objective: To evaluate axial elongation trajectories and related visual outcomes in children and adults with high myopia. Design, Setting, and Participants: In this cohort study, participants in the Zhongshan Ophthalmic Centre-Brien Holden Vision Institute high myopia cohort were followed up every other year for 8 years. Participants with axial length measurements at baseline (2011 or 2012) and at least 1 follow-up visit were included. Participants were grouped according to baseline age as children and adolescents (7 to <18 years), young adults (18 to <40 years), and older adults (≥40 to 70 years). Data were analyzed from November 1, 2022, to June 1, 2023. Exposure: High myopia (spherical power ≤-6.00 diopters). Main Outcomes and Measures: Longitudinal axial elongation trajectories were identified by cluster analysis. Axial elongation rates were calculated by linear mixed-effects models. A 2-sided P < .05 was defined as statistically significant. Results: A total of 793 participants (median [range] age, 17.8 [6.8-69.7] years; 418 females [52.7%]) and 1586 eyes were included in the analyses. Mean axial elongation rates were 0.46 mm/y (95% CI, 0.44-0.48 mm/y) for children and adolescents, 0.07 mm/y (95% CI, 0.06-0.09 mm/y) for young adults, and 0.13 mm/y (95% CI, 0.07-0.19 mm/y) for older adults. Cluster analysis identified 3 axial elongation trajectories, with the stable, moderate, and rapid progression trajectories having mean axial elongation rates of 0.02 mm/y (95% CI, 0.01-0.02 mm/y), 0.12 mm/y (95% CI, 0.11-0.13 mm/y), and 0.38 mm/y (95% CI, 0.35-0.42 mm/y), respectively. At 8 years of follow-up, compared with the stable progression trajectory, the rapid progression trajectory was associated with a 6.92 times higher risk of developing pathological myopic macular degeneration (defined as diffuse or patchy chorioretinal atrophy or macular atrophy; odds ratio, 6.92 [95% CI, 1.07-44.60]; P = .04), and it was associated with a 0.032 logMAR decrease in best-corrected visual acuity (ß = 0.032 [95% CI, 0.001-0.063]; P = .04). Conclusions and Relevance: The findings of this 8-year follow-up study suggest that axial length in high myopia continues to increase from childhood to late adulthood following 3 distinct trajectories. At 8 years of follow-up, the rapid progression trajectory was associated with a higher risk of developing pathological myopic macular degeneration and poorer best-corrected visual acuity compared with the stable progression trajectory. These distinct axial elongation trajectories could prove valuable for early identification and intervention for high-risk individuals.

Translation of Color Fundus Photography into Fluorescein Angiography Using Deep Learning for Enhanced Diabetic Retinopathy Screening.

Purpose: To develop and validate a deep learning model that can transform color fundus (CF) photography into corresponding venous and late-phase fundus fluorescein angiography (FFA) images. Design: Cross-sectional study. Participants: We included 51 370 CF-venous FFA pairs and 14 644 CF-late FFA pairs from 4438 patients for model development. External testing involved 50 eyes with CF-FFA pairs and 2 public datasets for diabetic retinopathy (DR) classification, with 86 952 CF from EyePACs, and 1744 CF from MESSIDOR2. Methods: We trained a deep-learning model to transform CF into corresponding venous and late-phase FFA images. The translated FFA images' quality was evaluated quantitatively on the internal test set and subjectively on 100 eyes with CF-FFA paired images (50 from external), based on the realisticity of the global image, anatomical landmarks (macula, optic disc, and vessels), and lesions. Moreover, we validated the clinical utility of the translated FFA for classifying 5-class DR and diabetic macular edema (DME) in the EyePACs and MESSIDOR2 datasets. Main Outcome Measures: Image generation was quantitatively assessed by structural similarity measures (SSIM), and subjectively by 2 clinical experts on a 5-point scale (1 refers real FFA); intragrader agreement was assessed by kappa. The DR classification accuracy was assessed by area under the receiver operating characteristic curve. Results: The SSIM of the translated FFA images were > 0.6, and the subjective quality scores ranged from 1.37 to 2.60. Both experts reported similar quality scores with substantial agreement (all kappas > 0.8). Adding the generated FFA on top of CF improved DR classification in the EyePACs and MESSIDOR2 datasets, with the area under the receiver operating characteristic curve increased from 0.912 to 0.939 on the EyePACs dataset and from 0.952 to 0.972 on the MESSIDOR2 dataset. The DME area under the receiver operating characteristic curve also increased from 0.927 to 0.974 in the MESSIDOR2 dataset. Conclusions: Our CF-to-FFA framework produced realistic FFA images. Moreover, adding the translated FFA images on top of CF improved the accuracy of DR screening. These results suggest that CF-to-FFA translation could be used as a surrogate method when FFA examination is not feasible and as a simple add-on to improve DR screening. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

