Comparison of B-Scan ultrasonography, ultra-widefield fundus imaging, and indirect ophthalmoscopy in detecting retinal breaks in cataractous eyes.

BACKGROUND/OBJECTIVES: To evaluate the diagnostic performance of B-scan kinetic ultrasonography (USG), standard ultra-widefield (UWF) imaging, and indirect ophthalmoscopy (IDO) in retinal break detection in cataractous eyes. SUBJECTS/METHODS: We consecutively enrolled 126 cataract patients (including 246 eyes) with no comorbidities that could decrease best corrected visual acuity (BCVA). Three index tests (USG, nonmydriatic UWF, and mydriatic IDO) were performed preoperatively to screen for retinal breaks. One week after cataract extraction, a dilated IDO examination was repeated for the definitive diagnosis of retinal break as the reference standard. The sensitivity, specificity, Youden index (YI), and predictive values of each index test were calculated according to postoperative ophthalmoscopic findings. A deep-learning nomogram was developed to quantify the risk of retinal break presence using patients' baseline data and findings reported from preoperative ophthalmic tests. RESULTS: Fifty-two eyes (21%) were excluded from appropriate preoperative UWF imaging because of massive lens opacity. The BCVA cutoff point with maximum YI indicating UWF applicability was 0.6 logMAR (YI = 0.3; area under curve [AUC] = 0.7). Among all 246 eyes, preoperative IDO, USG, and UWF showed fair interobserver agreement (all κ > 0.2). According to postoperative IDO findings, the index tests with the highest sensitivity and specificity were USG (100%) and preoperative IDO (99%), respectively. CONCLUSIONS: For cataractous eyes without vision-impairing comorbidities, a BCVA better than 0.6 logMAR (Snellen acuity, 20/80) allows for appropriate nonmydriatic standard UWF imaging. In a high-volume clinic equipped with skilled ophthalmic examiners, screening with USG followed by directed IDO allows the efficient identification of retinal breaks in cataractous eyes.

Influencing factors of effective lens position in patients with Marfan syndrome and ectopia lentis.

AIMS: The aim of this study was to analyse the effective lens position (ELP) in patients with Marfan syndrome (MFS) and ectopia lentis (EL). METHODS: Patients with MFS undergoing lens removal and primary intraocular lens (IOL) implantation were enrolled in the study. The back-calculated ELP was obtained with the vergence formula and compared with the theoretical ELPs. The back-calculated ELP and ELP error were evaluated among demographic and biometric parameters, including axial length (AL), corneal curvature radius (CCR) and white-to-white (WTW). RESULTS: A total of 292 eyes from 200 patients were included. The back-calculated ELP was lower in patients undergoing scleral-fixated IOL than those receiving in-the-bag IOL implantation (4.54 (IQR 3.65-5.20) mm vs 4.98 (IQR 4.56-5.67) mm, p<0.001). The theoretical ELP of the SRK/T formula exhibited the highest accuracy, with no difference from the back-calculated ELP in patients undergoing in-the-bag IOL implantation (5.11 (IQR 4.83-5.65) mm vs 4.98 (IQR 4.56-5.67) mm, p=0.209). The ELP errors demonstrated significant correlations with refraction prediction error (PE): a 1 mm ELP error led to PE of 2.42D (AL<22 mm), 1.47D (22 mm≤AL<26 mm) and 0.54D (AL≥26 mm). Multivariate analysis revealed significant correlations of ELP with AL (b=0.43, p<0.001), CCR (b=-0.85, p<0.001) and WTW (b=0.41, p=0.004). CONCLUSION: This study provides novel insights into the origin of PE in patients with MFS and EL and potentially refines existing formulas.

Novel compound heterozygous variants in LTBP2 associated with relative anterior microphthalmos.

