Association between Gestational Age, Birth Weight, Parental Age at Childbirth, Mode of Delivery, and Infantile Esotropia.

SIGNIFICANCE: This study investigated the potential perinatal risk factors associated with infantile esotropia in a Chinese population, including advanced parental age at childbirth and mode of delivery. The findings may be significant in developing better intervention strategies for infantile esotropia. PURPOSE: This study aimed to investigate the associations between gestational age, birth weight, parental age at childbirth, mode of delivery, family history of strabismus, and infantile esotropia in the Chinese population. METHODS: Ninety-nine patients with infantile esotropia and 117 control subjects were enrolled between March 2018 and March 2021. Detailed questionnaires were administered to parents to collect relevant information. Univariate and multivariate logistic regression models were used to identify possible risk factors of infantile esotropia. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Infantile esotropia was associated with low birth weight (<2500 g; OR, 4.235; 95% CI, 1.460 to 12.287; P = .008) and emergency cesarean delivery (OR, 2.230; 95% CI, 1.127 to 4.413; P = .02). CONCLUSIONS: The findings suggest that low birth weight and emergency cesarean deliveries are risk factors for infantile esotropia, highlighting a need for collaborative care between obstetricians, pediatricians, and vision care providers.

Identification of a De Novo Heterozygous Missense ACTB Variant in Baraitser-Winter Cerebrofrontofacial Syndrome.

Baraitser-Winter cerebrofrontofacial syndrome (BWCFF, OMIM: 243310) is a rare autosomal-dominant developmental disorder associated with variants in the genes ACTB or ACTG1. It is characterized by brain malformations, a distinctive facial appearance, ocular coloboma, and intellectual disability. However, the phenotypes of BWCFF are heterogenous, and its molecular pathogenesis has not been fully elucidated. In the present study, we conducted detailed clinical examinations on a Chinese patient with BWCFF and found novel ocular manifestations including pseudoduplication of the optic disc and nystagmus. Targeted gene panel sequencing and Sanger sequencing identified a de novo heterozygous missense c.478A > G (p.Thr160Ala) variant in ACTB. The mRNA and protein expression of ACTB was assessed by quantitative reverse transcription PCR and Western blots. Furthermore, the functional effects of the pathogenic variant were analyzed by protein structure analysis, which indicated that the variant may affect the active site for ATP hydrolysis by the actin ATPase, resulting in abnormal filamentous actin organization in peripheral blood mononuclear cells. This discovery extends the ACTB variant spectrum, which will improve genetic counseling and diagnosis, and may contribute to understanding the pathogenic mechanisms of actin-related diseases.

Complement factor H deficiency combined with smoking promotes retinal degeneration in a novel mouse model.

Age-related macular degeneration is the leading cause of blindness in the elderly. The Y402H polymorphism in complement factor H promotes disease-like pathogenesis, and a Cfh+/- murine model can replicate this phenotype, but only after two years. We reasoned that by combining CFH deficiency with cigarette smoke exposure, we might be able to accelerate disease progression to facilitate preclinical research in this disease. Wild-type and Cfh+/- mice were exposed to nose-only cigarette smoke for three months. Retinal tissue morphology and visual function were evaluated by optical coherence tomography, fundus photography and autofluorescence, and electroretinogram. Retinal pigment epithelial cell phenotype and ultrastructure were evaluated by immunofluorescence staining and transmission electron microscopy. Cfh+/- smoking mice showed a dome-like protruding lesion at the ellipsoid zone (drusen-like deposition), many retinal hyper-autofluorescence spots, and a marked decrease in A- and B-wave amplitudes. Compared with non-smoking mice, wild-type and Cfh+/- smoking mice showed sub-retinal pigment epithelium complement protein 3 deposition, activation of microglia, metabolic waste accumulation, and impairment of tight junctions. Microglia cells migrated into the photoreceptor outer segment layer in Cfh+/- smoking mice showed increased activation. Our results suggest that exposing Cfh+/- mice to smoking leads to earlier onset of age-related macular degeneration than in other animal models, which may facilitate preclinical research into the pathophysiology and treatment of this disease.

Abnormal lens thickening in a child with Weill-Marchesani syndrome 4: A 3-year follow-up case report.

