Loss-of-function mutations in FREM2 disrupt eye morphogenesis.

Cryptophthalmos is a rare congenital disorder characterized by ocular dysplasia with eyelid malformation. Complete cryptophthalmos is characterized by the presence of continuous skin from the forehead over the eyes and onto the cheek, along with complete fusion of the eyelids. In the present study, we characterized the clinical manifestations of three patients with isolated bilateral cryptophthalmos. These patients shared the same c.6499C > T missense mutation in the FRAS1-related extracellular matrix protein 2 (FREM2) gene, while each individual presented an additional nonsense mutation in the same gene (Patient #1, c.2206C > T; Patient #2, c.5309G > A; and Patient #3, c.4063C > T). Then, we used CRISPR/Cas9 to generate mice carrying Frem2R725X/R2156W compound heterozygous mutations, and showed that these mice recapitulated the human isolated cryptophthalmos phenotype. We detected FREM2 expression in the outer plexiform layer of the retina for the first time in the cryptophthalmic eyes, and the levels were comparable to the wild-type mice. Moreover, a set of different expressed genes that may contribute secondarily to the phenotypes were identified by performing RNA sequencing (RNA-seq) of the fetal Frem2 mutant mice. Our findings extend the spectrum of FREM2 mutations, and provide insights into opportunities for the prenatal diagnosis of isolated cryptophthalmos. Furthermore, our work highlights the importance of the FREM2 protein during the development of eyelids and the anterior segment of the eyeballs, establishes a suitable animal model for studying epithelial reopening during eyelid development and serves as a valuable reference for further mechanistic studies of the pathogenesis of isolated cryptophthalmos.

Preoperative profile of inflammatory factors in aqueous humor correlates with postoperative inflammatory response in patients with congenital cataract.

Purpose: To measure the aqueous humor concentrations of inflammatory factors in patients with congenital cataract and to investigate the relationship between the levels and postoperative inflammatory responses. Methods: Aqueous humor samples were prospectively collected from 65 eyes of children with congenital cataracts from January to June 2015. The levels of 41 inflammation-related cytokines, chemokines, and growth factors in aqueous humor were measured using multiplex bead immunoassay. Data on patient demographics and postoperative inflammatory response evaluation of posterior capsule opacification (EPCO) scores were collected for correlation analysis of short- and long-term postoperative inflammatory responses, respectively. Results: Fifteen inflammatory factors were differentially expressed between congenital cataract and age-related cataract. EGF and IL-3 were positively correlated, whereas IL-8 and MCP-1 were negatively correlated with age. TNFα, IL-17A, IL-3, and sCD40L were preferably expressed in specific morphological types of congenital cataract. One month and 3 months postoperatively, PDGF-AA exhibited a positive correlation with the EPCO scores, whereas IL-1RA exhibited a negative correlation. Macrophage-derived chemokine (MDC) showed a positive correlation with the EPCO scores 1 year postoperatively. Conclusions: This study provided a comprehensive preoperative profile of inflammatory factors and their correlations with postoperative inflammatory responses in patients with congenital cataract. These factors may serve as potential biomarkers to predict the postoperative inflammatory response. These findings will also facilitate the development of anti-inflammatory medications in the perioperative period.

Dynamic response to initial stage blindness in visual system development.

Sensitive periods and experience-dependent plasticity have become core issues in visual system development. Converging evidence indicates that visual experience is an indispensable factor in establishing mature visual system circuitry during sensitive periods and the visual system exhibits substantial plasticity while facing deprivation. The mechanisms that underlie the environmental regulation of visual system development and plasticity are of great interest but need further exploration. Here, we investigated a unique sample of human infants who experienced initial stage blindness (beginning at birth and lasting for 2-8 months) before the removal of bilateral cataracts. Retinal thickness (RT), axial length (AL), refractive status, visual grating acuity and genetic integrity were recorded during the preoperative period or at surgery and then during follow-up. The results showed that the development of the retina is malleable and associated with external environmental influences. Our work supported that the retina might play critical roles in the development of the experience-dependent visual system and its malleability might partly contribute to the sensitive period plasticity.

Automatic diagnosis of imbalanced ophthalmic images using a cost-sensitive deep convolutional neural network.