PURPOSE: Relative anterior microphthalmos (RAM) is a rare congenital defect associated with severe vision impairment that is primarily caused by genetic alterations. The purpose of this study was to identify the causative genetic variants in two Chinese families with RAM with an autosomal recessive inheritance pattern. METHODS: DNA samples were obtained from two probands and their family members. Targeted next-generation sequencing (NGS) was used to screen 425 genes associated with inherited eye diseases to identify possible disease-causing variants in the two patients. Sanger sequencing was subsequently used to validate the results in both families. RESULTS: The targeted NGS panel identified potentially causative novel variants of the latent transforming growth factor beta binding protein 2 (LTBP2) gene in the two RAM families: a missense variant (c.2771C > T; p.Ala924Val) and an intronic variant (c.4582 + 9A > G) in Family A and a different missense variant (c.5239C > A; p.Arg1747Ser) and a synonymous variant (c.951G > A; p.Pro317Pro) in Family B. These four novel variants all cosegregated with the disease phenotype. CONCLUSION: To our knowledge, this is the first study to report novel LTBP2 gene variants related to RAM. Considering the importance of LTBP2 in ocular development, we provide initial insights into the potential pathogenic mechanisms of LTBP2 in RAM.

Safety and Efficacy of Capsular Tension Ring and Capsular Hook Implantation for Managing Ectopia Lentis in Marfan Syndrome: A Real-World Study.

OBJECTIVE: To evaluate the safety and efficacy of capsular tension ring and capsular hook (CTR-CH) implantation in Marfan syndrome (MFS) patients with ectopia lentis (EL). SETTING: Eye and ENT Hospital of Fudan University. DESIGN: Retrospective propensity-score matched cohort study. METHODS: This study included MFS patients who had in-the-bag intraocular lens (IOL) implantation assisted by CTR-CH or modified capsular tension ring (MCTR). The safety analysis focused on the re-surgery rate. The efficacy analysis compared the best-corrected visual acuity (BCVA) and the incidence of laser capsulotomy after propensity score matching (PSM). RESULTS: This study encompassed 148 eyes that had the CTR-CH procedure and 162 eyes that received MCTR implantation. In the CTR-CH group, the median age at the time of surgery was 5 years old, with a mean follow-up duration of 1.81 ± 0.4 years. Five eyes (3.38%) required a second surgery due to retinal detachment (2, 1.35%), IOL decentration (2, 1.35%), and CH dislocation (1, 0.68%). The re-surgery rate was comparable to that of the MCTR group (P = 0.486). After PSM, a total of 108 patients were recruited in each group. Postoperative BCVA was significantly improved in both groups (both P < 0.001), but comparable between the groups (P = 0.057). The posterior capsular opacification took place earlier (P = 0.046), while the anterior capsular opacification required laser capsulotomy at a later stage (P = 0.037) compared to the MCTR group. CONCLUSIONS: The CTR-CH procedure was a feasible, safe, and efficient approach for managing EL in MFS patients.

Prevalence and causes of vision impairment in elderly Chinese people living in suburban Shanghai.

PURPOSE: To investigate the current prevalence and causes of moderate and severe visual impairment (MSVI) and blindness in elderly people in suburban Shanghai, China. METHODS: A cross-sectional study based on the population was conducted, which involved 5846 individuals (11,692 eyes) aged 65 years or older. Thorough eye examinations were performed to assess the prevalence and leading factors of MSVI (BCVA <20/63 to ≥20/400) and blindness (BCVA <20/400). RESULTS: The standardized prevalence of bilateral MSVI and blindness was 3.3% and 0.6%, correspondingly. The standardized prevalence of monocular MSVI and blindness was 7.4% and 2.0%, correspondingly. Cataract (47.9% and 20.7%, correspondingly) and myopic macular degeneration (MMD, 25.7% and 31.1%, correspondingly) were the principal causes of bilateral MSVI and blindness. As for monocular MSVI, the primary causes were cataract (39.4%), age-related macular degeneration (AMD, 16.6%), and MMD (16.6%). The primary causes of monocular blindness were other posterior segment eye diseases (30.1%) and MMD (14.2%). In adults aged 65-74 years, MMD was the foremost factor causing bilateral vision impairment. Conversely, cataract was identified as the primary cause of bilateral and monocular vision impairment among adults aged ≥ 75 years. AMD accounts for a significant proportion of individuals across all age groups. CONCLUSIONS: The significant prevalence of MSVI and blindness among Chinese adults represents a critical public health issue. In addition to cataract, the vision impairment caused by MMD and AMD become an important issue in the elderly Chinese people.

