Association of Retinal Nerve Fiber Layer Thinning With Elevated High Density Lipoprotein Cholesterol in UK Biobank.

Purpose: The purpose of this study was to investigate the association between retinal nerve fiber layer (RNFL) thickness and high-density lipoprotein cholesterol (HDL-C) in a healthy population. Methods: This cross-sectional study included 31,738 UK Biobank participants with high quality optical coherence tomography (OCT) images, excluding those with neurological or ocular diseases. The locally estimated scatterplot smoothing (LOESS) curve and multivariable piecewise linear regression models were applied to assess the association between HDL-C and RNFL thickness, and HDL-C subclasses were further analyzed using nuclear magnetic resonance (NMR) spectroscopy. Results: Multivariate piecewise linear regression revealed that high HDL-C levels (>1.7 mmol/L in women or > 1.5 mmol/L in men) were associated with thinner RNFL thickness (women: ß = -0.13, 95% confidence interval [CI] = -0.23 to -0.02, P = 0.017; male: ß = -0.23, 95% CI = -0.37 to -0.10, P = 0.001). Conversely, a significant positive association between HDL-C and RNFL thickness was observed when HDL-C was between 1.4 and 1.7 mmol/L for female participants (ß = 0.13, 95% CI = 0.02 to 0.24, P = 0.025). NMR analysis showed that these associations are potentially driven by distinct HDL-C subclasses. Conclusions: This study revealed an association between HDL-C levels and retinal markers of neurodegenerative diseases, suggesting that elevated HDL-C may serve as a new risk factor for neurodegenerative conditions. These findings may contribute to the implementation of preventive interventions and improved patient outcomes.

Depressive and anxiety symptoms in caregivers of children with congenital ectopia lentis: a prospective cross-sectional study.

OBJECTIVES: To evaluate the frequency and severity of depressive and anxiety symptoms and explore possible risk factors among caregivers of children with congenital ectopia lentis (CEL). DESIGN: A prospective cross-sectional study was conducted. PARTICIPANTS: 108 patients and 108 informal caregivers (mainly parents) were included. Participants were grouped based on whether patients had systemic abnormalities: group 1 were children without systemic abnormalities and group 2 were children with systemic abnormalities. OUTCOME MEASURES: The 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) were used to assess depressive and anxiety symptoms, respectively. RESULTS: More than half of caregivers (51.9%) have depressive or anxiety symptoms of some degree. 38.0% of caregivers suffered from both depressive and anxiety symptoms. 19.4% of caregivers had moderate to severe depressive symptoms (PHQ-9 score ≥10) while 16.7% reported moderate to severe anxiety symptoms (GAD-7 score ≥10). Between the two groups, the mean PHQ-9 and GAD-7 scores significantly differed (p=0.026 in PHQ-9; p=0.018 in GAD-7). The proportion of caregivers with moderate to severe symptoms was greater in group 2 than in group 1. In addition, there was a significant positive correlation between PHQ-9 and GAD-7 scores (r=0.827; p<0.001). Furthermore, best corrected visual acuity in the better eye of patients was positively correlated with both the PHQ-9 and GAD-7 scores (r=0.314, p<0.05 in PHQ-9; r=0.325, p<0.05 in GAD-7). CONCLUSIONS: Depressive and anxiety symptoms were common in caregivers of children with CEL, especially among those whose children had other systemic disease manifestations or low vision. This study illustrates the importance of depressive and anxiety symptom screening for these caregivers to implement effective psychological interventions and support strategies.

The burden, causes, and determinants of blindness and vision impairment in Asia: An analysis of the Global Burden of Disease Study.