Background: Weill-Marchesani syndrome 4 (WMS4) is caused by ADAMTS17 gene variant and clinical abnormalities including lenticular myopia, ectopia lentis, glaucoma, microspherophakia, brachydactyly, and short stature. Due to free of heart defects and joint stiffness compared with other WMS forms, WMS4 has an insidious onset and is often misdiagnosed as high myopia. We combined multiple imaging biometry and whole-exome sequencing to diagnose a case of WMS4 with a 3-year follow-up. Case presentation: An 8-year-old boy presented to our ophthalmology department with progressive myopia for 1 year. He had high myopia in both eyes with normal funds, intraocular pressure, and axial length. Ocular examination revealed thicker lenses (right 4.38 mm, left 4.31 mm) with a smaller equatorial diameter (right 7.33 mm and left 7.17 mm) compared to normal children of the same age. Finger length measurement indicates brachydactyly. Whole-exome sequencing identified compound heterozygous missense variants c.2984G > A (p.Arg995Gln) and c.2254A > G (p.Ile752Val) in the ADAMTS17 gene. During the 3 years of follow-up, the thickness of lenses increased significantly (right 4.49 mm, left 4.48 mm), but the equatorial diameter of the lenses had no significant change (right 7.32 mm, left 7.21 mm). As the equivalent lens power increased, the patient's myopia spherical refractive error rose accordingly. Although the anterior chamber angle remained open during follow-up, the intraocular pressure increased to right 20.4 mmHg and left 19.6 mmHg, Iridodonesis and short stature were present. Conclusion: This case report highlights the abnormal thickening of the lens in WMS4 compared to the physiological thinning process during childhood. Comprehensive clinical examinations and genetic testing may improve diagnosis, which allows early therapeutic interventions for complications and better visual outcomes for the patient.

Effect of capsular tension ring implantation on capsular stability after phacoemulsification in patients with weak zonules: a randomized controlled trial. CTR implantation in cataract patients with weak zonules.

BACKGROUND: The use of capsular tension ring (CTR) implantation to treat cataract patients with weak zonules is still controversial. The aim of this study was to examine the effects of CTR implantation on capsular stability after phacoemulsification in patients with weak zonules, especially patients who have undergone pars plana vitrectomy (PPV) or those who suffer from severe myopia. METHODS: A total of 42 patients who underwent phacoemulsification and received an intraocular lens (IOL) were randomized to undergo CTR implantation or not. The control and CTR groups were compared in terms of uncorrected distant visual acuity (UDVA), best corrected distant visual acuity (BCDVA), refractive prediction error, the area of anterior capsulorhexis, and IOL inclination angle. Follow-up visits were conducted postoperatively at 1 day, 1 week, 1 month and 3 months. Subgroup analyses were performed based on PPV and severe myopia. RESULTS: Surgery significantly improved UDVA and BCDVA to similar extents in CTR and control patients, and refraction prediction error was similar between the two groups at all follow-up times. At 3 months after surgery, the area of anterior capsulorhexis was significantly larger in CTR patients than in controls (p = 0.0199). These differences were also significant between the subgroups of patients with severe myopia. Vertical IOL inclination was less within CTR groups at 3 months after surgery, especially in patients with severe myopia (p = 0.0286). At 1 week postoperatively, the proportion of individuals whose posterior lens capsule that had completely adhered to the posterior IOL surface was significantly higher among CTR patients (p = 0.023). No serious surgical complications were observed. CONCLUSION: CTR implantation can benefit cataract patients with weak zonules by maintaining the shape of the capsular bag, reducing capsule shrinkage and stabilizing IOL inclination. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-INR-17011217 , date of registration April 22, 2017, prospectively registered.

[Expression of Complement Factor H in Human Embryonic Stem Cell-derived Retinal Pigment Epithelium].

OBJECTIVE: To study the expression and secretion of alternative complement pathway regulator complement factor H (CFH) in spontaneously produced or induced human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). METHODS: RPE cells were acquired by spontaneous differentiation from hESC (sdRPE), a source of hESC-RPE, according to the method used in clinical trials. RPE cells were also acquired under the induction of growth factors and small molecules for 14 d (iRPE). Acquired cells were kept culturing for 3 month for maturation. All differentiated cells（P3）were cultivated for 4-5 weeks prior to characterization with qRT-PCR and immunofluorescence. Secretion levels of CFH were investigated by ELISA. ARPE-19 cell line was served as control. RESULTS: Both sdRPE and iRPE showed high similarity in cell morphology and the pattern of specific gene expression with human RPE. The relative CFH mRNA expression levels of both sdRPE and iRPE were significantly higher than that of ARPE-19 ( P<0.05). The CFH secretion levels of sdRPE in the 24 h-, 48 h- and 72 h-culture medium were higher than those of iRPE ( P=0.000 2); and this CFH secretion levels of both sdRPE and iRPE were higher than that of the ARPE-19 cell line ( P<0.000 1). CONCLUSION: Both sdRPE and iRPE derived by different differentiation methods expressed and secreted CFH, suggesting that hESC-RPE may have certain ability to regulate the alternative complement pathway.

Effects of lutein supplementation in age-related macular degeneration.