The E156K mutation in the CRYAA gene affects the epithelial-mesenchymal transition and migration of human lens epithelial cells.

Purpose: To investigated the biological effects of E156K-mutated αA-crystallin (CRYAA) in human lens epithelial cells (HLECs). Methods: FLAG-tagged, human, full-length, wild-type (WT), or E156K-mutated CRYAA was expressed in HLECs under CRYAA knockdown. CRYAA expression was determined by quantitative reverse transcription polymerase chain reaction and western blotting (WB). Rhodamine cytoskeleton staining was used to observe the changes in cell morphology following transfection with WT or E156K-mutated CRYAA plasmids. WB was performed to assess the expression of markers related to epithelial-mesenchymal transition (EMT) and migration. Results: Rhodamine cytoskeleton staining revealed changes in the morphology of cells transfected with E156K-mutated CRYAA and opposite responses occurred after treatment with a ß-catenin inhibitor. Cells transfected with E156K-mutated CRYAA expressed remarkably higher levels of the mesenchymal biomarkers N-cadherin and vimentin but decreased levels of the epithelial biomarker E-cadherin, whereas opposite trends were observed in cells treated with the ß-catenin inhibitor, ICG001. The migratory capability of E156K-mutated CRYAA cells was significantly greater than that of WT cells (P < 0.001). This effect was accompanied by significantly increased expression levels of phosphorylated (p)-focal adhesion kinase (FAK) and p-Src. These changes were decreased significantly by treatment with FAK and Src inhibitors. Conclusion: E156K-mutated CRYAA induced EMT, in which the HLECs lost cell polarity, and acquired a mesenchymal phenotype with greater migratory capability. These biological effects may be associated with activation of the Wnt/ß-Catenin and FAK/Src signaling pathways.

Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome.

Ectopia lentis is a hallmark of Marfan syndrome (MFS), a genetic connective tissue disorder affecting 1/5000 to 1/10 000 individuals worldwide. Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified proteomics workflow with liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based data-independent acquisition (DIA) and field asymmetric ion mobility spectrometry (FAIMS) to profile the proteomes of aqueous humor (AH) and lens tissue from MFS children with ectopia lentis is utilized. Over 2300 and 2938 comparable proteins are identified in AH and the lens capsule, respectively. Functional enrichment analyses uncovered dysregulation of complement and coagulation-related pathways, collagen binding, and cell adhesion in MFS. Through weighted correlation network analysis (WGCNA) and machine learning, distinct modules associated with clinical traits are constructed and a unique biomarker panel (Q14376, Q99972, P02760, Q07507; gene names: GALE, MYOC, AMBP, DPT) is defined. These biomarkers are further validated using advanced parallel reaction monitoring (PRM) in an independent patient cohort. The results provide novel insights into the proteome characterization of ectopia lentis and offer a promising approach for developing a valuable biomarker panel to aid in the early diagnosis of Marfan syndrome via AH proteome.

Genotype Impacts Axial Length Growth in Pseudophakic Eyes of Marfan Syndrome.

