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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 Purpose To provide a genotype and phenotype characterization of the BEST1 mutation in Chinese patients with autosomal recessive bestrophinopathy (ARB) through multimodal imaging and next-generation sequencing (NGS). Methods Seventeen patients from 17 unrelated families of Chinese origin with ARB were included in a retrospective cohort study. Phenotypic characteristics, including anterior segment features, were assessed by multimodal imaging. Multigene panel testing, involving 586 ophthalmic disease-associated genes, and Sanger sequencing were performed to identify disease-causing variants. Results Among 17 ARB patients, the mean follow-up was 15.65 months and average onset age was 30.53 years (range: 9–68). Best corrected visual acuity ranged from light perception to 0.8. EOG recordings showed a typically decreased Arden ratio in 12 patients, and a normal or slightly decreased Arden ratio in two patients. Anterior features included shallow anterior chambers (16/17), ciliary pronation (16/17), iris bombe (13/17), iridoschisis (2/17), iris plateau (1/17), narrow angles (16/17) and reduced axial lengths (16/17). Sixteen patients had multiple bilateral small, round, yellow vitelliform deposits distributed throughout the posterior pole, surrounding the optic disc. Initial diagnoses included angle-closure glaucoma (four patients), Best disease (three patients), and central serous chorioretinopathy secondary to choroidal neovascularization (CNV) (one patient), with the remainder diagnosed with ARB. Fourteen patients underwent preventive laser peripheral iridotomy, four of whom also received combined trabeculectomy and iridotomy in both eyes for uncontrolled intraocular pressure. One patient received intravitreal conbercept for CNV. Overall, 15 distinct disease-causing variants of BEST1 were identified, with 14 (82.35%) patients having missense mutations. Common mutations included p. Arg255-256 and p. Ala195Val (both 23.68%), with the most frequent sites in exons 7 and 5. Conclusions This study provides a comprehensive characterization of anterior segment and genetic features in ARB, with a wide array of morphological abnormalities. Findings are relevant for refining clinical practices and genetic counseling and advancing pathogenesis research.

Familial exudative vitreoretinopathy (FEVR) is a severe genetic disorder characterized by incomplete vascularization of the peripheral retina and associated symptoms that can lead to vision loss. However, the underlying genetic causes of approximately 50% of FEVR cases remain unknown. Here, we report two heterozygous variants in calcyphosine-like gene (CAPSL) that is associated with FEVR. Both variants exhibited compromised CAPSL protein expression. Vascular endothelial cell (EC)-specific inactivation of Capsl resulted in delayed radial/vertical vascular progression, compromised endothelial proliferation/migration, recapitulating the human FEVR phenotypes. CAPSL-depleted human retinal microvascular endothelial cells (HRECs) exhibited impaired tube formation, decreased cell proliferation, disrupted cell polarity establishment, and filopodia/lamellipodia formation, as well as disrupted collective cell migration. Transcriptomic and proteomic profiling revealed that CAPSL abolition inhibited the MYC signaling axis, in which the expression of core MYC targeted genes were profoundly decreased. Furthermore, a combined analysis of CAPSL-depleted HRECs and c-MYC-depleted human umbilical vein endothelial cells uncovered similar transcription patterns. Collectively, this study reports a novel FEVR-associated candidate gene, CAPSL, which provides valuable information for genetic counseling of FEVR. This study also reveals that compromised CAPSL function may cause FEVR through MYC axis, shedding light on the potential involvement of MYC signaling in the pathogenesis of FEVR.

AIM: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress. METHODS: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro. Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data. RESULTS: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca2+-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress. CONCLUSION: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Acute transient or permanent retinal arterial ischemia is ocular and systemic emergency requiring immediate diagnosis and treatment. Transient monocular vision loss is transient retinal arterial ischemia which leaves no permanent deficits. Central retinal arterial occlusion and branch retinal arterial occlusion lead to permanent visual function deficits in the majority of patients. Current treatment include lowering intraocular pressure, dilating blood vessels, hyperbaric oxygen therapy, intravenous or intra-arterial thrombolysis and so on, but there is still no standard treatment procedure. High risk groups should receive primary prevention measures in order to reduce the incidence of the disease. Patients with acute retinal arterial ischemia are at high risk of subsequent stroke and adverse cardiovascular events. Relevant risk factors should be identified in time, the primary disease should be treated actively, and appropriate secondary prevention measures should be taken to improve the prognosis. This review summarizes the recent treatment and prevention procedures of acute retinal arterial ischemia, to provide references for the management of these diseases.