Background: Asia accounts for more than half of the world's population and carries a substantial proportion of the global burden of blindness and vision impairment. Characterising this burden, as well as its causes and determinants, could help with devising targeted interventions for reducing the occurrence of blindness and visual impairment. Methods: Using the Global Burden of Disease Study 2019 database, we retrieved data on the number of disability-adjusted life years (DALYs); crude and age-standardised rates; and the prevalence (with 95% uncertainty intervals (95%UIs)) of blindness and vision loss due to six causes (age-related macular degeneration, cataracts, glaucoma, near-vision impairment, refractive error, and other vision loss) for Asian countries for the period between 1990 and 2019. We defined DALYs as the sum of the years lost due to disability and years of life lost, and calculated age-standardised figures for the number of DALYs and prevalence by adjusting for population size and age structure. We then evaluated the time trend of the disease burden and conducted subgroup analyses by gender, age, geographic locations, and socio-demographic index (SDI). Results: In 2019, the DALYs and prevalence of blindness and vision loss had risen by 90.1% and 116% compared with 1990, reaching 15.84 million DALYs (95% UI = 15.83, 15.85) and 506.71 million cases (95% UI = 506.68, 506.74). Meanwhile, the age-standardised rate of DALYs decreased from 1990 to 2019. Cataracts, refractive error, and near vision impairment were the three most common causes. South Asia had the heaviest regional disease burden (age-standardised rate of DALYs = 517 per 100 000 population; 95% UI = 512, 521). Moreover, the burden due to cataracts ranked high in most Asian populations. Being a woman; being older; and having a lower national SDI were factors associated with a greater vision loss burden. Conclusions: The burden due to vision loss remains high in Asian populations. Cataracts, refractive error, and near vision loss were the primary causes of blindness and vision loss. Greater investment in ocular disease prevention and care by countries with lower socioeconomic status is needed, as well as specific strategies targeting cataract management, women and the elderly.

Changes in corneal endothelial cells after scleral-fixated intraocular lens surgery in children with congenital ectopia lentis: 2-year follow-up.

PURPOSE: To investigate the changing patterns of corneal endothelial cells and the associated factors in children with congenital ectopia lentis (CEL) after scleral-fixated intraocular lens (SF IOL) surgery. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Retrospective study. METHODS: Patients were divided into the surgery group and the control group. Central endothelial cell density (ECD), coefficient of variation in cell size, the percentage of hexagonal cells (hexagonality), average cell size (AVG), and central corneal thickness were analyzed for both groups at baseline and each follow-up visit. Clinic characteristic, ocular parameters, IOL decentration, and IOL tilt of patients in the surgery group were collected. Multiple linear regression was performed to assess the potential associated factors for the postoperative changes in corneal endothelial cells in the surgery group. RESULTS: After 2-year follow-up, the decline of ECD was 17.8% (95% CI, -21.8 to -13.9) in the surgery group and -3.1% (95% CI, -5.2 to -1.0) in the control group ( P < .001), while the increase of AVG was 24.3% (17.1-31.6) in the surgery group and 2.7% (1.0 to 4.5) in the control group ( P < .001). Multivariate analysis showed that axial length (AL) ≥24 mm and white-to-white (WTW) <12.2 mm were significantly associated with greater loss of ECD (ß = -241.41, 95% CI, -457.91 to -24.91, P = .030 and ß = 251.63, 95% CI, 42.10-461.17, P = .020, respectively) and AL ≥24 mm was significantly positively associated with the increase of AVG (ß = 34.81, 95% CI, 0.90-68.71, P = .044). CONCLUSIONS: The SF IOL had a significant impact on corneal endothelium in children with CEL. More attention should be paid to monitor postoperative corneal endothelium change during long-term follow-up in CEL children, especially for those with longer AL and smaller WTW.

Autosomal Dominant Weill-Marchesani-Like Syndrome in a Chinese Family due to Novel Haplotypic Mutations in LTBP2.

INTRODUCTION: Weill-Marchesani syndrome (WMS) is a hereditary connective tissue disorder with substantial heterogeneity in clinical features and genetic etiology, so it is essential to define the full mutation spectrum for earlier diagnosis. In this study, we report Weill-Marchesani-like syndrome (WMS-like) change to autosomal dominance inheritance caused by novel haplotypic mutations in latent transforming growth factor beta-binding protein 2 (LTBP2). METHODS: Twenty-five members from a 4-generation Chinese family were recruited from Guangzhou, of whom nine were diagnosed with WMS-like disease, nine were healthy, and seven were of "uncertain" clinical status because of their young age. All members received detailed physical and ocular examinations. Whole-exome sequencing, Sanger sequencing, and real-time PCR were used to identify and verify the causative mutations in family members. RESULTS: Genetic sequencing revealed novel haplotypic mutations on the same LTBP2 chromosome associated with WMS-like, c. 2657C>A/p.T886K in exon 16 and deletion of exons 25-36. Real-time PCR and Sanger sequencing verified both mutations in patients with clinically diagnosed WMS-like, and in one "uncertain" child. In these patients, the haplotypic mutations led to ectopia lentis, short stature, and obesity. CONCLUSION: Our study revealed that WMS-like may be associated with haplotypic LTBP2 mutations with autosomal dominant inheritance.

