Abstract:AIM: To investigate the role of transmembrane protein 206 (TMEM206) in corneal edema in mice by knockout the TMEM206 gene using CRISPR/Cas9 editing technology. METHODS: TMEM206-knockout mice were generated using the CRISPR-Cas9 system. Variations in ophthalmic pathology were observed using slit lamp microscope and optical coherence tomography (OCT), intraocular pressure (IOP) was measured using a TonoLab Rebound Tonometer, and the ultrastructure of the corneal was observed using a transmission electron microscope. RESULTS: Corneal opacity was observed in 4/18 homozygous TMEM206-/- mice whereas a similar change was not observed in heterozygous TMEM206+/- mice and wild-type littermates. OCT examination showed that the mean central cornea thickness was 125±5.4 µm in 4 homozygous TMEM206-/- mice developed corneal edema and 115±1.2 µm in wild-type mice (t=3.468, P<0.05) at 43wk. The mean IOP was 12.08±0.07 mm Hg in four right eyes with corneal edema and 12.03±0.03 mm Hg in three normal left eyes (P>0.05). Transmission electron microscopy revealed a disruption in the organization of the collagen fibrils in the central part of the cornea in homozygous TMEM206-/- mice. CONCLUSION: TMEM206 is associated with corneal edema which caused organizational disruption of collagen fibrils in corneas of mice.

Abstract:AIM: To characterize the N6-methyladenosine (m6A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC). METHODS: Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs. RESULTS: Large amount of m6A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair. CONCLUSION: Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Abstract:AIM: To understand the molecular connectivity between the intraocular pressure (IOP) and glaucoma which will provide possible clues for biomarker candidates. METHODS: The current study uncovers the important genes connecting IOP with the core functional modules of glaucoma. An integrated analysis was performed using glaucoma and IOP microarray datasets to screen for differentially expressed genes (DEGs) in both conditions. To the selected DEGs, the protein interaction network was constructed and dissected to determine the core functional clusters of glaucoma. For the clusters, the connectivity of IOP DEGs was determined. Further, enrichment analyses were performed to assess the functional annotation and potential pathways of the crucial clusters. RESULTS: The gene expression analysis of glaucoma and IOP with normal control showed that 408 DEGs (277 glaucoma and 131 IOP genes) were discovered from two GEO datasets. The 290 DEGs of glaucoma were extended to form a network containing 1495 proteins with 9462 edges. Using ClusterONE, the network was dissected to have 12 clusters. Among them, three clusters were linked with three IOP DEGs [N-Myc and STAT Interactor (NMI), POLR3G (RNA Polymerase III Subunit G), and APAF1-interacting protein (APIP)]. In the clusters, ontology analysis revealed that RNA processing and transport, p53 class mediators resulting in cell cycle arrest, cellular response to cytokine stimulus, regulation of phosphorylation, regulation of type I interferon production, DNA deamination, and cellular response to hypoxia were significantly enriched to be implicated in the development of glaucoma. Finally, NMI, POLR3G, and APIP may have roles that were noticed altered in glaucoma and IOP conditions. CONCLUSION: Our findings could help to discover new potential biomarkers, elucidate the underlying pathophysiology, and identify new therapeutic targets for glaucoma.