PurposeTo present the outcomes of a new technique for intrascleral fixation of a flanged three-piece foldable intraocular lens (IOL) without a conjunctival incision.Materials and methodsWe retrospectively reviewed a consecutive series of 12 eyes of 12 patients who underwent scleral IOL fixation using this technique.ResultsThe follow-up period ranged 3–12 months. There was a significant improvement in best-corrected visual acuity, from 0.8 (1.6) logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.45 (0.8) logMAR at the final postoperative follow-up (p = 0.012). Notable complications included one case of pupillary IOL capture and increased intraocular pressure.ConclusionOur novel technique is a viable solution for managing secondary IOL fixation, enabling the use of a wider variety of IOLs and simplifying the reposition process for dislocated three-piece IOLs. This approach has the potential to lower complication rates and enhance patients’ recovery.

Abstract Retinal detachment (RD) occurs in several major retinal conditions and often causes irreversible vision loss due to photoreceptor cell death. Retinal residential microglial cells are activated following RD and participate in photoreceptor cell death via direct phagocytosis and the regulation of inflammatory responses. Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor exclusively expressed on microglial cells in the retina, and has been reported to affect microglial cell homeostasis, phagocytosis and inflammatory responses in the brain. In this study, increased expression of multiple cytokines and chemokines in the neural retina was observed starting at 3 h following RD. Trem2 knockout (Trem2 −/− ) mice exhibited significantly more photoreceptor cell death than wild-type controls at 3 days after RD, and the number of TUNEL positive photoreceptor cells progressively decreased from day 3 to day 7 post-RD. A significant thinning of the outer nuclear layer (ONL), with multiple folds was observed in the Trem2 −/− mice at 3 days post-RD. Trem2 deficiency reduced microglial cell infiltration and phagocytosis of stressed photoreceptors. There were more neutrophils in Trem2 −/− retina following RD than in controls. Using purified microglial cells, we found Trem2 knockout is associated with increased CXCL12 expression. The aggravated photoreceptor cell death was largely reversed by blocking the CXCL12-CXCR4 mediated chemotaxis in Trem2 −/− mice after RD. Our findings suggested that retinal microglia are protective in preventing further photoreceptor cell death following RD by phagocytosing presumably stressed photoreceptor cells and by regulating inflammatory responses. TREM2 is largely responsible for such protective effect and CXCL12 plays an important role in regulating neutrophil infiltration after RD. Collectively, our study pinpointed TREM2 as a potential target of microglial cells to ameliorate RD-induced photoreceptor cell death.

AIM: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification. METHODS: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit. RESULTS: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion. CONCLUSION: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is.

AIM: To investigate the role of procollagen C-proteinase enhancer 1 (PCPE1) in retinal angiogenesis and relevant mechanisms. METHODS: The Pcolce1-knockout (KO) mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo. Pcolce1 siRNA were designed, cell count kit 8 (CCK8) assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells (hRMECs) in vitro. Mouse embryo fibroblasts (MEF) cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage. RESULTS: In vivo studies showed that the retinal vascular density of Pcolce1-/- mice was significantly lower than that of the control group. Furthermore, silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of hRMECs in vitro. Additionally, much more pro-collagen was found in Pcolce1-/- MEF cells, compared to wild type MEF cells. CONCLUSION: PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen, which may provide a potential therapeutic target of retinal vascular disease.