BACKGROUND: Ocular images play an essential role in ophthalmological diagnoses. Having an imbalanced dataset is an inevitable issue in automated ocular diseases diagnosis; the scarcity of positive samples always tends to result in the misdiagnosis of severe patients during the classification task. Exploring an effective computer-aided diagnostic method to deal with imbalanced ophthalmological dataset is crucial. METHODS: In this paper, we develop an effective cost-sensitive deep residual convolutional neural network (CS-ResCNN) classifier to diagnose ophthalmic diseases using retro-illumination images. First, the regions of interest (crystalline lens) are automatically identified via twice-applied Canny detection and Hough transformation. Then, the localized zones are fed into the CS-ResCNN to extract high-level features for subsequent use in automatic diagnosis. Second, the impacts of cost factors on the CS-ResCNN are further analyzed using a grid-search procedure to verify that our proposed system is robust and efficient. RESULTS: Qualitative analyses and quantitative experimental results demonstrate that our proposed method outperforms other conventional approaches and offers exceptional mean accuracy (92.24%), specificity (93.19%), sensitivity (89.66%) and AUC (97.11%) results. Moreover, the sensitivity of the CS-ResCNN is enhanced by over 13.6% compared to the native CNN method. CONCLUSION: Our study provides a practical strategy for addressing imbalanced ophthalmological datasets and has the potential to be applied to other medical images. The developed and deployed CS-ResCNN could serve as computer-aided diagnosis software for ophthalmologists in clinical application.

Construction and implications of structural equation modeling network for pediatric cataract: a data mining research of rare diseases.

BACKGROUND: The majority of rare diseases are complex diseases caused by a combination of multiple morbigenous factors. However, uncovering the complex etiology and pathogenesis of rare diseases is difficult due to limited clinical resources and conventional statistical methods. This study aims to investigate the interrelationship and the effectiveness of potential factors of pediatric cataract, for the exploration of data mining strategy in the scenarios of rare diseases. METHODS: We established a pilot rare disease specialized care center to systematically record all information and the entire treatment process of pediatric cataract patients. These clinical records contain the medical history, multiple structural indices, and comprehensive functional metrics. A two-layer structural equation model network was applied, and eight potential factors were filtered and included in the final modeling. RESULTS: Four risk factors (area, density, location, and abnormal pregnancy experience) and four beneficial factors (axis length, uncorrected visual acuity, intraocular pressure, and age at diagnosis) were identified. Quantifiable results suggested that abnormal pregnancy history may be the principle risk factor among medical history for pediatric cataracts. Moreover, axis length, density, uncorrected visual acuity and age at diagnosis served as the dominant factors and should be emphasized in regular clinical practice. CONCLUSIONS: This study proposes a generalized evidence-based pattern for rare and complex disease data mining, provides new insights and clinical implications on pediatric cataract, and promotes rare-disease research and prevention to benefit patients.

Height, weight and body mass index of children with congenital cataracts before surgical treatment.

BACKGROUND: To investigate the distribution of the height, weight and body mass index (BMI) of children with congenital cataracts (CC) before surgical treatment. METHODS: This prospective study included children with CC ≤14 years of age presenting at the Zhongshan Ophthalmic Center from Jan. 2013 to Aug. 2016. The height, weight, and BMI measurements of all participating children were obtained and compared with the World Health Organization Child Growth Reference (WHO Reference), matched by age and gender. The presence of a family history of CC or complicated systemic diseases as well as parental education levels and family income were also recorded. RESULTS: In total, 595 children with CC were included. The mean age was 52.75 ± 33.99 months, and 34.29% (204/595) of them were unilateral cases. Among all of the children, 6.72% (40/595) of cases were complicated by systemic diseases. More than 1/5 (21.01%, 125/595) of the children had a family history of CC and exhibited bilateral involvement. Less than 1/4 (23.2) of the mothers were highly educated, and more than half of the families had a family income below the city average. Height, weight, and BMI measurements of most children with CC were within the normal ranges (±95% CI of the WHO Reference). Compared to the WHO Reference, both girls and boys aged 2-5 years revealed shorter heights, and the girls aged 5-14 years exhibited a shorter height, lower body weight and lower BMI. The heights of the children with CC and systemic diseases were also shorter than the WHO Reference. The children with CC who had a family history of disease had shorter heights and lower BMIs than children with CC but no family history, and the measurements of both groups were lower than the WHO Reference values. CONCLUSIONS: The height, weight and BMI of most of the children with CC in this study were within the normal ranges of the WHO Reference. However, the children with CC and concomitant systemic diseases and those with a family history of CC had shorter heights and lower BMIs. This information aids in our understanding of the physical development of children with CC.

Distribution of axial length, anterior chamber depth, and corneal curvature in an aged population in South China.