Abstract:AIM: To investigate the proliferation regulatory effect of cone-rod homeobox (CRX) in retinal pigment epithelium (RPE) and retinoblastoma (RB) cells to explore the potential application and side effect (oncogenic potential) of CRX-based gene therapy in RPE-based retinopathies. METHODS: Adult human retinal pigment epithelial (ARPE)-19 and human retinal pigment epithelial (RPE)-1 cells and Y79 RB cell were used in the study. Genetic manipulation was performed by lentivirus-based technology. The cell proliferation was determined by a CellTiter-Glo Reagent. The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction (qPCR) and Western blot assay. The transcriptional activity of the promoter was determined by luciferase reporter gene assay. The bindings between CRX and transcription factor 7 (TCF7) promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation (ChIP) assay. The transcription of the TCF7 was determined by a modified nuclear run-on assay. RESULTS: CRX overexpression and knockdown significantly increased (n=3, P<0.05 in all the cells) and decreased (n=3, P<0.01 in all the cells) the proliferation of RPE and RB cells. CRX overexpression and knockdown significantly increased and deceased the mRNA levels of Wnt signaling target genes [including MYC proto-oncogene (MYC), JUN, FOS like 1 (FOSL1), CCND1, cyclin D2 (CCND2), cyclin D3 (CCND3), cellular communication network factor 4 (CCN4), peroxisome proliferator activated receptor delta (PPARD), and matrix metallopeptidase 7 (MMP7)] and the luciferase activity driven by the Wnt signaling transcription factor (TCF7). TCF7 overexpression and knockdown significantly increased and decreased the proliferation of RPE and RB cells and depletion of TCF7 significantly abolished the stimulatory effect of CRX on the proliferation of RPE and RB cells. CRX overexpression and knockdown significantly increased and decreased the mRNA level of TCF7 and the promoter of TCF7 was significantly immunoprecipitated by CRX antibody. CONCLUSION: CRX transcriptionally activates TCF7 to promote the proliferation of RPE and RB cells in vitro. CRX is a potential target for RPE-based regenerative medicine. The potential risk of this strategy, tumorigenic potential, should be considered.

Abstract:AIM: To investigate the relationship between benign essential blepharospasm (BEB) symptoms and depression/anxiety/sleep disorder in a prospective manner and to determine whether treatment the BEB with botulinum toxin type A (BoNT/A) can impact psychological symptoms. METHODS: This prospective interventional case series recruited 61 adults with evidence of BEB. Patients were administered the Jankovic Rating Scale (JRS), the Blepharospasm Disability Index (BSDI), Personal Health Questionnaire Depression Scale (PHQ-8), Generalized Anxiety Disorder 7-item scale (GAD-7) and the Athens insomnia scale (AIS) to evaluate the severity of BEB symptoms, depression, anxiety and sleep disorder before and 1wk, 1, 3mo after the BoNTA treatment. Statistical analysis was performed to assess the relationships between changes in the survey scores. RESULTS: The mean score for JRS, BSDI, PHQ-8, and GAD-7 improved significantly (P<0.0001), respectively, compared to the initial visit at follow-up. At baseline, worse BSDI scores were correlated with worse GAD-7 and PHQ-8, but not with worse AIS. At 1mo follow-up visit, there was no correlation between change in BSDI and PHQ-8/AIS, the change in GAD-7 showed a mild association with change in BSDI. The change in BSDI was correlated with the change in both PHQ-8 and GAD-7 in the subgroup of patients without a prior diagnosis of depression or anxiety. Patient satisfaction with BoNT/A treatment reached the highest at 1mo of follow-up (83.6%, 51/61). CONCLUSION: BEB may lead to psychological diseases. BoNT/A can significantly improve motor and non-motor symptoms of BEB, which emphasize the effectiveness of BoNT/A and therefore pave the way for its use in the field of psychiatry. However, further research is needed to confirm these findings and understand the underlying mechanisms.

Abstract:AIM: To investigate the efficacy and mechanisms of indirect intense pulsed light (IPL) irradiation on meibomian gland dysfunction (MGD). METHODS: A total of 60 MGD patients was included in this prospective randomized controlled trial. Patients were randomly assigned 1:1 into two groups (3-mm group and 10-mm group) in which IPL was applied at distances from the lower eyelid margin of 3 and 10 mm, respectively. Both groups received three times treatment with 3-week interval. Meibomian gland yield secretion score (MGYSS), standard patient evaluation of eye dryness (SPEED) questionnaire, tear break-up time (TBUT), corneal fluorescein staining (CFS), and in vivo confocal microscopy were performed at baseline and after every treatment. RESULTS: After three IPL treatments, both groups had significant improvement in MGYSS (both P<0.05). The non-inferiority test showed that improvement in 10-mm group was not inferior to that in 3-mm group (P<0.001). In both groups, temporal regions of both upper and lower eyelids showed significant improvement in MGYSS. Scores of SPEED questionnaire in both groups declined significantly (both P<0.001) and changes of SPEED had no difference between two groups (P=0.57). Density of central corneal subepithelial nerves and TBUTs showed no statistically significant changes. The 3-mm group had improvement on corneal fluorescein staining (P=0.048) and meibomian gland morphology (acini wall thickness P=0.003, hyperreflective points P=0.024) while the 10-mm group had not. CONCLUSION: The efficacy of IPL indirect irradiation in improving meibomian gland secretion and alleviating dry eye symptoms remains unchanged with increase in treatment distance. IPL may primarily act on the functional improvement of the meibomian glands and corneal nerves.