De Novo Mutations Contributes Approximately 7% of Pathogenicity in Inherited Eye Diseases.

Purpose: The purpose of this study was to describe genotype-phenotype associations and novel insights into genetic characteristics in a trio-based cohort of inherited eye diseases (IEDs). Methods: To determine the etiological role of de novo mutations (DNMs) and genetic profile in IEDs, we retrospectively reviewed a large cohort of proband-parent trios of Chinese origin. The patients underwent a detailed examination and was clinically diagnosed by an ophthalmologist. Panel-based targeted exome sequencing was performed on DNA extracted from blood samples, containing coding regions of 792 IED-causative genes and their flanking exons. All participants underwent genetic testing. Results: All proband-parent trios were divided into 22 subgroups, the overall diagnostic yield was 48.67% (605/1243), ranging from 4% to 94.44% for each of the subgroups. A total of 108 IED-causative genes were identified, with the top 24 genes explaining 67% of the 605 genetically solved trios. The genetic etiology of 6.76% (84/1243) of the trio was attributed to disease-causative DNMs, and the top 3 subgroups with the highest incidence of DNM were aniridia (n = 40%), Marfan syndrome/ectopia lentis (n = 38.78%), and retinoblastoma (n = 37.04%). The top 10 genes have a diagnostic yield of DNM greater than 3.5% in their subgroups, including PAX6 (40.00%), FBN1 (38.78%), RB1 (37.04%), CRX (10.34%), CHM (9.09%), WFS1 (8.00%), RP1L1 (5.88%), RS1 (5.26%), PCDH15 (4.00%), and ABCA4 (3.51%). Additionally, the incidence of DNM in offspring showed a trend of correlation with paternal age at reproduction, but not statistically significant with paternal (P = 0.154) and maternal (P = 0.959) age at reproduction. Conclusions: Trios-based genetic analysis has high accuracy and validity. Our study helps to quantify the burden of the full spectrum IED caused by each gene, offers novel potential for elucidating etiology, and plays a crucial role in genetic counseling and patient management.

Development and Validation of a Model to Predict Who Will Develop Myopia in the Following Year as a Criterion to Define Premyopia.

PURPOSE: To develop and validate models to predict who will develop myopia in the following year based on cycloplegic refraction or ocular biometry and to identify thresholds of premyopia. METHODS: Prospective longitudinal data of nonmyopic children at baseline from the Guangzhou Twins Eye Study and the Guangzhou Outdoor Activity Longitudinal Study were used as the training set, and the Singapore Cohort Study of the Risk factors for Myopia study formed the external validation set. Age, sex, cycloplegic refraction, ocular biometry, uncorrected visual acuity, and parental myopia were integrated into 3 logistic regression models to predict the onset of myopia in the following year. Premyopia cutoffs and an integer risk score system were derived based on the identified risk. RESULTS: In total, 2896 subjects with at least 2 visits were included. Cycloplegic refraction at baseline is a better predictor to identify the children with myopia onset [C-statistic=0.91, 95% confidence interval (CI), 0.87-0.94; C-statistic=0.92, 95% CI, 0.92-0.92 for internal and external validation, respectively], comparing to axial length, corneal curvature radius (CR) and anterior chamber depth (C-statistic=0.81, 95% CI, 0.73-0.88; C-statistic=0.80, 95% CI, 0.79-0.80, respectively), and axial length/CR (C-statistic=0.78, 95% CI, 0.71-0.85; C-statistic=0.76, 95% CI, 0.75-0.76). With a risk of >70%, the definitions of premyopia indicating approaching myopia onset were 0.00 D for 6-8 years and -0.25 D for ≥9 years in children with 2 myopic parents. CONCLUSIONS: Either cycloplegic refraction or ocular biometry can predict 1-year risk of myopia. Premyopia can be successfully defined through risk assessments based on children's age and predict who would require more aggressive myopia prophylaxis.