Purpose: The purpose of this study was to investigate the relationship between axial length (AL) growth and FBN1 genotype in patients with Marfan syndrome (MFS) after lens surgery and customize the selection of intraocular lens (IOL) power. Methods: Patients with MFS who had lens surgery and primary IOL implantation received panel-based next-generation sequencing (NGS). The rate of axial length growth (RALG) was calculated using pre- and postoperative AL measurements and corrected log10-transformed age. A multivariable regression model of RALG was developed after analyzing the effect of FBN1 genotypes and confounding factors. Results: A total of 139 probands of MFS with a median age at lens surgery of 6.25 years (interquartile range [IQR] = 4.67, 12.50 years) were followed up for a median duration of 2.08 years (IQR = 1.16, 3.00 years). The AL growth curve between the age of 3 and 15 years old was logarithmic. Dominant-negative (DN) variants affecting the disulfide-bridge forming cysteines and the conserved residues for calcium-binding had significantly higher RALG than DN variants affecting other structures (P = 0.001) but comparable to that of haplo-insufficiency variants (P = 1.000). Pre-operative AL (b = 0.563, P = 0.011) and genotype constant (b = 2.603, P = 0.011) were significantly associated with RALG in the final model. A Python-based calculator, Marfan IOL Calculator version 2.0, was programmed using the RALG to predict postoperative AL and customize IOL selection based on the ocular biometric parameters and FBN1 genotype. Conclusions: FBN1 genotype impacted the growth of AL in patients with MFS after IOL implantation. Knowing the FBN1 genotype could help cataract surgeons to customize IOL selection.

What Should We Pay More Attention to Marfan Syndrome Expecting Ectopia Lentis: Incidence and Risk Factors of Retinal Manifestations.

(1) Background: This paper investigates the incidence and risk factors of retinal manifestations in patients with Marfan syndrome (MFS) in a Chinese cohort. (2) Methods: This is a population-based cross-sectional study. In total, 344 eyes (172 MFS participants) were enrolled, each of whom underwent a detailed ocular examination. B-scan ultrasonography, ultra-wide-angle fundus images and optical coherence tomography images were conducted to assess posterior staphyloma, types of retinal damages and maculopathy. (3) Results: MFS patients have a high proportion (32.5%) of maculopathy, among which atrophy is the most common type (27.6%). Compared with participants without maculopathy, participants with maculopathy had a longer axial length (AL), higher incidence of posterior staphyloma, macular split and retinal detachment (RD) (p < 0.001, p < 0.001, p < 0.001 and p = 0.001). Moreover, the stage of RD has a significant correlation with longer AL and shallower anterior chamber depth (ACD) (p = 0.001 and p = 0.034, respectively). (4) Conclusions: A higher incidence and earlier onset of fundus lesions were found in MFS patients. Yearly systematic examination is recommended for MFS children with fundus manifestation until the cardiovascular and skeletal development is complete.

Morphometric Assessment of the Ciliary Body in Patients With Marfan Syndrome and Ectopia Lentis: A Quantitative Study Using Ultrasound Biomicroscopy.

PURPOSE: To explore the biometric characteristics of the ciliary body in patients with Marfan syndrome (MFS) and ectopia lentis (EL). DESIGN: Cross-sectional study. METHODS: Seventy-two consecutive patients with MFS and EL and 72 nondiseased control subjects were recruited. Ciliary body biometric parameters such as ciliary muscle cross-sectional area at 2000 µm from the scleral spur (CMA2000), ciliary muscle thickness at 1000 µm from the scleral spur (CMT1000), and maximum ciliary body thickness (CBTmax) were measured from multiple directions with ultrasound biomicroscopy (UBM). The relationship between ciliary body parameters and other ocular characteristics was also evaluated. RESULTS: Average CMA2000, CMT1000, and CBTmax were 0.692 ± 0.015 mm2, 0.405 ± 0.010 mm, and 0.855 ± 0.023 mm in eyes of patients with MFS, respectively, and were significantly smaller than these values in control subjects (all P < .001). The prevalence of ciliary body thinning was 22.2% in the MFS group vs 0 in the control group (P < .001); eyes with more severe EL had smaller CMA2000 (P = .050), thinner CMT1000 (P = .022), and shorter CBTmax (P = .015). Patients with microspherophakia (MSP) had even smaller CMA2000 (P = .033) and CMT1000 (P = .044) than those without MSP. The most common subluxation direction was in the superonasal quadrant (n = 25; 39.7%), which probably correlates with the thinnest CMT1000 in the inferotemporal quadrant (P = .005). CONCLUSIONS: Patients with MFS and EL had thinner ciliary muscles, shorter ciliary processes, and a higher prevalence of ciliary body thinning, especially those with MSP. Both the extent and direction of subluxation were associated with ciliary body biometry..