Abstract:AIM: To evaluate the clinical outcomes after subsequent implantation of a new intrastromal corneal ring segment (ICRS) model followed by an additional short-arc ICRS implant in keratoconus patients. METHODS: This retrospective single-arm cohort study evaluated 25 eyes of 21 keratoconus patients implanted with the new ICRS followed by 140-arch length ICRS (140-ICRS) implantation. Uncorrected distance visual acuity (UDVA, logMAR), corrected distance visual acuity (CDVA, logMAR), sphere, astigmatism, keratometry, spherical equivalent (SE), and asphericity were compared preoperatively and postoperatively after both ICRS implantation. RESULTS: The average follow-up time after 140-ICRS implantation was 6.40±2.20mo. The mean preoperative UDVA improved from 1.27±0.14 preoperative to 0.52±0.26 after both ICRS implantation (P=0.03). The mean sphere value reduced from -5.34±2.74 preoperatively to -2.06±1.84 postoperatively (P<0.001) after the first ICRS implantation and decreased to -0.59±1.54 postoperatively (P<0.001) after 140-ICRS implantation. The mean preoperative astigmatism was -3.72±1.56 and improved to -2.82±1.08 after the first ICRS implantation, and following the 140-ICRS implantation, the mean astigmatism was -1.37±0.67 (P=0.001). The SE and asphericity changes were statistically significant (P<0.001). The researchers did not find intraoperative or postoperative complications for both procedures. CONCLUSION: The combination of 2 different ICRSs can efficiently regularize the cornea, reduce the SE, and improve visual acuity in selected keratoconus patients.

Abstract:AIM: To report incidence, indications, and visual outcomes of intraocular lens (IOL) exchange/explantation surgery. METHODS: Retrospective analysis of 60 eyes requiring IOL exchange/explantation surgery between 1st January 2017 and 31st December 2022. The overall outcomes as well as comparison between the trainee versus experienced surgeons were analyzed. RESULTS: Out of 39 778 cataract surgeries (with no preexisting ocular co-morbidities) during a six-year period (2017–2022), 60 (0.15%) needed IOL exchange/explantation. Surgeons-under-training performed 36/60 cases (60%) while 24/60 (40%) were by experienced surgeons. The commonest indication was subluxated IOL in 26 (43.3%), followed by dislocated IOL in 20 (33.3%), postoperative refractive surprise in 7 (11.6%), IOL induced uveitis in five and broken haptic in two eyes. Twenty-four (40%) eyes had intraoperative complications during primary surgery. Posterior chamber IOL (PCIOL) was the commonest secondary IOL in 21 (35%) eyes, scleral fixated in 20 (31.6%), anterior chamber IOL (ACIOL) in 13 (21.6%), iris fixated IOL in three (5%) and three eyes (5%) were left aphakic. The mean time between primary and secondary surgery was 168d (168±338.8). Best corrected visual acuity (BCVA) of >20/60 was obtained in 43 eyes (71.66%), 20/80–20/200 in 14 (23.33%), 20/250 in two and hand movements in one. No statistically significant difference in visual outcome was noted at post-op one month between trainees versus experienced surgeons (UCVA 0.45±0.29 vs 0.53±0.32, P=0.20, BCVA 0.34±0.25 vs 0.37±0.26, P=0.69). CONCLUSION: IOL subluxation as the commonest indication and posterior capsular rupture is the commonest intraoperative risk factor. This complication can be effectively addressed with selection of the appropriate secondary IOL achieving good visual outcomes in over 70% of patients.