Interventions recommended for myopia prevention and control among children and adolescents in China: a systematic review.

In 2018, a consortium of government bodies in China led by the Ministry of Education released the Comprehensive Plan to Prevent Nearsightedness among Children and Teenagers (CPPNCT), aiming to reduce the incidence of myopia and control myopic progression in China. Recommendations span from home-based to school-based interventions, including time outdoors, physical activity, light exposure, near-work activity, screen time, Chinese eye exercises, diet and sleep. To date, the levels of evidence for this suite of interventions have not been thoroughly investigated. This review has summarised the evidence of the interventions recommended by the CPPNCT in myopia prevention and control. Thus, the following statements are supposed by the evidence: (1) Increasing time outdoors and reducing near-work time are effective in lowering incident myopia in school-aged children. (2) All interventions have a limited effect on myopia progression. Ongoing research may lead to a better understanding of the underlying mechanisms of myopia development, the interaction of different interventions and recommendations, confounding variables and their true effect on myopia prevention, and the identification of those most likely to respond to specific interventions. This field may also benefit from longer-term studies of the various interventions or strategies covered within this review article, to better understand the persistence of treatment effects over time and explore more novel approaches to myopia control.

A Systematic Review of Clinical Practice Guidelines for Age-related Macular Degeneration.

BACKGROUND: In response to the recommendations of the World Health Organization (WHO) World report on vision, the WHO is developing a Package of Eye Care Interventions (PECI) to support the integration of eye care into health systems within countries. This study was done to systematically review clinical practice guidelines (CPGs) related to age-related macular degeneration (AMD) to provide evidence-based recommendations. METHODS: All AMD-related CPGs published between 2010 and 2020 were reviewed and evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. RESULTS: Of 3778 CPGs identified, 48 underwent full-text screening and eight underwent quality appraisal. Five National Institute for Health and Care Excellence (NICE, UK) guidelines for AMD were finally selected for data extraction. Intravitreal anti-vascular endothelial growth factor (VEGF) treatment was strongly recommended for advanced, active neovascular AMD based on high-quality evidence. Photodynamic therapy and laser photocoagulation were not recommended as an adjunct to anti-VEGF therapy as first-line treatment for AMD. Recommendations on other interventions, including epiretinal brachytherapy, miniature lens system implantation, and limited macular translocation, were weak and evidence mostly came from low-quality case series studies. Hence these interventions were recommended to be used only with special arrangements or research. Existing evidence on treating geographic atrophy was limited, an implantable miniature telescope might be an effective intervention to improve vision but was still under investigation. DISCUSSION: Current CPGs recommend anti-VEGF therapy for patients with late active neovascular AMD, while other interventions should be used with caution and further researches are warranted.

Edible bird's nest, an Asian health food supplement, possesses anti-inflammatory responses in restoring the symptoms of atopic dermatitis: An analysis of signaling cascades.