Evaluation of systemic medications associated with diabetic retinopathy: a nested case-control study from the UK Biobank.

AIMS: This study aims to investigate the associations between commonly used systemic medications and diabetic retinopathy (DR). METHODS: Individuals with linked primary care prescription data from the UK Biobank were included. Cases were defined as individuals with a Hospital Episode Statistics-coded or primary care recorded diagnosis of DR or self-reported DR. Controls were matched for age, sex, glycosylated haemoglobin, duration of diabetes mellitus (DM), hypertension status and cardiovascular disease status. ORs and 95% CIs were calculated using conditional univariate and multivariable logistic regression models. RESULTS: A total of 3377 case subjects with DR were included in the study and matched with 3377 control subjects. In multivariable logistic regression, increased odds of incident DR were observed for exposure to short-acting insulins (OR 1.63; 95% CI 1.22 to 2.18), medium-acting insulins (OR 2.10; 95% CI 1.60 to 2.75), sulfonylureas (OR 1.30; 95% CI 1.16 to 1.46). Instead, the use of fibrates (OR 0.71; 95% CI 0.53 to 0.94) and Cox-2 inhibitors (OR 0.68; 95% CI 0.58 to 0.79) was associated with decreased odds of incident DR. Dose-response relationships were observed for all five drug categories (all p<0.05). CONCLUSIONS: This study comprehensively investigated the associations between systemic medication use and DR and found significant associations between the use of short-acting insulins, medium-acting insulins and sulfonylureas with increased odds of incident DR. In contrast, fibrates and Cox-2 inhibitors were associated with decreased odds of incident DR. These findings may provide valuable insights into DM medication management and serve as a reference for the prevention of DR in patients with DM.

Corneal biomechanics and their association with severity of lens dislocation in Marfan syndrome.

PURPOSE: To investigate corneal biomechanical properties and its associations with the severity of lens dislocation in patients with Marfan syndrome. METHODS: A total of 30 patients with Marfan syndrome and 30 age-, sex- and axial length (AL)-matched controls were recruited. Corneal biomechanical parameters of both groups were measured by CorVis ST and were compared between groups. Potential associations between corneal biomechanical parameters and severity of lens dislocation were also investigated. RESULTS: Lower applanation 1 velocity (A1V) (0.13 ± 0.004 vs. 0.15 ± 0.003, P = 0.016), shorter applanation 2 time (A2T)(22.64 ± 0.11 vs. 22.94 ± 0.11, P = 0.013), longer peak distance (PD) (5.03 ± 0.07 vs. 4.81 ± 0.05, P = 0.008), longer radius (R) of highest concavity (7.44 ± 0.16 vs. 6.93 ± 0.14, P = 0.012), greater Ambrosio relational thickness horizontal (ARTh) (603 ± 20 vs. 498 ± 12, P < 0.001), and integrated radius (IR) (8.32 ± 0.25 vs. 8.95 ± 0.21, P = 0.033) were detected among Marfan eyes compared with controls (all P < 0.05). Marfan individuals with more severe lens dislocation tended to have increased stiffness parameter as longer A1T, slower A1V, shorter A2T, slower application 2 velocity (A2V), smaller PD and smaller Distance Amplitude (DA) (P < 0.05). CONCLUSION: Marfan patients were detected to have increased corneal stiffness compared with normal subjects. Corneal biomechanical parameters were significantly associated with the severity of lens dislocation in Marfan patients.

Predicting Marfan Syndrome in Children With Congenital Ectopia Lentis: Development and Validation of a Nomogram.

Purpose: To derive an effective nomogram for predicting Marfan syndrome (MFS) in children with congenital ectopia lentis (CEL) using regularly collected data. Methods: Diagnostic standards (Ghent nosology) and genetic test were applied in all patients with CEL to determine the presence or absence of MFS. Three potential MFS predictors were tested and chosen to build a prediction model using logistic regression. The predictive performance of the nomogram was validated internally through time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis. Results: Eyes from 103 patients under 20 years old and with CEL were enrolled in this study. Z score of body mass index (odds ratio [OR] = 0.659; 95% confidence interval [CI], 0.453-0.958), corneal curvature radius (OR = 3.397; 95% CI, 1.829-6.307), and aortic root diameter (OR = 2.342; 95% CI, 1.403-3.911) were identified as predictors of MFS. The combination of the above predictors shows good predictive ability, as indicated by area under the curve of 0.889 (95% CI, 0.826-0.953). The calibration curves showed good agreement between the prediction of the nomogram and the actual observations. In addition, decision curve analysis showed that the nomogram was clinically useful and had better discriminatory power in identifying patients with MFS. For better individual prediction, an online MFS calculator was created. Conclusions: The nomogram provides accurate and individualized prediction of MFS in children with CEL who cannot be identified with the Ghent criteria, enabling clinicians to personalize treatment plans and improve MFS outcomes. Translational Relevance: The prediction model may help clinicians identify MFS in its early stages, which could reduce the likelihood of developing severe symptoms and improve MFS outcomes.