Predicting axial length in patients with Marfan syndrome and ectopia lentis after modified capsular tension ring and intraocular lens implantation.

PURPOSE: To predict the growth of axial length (AL) in patients with Marfan syndrome (MFS) and ectopia lentis (EL). SETTING: Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Consecutive retrospective case series. METHODS: Eyes were evaluated that had modified capsular tension ring and intraocular lens (IOL) implantation. The rate of AL growth (RALG) was calculated using AL divided by log10-transformed age. A multivariate linear regression model of RALG was developed after validation. RESULTS: 128 patients with MFS and EL were enrolled with a median follow-up duration of about 3 years. RALG was independent of age between 3 years and 15 years old ( P = .799) and decreased to 0 thereafter ( P = .878). Preoperative AL was associated with RALG in patients under 15 years old ( P = .003). Beta values for the final model of RALG were as below: intercept (-9.794) and preoperative AL (0.664). The postoperative AL was predicted as: postAL = preAL + RALG × log 10 ([postAge + 0.6]/[preAge + 0.6]). The mean prediction error was -0.003 (95% CI, -0.386 to 0.3791) mm and the mean absolute percentage error was 1.93% (95% CI, 0.73% to 3.14%). A Python-based calculator was developed to use the predicted AL in selecting IOL power and setting undercorrection. CONCLUSIONS: The AL growth of patients with MFS followed a logarithmic pattern and ceased at about age 15. A prediction model of postoperative AL was established for individual MFS patients between 3 and 15 years old, which could potentially optimize the IOL power selection.

The Differential Expression of Circular RNAs and the Role of circAFF1 in Lens Epithelial Cells of High-Myopic Cataract.

High-myopic cataract (HMC) is a complex cataract with earlier onset and more rapid progress than age-related cataract (ARC). Circular RNAs (circRNAs) have been implicated in many diseases. However, their involvement in HMC remain largely unexplored. To investigate the role of dysregulated circRNAs in HMC, lens epithelium samples from 24 HMC and 24 ARC patients were used for whole transcriptome sequencing. Compared with ARC, HMC had 3687 uniquely expressed circRNAs and 1163 significantly differentially expressed circRNAs (DEcRs) (|log2FC| > 1, p < 0.05). A putative circRNA-miRNA-mRNA network was constructed based on correlation analysis. We validated the differential expression of 3 DEcRs by quantitative polymerase chain reaction (qPCR) using different sets of samples. We further investigated the role of circAFF1 in cultured lens epithelial cells (LECs) and found that the overexpression of circAFF1 promoted cell proliferation, migration and inhibited apoptosis. We also showed that circAFF1 upregulated Tropomyosin 1 (TPM1) expression by sponging miR-760, which was consistent with the network prediction. Collectively, our study suggested the involvement of circRNAs in the pathogenesis of HMC and provide a resource for further study on this topic.

Supracapsular scleral sutured intraocular lens implantation in anterior segment dysgenesis patients with ectopia lentis.

OBJECTIVE: To describe a new strategy to manage ectopia lentis in ASD patients assessing the visual outcomes and safety of supracapsular scleral sutured intraocular lens implantation and analyzing the accuracy of different intraocular lens (IOL) power calculation formulae. METHODS: Eight patients with ASD (13 eyes) were underwent supracapsular scleral suture fixation of posterior chamber (PC) IOL without capsular extirpation. The preoperative and postoperative clinical features were compared. The prediction error values from four formulae (SRK/T, Holladay 1, Hoffer Q, Haigis), with or without Wang-Koch (WK) adjustment, were calculated for the cases. RESULTS: Zonulodialysis and premature cataracts could be the main reason for the decreased vision in patients with ASD. There was a significant improvement in best corrected visual acuity on 3-month follow-up after applying supracapsular scleral suture fixation of PC IOL. The prediction errors of the different formulae showed a slight tendency towards postoperative myopia. The Haigis formula with WK adjustment showed the best performance. CONCLUSIONS: Supracapsular scleral suture fixation of IOLs for retaining the capsule-zonule barrier is a good option for ASD patients. The Haigis formula is recommended for ASD patients treated with supracapsular scleral suture fixation of IOLs. The predicted IOL power should be reduced based on the effect of the new anatomic position of the IOL to achieve a satisfactory visual outcome.