Edible bird's nest (EBN) is a Chinese delicacy possessing skin rejuvenating functions. To verify skin anti-inflammatory function of EBN, water extract and enzymatic digest of EBN, as well as the major sialic acid, N-acetyl neuraminic acid (NANA), were probed in TNF-α-treated HaCaT keratinocytes. The mRNA expressions of pro-inflammatory cytokines, e.g., IL-1ß, IL-6, TNF-α, and an enzyme responsible for inflammatory response, i.e., Cox-2, as well as filaggrin and filaggrin-2, were markedly altered after treating with different preparations of EBN. The EBN-mediated responses could be accounted by its robust reduction of reactive oxygen species (ROS), NF-κB signaling and phosphorylation of p38 MAPK and JNK, as triggered by TNF-α-induced inflammation. The anti-inflammatory response of EBN was further supported in animal model. In 2,4-dinitrochlorobenzene (DNCB)-induced dermatitic mice, the effects on skin thickness, severity level of damage and scratching behavior, exerted by DNCB, were reversed after EBN treatments, in dose-dependent manners. In parallel, the levels of immune cells and pro-inflammatory cytokines in dermatitic skin were markedly reduced by treatment of EBN preparations. In general, NANA and enzymatic digest of EBN showed better anti-inflammatory responses in both models of in vitro and in vivo. These lines of evidence therefore suggest the possible application of EBN in treating atopic dermatitis.

Efficacy Comparison of Repeated Low-Level Red Light and Low-Dose Atropine for Myopia Control: A Randomized Controlled Trial.

Purpose: To compare the treatment efficacy between repeated low-level red light (RLRL) therapy and 0.01% atropine eye drops for myopia control. Methods: A single-masked, single-center, randomized controlled trial was conducted on children 7 to 15 years old with cycloplegic spherical equivalent refraction (SER) ≤ -1.00 diopter (D) and astigmatism ≤ 2.50 D. Participants were randomly assigned to the RLRL group or low-dose atropine (LDA, 0.01% atropine eye drops) group and were followed up at 1, 3, 6, and 12 months. RLRL treatment was provided by a desktop light therapy device that emits 650-nm red light. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in SER. Results: Among 62 eligible children equally randomized to each group (31 in the RLRL group, 31 in the LDA group), 60 children were qualified for analysis. The mean 1-year change in AL was 0.08 mm (95% confidence interval [CI], 0.03-0.14) in the RLRL group and 0.33 mm (95% CI, 0.27-0.38) in the LDA group, with a mean difference (MD) of -0.24 mm (95% CI, -0.32 to -0.17; P < 0.001). The 1-year change in SER was -0.03 D (95% CI, -0.01 to -0.08) in the RLRL group and -0.60 D (95% CI, -0.7 to -0.48) in the LDA group (MD = 0.57 D; 95% CI, 0.40-0.73; P < 0.001). The progression of AL < 0.1 mm was 53.2% and 9.7% (P < 0.001) in the RLRL and LDA groups, respectively. For AL ≥ 0.36 mm, progression was 9.7% and 50.0% (P < 0.001) in the RLRL and LDA groups, respectively. Conclusions: In this study, RLRL was more effective for controlling AL and myopia progression over 12 months of use compared with 0.01% atropine eye drops. Translational Relevance: RLRL therapy significantly slows axial elongation and myopia progression compared with 0.01% atropine; thus, it is an effective alternative treatment for myopia control in children.

Normal range of ocular biometry in healthy children: A systemic review and meta-analysis of 33,559 individuals under seven years of age.