BACKGROUND: Ocular biometry is important for preoperative assessment in cataract and anterior segment surgery. The purpose of this study was to investigate normative ocular biometric parameters and their associations in an older Chinese population. METHODS: This was a cross-sectional observational study. From 2013 to 2014, we recruited inhabitants aged 50 years or older in Guangzhou, China. Among 1,117 participants in the study, data from 1,015 phakic right eyes were used for analyses. Ocular parameters including axial length (AL), anterior chamber depth (ACD), and corneal curvature (K) were measured using an IOL Master. RESULTS: The mean AL, ACD, and K were 23.48 mm [95 % confidence interval (CI), 23.40-23.55], 3.03 mm (CI, 3.01-3.05), and 44.20 mm (CI, 44.11-44.29), respectively. A mean reduction in ACD with age was observed (P = 0.002) in male subjects but not in female subjects (P = 0.558). Male subjects had significantly longer ALs (23.68 mm versus 23.23 mm, P < 0.001), deeper ACDs (3.13 mm versus 2.95 mm, P < 0.001), and flatter Ks (43.85D versus 44.50 D, P < 0.001) than female subjects. Eyes with axial elongation had a flatter cornea (r = -0.437, P < 0.001) and a deeper anterior chamber (r = 0.652, p < 0.001). The ACD was correlated with K (r = -0.266, P < 0.001). CONCLUSIONS: These data provide normative values for AL, ACD, and K using the IOL Master for a population in South China. The AL in this Chinese cohort was greater than that observed in the Singaporean Chinese but smaller than that observed in Malaysia and for Caucasians. The Chinese have a shallower ACD than some other racial groups. Age and sex were the most consistent predictors of ocular biometry in the older population from South China.

Comparisons of the in-the-bag stabilities of single-piece and three-piece intraocular lenses for age-related cataract patients: a randomized controlled trial.

BACKGROUND: To compare the in-the-bag stability and visual function of single-piece intraocular lenses (IOLs) and three-piece IOLs. METHODS: A total of 65 patients with age-related cataracts (80 eyes) were enrolled and randomly assigned to receive in-the-bag implantation of either a single-piece IOL (40 eyes) or a three-piece IOL (40 eyes). Follow-up visits were conducted at 1 week, 1 month and 3 months postoperatively. Visual acuity, refraction and total aberration were examined. IOL position stability (including axial movement, decentration and tilt) was measured using a Scheimpflug imaging system. RESULTS: At the 3-month follow-up visit, single-piece IOLs did not exhibit significant axial movement (0.07 ± 0.30 mm, p = 0.13) compared with their axial position at 1 week postoperatively, whereas three-piece IOLs displayed forward axial movement of -0.22 ± 0.23 mm (p < 0.0001). The mean manifest spherical equivalence (SE) of eyes with single-piece IOL was 0.15 ± 0.18D, whereas in eyes with three-piece IOLs, the mean manifest SE was -0.34 ± 0.15D (p < 0.001). There was no statistically significant difference in IOL decentration, tilt, uncorrected visual acuity, best-corrected visual acuity or total spherical aberration between the two groups. CONCLUSIONS: Three months after implantation, single-piece IOLs exhibit better axial stability and more stable refractive outcome than three-piece IOLs, but both IOLs perform equally well in terms of decentration, tilt, visual acuity and total aberration. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02609997 , 11/18/2015, retrospectively registered.

Interocular anatomical and visual functional differences in pediatric patients with unilateral cataracts.

BACKGROUND: Congenital cataracts are often complicated by anterior segment dysgenesis. This study aims to compare bilateral anterior segment parameters, macular thickness, and best-corrected visual acuity (BCVA) in pediatric cataract patients at 3 months after unilateral cataract extraction with intraocular lens implantation. METHODS: Fifty-three pediatric patients with uncomplicated unilateral total cataracts were included. At 3 months post-surgery, bilateral corneal thickness at the thinnest location (CTTL), anterior chamber depth (ACD), and anterior chamber volume (ACV) were measured using Pentacam. Central macular thickness (CMT) was evaluated using spectral-domain optical coherence tomography. BCVA was measured by experienced optometrists concurrently. Descriptive statistics and bivariate corrections were performed to analyze the interocular differences in bilateral anatomic parameters and their relationships with BCVA. RESULTS: For all 53 included patients (mean age 5.2 ± 2.3 years), the median BCVA was 10/40 in the operated eyes and 40/40 in the contralateral eyes, which indicates a significant interocular difference. BCVA values in the contralateral eyes were significantly correlated with patient age at surgery, but this result differed for BCVA in the operated eyes. The Pentacam analysis revealed no significant interocular differences in bilateral CTTL and ACV, but significant differences were found for ACD. CONCLUSIONS: At 3 months after surgery, unilateral pediatric cataract patients exhibited no significant interocular differences in identified anatomical parameters (except for ACD), and these parameters were not significantly correlated with BCVA in bilateral eyes. Therefore, amblyopia, but not anatomical factors, might be the main cause of interocular visual functional differences in our study population. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02765230 , 05/05/2016, retrospectively registered.