The purpose of this meta-analysis was to evaluate the effects of lutein supplementation on macular pigment optical density (MPOD) in randomized controlled trials involving patients with age-related macular degeneration (AMD). A comprehensive search of the literature was performed in PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan Fang database through December 2018. Nine randomized controlled trials involving 920 eyes (855 with AMD) were included. Meta-analysis suggested that lutein supplementation (10 or 20 mg per day) was associated with an increase in MPOD (mean difference (MD) 0.07; 95% confidence interval (CI) 0.03 to 0.10), visual acuity (MD 0.28; 95%CI 0.06 to 0.50) and contrast sensitivity (MD 0.26; 95%CI 0.22 to 0.30). Stratified analyses showed the increase in MPOD to be faster and greater with higher dose and longer treatment. The available evidence suggests that dietary lutein may be beneficial to AMD patients and the higher dose could make MPOD increase in a shorter time.

Surgical management of intraocular lens dislocation: A meta-analysis.

PURPOSE: To compare the efficacy and safety of intraocular lens (IOL) repositioning and IOL exchange for the treatment of patients with IOL dislocation. METHODS: We systematically searched for relevant publications in English or Chinese in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, WHO International Clinical Trial Registration Platform, Clinical Trial.gov, China Biology Medicine Database, China National Knowledge Infrastructure Database and grey literature sources. Study quality was assessed using the STROBE template for observational studies and the Cochrane template for randomized controlled trials (RCTs). Data were meta-analyzed using RevMan 5.3. RESULTS: The review included 14 English-language studies reporting 1 RCT and 13 retrospective case series involving 1,082 eyes. Average follow-up time was 13.7 months. Pooled analysis of 10 studies showed that the two procedures had a similarly effect on best corrected visual acuity (MD -0.00, 95%CI: -0.08 to 0.08, P = 0.99). Pooled analysis of nine studies showed no significant difference in incidence of IOL redislocation (RR 2.12, 95%CI 0.85 to 5.30, P = 0.11); pooled analysis of seven studies showed greater extent of incidence of cystoid macular edema in IOL exchange (RR 0.47, 95%CI 0.21 to 1.30, P = 0.06). Pooled analysis of three studies showed greater extent of incidence of anterior vitrectomy in IOL exchange (RR 0.11, 95%CI 0.04 to 0.33, P<0.0001). Pooled analysis of two studies showed greater postoperative spherical equivalents in IOL repositioning (MD 1.02, 95%CI 0.51 to 1.52, P<0.0001). pooled analysis suggested no significant differences between the two procedures in terms of intraocular pressure, endothelial cell density, surgically induced astigmatism, or incidence of retinal detachment, intraocular hemorrhage or pupillary block. CONCLUSION: IOL repositioning and exchange are safe and effective procedures for treating IOL dislocation. Neither procedure significantly affects best corrected visual acuity and IOL redislocation. IOL exchange was superior to repositioning in terms of postoperative SE, but IOL repositioning was associated with lower incidence of anterior vitrectomy, potentially lower incidence of cystoid macular edema.

Diagnostic value of a combination of next-generation sequencing, chorioretinal imaging and metabolic analysis: lessons from a consanguineous Chinese family with gyrate atrophy of the choroid and retina stemming from a novel OAT variant.

BACKGROUND/AIM: Gyrate atrophy of the choroid and retina (GACR) is an extremely rare autosomal recessive inherited disorder characterised by progressive vision loss. To identify the disease-causing gene in a consanguineous Chinese pedigree with GACR, we aimed to accurately diagnose patients with GACR through a combination of next-generation sequencing (NGS) genetic diagnosis, clinical imaging and amino acid metabolic analysis. METHODS: A consanguineous Chinese pedigree with GACR, including two patients, was recruited and a comprehensive ophthalmological evaluation was performed. DNA was extracted from a proband and her family members, and the sample from the proband was analysed using targeted NGS. Variants detected by NGS were confirmed by Sanger sequencing and subjected to segregation analysis. Tandem mass spectrometry (MS/MS) was subsequently performed for metabolic assessment. RESULTS: We identified a novel, deleterious, homologous ornithine aminotransferase (OAT) variant, c.G248A: p.S83N, which contributes to the progression of GACR in patients. Our results showed that the p.S83N autosomal recessive variant of OAT is most likely pathogenic, with changes in protein stability drastically decreasing functionality. MS/MS verified that ornithine levels in patients were significantly elevated. CONCLUSIONS: Recruitment of a third-degree first cousin consanguineous marriage family with GACR allowed us to identify a novel pathogenic OAT variant in the Chinese population, broadening the mutation spectrum. Our findings reported the diagnostic value of a combination of NGS, retinal imaging and metabolic analysis of consanguineous marriage pedigrees in low-income/middle-income and low-incidence countries, including China, and may help to guide accurate diagnosis and treatment of this disease.