PURPOSE: To conduct a systemic review and meta-analysis on the normative range of ocular biometry in healthy children under seven years of age. METHODS: A literature search was performed using the PubMed (MEDLINE) database. The main outcomes were normative values of axial length (AL), central corneal thickness (CCT), cornea curvature (CC), anterior chamber depth (ACD), lens thickness (LT) and vitreous chamber depth (VCD). Pooled estimates were obtained with a random-effects meta-analysis. Multivariate meta-regressions ascertained the moderator-related trends. RESULTS: We included 47 studies for a total of 33,559 subjects. The pooled ALs for 0.0-1.9 years, 2.0-3.9 years and 4.0-6.9 years were 18.33 mm (95% confidence interval [CI] 17.57-19.09), 21.71 mm (21.49-21.93) and 22.37 mm (22.29-22.45), respectively. Children aged 0.0-1.9 years had a greater CCT (576.70 µm, 567.20-586.21), steeper cornea (7.41 mm, 7.16-7.65) and shallower ACD (2.46 mm, 2.23-2.69). LT ranged from 3.65 to 3.74 mm for 0-6 years, and VCD increased from 11.94 mm at birth to 15.36 mm at 4.0-6.9 years. Differences in AL between East Asian and non-East Asian children were found below two years of age (17.30 mm vs. 18.40 mm, p = 0.008) and for CC at 4.0-6.9 years of age (7.82 mm vs. 7.79 mm, p = 0.004). In a multivariate meta-regression, AL, CC, ACD and VCD increased with age (p < 0.05 for all), while CCT decreased with age (p = 0.0007). CONCLUSIONS: This study reports normative data for ocular biometry in children. Few differences were found with ethnicity in the ocular biometry of infants and pre-schoolers.

Mutation spectrum in a cohort with familial exudative vitreoretinopathy.

PURPOSE: To expand the mutation spectrum of patients with familial exudative vitreoretinopathy (FEVR) disease. PARTICIPANTS: 74 probands (53 families and 21 sporadic probands) with familial exudative vitreoretinopathy (FEVR) disease and their available family members (n = 188) were recruited for sequencing. METHODS: Panel-based targeted screening was performed on all subjects. Before sanger sequencing, variants of LRP5, NDP, FZD4, TSPAN12, ZNF408, KIF11, RCBTB1, JAG1, and CTNNA1 genes were verified by a series of bioinformatics tools and genotype-phenotype co-segregation analysis. RESULTS: 40.54% (30/74) of the probands were sighted to possess at least one etiological mutation of the nine FEVR-causative genes. The etiological mutation detection rate was 37.74% (20/53) in family-attainable probands while 47.62% (10/21) in sporadic cases. The diagnosis rate of patients in the early-onset subgroup (≤5 years old, 45.4%) is higher than that of the children or adolescence-onset subgroup (6-16 years old, 42.1%) and the late-onset subgroup (≥17 years old, 39.4%). A total of 36 etiological mutations were identified in this study, comprising 26 novel mutations and 10 reported mutations. LRP5 was the most prevalent mutant gene among the 36 mutation types with a percentage of 41.67% (15/36). Followed by FZD4 (10/36, 27.78%), TSPAN12 (5/36, 13.89%), NDP (4/36, 11.11%), KIF11 (1/36, 2.78%), and RCBTB1 (1/36, 2.78%). Among these mutations, 63.89% (23/36) were missense mutations, 25.00% (9/36) were frameshift mutations, 5.56% (2/36) were splicing mutations, 5.56% (2/36) were nonsense mutations. Moreover, the clinical pathogenicity of these variants was defined according to American College of Medical Genetics (ACMG) and genomics guidelines: 41.67% (15/36) were likely pathogenic variants, 27.78% (10/36) pathogenic variants, 30.55% (11/36) variants of uncertain significance. No etiological mutations discovered in the ZNF408, JAG1, and CTNNA1 genes in this FEVR cohort. CONCLUSIONS: We systematically screened nine FEVR disease-associated genes in a cohort of 74 Chinese probands with FEVR disease. With a detection rate of 40.54%, 36 etiological mutations of six genes were authenticated in 30 probands, including 26 novel mutations and 10 reported mutations. The most prevalent mutated gene is LRP5, followed by FZD4, TSPAN12, NDP, KIF11, and RCBTB1. In total, a de novo mutation was confirmed. Our study significantly clarified the mutation spectrum of variants bounded up to FEVR disease.

Association of Myopia With Risk of Incident Metabolic Syndrome: Findings From the UK Biobank Study Cohort of 91,591 Participants.