Longitudinal changes of refractive error in preschool children with congenital ectopia lentis.

BACKGROUND: Congenital ectopia lentis (CEL) is a hereditary eye disease which severely impacts preschool children's visual function and development. This study aimed to evaluate the longitudinal changes in spherical equivalent (SE) refractive error in preschool children with CEL. METHODS: A retrospective cohort study was conducted at Zhongshan Ophthalmic Center, Guangzhou, China. Medical records of CEL patients under 6-year-old who were diagnosed with Marfan syndrome at the initial visit from January 2014 to March 2022 were collected and were divided into surgery and non-surgery groups. Mean change rate of SE in the two groups was evaluated, and the potential associated factors of SE change rate were investigated by mixed-effect regression model. RESULTS: A total of 94 preschool patients from 14 provinces of China were included. Among the 42 children of the surgery group, the mean age with standard deviation (SD) was 5.02 ± 0.81 years and patients experienced a myopic shift of -0.05 ± 0.09 D/month in average. The mean age with SD of the 52 children of the non-surgery group was 4.34 ± 1.02 years, and the mean myopic shift was -0.09 ± 0.14 D/month. The mixed-effect regression model identified that higher degree of myopia at baseline was associated with slower myopic shift both in surgery (ß = 0.901, 95% CI: 0.822 ~ 0.980, P < 0.001) and in non-surgery group (ß = 1.006, 95% CI: 0.977 ~ 1.034, P < 0.001) in CEL patients. Surgical treatment (ß = 2.635, 95% CI: 1.376 ~ 3.894, P < 0.001) was associated with slower myopic shift in all participants CEL patients. CONCLUSIONS: Myopic progression was slower in the surgery group than in the non-surgery group of CEL. Preschool CEL patients who met the surgical indication are suggested being performed with timely surgery to slow down the myopic progression.

Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis.

AIM: To evaluate the effect of lens surgery on health-related quality of life (HRQoL) of preschool children with congenital ectopia lentis (CEL). METHODS: A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center. Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study. All of them completed the child and proxy (parental) PedsQL™ 4.0 before and after the surgery. Their preoperative scores were compared to their postoperative ones. Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children. RESULTS: Thirty-two children with CEL successfully underwent surgery without any complications, among whom 8 had monocular surgery and 24 had binocular surgery. Preoperative and postoperative questionnaires were completed by 32 child-parent pairs. Surgical intervention could significantly improve the vision of affected children (P<0.001). The medians of physical, psychosocial and total health scores self-reported by the children were 68.75 (62.50, 81.25), 65.00 (60.00, 80.00) and 67.39 (60.87, 78.26) preoperatively and were 93.75 (87.50, 100.00), 90.00 (83.33, 96.67) and 89.13 (85.32, 95.65) postoperatively. The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children (P<0.001). All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents (P<0.001). In the physical functioning evaluation, the preoperative score reported by parents of girls was higher than parents of boys (P=0.041), and the postoperative score of girls was higher than that of boys (P=0.036). CONCLUSION: CEL is associated with significantly worse quality of life in preschool children. Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

Predicting the risk of glaucoma-related adverse events following secondary intraocular lens implantation in paediatric eyes: a 3-year study.