Association between single nucleotide polymorphisms in exon 3 of the alpha-A-crystallin gene and susceptibility to age-related cataract.

BACKGROUND: The mutations in the αA-crystallin (CRYAA) gene may contribute to the development of age-related cataract (ARC). In this study, we searched for single nucleotide polymorphisms (SNP) in exons of CRYAA and investigated the associations between the identified SNPs and the subtypes of ARC. MATERIALS AND METHODS: Peripheral venous blood was collected for the extraction of genomic DNA. Three exons of CRYAA were sequenced to detect SNPs. The frequency distributions of alleles and genotypes were compared between the ARC and control groups. RESULTS: There were 618 patients with various subtypes of ARC (nuclear cataract [NC], cortical cataract [CC], posterior subcapsular cataract [PSC]). The control group comprised 236 patients. The incidence of early-onset cataract was significantly greater in PSC patients (P = .002 for NC; P = .036 for CC). One SNP was detected in exon 3 of CRYAA (rs76740365 G>A). When the distribution of rs76740365 was compared among the ARC subtypes, only the difference between the PSC group and the control group was statistically significant (allele frequency: P = .000057, OR 2.945; genotype distribution frequency: P = .000458). The heterozygote genotype (GA) carried a significantly greater risk than the homozygous wild-type genotype (GG) by 1.742 times for all types of cataracts and 2.369 times for the PSC subtype. CONCLUSIONS: The SNP rs76740365 G>A in exon 3 of the CRYAA gene is associated with greater susceptibility of ARC, particularly the PSC subtype. Individuals carrying the SNP rs76740365 G>A may be more likely to develop PSC at a younger age than other subtypes.

Changes in Vector Astigmatism After Superotemporal Versus Temporal Clear Corneal Incision Cataract Surgery.

PURPOSE: To investigate vector and refractive astigmatism changes after superotemporal versus temporal clear corneal incision cataract surgery. METHODS: Patients were diagnosed with age-related cataract with corneal astigmatism < 1.5 diopters (D) and were divided into two groups: superotemporal incision (R group) and temporal incision (L group). Uncorrected visual acuity, manifest refraction, corneal topography, anterior segment optical coherence tomography was performed pre- and six months postoperatively. Total ocular astigmatism, corneal astigmatism, vector of surgically induced corneal astigmatism (SICA), non-corneal ocular residual astigmatism (N-CORA), postoperative intraocular lens decentration and tilt were analyzed.  Results: Thirty-eight subjects were included: 21, R group; 17, L group. After surgery, the N-CORA decreased significantly from 1.17±0.72 D to 0.73±0.47 D in all patients (P=0.001), 1.03±0.52 D to 0.70±0.40 D in the R group (P=0.005) and 1.35±0.90 D to 0.78±0.55 D in the L group (P=0.033). Significant differences between t:he R and L groups were found in the postoperative meridian of anterior corneal astigmatism (75.95±52.50 vs 116.79±47.29; P=0.017), total corneal astigmatism (51.65±42.75 vs 95.20±57.32; P=0.011), J45 change vector of SICA in the anterior cornea (-0.10±0.18 vs 0.00±0.11; P=0.048) and total cornea surface (-0.14±0.17 vs 0.03±0.12; P=0.001).  Conclusion: The N-CORA decreased significantly after cataract surgery. Superotemporal and temporal incisions caused differences in the meridian components of oblique astigmatism in some patients but did not have a significant effect on the magnitude of corneal astigmatism.