AIM: To determine the anatomic and visual outcomes of prophylactic juxtapapillary laser photocoagulation treatment alone in the prevention of retinal detachment (RD) in a cohort of pediatric patients diagnosed with morning glory syndrome (MGS). METHODS: A total of 24 eyes of 22 consecutive patients aged 0-15y diagnosed with MGS treated with prophylactic juxtapapillary laser photocoagulation alone were reviewed. Data including demographics, ocular examination, anatomic and visual outcomes, following treatment and complications were collected. RESULTS: Two patients had bilateral laser treatment and 20 had monocular laser treatment. The age at treatment of 13 (59.1%) patients was less than 12mo. The presenting symptoms included strabismus (6/22, 27.3%), decreased vision (2/22, 9.1%), and routine fundus screening (14/22, 63.6%). Fifteen (68.2%) patients underwent cranial magnetic resonance imaging (MRI) examinations, and 3 of those 15 (20.0%) had abnormal findings in the nervous system. Based on preoperative wide-field fundus photography and B-scan echography, all (100.0%) eyes had no obvious RD. On postoperative 1mo and 6mo and the following follow-ups, the anatomic outcomes of all eyes remained stable. The mean follow-up duration was 27.7±17.5mo. No severe complications were found. Preoperative visual acuity acquired from 2 (9.1%) patients ranged from light perception to 20/200. Postoperative acuity acquired from 11 (50.0%) patients ranged from light perception to 20/125. CONCLUSION: The preliminary anatomic and visual outcomes of prophylactic juxtapapillary laser treatment alone in pediatric MGS patients are relatively stable in a short-term follow-up. Further long-term clinical observation will be needed to confirm its efficacy and safety.

To report potential vaccine-induced inflammatory ocular adverse events following inactivated COVID-19 vaccination. Retrospective study of patients with uveitis and other ocular complications following inactivated coronavirus disease 2019 (COVID-19) vaccination at a tertiary referral center between May 2021 and August 2021. Data collection consisted of demographic and clinical data. The study included 8 eyes of 5 patients (4 females, 1 male), with a mean age of 37.2 ± 12.5 years (range 28–59 years). Mean time between vaccination and ocular complications onset was 13.2 ± 11.9 days (range 3–30 days), including two patients after the first dose of the vaccine and 3 patients after the second dose. The cases reported were three anterior uveitis, one herpetic keratitis and iridocyclitis, and one posterior uveitis. Patients received treatment with local and/or systemic steroids and all the patients had good visual outcomes. Ocular inflammatory events may occur after vaccination with possible gender preponderance. However, they are rare and manageable. Overall, the efficacy and safety of vaccination should be emphasized.

Familial exudative vitreoretinopathy (FEVR) is an important cause of childhood blindness and is clinically characterized by phenotypic heterogeneity. FEVR patients harboring the same genetic mutation vary widely in disease severity. The purpose of this study was to explore non-genetic factors that regulate FEVR phenotypic heterogeneity. We detected methylation levels of 21 CpG sites located at the FZD4 exon 1 region of 11 probands, 12 asymptomatic/paucisymptomatic carriers and 11 non-carriers from 10 unrelated FZD4-associated FEVR families using bisulfite amplicon sequencing (BSAS). Our results showed reduced methylation level of FZD4 exon 1 in probands, suggesting that FZD4 exon 1 methylation level may be negatively linked with FEVR disease severity. It provided a new research direction for follow-up research, helping us better understand the complexity of the FEVR-causing mechanism.

PurposeTo present a novel usage of iris puncture-assisted lensectomy with anterior vitrectomy or vitrectomy in pediatric patients with the absence of anterior chamber caused by various advanced vitreoretinopathies complicated with capsule-endothelial, iris-endothelial adhesion, and secondary glaucoma.DesignProspective study.Materials and methodsForty-one patients were enrolled in this consecutive, prospective study. The iris puncture was performed in all patients using a 20G Vitrectomy Microsurgical Knife, followed by the lensectomy with anterior vitrectomy or vitrectomy. Demographic information, the number of iris puncture times, surgical procedure, intraoperative and postoperative complications, therapy, and prognosis were collected. Patients were followed up for at least 6 months.ResultsA total of 18 female patients and 23 male patients were included, with a mean age of 9.5 ± 7.5 months. The formation of anterior chamber formation was achieved in 28 (68.3%) eyes, with only 1 initial episode of iris puncture, 11 (26.8%) patients required 2 episodes, and 3 episodes of iris puncture, with additional external drainage of subretinal fluid, were needed in the remaining 2 (4.9%) patients. Except for iris incarceration, which occurred in 7 (17%) eyes during operation, there was no iridodialysis or subretinal fluid overflow during operation. At the last visit (mean: 12.16 ± 5.38 months of follow-up), all eyes had a reconstructed anterior chamber with normal depth. No synechiae between the iris and the cornea occurred after surgery. The mean postoperative intraocular pressure was 6.23 ± 1.64 mmHg. A hazy cornea vanished in 31 out of 41 (75.6%) eyes, relieved in 8 out of 41 eyes (19.5%), and 2 out of 41 eyes (4.88%) did not change. In the 25 eyes accepting vitrectomy and lensectomy, 20 out of 25 (80%) achieved different degrees of reattachment.ConclusionThe innovative iris puncture technique is effective, simple, and safe management for the anterior chamber disappearance caused by various advanced pediatric vitreoretinopathies, which helped to lower the intraocular pressure and offers a chance for lensectomy with anterior vitrectomy or vitrectomy.