Abstract:AIM: To compare the safety and clinical outcomes of subconjunctival trypsin and dexamethasone (DEX) injections in the treatment of anterior chamber fibrin exudates in eyes with globe rupture following primary wound repair and vitrectomy. METHODS: A retrospective analysis included 42 males and 10 females (mean age 46.0±6.0y, range 34 to 58y) who underwent primary wound sutures and vitrectomy for globe rupture. Patients with pupil-covered fibrinous exudate or/and membrane in the anterior chamber were treated. On the first postoperative day, subconjunctival injections of either 5000 units (0.4 mL) of trypsin solution (n=25) or 0.5 mL (1 mg) DEX (n=27) were administered to accelerate exudate absorption. Efficacy was assessed by observing break time and partial absorption of the fibrin exudate membrane. Safety and comfort were evaluated by monitoring intraocular pressure (IOP), allergy, pain, and foreign body sensation. RESULTS: Both groups achieved 1/3 absorption of the anterior chamber fibrin exudate membrane, but the trypsin group exhibited shorter break time and partial absorption time compared to the DEX group (P<0.05). Trypsin treatment was also less irritating to patients. No adverse reactions were reported, and IOP remained stable. Visual acuity improved in both groups without statistical difference. CONCLUSION: Compared to DEX, trypsin demonstrates a shorter absorption time for the fibrin exudate membrane with a more comfortable process in treating pupil-covered fibrinous exudate or/and membrane after vitrectomy for globe rupture.

Abstract:AIM: To compare the short-term effectiveness of intelligent navigated laser photocoagulation and 577-nm subthreshold micropulse laser (SML) treatment in patients with chronic central serous chorioretinopathy (cCSC). METHODS: This observational retrospective cohort study included 60 consecutive patients who underwent intelligent navigated laser photocoagulation (n=30) or 577-nm SML treatment (n=30) for cCSC between Jan. 2021 and Oct. 2022. During 3mo follow-up, all patients underwent assessments of best correct visual acuity (BCVA) and optical coherence tomography (OCT). RESULTS: The operation of laser treatment was successful in all cases. At 1mo, BCVA improved significantly more in the intelligent navigated laser photocoagulation group compared to the SML group (P<0.05). The change was not significantly different at 3mo (P>0.05). Central macular thickness (CMT) in the intelligent navigated laser photocoagulation group was lower than in the SML group at 1mo (P<0.05). The subfoveal choroidal thickness (SFCT) in two groups were all significantly improved at 3mo (all P<0.05). The change between two groups was not significantly different at 1mo or at 3mo (P>0.05). CONCLUSION: Intelligent navigated laser photocoagulation is superior to SML for treating cCSC, leading to better improvements in vision and CMT for short term.

Abstract:AIM: To investigate the patterns of short-term intraocular pressure (IOP) fluctuations and identify the contributing factors following intravitreal injection in patients with retinal vascular diseases. METHODS: Totally 81 patients were enrolled in this case control study. Eyes were categorized into 7 groups, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), idiopathic choroidal neovascularization (CNV), proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), macular edema secondary to branch (BVOME) and central (CVOME) retinal vein occlusion. IOP was measured in all patients using rebound tonometer at 7 preset time points perioperatively. Additionally, based on the administered medication, the eyes were classified into three treatment groups, including dexamethasone intravitreal implant (IVO), intravitreal conbercept (IVC), and intravitreal ranibizumab (IVR). To compare IOP values at various time points across groups, we employed one-way ANOVA, independent sample t-test or χ2 test and multivariate logistic regression analysis. RESULTS: Peak IOP values across all groups were observed at 40s, and 5min after intravitreal injection. Statistical differences in IOP were detected at the 5min among the 7 indication groups (F=2.50, P=0.029). When examing the impact of medications, the IVO group exhibited lower average IOP values at both 40s and 5min compared to the IVC and IVR groups (P<0.001; P=0.007). The IOP values at 40s and 5min were significantly higher in BVOME and CVOME group compared to non-retinal vein occlusion-secondary macular edema (RVOME) group (P<0.001). Multivariate logistic regression analysis further confirmed that IOP measurement at 40s was significantly higher in CVOME group than in non-RVOME group (OR=1.64, 95%CI: 1.09-2.47; P=0.018). CONCLUSION: Needle size plays a crucial role in the transient changes of IOP following intravitreal injection. Before administering intravitreal injection to patients with central retinal vein occlusion, it is essential to exclude any underlysing causes of increased IOP.