Purpose: To investigate the association between myopia and risk of metabolic syndrome (MetS) in a prospective cohort from the UK Biobank Study. Methods: Volunteers (aged 40 years and above) free of baseline MetS and cataract included from the UK Biobank Study, a prospective follow-up cohort. Myopia was defined using uncycloplegic autorefraction, self-report-myopia, and medical records for refractive error at baseline. MetS as well as components of MetS were diagnosed based on health records, blood biochemistry, and questionnaires. Questionnaires determined the status of smoking, drinking, physical activity and dietary supplements, as well as ethnicity and education. Results: A total of 91,591 participants were available in the analysis, with a mean age of 55.37 ± 8.07 years at baseline and a median follow-up years of 11.16 years. The proportion of myopia was 49.7%, and a total of 937 (1.0%) participants were identified as having incident MetS (0.09/100 person years). Subjects with myopia were more likely to have MetS compared with non-myopic subjects (0.82 vs. 0.21%, Log-rank test P < 0.001). Mopes had greater risk of incident MetS (Hazard ratio [HR] = 4.19, 95% confidence interval [CI] 3.57-4.93, P < 0.001) adjusting for baseline age, gender, education and ethnicity. After further controlling for lifestyle factors (smoking, drinking, physical activity, and fish oil supplement) or baseline metabolic disorders, the risk of incident MetS were 3.88- and 4.06-fold greater in myopic subjects than those without myopia, respectively (P < 0.001 for both models). The severity of myopia was not significantly correlated to incident MetS in multivariate-adjusted models. Conclusions: An increased risk of incident MetS among the elderly is associated with myopia, but not the degree of myopia. These findings highlighted the need of prevention of MetS among older adults with myopia.

A systematic review of clinical practice guidelines for myopic macular degeneration.

Background: Myopic macular degeneration (MMD) is a primary cause of blindness and visual impairment in many parts of the world. A review of clinical practice guidelines (CPGs) for intervention selection are required with the increasing demand for MMD management in clinical practice as well as in national health services. Therefore, we aim to systematically review CPGs for MMD and assist the recommendations development of the Package of Eye Care Interventions (PECI) program of the World Health Organization. Methods: A systematic review of CPGs published on MMD between 2010 and April 2020 was conducted. Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Cochrane systematic reviews were also included when the evidence from included CPGs were inadequate or contradict. Results: After applying exclusion criteria and conducting the quality appraisal, two CPGs were finally included. The average of the AGREE II ratings for the identified Guidelines were 56 and 63 respectively (7 for each item). To provide further information on interventions for MMD, one Cochrane review on MMD was additionally identified and included in the study. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs were recommended for patients with myopic choroidal neovascularization (mCNV) as first-line therapy to improve vision and reduce central macular thickness, and ranibizumab showed significant effectiveness compared to photodynamic therapy (PDT). PDT was recommended to be performed in those resistant to the treatment by one CPG but lacked of adequate description and support. Data extracted from the Cochrane systematic reviews indicated that anti-VEGF therapy for mCNV had significant effectiveness in improving visual acuity and reducing CMT compared to PDT with moderate to low certainty of evidence. Ranibizumab and bevacizumab were considered as equally effective with moderate certainty. Conclusions: The outcomes of this review suggest that high quality clinical practice guidelines for MMD management are limited. Intravitreal injection of anti-VEGF agents was recommended as an effective intervention to treat myopic CNV as the first-line treatment, while there was inadequate guidance for the application of PDT in myopic CNV management. The use of other interventions for MMD were not recommended at this time and additional evidence is called for.

Myopia prediction: a systematic review.

Myopia is a leading cause of visual impairment and has raised significant international concern in recent decades with rapidly increasing prevalence and incidence worldwide. Accurate prediction of future myopia risk could help identify high-risk children for early targeted intervention to delay myopia onset or slow myopia progression. Researchers have built and assessed various myopia prediction models based on different datasets, including baseline refraction or biometric data, lifestyle data, genetic data, and data integration. Here, we summarize all related work published in the past 30 years and provide a comprehensive review of myopia prediction methods, datasets, and performance, which could serve as a useful reference and valuable guideline for future research.