Structural and functional analysis of SNP rs76740365 G>A in exon-3 of the alpha A-crystallin gene in lens epithelial cells.

Purpose: To clarify the effect of a previously identified single nucleotide polymorphism (SNP; rs76740365 G>A) in the exon-3 of the alpha A-crystallin (CRYAA) gene on the properties of CRYAA and to investigate its function in human lens epithelial cells (HLECs). Methods: The human recombinant wild-type and mutant CRYAA (E156K) were constructed, and the molecular weight was measured by mass spectrometry. The structural changes induced by E156K mutation were analyzed by UV circular dichroism spectra and intrinsic tryptophan fluorescence and were predicted using Schrödinger software. The chaperone-like ability of wild-type and E156K mutant CRYAA was invested against the heat-induced aggregation of ßL-crystallin and the DTT-induced aggregation of insulin. HLECs expressing wild-type and mutated CRYAA were subjected to quantitative PCR (qPCR) and western blot. Cell apoptosis was determined using flow cytometry analysis, and the expression of apoptosis-related proteins were determined using western blot. Results: The mass spectrometric detection revealed that E156K mutation had no significant effect on the apparent molecular mass of the CRYAA oligomeric complex. Evaluation of the structures of the CRYAA indicated that E156K mutation did not significantly affect the secondary structures, while causing perturbations of the tertiary structure. The mutant CRYAA displayed an increase in chaperone-like activity, which might be related to the increase of the surface hydrophobicity. We also predicted that E156K mutation would induce a change from negatively charged surface to positively charged, which was the possible reason for the disturbance to the surface hydrophobicity. Transfection studies of HLECs revealed that the E156K mutant induced anti-apoptotic function in HLECs, which was possibly associated with the activation of the p-AKT signal pathway and downregulation of Casepase3. Conclusions: Taken together, our results for the first time showed that E156K mutation in CRYAA associated with ARC resulted in enhanced chaperone-like function by inducing its surface hydrophobicity, which was directly related to the activation of its anti-apoptotic function.

Mutation analysis of SUOX in isolated sulfite oxidase deficiency with ectopia lentis as the presenting feature: insights into genotype-phenotype correlation.

BACKGROUND: Isolated sulfite oxidase deficiency (ISOD) caused by sulfite oxidase gene (SUOX) mutations is a rare neurometabolic disease associated with ectopia lentis (EL). However, few genotype-phenotype correlations have been established yet. METHODS: Potentially pathogenic SUOX mutations were screened from a Chinese cohort of congenital EL using panel-based next-generation sequencing and analyzed with multiple bioinformatics tools. The genotype-phenotype correlations were evaluated via a systematic review of SUOX mutations within our data and from the literature. RESULTS: A novel paternal missense mutation, c.205G > C (p.A69P), and a recurrent maternal nonsense mutation, c.1200 C > G (p.Y400*), of SUOX were identified in a 4-year-old boy from 312 probands. The biochemical assays manifested elevated urine sulfite and S-sulfocysteine accompanied by decreased homocysteine in the blood. The patient had bilateral EL and normal fundus, yet minimal neurological involvement and normal brain structure. Molecular modeling simulation revealed the p.A69P mutant had an unstable structure but an unchanged affinity for sulfite, while the truncated p.Y400* mutant showed decreased binding capacity. Genotype-phenotype analysis demonstrated patients with biallelic missense mutations had milder symptoms (P = 0.023), later age of onset (P < 0.001), and a higher incidence of regression (P = 0.017) than other genotypes. No correlations were found regarding EL and other neurological symptoms. CONCLUSION: The data from this study not only enrich the known mutation spectrum of SUOX but also suggest that missense mutations are associated with mild and atypical symptoms.

Biallelic ADAMTSL4 variants in a Chinese cohort of congenital ectopia lentis: Implications for genotype-phenotype relationships.