Abstract:AIM: To observe the changes in corneal subepithelial nerve fibers (CNFs) and Langerhans cells (LCs) in patients with type 2 diabetes using corneal laser confocal microscopy (CLCM). METHODS: A total of 60 patients (64 eyes), including 40 patients with type 2 diabetes (DM group) and 20 subjects without diabetes (control group) were included with CLCM. Neuron J plugin of Image J software were used for quantitative analysis of CNF length (CNFL), CNF density (CNFD), corneal nerve branch fiber density (CNBD), main branch length density, branch length density, corneal nerve fiber tortuosity (NT) score, and LCs density. An independent samples t-test to analyze the variability between the two groups was performed, and Pearson correlation analysis was used to analyze the relationships between CNF and multiple biochemical indicators in the DM group. The predictive power of CNF for type 2 diabetes was assessed using the receiver operating characteristic (ROC) curve. RESULTS: There were significant differences in the CNFL, CNFD, and main branch length density between two groups. The results of Pearson correlation analysis showed a significant negative correlation between CNFD and the duration of diabetes as well as triglyceride levels and total cholesterol, and a significant positive correlation between CNFD and serum albumin. In addition, the NT score showed a positive correlation and urea nitrogen, similar to the positive correlation observed between LC density and glycosylated hemoglobin (HbA1c) levels. CNFD showed the highest area under the curve (AUC of ROC) value, followed by main branch length density and CNFL. The AUC of the ROC curve under the logistic regression model also demonstrated good predictive values. The cut-off values of CNFD, CNFL, and main branch length density for diabetes showed 31.25, 18.85, and 12.56, respectively. CONCLUSION: In patients with type 2 diabetes, there is a notable reduction in both CNFL and CNFD. These measurements can be influenced by various blood biochemical factors. However, the compromised nerve fibers can serve as valuable indicators for predicting the onset of type 2 diabetes and also as biomarkers for detecting diabetic neuropathy and its related complications.

Abstract:AIM: To compare the differences of choroidal neovascularization (CNV) measurements between swept-source and spectral-domain optical coherence tomography angiography (SS-OCTA and SD-OCTA) in neovascular age-related macular degeneration (nAMD) and the imaging reliability of the two devices. METHODS: Prospective comparative study. SS-OCTA and SD-OCTA were used to scan the same eye with the modes of 3×3 and 6×6 mm2 centered on the neovascularization. Only qualified images were chosen and the border of CNV was manually delineated by two graders independently. The area of CNV (ACNV), vascular perfusion density (PD), and vessel length density (VLD) within the delineation were calculated using Image J. The differences of CNV measurements between the two OCTA devices were compared using Bland-Altman analysis. The agreement between the two graders on the measurements of each device was compared using the intraclass correlation coefficient (ICC). RESULTS: A total of 18 patients (22 eyes) with nAMD were included. The measurements of ACNV, PD, and VLD were 7.247±4.586 and 4.901±3.741 mm2, 43.202±9.636 and 34.904±10.489, 6.339±1.228 and 5.908±1.741 mm-1 for SS-OCTA and SD-OCTA, respectively. The differences between the two devices were 2.346±3.030 mm2 (Z= -3.782, P<0.0001), 8.298±14.160 (Z=-2.419, P=0.016), and 0.431±2.114 mm-1 (Z=-0.828, P=0.408) for ACNV, PD and VLD, respectively. The ICC between two graders were 0.893 (P<0.001), 0.902 (P<0.001), 0.885 (P<0.001) for ACNV, PD, VLD in SS-OCTA, and 0.971 (P<0.001), 0.976 (P<0.001), 0.973 (P<0.001) in SD-OCTA, respectively. CONCLUSION: Both OCTA devices have high imaging reliability. Compared with SD-OCTA, SS-OCTA has a larger ACNV measurements, but doesn’t show better resolution of internal vessels of CNV and well signal strength.