AIMS: To establish and evaluate predictive models for glaucoma-related adverse events (GRAEs) following secondary intraocular lens (IOL) implantation in paediatric eyes. METHODS: 205 children (356 aphakic eyes) receiving secondary IOL implantation at Zhongshan Ophthalmic Center with a 3-year follow-up were enrolled. Cox proportional hazard model was used to identify predictors of GRAEs and developed nomograms. Model performance was evaluated with time-dependent receiver operating characteristic (ROC) curves, decision curve analysis, Kaplan-Meier curves and validated internally through C-statistics and calibration plot of the bootstrap samples. RESULTS: Older age at secondary IOL implantation (HR=1.5, 95% CI: 1.03 to 2.19), transient intraocular hypertension (HR=9.06, 95% CI: 2.97 to 27.67) and ciliary sulcus implantation (HR=14.55, 95% CI: 2.11 to 100.57) were identified as risk factors for GRAEs (all p<0.05). Two nomograms were established. At postoperatively 1, 2 and 3 years, model 1 achieved area under the ROC curves (AUCs) of 0.747 (95% CI: 0.776 to 0.935), 0.765 (95% CI: 0.804 to 0.936) and 0.748 (95% CI: 0.736 to 0.918), and the AUCs of model 2 were 0.881 (95% CI: 0.836 to 0.926), 0.895 (95% CI: 0.852 to 0.938) and 0.848 (95% CI: 0.752 to 0.945). Both models demonstrated fine clinical net benefit and performance in the interval validation. The Kaplan-Meier curves showing two distinct risk groups were well discriminated and robust in both models. An online risk calculator was constructed. CONCLUSION: Two nomograms could sensitively and accurately identify children at high risk of GRAEs after secondary IOL implantation to help early identification and timely intervention.

Clinical and Genetic Landscape of Ectopia Lentis Based on a Cohort of Patients From 156 Families.

Purpose: To extend the mutation spectrum and explore the characteristics of genotypes and ocular phenotypes in ectopia lentis (EL). Methods: Variants in all 14 reported EL-associated genes were selected from in-house data sets as well as literature review, and available clinical data were analyzed. Results: Likely pathogenic variants in three genes were identified in 156 unrelated families with EL from the in-house cohort, of which 97.4% resulted from variants in FBN1, whereas the remaining were caused by variants in ADAMTSL4 (1.3%) and LTBP2 (1.3%). A comparative analysis of the in-house data and literature review suggested several characteristics: (1) a higher proportion of cysteine involvement variants in FBN1, either variants introducing or eliminating cysteine, and an earlier diagnosis age were presented in our cohort than in published literature; (2) the axial length (AL) and refractive error increased more rapidly with age in preschool EL children than normal children, and the increased rate of AL was slower in patients with surgery than those without surgery; (3) aberrant astigmatism was common in EL; and (4) worse vision and earlier onset age were observed in patients with non-FBN1 variants (all P < 0.05). Conclusions: Variants in FBN1 are the predominant cause of EL, with the most common cysteine involvement variants. Early-stage EL manifests refractive error but gradually converts to axial myopia through defocus introduced by lens dislocation. Aberrant astigmatism is a suggestive sign of EL. Non-FBN1 variants cause early-onset and severe phenotypes. These results provide evidence for early diagnosis as well as timely treatment for EL.

Postoperative longitudinal refractive changes in children younger than 8 years with ectopia lentis and Marfan syndrome.

PURPOSE: To evaluate the postoperative longitudinal refractive changes in children younger than 8 years with ectopia lentis and Marfan syndrome (MFS). SETTING: Zhongshan ophthalmic center, Guangzhou, China. DESIGN: Retrospective cohort study. METHODS: Medical data of patients diagnosed with ectopia lentis and MFS that underwent surgery younger than 8 years were collected. Refractive errors and ocular biometric parameters were collected preoperatively and at each follow-up visit. Patients were stratified into groups according to age at surgery, and only the eye operated on first was selected. Multivariate analysis was performed to determine the association between refractive shift and potential risk factors. RESULTS: In total, 54 eyes of 54 patients were enrolled. The median age at surgery was 6.21 years (interquartile range [IQR], 5.25 to 6.85), and the median follow-up was 2.0 years (IQR, 1.2 to 2.8 years). At age 8 years, patients demonstrated a median myopic shift ranged from -1.75 diopters (D) (IQR, -2.75 to -1.00 D) for the 4-year-old group to -0.13 D (IQR, -0.50 to -0.06 D) for the 7-year-old group. Multivariate analysis showed that greater myopic shift was associated with younger age at surgery ( P = .004), male sex ( P = .026), and shorter preoperative axis length ( P = .005). CONCLUSIONS: A tendency toward increasing postoperative myopic was demonstrated in children with ectopia lentis and MFS, with the greatest myopic shift in the younger age groups. If the goal is to reach emmetropia by age 8 years, the immediate postoperative hypermetropic targets should be 1.75 D for age 4 years, 1 D for age 5 years, 0.5 D for age 6 years, and 0 to 0.25 D for age 7 years.