Spatial distribution of rare earth elements and their impact factors in an area with a high abundance of regolith-hosted deposits.

Despite the widespread occurrence of regolith-hosted rare earth elements (REEs) across South China, their spatial distribution characteristics in soils and their impact factors remain largely uncertain. This knowledge gap impedes the exploration of regolith-hosted REE deposits and the assessment of the environmental risks associated with REEs. To address this issue, 180 soil samples were collected from Meizhou City, Guangdong Province, a region known for its high abundance of regolith-hosted REEs. Subsequently, the correlations between REE enrichment/fractionation and various factors, i.e., topography, climate conditions, land use, and landform were analysed using the geo-detector method. The results revealed a highly uneven spatial distribution of REEs and their fractionation features with some regions displaying distinct spatial patterns. Elevation was the dominant factor influencing this distribution, and showed strong correlations with the concentrations of REEs, light REEs (LREEs) and heavy REEs (HREEs); the LREE/HREE ratio; and the positive Ce anomaly (δCe). The negative Eu anomaly (δEu) showed a good correlation with rock type. The enrichment and fractionation of REEs indicated a coupling among the abovementioned factors. For REE enrichment, areas with elevations of 138-148 m, precipitation levels of 1553-1574 mm, annual average land surface temperatures of 30.4-30.5 °C, leaf area index values of 22-29 and surface cutting degree of 21.5-29.9 m showed the highest average abundance within each type (scope) of the predominant factors. These findings highlight the key factors affecting REE distribution, thereby aiding the efficient utilization of regolith-hosted REE resources and the evaluation of their environmental risks.

Reopening the capsular bag by removing the capsular proliferative membrane to enable secondary in-the-bag intraocular lens implantation in pediatric aphakic eyes.

PURPOSE: To present a surgical technique for reopening the capsular bag in pediatric aphakia. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Case series study. METHODS: Consecutive pediatric patients with bilateral aphakia requiring secondary intraocular lens (IOL) implantation between July 2021 and June 2022 were included. The diameter of the capsular proliferative membranous ring (PMR) and position of IOL implantation were documented. Various parameters of capsular bag opening during primary cataract removal and secondary surgery were also analyzed. RESULTS: 48 eyes were included with a mean follow-up of 8.1 ± 4.4 months. Using the surgical technique developed in this study, the capsular bag was successfully reopened with in-the-bag (ITB) implantation in 43 eyes (89.6%). ITB implantation was accomplished in all eyes with an outer diameter of PMR ≤5.5 mm and in 3 of 8 eyes (37.5%) with an outer diameter of PMR >5.5 mm. A positive correlation was observed between the primary and secondary anterior capsular opening diameters (ACODs) ( r = 0.422, P = .007) and the primary and secondary posterior capsular opening diameters (PCODs) ( r = 0.619, P < .001). The inner diameter of PMR was found to be positively correlated with secondary PCOD ( r = 0.728, P < .001) and the outer diameter with secondary ACOD ( r = 0.669, P < .001). CONCLUSIONS: This was a safe and effective surgical technique for pediatric secondary IOL implantation with maximum preservation of the peripheral capsule. Aphakic eyes with an outer diameter of PMR ≤5.5 mm are preferred for secondary ITB implantation.

Incidence of and risk factors for suspected and definitive glaucoma after bilateral congenital cataract surgery: a 5-year follow-up.