ADAMTSL4 variants are one of the common causes of congenital ectopia lentis (EL), reported ocular comorbidities of which include iris anomalies, cataract, and glaucoma. However, a genotype-phenotype correlation has not been established. Potentially pathogenic ADAMTSL4 variants were screened from a Chinese cohort of congenital EL using panel-based next-generation sequencing followed by multiple bioinformatics analyses. The genotype-phenotype correlation was assessed via a systematic review of ADAMTSL4 variants within our data and those from the literature. A total of 12 variants of ADAMTSL4, including seven frameshift variants, one nonsense variant, two splicing variants, and two missense variants, were found in nine probands. Combing genetic and clinical information from 72 probands in the literature revealed 37 ADAMTSL4 variants known to cause EL, and the ethnic difference was prominent. The lens was inclined to dislocate inferior temporally (22, 27.16%), while the pupil was always located oppositely (9, 81.82%). Several anterior segments anomalies were identified, including ectopia pupillae (15, 18.52%), persistent pupillary membrane (9, 11.10%), poor pupil dilation (4, 30.8%), cataract (13, 24.10%), and glaucoma (8, 13.33%). Genotype-phenotype analysis revealed that truncation variants had higher risks of combined iris anomalies, including either ectopia pupillae or a persistent pupillary membrane (p = 0.007). The data from this study not only extend our knowledge of the ADAMTSL4 variant spectrum but also suggest that deleterious variants of ADAMTSL4 might be associated with severe ocular phenotypes.

Genotype-phenotype correlations of marfan syndrome and related fibrillinopathies: Phenomenon and molecular relevance.

Marfan syndrome (MFS, OMIM: 154700) is a heritable multisystemic disease characterized by a wide range of clinical manifestations. The underlying molecular defect is caused by variants in the FBN1. Meanwhile, FBN1 variants are also detected in a spectrum of connective tissue disorders collectively termed as 'type I fibrillinopathies'. A multitude of FBN1 variants is reported and most of them are unique in each pedigree. Although MFS is being considered a monogenic disorder, it is speculated that the allelic heterogeneity of FBN1 variants contributes to various manifestations, distinct prognoses, and differential responses to the therapies in affected patients. Significant progress in the genotype-phenotype correlations of MFS have emerged in the last 20 years, though, some of the associations were still in debate. This review aims to update the recent advances in the genotype-phenotype correlations of MFS and related fibrillinopathies. The molecular bases and pathological mechanisms are summarized for better support of the observed correlations. Other factors contributing to the phenotype heterogeneity and future research directions were also discussed. Dissecting the genotype-phenotype correlation of FBN1 variants and related disorders will provide valuable information in risk stratification, prognosis, and choice of therapy.

Plasma Surface Engineering of NiCo2S4@rGO Electrocatalysts Enables High-Performance Li-O2 Batteries.

The sluggish redox reaction kinetics for aprotic Li-O2 batteries (LOBs) caused by the insulating discharge product of Li2O2 could result in the poor round-trip efficiency, low rate capability, and cyclic stability. To address these challenges, we herein fabricated NiCo2S4 supported on reduced graphene oxide (NiCo2S4@rGO), the surface of which is further modified via a unique low-pressure capacitive-coupled nitrogen plasma (CCPN-NiCo2S4@rGO). The high ionization environment of the plasma could etch the surface of NiCo2S4@rGO, introducing effective nitrogen doping. The as-prepared CCPN-NiCo2S4@rGO has been employed as an efficient catalyst for advanced LOBs. The electrochemical analysis, combined with theoretical calculations, reveals that the N-doping can effectively improve the thermodynamics and kinetics for LiO2 adsorption, giving rise to a well-knit Li2O2 formation on CCPN-NiCo2S4@rGO. The LOBs based on the CCPN-NiCo2S4@rGO oxygen electrode deliver a low overpotential of 0.75 V, a high discharge capacity of 10,490 mA h g-1, and an improved cyclic stability (more than 110 cycles). This contribution may pave a promising avenue for facile surface engineering of the electrocatalyst in LOBs and other energy storage systems.