Network Meta-analysis of Intraocular Lens Power Calculation Formula Accuracy in 1016 Eyes With Long Axial Length.

PURPOSE: To systematically review the literature and quantitatively synthesize the currently available evidence to compare the accuracy of different intraocular lens calculation formulas in eyes with long axial length (AL). DESIGN: Network meta-analysis. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for studies published between January 2000 and June 2022. Included were prospective or retrospective clinical studies reporting the following outcomes in cataract patients with long AL (ie, ≥26 mm): percentage of eyes with a prediction error (PE) within ±0.25, ±0.50, and ±1.00 diopters (D). Network meta-analysis was conducted using R software (version 4.2.1). RESULTS: Ten prospective or retrospective clinical studies, including 1016 eyes and 11 calculation formulas, were identified. A traditional meta-analysis showed that for the percentage of eyes with PE within ±0.25 and ±0.50 D, the Olsen, Kane, and Emmetropia Verifying Optical (EVO) all had insignificantly higher percentages compared with others. Considering the percentage of eyes with PE within ±1.00 D, the original and modified Wang-Koch adjustment formulas for Holladay 1 (H1-WK and H1-MWK) and EVO formulas showed superiority, but the difference was insignificant. This network meta-analysis revealed that compared with the widely used Barrett Universal II (BUII) formula, the Olsen, Kane, and EVO formulas had higher percentages of eyes with PE within ±0.25, ±0.50, and ±1.00 D (all odds ratios >1 but P >.05). Based on the surface under the cumulative ranking area (SUCRA) values for the percentage of eyes with PE within ±0.25 D, the Olsen (96.4%), Kane (77.5%), and EVO (75.9%) formulas had the highest probability of being in the top 3 of the 11 formulas. CONCLUSIONS: The Olsen, Kane, and EVO formulas may perform better than others in calculating IOL power in eyes with long AL. Nevertheless, there is still considerable uncertainty in this regard and the accuracy of these formulas in highly myopic eyes should be confirmed in studies based on large multicenter registries.

Evaluation of functional vision and eye-related quality of life in children with congenital ectopia lentis: a prospective cross-sectional study.

OBJECTIVES: This study aims to evaluate the effect of congenital ectopia lentis (CEL) on functional vision and eye-related quality of life (ER-QOL) in children and their families using the Paediatric Eye Questionnaire (PedEyeQ). DESIGN: A questionnaire survey administered via in-person interviews of patients with CEL and their parents. PARTICIPANTS: 51 children with CEL and 53 visually normal controls accompanied by 1 parent completed the survey questionnaires for the study from March 2022 to September 2022. OUTCOME MEASURES: PedEyeQ domain scores. Functional vision and ER-QOL of children and their families were evaluated by calculating and comparing the Rasch domain scores of the PedEyeQ. RESULTS: PedEyeQ domain scores were significantly worse with CEL compared with controls (p<0.01 for each), with the exception of the Proxy Social domain among children aged 0-4 years (p=0.283). Child PedEyeQ greatest differences were in the functional vision domain (5-11 years, -20 points (95% CI -27 to -12)) and frustration/worry domain (12-17 years, -41 (95% CI -37 to -6)). Proxy PedEyeQ greatest differences were in the functional vision domain (0-4 years, -34 (95% CI -45 to -22)) and frustration/worry domain (5-11 years, -27 (95% CI -39 to -14); 12-17 years, -37(95% CI (-48 to -26))). Parent PedEyeQ greatest difference was in the 'worry about child's eye condition' (-57 (95% CI (-63 to -51))). CONCLUSIONS: In this study, children with CEL had reduced functional vision and ER-QOL compared with controls. Parents of children with CEL also experience reduced quality of life.

Standard ophthalmology residency training in China: an evaluation of resident satisfaction on training program in Guangdong Province.