AIMS: To report the incidence and associated risk factors for developing suspected and definitive glaucoma after bilateral congenital cataract (CC) removal with a 5-year follow-up. METHODS: Secondary analysis of a prospective longitudinal cohort study. Bilateral CC patients who had undergone cataract surgery between January 2011 and December 2014 at Zhongshan Ophthalmic Centre were recruited. Suspected glaucoma was defined as persistent ocular hypertension requiring medical treatment. Definitive glaucoma was defined as accompanied by the progression of glaucomatous clinical features. According to postoperative lens status in 5 years follow-up: 130 eyes in the aphakia group; 219 in the primary intraocular lens (IOL) implantation group and 337 in the secondary IOL implantation group. The Kaplan-Meier survival and Cox regression analyses were used to explore the cumulative incidence and risk factors for suspected and definitive glaucoma. RESULTS: Three hundred fifty-one children (686 eyes) with bilateral CCs were enrolled in the study. The mean age at surgery was 1.82±2.08 years, and the mean follow-up duration was 6.26±0.97 years. Suspected and definitive glaucoma developed at a mean time of 2.84±1.75 years (range 0.02-7.33 years) postoperatively. The cumulative incidence of suspected and definitive glaucoma was 9.97% (35 of 351 patients), including 6.12% (42 eyes) for definitive glaucoma and 2.48% (17 eyes) for suspected glaucoma. Microcornea (HR 4.103, p<0.0001), CC family history (HR 3.285, p=0.001) and initial anterior vitrectomy (HR 2.365 p=0.036) were risk factors for suspected and definitive glaucoma. Gender, age at surgery, intraocular surgery frequency, length of follow-up and frequency of neodymium-doped yttrium aluminumaluminium garnet laser were non-statistically significant. Primary IOL implantation was a protective factor (HR 0.378, p=0.007). CONCLUSIONS: Identifying suspected and definitive glaucoma after bilateral CC surgery can lower the risk of secondary blindness in children. Patients with related risk factors need to pay more attention and thus reach early intervention and treatment during clinical practice. Primary IOL implantation may be a potential protective factor, need more clinical trials to be verified. TRIAL REGISTRATION NUMBER: NCT04342052.

Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

Background: This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Methods: Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. Results: A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Conclusion: Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

Surgical approach to and morphology of visually significant persistent pupillary membranes.

PURPOSE: To characterize the morphology of persistent pupillary membranes (PPMs) in pediatric patients and explore the corresponding surgical approaches. SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Prospective observational study. METHODS: Consecutive pediatric patients with PPMs who underwent surgery from April 2020 to July 2022 were included. PPM morphology was assessed and categorized according to its anatomic relationship with crystalline lens and distribution of iris strands. The surgical approaches for different morphologies of PPMs were described in detail. The visual outcome and operation-related complications were recorded. RESULTS: 31 eyes from 19 patients were included with the mean age of 7.2 years. 3 morphological variants of PPMs were observed: type I (51.6%, 16/31), a spider-like appearance and no adhesion to the anterior lens capsule (ALC); type II (38.7%, 12/31), a loose central adherence to the ALC and partially thick iris strands attached to the iris collarette; type III (9.7%, 3/31), a tight central adherence to the ALC and only silk-like iris strands. Surgeries were performed with a natural pupil size in type I, while dilated pupil in the other types. The adhesions between PPM and the ALC were separated by viscoelastic injection in type II and by discission needles in type III. The corrected distance visual acuity was significantly improved from 0.34 ± 0.18 logMAR preoperatively to 0.17 ± 0.09 logMAR postoperatively ( P < .001). No operation-related complications were observed during 9.5-month follow-up. CONCLUSIONS: PPMs were categorized into 3 types according to their different morphologies, which helped to determine the best surgical strategy.

Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts.

PURPOSE: To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients. DESIGN: Prospective cohort study. METHODS: Setting: the participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre- and postoperative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data. PARTICIPANTS: 115 patients with unrelated congenital cataract. INTERVENTIONS: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants. MAIN OUTCOMES AND MEASURES: factors related to the genetic diagnosis yield of syndromic congenital cataracts. RESULTS: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A phenotype-genotype correlation was detected for some genes and deep phenotypes. CONCLUSIONS: We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of whole-exome sequencing helps provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible.

Transient vacuolar changes of the crystalline lens in patients using a dispersive ophthalmic viscosurgical device.