Abstract:AIM: To compare relative peripheral refractive errors (RPREs) in Chinese children with and without myopic anisometropia (MAI) and to explore the relationship between RPRE and myopia. METHODS: This observational cross-sectional study included 160 children divided into two groups according to the interocular spherical equivalent refraction (SER) difference ≥1.0 D in the MAI group (n=80) and <1.0 D in the non-MAI group (n=80). The MAI group was further divided into two subgroups: ∆SER<2.0 D group and ∆SER≥2.0 D group. Basic ocular biometric parameters of axial length (AL), average keratometry (Ave K), cylinder (CYL), surface regularity index (SRI), and surface asymmetry index (SAI) were recorded. In addition, multispectral refraction topography was performed to measure RPRE, and the parameters were recorded as total refraction difference value (TRDV), refraction difference value (RDV) 0-10, RDV10-20, RDV20-30, RDV30-40, RDV40-53, RDV-superior (RDV-S), RDV-inferior (RDV-I), RDV-temporal (RDV-T) and RDV-nasal (RDV-N). RESULTS: In the non-MAI group, the interocular differences of all parameters of RPRE were not significant. In the MAI group, the interocular differences of TRDV, RDV10-53, RDV-S, RDV-I, RDV-T, and RDV-N were significant. In subgroup analysis, the interocular differences of TRDV, RDV30-53, RDV-I, and RDV-T were significant in ∆SER<2.0 D group and ∆SER≥2.0 D group, but the interocular differences of RDV10-30, RDV-S and RDV-N were only significant in the ∆SER≥2.0 D group. In correlation analysis, ∆TRDV, ∆RDV 10-53, ∆RDV-S, and ∆RDV-N were negatively correlated with ∆SER but positively correlated with ∆AL. CONCLUSION: The more myopic eyes have larger hyperopic RPRE in Chinese children with MAI in certain retinal range, and partial ∆RPRE is closely associated with ∆SER and ∆AL.

Abstract:AIM: To study the causal relationship between obesity-related anthropometric traits and myopia and the mediating role of educational attainment (EA). METHODS: Univariable Mendelian randomization (UVMR) was performed to evaluate the causal association between body mass index (BMI), height, waist-hip ratio (WHR, adjusted for BMI), and mean spherical equivalent (MSE). BMI was divided into fat and fat-free mass and included in multivariable Mendelian randomization (MVMR) to explore the roles of different BMI components in the causal relationship between BMI and MSE. A mediation analysis based on two-step Mendelian randomization (MR) was carried out. Specifically, UVMR was conducted to estimate the causal effect of BMI on EA. The direct effect of EA on MSE was estimated from MVMR. The mediation effect of EA in the BMI-EA-MSE model was calculated by the product of coefficients method. Expression quantitative trait loci (eQTL)-MR, reverse MR, and Linkage Disequilibrium Score Regression (LDSC) were performed to assess the robustness. RESULTS: Genetically predicted higher BMI had a positive total effect on MSE (βIVW=0.26 D, 95%CI=0.14 to 0.37 D, P<0.001), whereas there was no significant association between height, WHR, and MSE. Fat mass was found to play a significant role in the effect of body mass on MSE (βIVW=0.50 D, 95%CI=0.21 to 0.78 D, P=0.001), but there was no significant association between fat-free mass and MSE. The causal effect of BMI on EA was -0.14 (95%CI=-0.16 to -0.11, P<0.001), and the direct effect of EA on MSE was -0.63 D (95%CI=-0.81 to -0.44 D, P<0.001). The mediating effect of EA in the BMI-EA-MSE model was 0.09 D (95%CI=0.06 to 0.12 D), with a mediation proportion of 33% (95%CI=22.1% to 44.6%). No reverse causal associations were detected except for BMI on EA. The results of eQTL-MR and LDSC were consistent with each MR analysis. CONCLUSION: Genetically predicted higher BMI decreases the degree of myopia with a 33% mediation proportion by EA, and fat mass provides a dominant protective role in body mass-myopia. As a supplement to previous observational studies, it provides strong evidence for the relationship between anthropometric traits and refractive errors and offers a theoretical basis for future measures to prevent and control myopia.