Who needs myopia control?

Myopia has become a major visual disorder among school-aged children in East Asia due to its rising prevalence over the past few decades and will continue to be a leading health issue with an annual incidence as high as 20%-30%. Although various interventions have been proposed for myopia control, consensus in treatment strategies has yet to be fully developed. Atropine and orthokeratology stand out for their effectiveness in myopia progression control, but children with rapid progression of myopia require treatment with higher concentrations of atropine that are associated with increased rates of side effects, or with orthokeratology that carries risk of significant complication. Therefore, improved risk assessment for myopia onset and progression in children is critical in clinical decision-making. Besides traditional prediction models based on genetic effects and environmental exposures within populations, individualized prediction using machine learning and data based on age-specific refraction is promising. Although emerging treatments for myopia are promising and some have been incorporated into clinical practice, identifying populations who require and benefit from intervention remains the most important initial step for clinical practice.

Association of refraction and ocular biometry in highly myopic eyes.

Clinical relevance: Ocular biometry is key to understanding the determinants of ocular development and pathology changes, especially for the thriving myopic population in Asia. Investigating biometric data in highly myopic eyes within a wide age spectrum is therefore of high importance.Background: To report the magnitude of change in spherical equivalent for each unit of change in the ocular biometry parameters in a highly myopic population in China.Methods: Highly myopic patients aged 7 to 70 years were recruited from the Zhongshan Ophthalmic Center, China. Each patient had a cycloplegic refraction and a measurement of ocular biometry.Results: Data from 823 right eyes were available for analysis, with a mean age of 22.7 years and a median spherical equivalent of -8.88 D. Axial length and lens thickness increased with age, while anterior chamber depth (ACD) decreased in older subjects. There was a significant trend of increasing axial length, lens thickness, vitreous chamber depth (VCD) and decreasing ACD and calculated lens power over spherical equivalent quartiles (all p < 0.001). The univariate linear regression models showed that 1-D change in refraction equalled to a 0.33- to 0.34-mm increase of axial length, and a 0.32 to 0.33-mm increase of VCD in highly myopic eyes. Among the three components of axial length, lens thickness was associated with myopia shift in the groups of 7-18 years and 19-39 years (both p < 0.001), and VCD was significant in all groups (all p < 0.001), while ACD was not significant in any age group.Conclusion: The associations between refraction and axial length were consistent in children, young adults and the elderly with high myopia. Lens thickening with a higher degree of myopia appeared at a very early age, and vitreous chamber depth remained to be a prominent factor of refraction change in highly myopic eyes throughout seven to 70 years of age.

Clinical significance of focal adhesion kinase (FAK) in cervical cancer progression and metastasis.

Focal adhesion kinase is a non-receptor, tyrosine kinase of cells whose key functions are cell adhesion, migration, and invasion. Aberrant expression and regulation of FAK-mediated intracellular signaling pathways has been reported in several cancers and they are involved in cancer cell migration and apoptosis resistance. By RT-PCR, we found that cervical cancer cells showed a 4-fold increase of relative mRNA expression of FAK compared to control cells. In parallel, the FAK protein expression level was also elevated in cervical cancer cells. Interestingly, knockdown of FAK in cervical cancer cells showed attenuated cell proliferation and migration. Further, the FAK RNAi cells became more sensitive to chemotherapeutic drugs such as 5-FU and docetaxel and therefore the rate of cell survival is declined. The significant over-expression of FAK in cervical cancer cells might involve in cervical carcinogenesis and prolonged cell survival. This FAK overexpression might be a potential target for anti-cancer drugs to attenuate rapid cell proliferation and invasion by inducing apoptosis.

Association of Age at Myopia Onset With Risk of High Myopia in Adulthood in a 12-Year Follow-up of a Chinese Cohort.