PurposeThis study aimed to present the 1-year follow-up of a modified technique for scleral fixation of three-piece intraocular lens (IOLs) without conjunctival incision.Materials and MethodsA retrospective chart review of a consecutive series of 10 eyes of nine patients who underwent scleral IOL fixation using the modified technique was performed. Data were collected 1 year after surgery for all patients.ResultsThe range of follow-up time was between 1 year and 31 months. At the last follow-up point, the IOL was well-positioned and the visual acuity was good (as limited by primary diseases). Short-term complications included pupillary IOL capture (n = 1) and decreased intraocular pressure (n = 1), and no long-term complications were observed.ConclusionOutcome data support this technique as a viable option for the management of secondary IOL fixation with flexible usage of more designs of IOLs.

AIM: To demonstrate local dry vitrectomy combined with segmental scleral buckling and viscoelastic tamponade for the treatment of partial rhegmatogenous retinal detachment (RRD) with local vitreous traction in patients at high-risk for proliferative vitreoretinopathy (PVR). METHODS: Eleven eyes of 11 patients were retrospectively studied, including 5 retinal dialysis and 6 retinal detachment (RD; 5 eyes with peripheral retinal hole and 1 eye with giant tear). All patients exhibited partial RD and local vitreous traction. Combined local dry vitrectomy without conventional infusion and segmental scleral buckling was performed. Viscoelastic fluid was injected into the vitreous cavity if needed. Demographic information, preoperative and post-operative complications, and outcomes were recorded. RESULTS: The mean age of the patients at presentation was 26.55±13.52y. All 11 patients obtained retinal reattachment after a single surgical intervention. Postoperative visual acuities were improved or remained stable in all patients. None of them developed complications, except for temporary mildly increased intraocular pressure in 3 cases. CONCLUSION: Combined local dry vitrectomy and segmental scleral buckling are effective for patients of RRD with local vitreous traction. The technique avoids many complications associated with regular surgery and was minimally invasive to both the external and internal eye.

PurposeTo report the clinical and echographic features, the prevalence of retinal detachment (RD), and associated visual acuity in a cohort of pediatric patients with morning glory disc anomaly (MGDA).MethodsThis was a retrospective review of 249 pediatric patients with MGDA (271 eyes) seen at the Dept. of Ophthalmology, Xinhua Hospital. Their medical records were reviewed for demographic data and ocular and systemic findings. The maximal depth and width of the cavity were measured using standardized echographic images. The ratios of cavitary depth to axial length, cavitary depth to maximal cavitary width, and the product of cavitary depth and width were calculated and used to indicate the relative size of the excavation. The clinical and echographic findings were correlated with visual acuity and the occurrence of RD of the patient.ResultsThe relative size of the excavation and the presence of RD were positively associated with increased risk of poor vision (p < 0.05). The presence of persistent fetal vasculature was not associated with the risk of RD and poor vision. The ratio of cavitary depth to axial length more than or equal to 0.25 conferred an increased risk of RD (OR, 2.101; 95% CI, 1.469–3.003).ConclusionsClinical and echographic features of MGDA may be used in predicting the risk of RD. Measuring the relative size of excavation via echography may guide the follow-ups and assist in the early diagnosis of RD.