Abstract:AIM: To determine the smartphone use patterns and effects of smartphone use on accommodation and convergence system of the eyes among Malaysian teenagers. METHODS: A total of 62 participants aged between 13 and 17y were involved. A self-administered questionnaires containing 12 items was used to evaluate the smartphone usage patterns. This was followed by an eye examination, involving a battery of accommodation and convergence assessments before and after the smartphone use. The data analysis comprised descriptive statistics, paired t-test, and correlation coefficients. RESULTS: The use of smartphones is at a high level and at an optimal distance daily, with more than 6h a day watching video films, games, and completing school projects. Majority of the participants not reported eye strain factors and eye prescription changes with the use of digital devices. The use of a smartphone continuously for 30min was found to significantly decrease amplitude of accommodation, accommodative facility, and positive relative accommodation (P<0.001). Meanwhile, the lag of accommodation parameters and negative relative accommodation increased with the use of smartphones significantly (P<0.001). The near point of convergence (NPC) and distance and near negative fusional vergence decreased significantly (P<0.001). The NPC parameter was found to have a weak negative association with the frequency of smartphone use (R=-0.276, P<0.05). CONCLUSION: Frequent and continuous use of smartphones have increased visual stress and resulted in weakness of accommodation and vergence functions. Therefore, frequent break is mandatory when using a smartphone and appropriate visual hygiene, the 20-20-20 rule (every 20min, view something 20 feet away for 20s) are required during smartphone use to maintain visual function.

Abstract:AIM: To investigate the causal effect of inflammatory bowel disease (IBD) on ocular inflammation using Mendelian randomization (MR) analysis. METHODS: Genetic instruments associated with inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn’s disease (CD) were derived from the largest genome-wide association studies (GWAS) published to date. The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis, keratitis, iridocyclitis, chorioretinitis, episcleritis, and optic neuritis. All participants were of European ancestry. Three methods which included inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression were performed to estimate the causal association in this study. IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes, to summarize the effect sizes of multiple independent studies, which could provide the most precise estimated results. IVW was used as the primary outcome, while WM and MR-Egger were used to improve the estimation of IVW. RESULTS: A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis, keratitis, iridocyclitis, and optic neuritis, but not on chorioretinitis or episcleritis. After Bonferroni correction, the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis (IVW: OR, 1.17; 95%CI, 1.10-1.24, P=2.54×10-7). CD was significantly associated with conjunctivitis (IVW: OR, 1.05; 95%CI, 1.03-1.08, P=3.20×10-5), keratitis (IVW: OR, 1.06; 95%CI, 1.02-1.09; P=1.13×10-3), and iridocyclitis (IVW: OR, 1.09; 95%CI, 1.04-1.14; P=1.43×10-4). CONCLUSION: IBD causally poses a risk of inflammation of conjunctiva, cornea, Iris-ciliary body complex, and optic neuritis. CD is more closely associated with the eye inflammation than UC. These impliy that the relationship of IBD and different parts of the eye structure are different, and provide novel evidence linking based on the association of the gut-eye axis.