BACKGROUND: National standardized training for resident doctors (STRD) in mainland China has been formally established since 2014 as a kind of postgraduate education. The purpose of this survey was to assess the satisfaction of the training residents in Guangdong Province on the ophthalmology STRD program after a duration of 5 years. METHOD: A 48-item survey was sent to all postgraduate ophthalmology residents from bases in Guangdong Province to inquire about their attitude towards the program. The survey contained questions about demographic and work-related information, job satisfaction, psychological resilience, and job performance. All responses were verified, and invalid questionnaires were excluded. Statistical analyses were performed using SPSS software version 22.0 (SPSS, Inc., Chicago, IL). Multiple logistic regression analysis was used to evaluate the factors (demographic information, working environment, clinical exposure, supervision and hands-on training opportunities, and involvement in academic activities) impacting the overall satisfaction. P < 0.05 was considered statistically significant. RESULTS: A total of 471/635 (74.17%) valid questionnaires were returned from all the STRD bases of Guangdong Province, which included 38 hospitals. 60.3% of the respondents reported overall satisfaction with their training. The satisfaction with operative teaching (60.7%) was slightly lower than the other settings of teaching experience (above 65%). Meanwhile, the satisfaction on different secessions of operative experience was all below 70%, of which in the areas of cornea and orbit were 55.42% and 57.53%, respectively. Some potential factors were found to affect general satisfaction, including the training grade, marriage, working time, income level, the doctor-patient relationship, family members working as doctors, the time proportion spent on writing medical documents during clinical work, and the frequency of attending academic meetings. Improvement was observed in both performing and reporting clinical examinations in the last year of training in comparison to the first year. Finally, 82.8% of the residents acknowledged this training was helpful for future clinical work. The first five career preferences for residents were cataract (67.1%), refractive surgery (42.3%), vitreo-retina (36.5%), optometry (28.7%), and oculoplastic (27.2%). CONCLUSION: Ophthalmology residents in Guangdong Province expressed comparable satisfaction with the STRD program. To further improve satisfaction, factors such as resident subsidy, harmonious marriage, the patient-doctor relationship, and chances of attending academic conferences should be emphasized.

Characteristics and genotype-phenotype correlations in ADAMTS17 mutation-related Weill-Marchesani syndrome.

Weill-Marchesani syndrome (WMS) manifests as ectopia lentis (EL), microspherophakia and short stature, which is caused by ADAMTS10, LTBP2, or ADAMTS17 gene defects. This study aims to investigate the characteristics and genotype-phenotype correlations of WMS with ADAMTS17 mutations. WMS patients with ADAMTS17 variants were identified by whole-exome sequencing from 185 patients with EL. All the included patients underwent comprehensive ocular and systemic examinations. ADAMTS17 variants were reviewed from included patients, published literature, and public databases. Bioinformatics analysis, co-segregation analysis, species sequence analysis, and protein silico modeling were used to verify the pathogenic mutations. A total of six novel ADAMTS17 mutations (c.1297C > T, c.2948C > T, c.1322+2T > C, c.1716C > G, c.1630G > A, and c.1669C > T) were identified in four WMS probands in our EL cohort (4/185, 2.16%). All probands and their biological parents presented with apparent short stature compared with the standard value. In particular, one child was detected with valvular heart disease, which has not previously been reported in patients with ADAMTS17 mutations. Conserved residues were greatly affected by the substitution of amino acids caused by these six mutations. Short stature could be considered a clue for EL patients with ADAMTS17 mutations, and much more attention needs to be paid to heart disorders among these patients. This study not only reported the characteristics of ADAMTS17 mutation-related WMS but also helped to recognize the genotype-phenotype correlations in these patients.

Ocular, cardiovascular, and genetic characteristics and their associations in children with Marfan syndrome and related fibrillinopathies.

PURPOSE: Congenital ectopia lentis (CEL) and heart abnormalities are common clinical symptoms in patients with Marfan syndrome (MFS) and related fibrillinopathies, which is caused by mutations in fibrillin-1 (FBN1) gene. This study aims to explore the ocular and cardiovascular characteristics and their association with genotype in children with MFS and related fibrillinopathies. METHODS: Seventy-nine children diagnosed with CEL and with FBN1 mutations confirmed via whole-exome sequencing were included for genotypes and phenotypes analysis. The axial length (AL), corneal curvature, and refractive status were included for ocular phenotypes analysis. The cardiovascular examination was performed by echocardiography, and aortic root Z score was calculated to evaluate the severity of aortic dilatation. The heart disorders were classified as aortic root dilatation, valvular disorders, and others. Both the ocular and cardiac manifestations were collected for comprehensive analysis and compared among patients with different genotypes, including the mutation involving cysteine substitution or mutation in different regions. RESULTS: In CEL children with FBN1 mutations, 77.2% patients could be diagnosed as MFS. It was observed that children with mutations in exons 22-42 had significant higher aortic root Z score (P = 0.003) and higher incidence of cardiovascular disorders (P = 0.004). Additionally, children with cysteine substitution mutations had significant higher aortic root Z score (P = 0.011), and the aortic root Z score was positively associated with axial length (AL) in children under 6 years old (P = 0.035). Those with long AL (≥ 26 mm) had significant higher incidence of valve disorders (P = 0.023). In addition, nearly half the children with CEL (46.8%) were diagnosed with cardiovascular disease for the first time. CONCLUSIONS: CEL children with FBN1 mutations involving cysteine substitution or mutations in exons 22-42 or with long AL had higher risks of severe cardiovascular complications. Knowing the phenotype may help in anticipating severe cardiovascular disease in CEL patients.