Abstract Background To delineate the characteristics of complicated familial exudative vitreoretinopathy (FEVR) patients diagnosed before surgery or intra−/post-operatively and to analyze the risk factors for the diagnostic timing. Methods Forty-eight patients who underwent surgery and were diagnosed as FEVR in our department were retrospectively reviewed. Data were collected including the demographic and clinical characteristics of these patients. FEVR patients were divided into 2 groups according to the diagnostic timing: FEVR diagnosed pre-operatively (23 patients), FEVR diagnosed intra−/post-operatively (25 patients). Multivariable analysis was applied for analyzing the risk factors for diagnostic timing. Results The clinical characteristics of the FEVR patients were of great variability, including retinal detachment (RD), disappear of anterior chamber, retrolental membrane, epiretinal membrane (ERM), vitreous hemorrhage (VH), myopic foveoschisis (MF), lamellar macular hole (LMH), high myopia (HM). And the referral diagnosis or pre-operative diagnosis were always non-specific. The majority of the referral or preoperative diagnosis were unilateral RD (52.1%), bilateral RD (8.3%), unilateral persistent fetal vasculature (PFV) (8.3%), bilateral PFV (4.2%). There are two risk factors for the complicated FEVR cases diagnosed as FEVR preoperatively: pre-operative ocular manifestations with RD only (OR, 0.104; p-value, 0.022), positive parent’s fluorescein angiography (FA) (OR, 0.105; p-value, 0.035). Conclusions The phenotypes of FEVR were greatly variable, they can mimic many non-specific vitreoretinal disorders. The most non-specific referral diagnosis/pre-operative diagnosis was unilateral RD, bilateral RD, unilateral PFV, bilateral PFV. A positive family history or a simple ocular presentation with RD only could contribute to diagnose FEVR preoperatively.

Background: Although domestic pet ownership is on the rise, the impact of early life pet ownership on children's pet sensitization and atopic dermatitis (AD) remains controversial.Methods: Shanghai Allergy Cohort is an ongoing prospective study followed up to the age of 5 years. Pregnant mothers were recruited and their offspring were followed up every year by a group of pediatricians. Information on furred pet ownership was collected by the questionnaire. AD was diagnosed by dermatologists according to disease history and Williams criteria at 5 years ± 1 months. Skin prick test (SPT) was performed to determine sensitization to specific allergens. Multiple logistic regression models were used to evaluate the associations between pet ownership and AD, dog/cat sensitization.Results: In the 538 children at preschool age, 112 (20.82%) were diagnosed with AD. Dermatophagoides pteronyssinus and Dermatophagoides farina were the most common allergens, and almost 10% of children were positive to dog and cat. The percentage of positive SPT reactors at 5-year old was 65.28% in the group of children with AD, higher than that in non-AD group (44.57%). Domestic pet ownership at both infant and preschool period was positively associated with an increased risk of sensitization to dog (OR adjusted = 2.85 [95% CI: 1.08–7.50 for infant exposure], OR adjusted = 2.73 [95% CI: 1.33–5.61] for preschool exposure), and interestingly, pet ownership at infant period negatively associated with higher risk of AD at 5-year old (OR adjusted = 0.33 [95% CI: 0.12–0.88]).Conclusion: This is the first prospective birth cohort study in Shanghai that found half of preschool children had positive allergen sensitization even in the non-AD children. Although early life exposure to dog may increase the risk of dog sensitization, it significantly decreased the risk of AD. The underlying mechanisms warrant further investigations.

Purpose. To present cases with retinopathy of prematurity (ROP), who were treated with intravitreal injection of ranibizumab (IVR) and had unpredictable asymmetric outcomes. Methods. A retrospective review was performed in infants with type 1 ROP and had bilateral IVR (0.25 mg/0.025 mL) as initial treatment. Patients were classified into the asymmetric outcome group and the symmetric outcome group. Results. Eighty-four patients (168 eyes) were included. There were 18 eyes of 9 patients (10.7%) in the asymmetric outcome group and 150 eyes of 75 patients (89.3%) in the symmetric outcome group. In the symmetric outcome group, 86 eyes (57.3%) had ROP regression, 60 eyes (40%) had reactivation requiring laser treatment, and 4 eyes (2.7%) progressed to retinal detachment requiring vitrectomy. In the asymmetric outcome group, one of the eyes of the 9 patients had ROP regression with/without reactivation after IVR, while the contralateral eyes had negative response, including remarkable posterior fibrosis, partial or total retinal detachment, and vitreous hemorrhage. There was statistically significant difference between the birth weight of the two groups. Conclusion. Contralateral eyes with ROP can take a different clinical course after ranibizumab treatment. High rate of reactivation after IVR is another concern that ophthalmologists should pay attention to.