Abstract:AIM: To understand the current situation of parental perspectives, knowledge, and practices concerning myopia prevention and control for both pre- and school-aged children. METHODS: This study was a cross-sectional survey that involved children aged 0 to 15y and their parents. Participants were required to respond to an online questionnaire by scanning a quick response (QR) code. The questionnaire consisted of 25 tick-box questions and was open to response from December 22, 2022, to January 5, 2023. The dioptric traits of the children, the visual status and educational background of the parents, the parental perspectives towards myopia and its risks, and the parents’ knowledge and practices related to myopia prevention and control were recorded and measured. The Chi-square test and binomial logistic regression were used for statistics. RESULTS: Totally 350 parents responded to the questionnaire. The prevalence and severity of myopia among the surveyed children exhibited a positive correlation with advancing age (P<0.001 and P=0.004, respectively). Nearly half of parents with myopic children considered myopia did not pose any health threat and could be effectively corrected (P<0.001). Parents who held master’s or doctoral degree demonstrated a better understanding of children’s vision standards for each age group (P=0.001), and 31.63% of them could undergo initial vision screening for their children during the age of 0 to 3y while parents with bachelor’s degree (34.04%) and below (32.43%) mainly initiated the vision examination for their children at the age of 4 to 6y (P=0.05). Parents with master’s or doctoral degree also exhibited more rational practices concerning outdoor time (P=0.048) and sleep time (P=0.044). No other significant discrepancy among the different educational groups in additional conceptions of myopia, such as hyperopia reserve, axis length, and corneal curvature alterations. Most parents preferred to employ conventional interventions, such as enhancing indoor lighting condition (80.00%) and ensuring appropriate reading posture and distance (71.71%). CONCLUSION: The current status of parental knowledge and practices about myopia prevention and control remains outdated and deficient. The administrative department should implement efficacious and adaptable measures to enhance parental awareness and foster their commitment towards myopia prevention and control.

Abstract:AIM: To conduct a bibliometric analysis of studies on microphthalmos and anophthalmos (M/A), explore research hotspots, and provide information on future research interests in this field to benefit clinicians and researchers. METHODS: Totally 751 publications related to M/A from the year 2004 to 2023 were collected from the Web of Science Core Collection database. These publications consist of both original and review articles, that are composed in English. The contributions of different countries, institutions, journals, and authors were analyzed, and network analysis was conducted by using Microsoft Excel 2021, VOSviewer, and R Studio to visualize research hotspots. RESULTS: Among all publications included, the highest number of publications came from USA (218, 29.03%). China followed with 99 publications (13.18%), and England with 86 publications (11.45%). The publications from the USA had the highest frequency of citations, with 16 699 citations, and the highest H-index of 49. The American Journal of Medical Genetics Part A (43, 5.73%) published the largest number of papers, and the University of London had the most publications (41, 5.46%). The genetic and molecular mechanisms of M/A were still unclear and the clinical intervention for M/A had gained a lot of attention as an emerging area of interest. CONCLUSION: Data have been gathered on the yearly count of published materials and citations, as well as the rise in publication trends, the efficiency of regions or countries, authors, journals, and organizations, along with the high-cited publications in M/A. The recent trend of research has shifted from genetic mechanisms to different clinical phenotypes and corresponding clinical interventions, which can give direction to future research.

Abstract:Myopia is a huge health problem due to its high frequency, vision losses and public health cost. According to the World Health Organization, at least 2.2 billion people have vision impairment. Although myopia can be controlled at its early and middle stages, unfortunately, no cure can be achieved so far. Among the methods to control myopia, atropine, a muscarinic receptor antagonist, is the oldest but still the most effective for retardation of myopia progression. Despite such a fact, standard protocols have not been established for clinicians to use atropine for treatment of myopia. In this article, a concise and up to date summary of myopia epidemiology and pathogenesis and summarized therapeutic effects and side effects, possible mechanisms and application methods of atropine were provided in hope for clinical doctors to effectively control this problematic disease. At present, the protocol is recommend: use higher dose (1%) of atropine intermittently to effectively slowdown myopia progression in schoolchildren for 2y, and to significantly reduce side effects of atropine by decrease of atropine frequency for 1y and inhibit myopic rebound by withdrawal of topical atropine gradually for 1y. Application of a lower dose (0.05%) atropine regime should also be considered due to its effectiveness and application at regular basis.

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