AIM: To report the clinical prognosis and pathological findings of accidental lens vacuolar changes in eyes with intraoperative exposure to a dispersive ophthalmic viscosurgical device (OVD). METHODS: Two patients who developed transient lens vacuolar changes during uneventful persistent pupillary membrane (PPM) removal surgery were presented and followed up. This event was speculated to be associated with an intraoperative dispersive OVD DisCoVisc (hyaluronic acid 1.6%-chondroitin sulfate 4.0%) exposure. Then, to provide the pathological basis for our speculation, another four cataract patients were randomly exposed to different OVDs, and their anterior lens capsules were investigated with transmission electron microscopy (TEM). RESULTS: After months, the subcapsular vacuoles in both PPM cases were gradually disappeared without visual deterioration. For the cataract patients, similar lens changes were observed intraoperatively in those exposed to a dispersive DisCoVisc but not a cohesive OVD IVIZ (sodium hyaluronate gel 1.0%). In addition, marked ultrastructural changes, including chromatin condensation, extensive cytoplasmic vacuoles, and obvious intercellular space between lens epithelial cells in the anterior lens capsules of all eyes exposed to DisCoVisc, were observed by TEM. CONCLUSION: The lens vacuolar changes may be associated with a dispersive OVD exposure. Therefore, it is not preferable to use dispersive OVDs in patients with transparent lenses or without the intention of lens extraction. In addition, close follow-ups instead of immediate lens extraction are recommended for the occurrence of similar lens lesions.

Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients.

BACKGROUND: Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). METHODS: We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. RESULTS: Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. CONCLUSION: This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD.

Early Visual Deprivation Impairs Functional Development of the Visual Ventral Stream.

Purpose: To probe the dynamic alternations of neural networks in real-time visual processing after visual deprivation (VD) removal. Methods: A prospective cross-sectional study was conducted. Twenty children with a history of early binocular VD caused by congenital cataracts and 20 matched typically developing (TD) children were enrolled. The event-related potential (ERP) data were obtained via high-density electroencephalography. ERP data were analyzed based on three components (P1, N170, and P2), three test conditions (objects, human faces, and Chinese characters), and peak time and region of interest (ROI) chosen on a grand average head map collapsed from the averaged waveform of each group. Source localization and alpha power spectrum density were applied to define the functional pattern of brain areas and evaluate the attention function. Results: The VD group showed significantly lower P1 amplitudes than the TD group under all conditions in peak ROIs, which were situated in the left occipito-temporal region. For both VD and TD groups, there were strong N170 effects in the character and human face conditions in the component's peak ROIs. Furthermore, source mapping indicated that the VD group generally showed significantly lower activation in the visual cortex and ventral stream, whereas the beyond network areas (mostly frontal areas) intensively participated in functional compensation in the VD group. The VD group showed significant poststimulus alpha desynchronization in object recognition. Conclusions: Our research described the mechanisms of visual networks after early binocular VD removal. Our findings may provide a new basis for the poor visual recovery after early binocular VD removal and offer clues for visual recovery strategies.

Accuracy of Intraocular Lens Power Calculation in Pediatric Secondary Implantation: In-the-Bag Versus Sulcus Placement.

PURPOSE: To compare the effects of secondary in-the-bag vs ciliary sulcus intraocular lens (IOL) implantation on the accuracy of IOL power calculation in pediatric eyes. DESIGN: Prospective nonrandomized interventional study. METHODS: Pediatric aphakic eyes that underwent either in-the-bag or ciliary sulcus secondary IOL implantation were included. The mean prediction error (PE), mean absolute error (MAE), median absolute error, and percentages of eyes with PE within ±0.25 diopter (D), ±0.50 D, ±0.75 D, and ±1.00 D were calculated and compared using SRK/T formula. RESULTS: One hundred fourteen eyes (38.26%) received in-the-bag IOL implantation and 184 (61.74%) underwent ciliary sulcus IOL implantation. Compared with the sulcus group, the capsular group displayed significantly lower MAE and higher percentage of eyes within ±0.50 D of PE (MAE: 0.90 vs 1.56 D; ±0.50 D: 40.40% vs 14.29%, both P < .001). The eyes receiving in-the-bag IOL implantation (sulcus IOL implantation ß: -1.060, 95% CI: -1.415 to -0.705; P < .001), unilateral (ß: 0.647, 95% CI: 0.144-1.150; P = .012), or with deeper anterior chamber depth (ß: 0.362, 95% CI: 0.068-0.656; P = .016) were prone to maintain hyperopia (PE > 0). To reduce PE, when the predicted capsular IOL power was between 11.50 and 30.00 D, the power of a sulcus-implanted IOL should be reduced by 0.50 to 2.50 D accordingly (the exact amount of reduction is positively related to the predicted power). CONCLUSIONS: In-the-bag implantation yielded smaller PE in pediatric eyes undergoing secondary IOL implantation. Adjustment of IOL power for ciliary sulcus implantation is required to reduce PE, and the amount of adjustment is positively correlated with the IOL power predicted by SRK/T formula.

Early detection of visual impairment in young children using a smartphone-based deep learning system.

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.