Letter to the editor

Although much research has explored the personal, family, school, and social influences on adolescents' career expectations, little is known about the types of family-related career expectations of students and career expectation contexts in school. Using PISA 2018 test data, a multilevel latent profile analysis was conducted with indicators of parents' occupational status and children's career expectations. This research found that family-related career expectations of Estonian secondary school students can be divided into three types: enterprising, resilient, and disengaged. At the organizational level, contexts for career expectations in schools can be classified as enterprising, enterprising and resilient composite, and disengaged and resilient composite types. The research also found that science achievement and gender predicted latent profile memberships at the individual level. It is proposed that to value the science curriculum and its teaching is to invest in future human resources. It is suggested that families and schools should pay attention to stimulating male students' career aspirations. The career expectation types of secondary school students within and between schools are of great significance to the construction of national human resources, the development of schools, and the research of families.

The choroidal circulation plays a central role in maintaining the health of outer retina and photoreceptor function. Alterations in this circulation contribute to pathogenesis of many eye diseases including exudative age-related macular degeneration. Unfortunately, very little is known about the choroidal circulation and its molecular and cellular regulation. This has been further hampered by the lack of methods for routine culturing of choroidal endothelial cells (ChEC), especially from wild type and transgenic mice. Here we describe a method for isolation and culturing of mouse ChEC. We show that expression of thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis and inflammation, has a significant impact on phenotype of ChEC. ChEC from TSP1-deficient (TSP1-/-) mice were less proliferative and more apoptotic, less migratory and less adherent, and failed to undergo capillary morphogenesis in Matrigel. However, re-expression of TSP1 was sufficient to restore TSP1-/- ChEC migration and capillary morphogenesis. TSP1-/- ChEC expressed increased levels of TSP2, phosphorylated endothelial nitric oxide synthase (NOS) and inducible NOS (iNOS), a marker of inflammation, which was associated with significantly higher level of NO and oxidative stress in these cells. Wild type and TSP1-/- ChEC produced similar levels of VEGF, although TSP1-/- ChEC exhibited increased levels of VEGF-R1 and pSTAT3. Other signaling pathways including Src, Akt, and MAPKs were not dramatically affected by the lack of TSP1. Together our results demonstrate an important autocrine role for TSP1 in regulation of ChEC phenotype.

Background: Large language models (LLMs), such as ChatGPT, have considerable implications for various medical applications. However, ChatGPT's training primarily draws from English-centric internet data and is not tailored explicitly to the medical domain. Thus, an ophthalmic LLM in Chinese is clinically essential for both healthcare providers and patients in mainland China. Methods: We developed an LLM of ophthalmology (MOPH) using Chinese corpora and evaluated its performance in three clinical scenarios: ophthalmic board exams in Chinese, answering evidence-based medicine-oriented ophthalmic questions and diagnostic accuracy for clinical vignettes. Additionally, we compared MOPH's performance to that of human doctors. Results: In the ophthalmic exam, MOPH's average score closely aligned with the mean score of trainees (64.7 (range 62-68) vs 66.2 (range 50-92), p=0.817), but achieving a score above 60 in all seven mock exams. In answering ophthalmic questions, MOPH demonstrated an adherence of 83.3% (25/30) of responses following Chinese guidelines (Likert scale 4-5). Only 6.7% (2/30, Likert scale 1-2) and 10% (3/30, Likert scale 3) of responses were rated as 'poor or very poor' or 'potentially misinterpretable inaccuracies' by reviewers. In diagnostic accuracy, although the rate of correct diagnosis by ophthalmologists was superior to that by MOPH (96.1% vs 81.1%, p>0.05), the difference was not statistically significant. Conclusion: This study demonstrated the promising performance of MOPH, a Chinese-specific ophthalmic LLM, in diverse clinical scenarios. MOPH has potential real-world applications in Chinese-language ophthalmology settings. [ABSTRACT FROM AUTHOR]