Importance: Early-onset myopia is well known to progress to high myopia in adulthood. However, no accurate estimation of how a specific age at myopia onset is associated with the probability of developing high myopia in adulthood is available, and a very-long-term follow-up study with data from annual visits is needed. Objective: To estimate the risk of developing high myopia in adulthood associated with a specific age at myopia onset from a data set with a 12-year annual follow-up. Design, Setting, and Participants: This ongoing, population-based prospective cohort study of twins was conducted in Guangzhou, China, on July 11, 2006. Data from baseline to August 31, 2018, were analyzed. The first-born twins completed follow-up until 17 years or older, and the 443 participants (after exclusions) who developed myopia were included in the analysis. Data were analyzed from September 1, 2018, to January 20, 2020. Main Outcomes and Measures: Age at myopia onset was determined by prospective annual cycloplegic refractions (365 participants [82.4%]) or with a questionnaire. Refraction in adulthood was defined as the cycloplegic refraction measured at the last follow-up visit. Results: Among the 443 eligible participants (247 [55.8%] female; mean [SD] age at myopia onset, 11.7 [2.0] years), 54 (12.2%) developed high myopia (spherical equivalent, -6.00 diopters or worse determined by cycloplegic refractions) in adulthood. Among participants with age at myopia onset of 7 or 8 years, 14 of 26 (53.9%; 95% CI, 33.4%-73.4%) developed high myopia in adulthood; among those with onset at 9 years of age, 12 of 37 (32.4%; 95% CI, 18.0%-49.8%); among those with onset at 10 years of age, 14 of 72 (19.4%; 95% CI, 11.1%-30.5%); among those with onset at 11 years of age, 11 of 78 (14.1%; 95% CI, 7.3%-23.8%); and among those with onset at 12 years or older, 3 of 230 (1.3%; 95% CI, 0.2%-3.8%). Results of multivariate logistic regression analysis suggested that the risk of developing high myopia in adulthood decreased significantly with delay in the age at myopia onset (odds ratio, 0.44; 95% CI, 0.36-0.55; P < .001), from greater than 50% for 7 or 8 years of age to approximately 30% for 9 years of age and 20% for 10 years of age. Conclusions and Relevance: These findings suggest that the risk of high myopia is relatively high in children with myopia onset during the early school ages. Each year of delay in the age at onset substantially reduces the chance of developing high myopia in adulthood, highlighting the importance of identifying effective prevention strategies under investigation, such as increasing outdoor time.

Female Gender Remains a Significant Barrier to Access Cataract Surgery in South Asia: A Systematic Review and Meta-Analysis.

PURPOSE: To determine whether the female gender is a barrier for the access to cataract surgery services in South Asia in the last two decades. METHODS: Eligible cross-sectional studies were identified via computer searches and reviewing the reference lists of the obtained articles. The cataract surgical coverage (CSC) by sex based on person and eyes at visual acuity <3/60 and 6/18 is extracted. Pooled odds ratios (ORs) for males receiving cataract surgery in comparison with females were calculated by a random effect model. RESULTS: Sixteen studies with 135972 subjects were included in the final analysis. The pooled ORs of CSC by sex on a person basis at visual acuity <3/60 and at visual acuity <6/18 were 1.46 (95% CI: 1.23-1.75) and 1.14 (95% CI: 1.05-1.24), respectively. For CSC on a per-eye basis at visual acuity <3/60, the associations were statistically significant, with a pooled OR of 1.40 (95% CI: 1.16-1.70). The values of population attributable risk percentage at a per-person and per-eye basis at visual acuity <3/60 were 6.28% and 7.48%, respectively. Subgroup analyses by design and location types attained similar results as the primary analyses. There was no evidence of publication bias. CONCLUSIONS: The female gender remains a significant barrier for the access to cataract surgery in South Asia. Visual impairment, including blindness, from unoperated cataract, could be reduced by approximately 6.28% with the elimination of gender disparities to access. More efforts are needed to increase eye care service utilization by female population.