Visual prognosis and complications of congenital ectopia lentis: study protocol for a hospital-based cohort in Zhongshan Ophthalmic Center.

INTRODUCTION: Congenital ectopia lentis (CEL) is a rare ocular disease characterised by the dislocation or displacement of the lens. Patients with mild lens dislocations can be treated with conservative methods (eg, corrective eyeglasses or contact lenses). In contrast, patients with severe CEL usually require surgical management. However, few studies have focused on the visual prognosis and complications in conservative and surgical management of patients. This study aims to investigate the prognosis and complications in patients with CEL with conservative and surgical management, which is vital for CEL management, especially the choice of surgical timing and surgical method. METHODS AND ANALYSIS: A cohort study will be conducted at Zhongshan Ophthalmic Center. We plan to recruit 604 participants diagnosed with CEL and aged ≥3 years old. Patients with mild lens subluxation and stable visual conditions will be included in the non-surgical group and follow-up at 1, 2 and 3 years after enrolment. Patients with severe lens subluxation who accept CEL surgery will be included in the surgical group. Different surgical techniques, including phacoemulsification, in-the-bag intraocular lens implantation (with or without capsular tension ring) and trans-scleral fixation, will be used depending on the severity of dislocation. Patients will be followed up at 3 months, and 1, 2 and 3 years postoperatively. Over a 5-year follow-up period, patients will receive a detailed ocular examination, including optometry, biological measurement, specular microscopy, ultrasound biomicroscopy, anterior segment and posterior segment optical coherence tomography (OCT), OCT angiography, echocardiography and questionnaires on vision-related quality of life. The primary outcome is the change of best-corrected visual acuity and the incidence of complications in both groups. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethics committee of the Zhongshan Ophthalmic Center (number: 2022KYPJ207). Study findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05654025.

Comparison of Functional Vision and Eye-Related Quality of Life between Myopic Children Treated with Orthokeratology and Single-Vision Spectacles in Southern China.

Objective: To compare eye-related quality of life between Chinese children wearing orthokeratology (OK) contact lenses and single-vision spectacles (SVS) using the Pediatric Eye Questionnaire (PedEyeQ) and to evaluate the impact of different myopia correction methods on children and their parents. Methods: Children aged 12-17 years and their parents/legal guardians were recruited. The children's myopia ranged from -0.50 to -5.00 diopters (D), and their astigmatism was <1.50 D. They had all been wearing OK contact lenses or SVS for at least 12 months. The children completed the Child PedEyeQ. One of their parents (or a legal guardian) completed the Proxy PedEyeQ and the Parent PedEyeQ. Rasch-calibrated PedEyeQ scores were calculated for each domain and were converted to a scale from 0 to 100 for statistical analysis. Results: A total of 50 children wearing OK contact lenses, 43 children wearing SVS, and their parents/legal guardians completed the questionnaires. The scores of all Child, Proxy, and Parent PedEyeQ domains in the OK contact lens group were higher than those in the SVS group (all P < 0.05). In the mild and moderate myopia subgroups, the Child, Proxy, and Parent PedEyeQ scores in the mild myopia OK contact lens subgroup were higher than those in the mild myopia SVS group (all P < 0.05) except functional vision and bothered by eyes/vision domains for the proxy PedEyeQ. Similarly, the Child, Proxy, and Parent PedEyeQ scores in the moderate myopia OK contact lens subgroup were higher than those in the moderate myopia SVS subgroup (all P < 0.05) except impact on parent and family domain for the parent PedEyeQ. In the subgroup analysis of glasses type, no significant score difference of any Child, Proxy, and Parent PedEyeQ domain was detected between mild and moderate myopia in either the OK contact lens group or the SVS group (all P > 0.05). Conclusion: Compared with children wearing SVS, children wearing OK contact lenses have better functional vision and eye-related quality of life. Moreover, OK contact lens has a better correction effect, higher acceptance rates, and less impact on parents and families than SVS.