Lens Thickness in Infants and Children with Cataracts.

Purpose: The purpose of this study was to determine the association between lens thickness and cataract in participants aged 0 to 5 years. Design: This was a prospective, multicenter, case-control study. Participants: We enrolled 118 participants (171 eyes) aged 0 to 5 years, mean age 14.6 ± 17.0 months, range 0 to 60 months. Methods: Lens thickness was measured on 342 ultrasound biomicroscopy (UBM) images. Main Outcome Measures: Lens thickness; feasibility of lens thickness measurement from UBM images. Results: The mean lens thickness among noncataracts was 3.60 ± 0.17 mm, compared with 3.16 ± 0.61 mm among cataracts (P < 0.0001). Lens thickness <3.5 mm was significantly associated with increased odds of cataract; adjusted odds ratio = 5.99 (95% confidence interval, 2.41-14.88; P < 0.0003) among participants age 0 to 7 months. Lens thickness was significantly associated with cataract laterality among participants age 0 to 7 months (P < 0.0001). Conclusions: Quantitative UBM can be used to evaluate lens thickness in infants and children with congenital cataracts. The lens in congenital cataract eyes was thinner than that of controls among infants. Abnormal lens thickness was significantly associated with cataract. Future longitudinal studies will examine the association between lens thickness and postcataract surgery outcomes. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

From Cats to the Cortex: Unravelling the Hierarchical Processing System of Vision and Brain Plasticity.

The groundbreaking research conducted by neurophysiologists David Hubel and Torsten Wiesel during the late 1950s and 1960s revolutionized the field of visual neuroscience. Through single-unit recordings in the visual cortex of cats, they made several key discoveries that fundamentally changed our understanding of visual processing. Their work introduced the concept of orientation selectivity, revealing that neurons in the visual cortex are specifically tuned to line orientations, thereby illustrating how the brain constructs visual representations through edge detection. Additionally, they discovered ocular dominance columns, the specialized cortical regions that respond preferentially to input from one eye, providing crucial insights into the organization of visual processing and the importance of binocular vision. Hubel and Wiesel's research also established the concept of a critical period in visual development, demonstrating that early visual experiences are essential for the proper maturation of the visual system. This discovery has had significant implications for understanding neural plasticity and the role of sensory input in neural development. The impact of their work goes beyond theoretical knowledge, contributing to the development of therapeutic strategies for some visual disorders and guiding current research into brain plasticity and visual processing. This review synthesizes the monumental contributions of Hubel and Wiesel, evaluating how their key discoveries have shaped subsequent research in visual neuroscience. It traces the evolution of knowledge related to visual pathways, feature detection, and brain plasticity, highlighting the enduring influence of their foundational work on contemporary studies. By exploring the progression from their pioneering findings to modern advancements, this review emphasizes the legacy of Hubel and Wiesel's contributions to our understanding of vision and neural function.

Comparing glaucoma risk in children receiving low-dose and high-dose glucocorticoid treatment after cataract surgery.

PURPOSE: Treatment with glucocorticoids following paediatric cataract surgery is crucial to prevent inflammation, but may lead to secondary glaucoma, and hypothalamic-pituitary-adrenal axis suppression. We wish to compare glaucoma outcomes following high-dose and low-dose glucocorticoid treatment after paediatric cataract surgery. METHODS: This cohort study included Danish children undergoing cataract surgery before 10 years of age, receiving either a low-dose or high-dose postoperative glucocorticoid treatment. Case identification and collection of a standardized dataset were retrospective, from 1 January 2010 to 31 December 2016, and prospective thereafter, until 31 December 2021. High-dose treatment included 0.5-1.0 mg subconjunctival depot dexamethasone or methylprednisolone, followed by 6-8 drops of dexamethasone for 1 week, tapered by one drop weekly. Low-dose treatment included 6 drops for 3 days, followed by 3 drops for 18 days. Sustained (>3 months) ocular hypertension or glaucoma was compared between the two groups. RESULTS: Overall, 267 children (388 eyes) were included in the study. Ninety-five children (133 eyes) had received high-dose treatment and had a median follow-up time of 89 months (IQR: 57.2-107.4), while 173 children (255 eyes) had received the low-dose treatment and had a median follow-up time of 40.5 months (IQR: 22.9-60.4). Survival curves showed a lower risk of glaucoma in the low-dose group for children with axial lengths ≥18 mm. CONCLUSION: Low-dose glucocorticoid treatment was associated with a lower risk of glaucoma in children with axial lengths ≥18 mm. The same effect was not observed in children with shorter eyes. High-dose glucocorticoid should be limited in children undergoing cataract surgery.

Truncation mutations of CRYGD gene in congenital cataracts cause protein aggregation by disrupting the structural stability of γD-crystallin.

Congenital cataracts, a prevalent cause of blindness in children, are associated with protein aggregation. γD-crystallin, essential for sustaining lens transparency, exists as a monomer and exhibits excellent structural stability. In our cohort, we identified a nonsense mutation (c.451_452insGACT, p.Y151X) in the CRYGD gene. To explore the effect of truncation mutations on the structure of γD-crystallin, we examined the Y151X and T160RfsX8 mutations, both located in the Greek key motif 4 at the cellular and protein level in this study. Both truncation mutations induced protein misfolding and resulted in the formation of insoluble aggregates when overexpressed in HLE B3 and HEK 293T cells. Moreover, heat, UV irradiation, and oxidative stress increased the proportion of aggregates of mutants in the cells. We next purified γD-crystallin to estimate its structural changes. Truncation mutations led to conformational disruption and a concomitant decrease in protein solubility. Molecular dynamics simulations further demonstrated that partial deletion of the conserved domain within the Greek key motif 4 markedly compromised the overall stability of the protein structure. Finally, co-expression of α-crystallins facilitated the proper folding of truncated mutants and mitigated protein aggregation. In summary, the structural integrity of the Greek key motif 4 in γD-crystallin is crucial for overall structural stability.

Secondary IOL implantation for an aphakic patient with congenital cataract living in Bonin Islands; follow-up study.

Introduction: We previously reported a case of a patient with bilateral congenital cataract identified in the Ogasawara village, Bonin Islands, Japan, on a visit by an ophthalmologist and describe its course over 17 years from initial surgery. Here, we report on a secondary intraocular lens (IOL) implantation that was subsequently performed at 22 years and 5 months of age. Methods: After cataract surgery at 7 months, the aphakic patient began amblyopia treatment using extended-wear soft contact lenses (SCLs). After 10 years of age, SCLs were chosen to achieve crossed monovision considering the cosmetic appearance when facing other people. At 22 years of age, a secondary IOL implantation was performed. Secondary implant in the patient considered appearance and postoperative vision without glasses, we selected the crossed monovision method using a monofocal IOL. The postoperative targeted refraction for the right (non-dominant eye) and left eyes (dominant eye) planed - 0.33D and - 2.25D, respectively. Results: At 3 months after surgery, the corrected distance visual acuity (CDVA) with IOLs for the right and left eyes was 20/16 and 20/60, respectively, and the binocular visual acuity was 20/16 for distant vision and 20/25 for near vision. The CDVA for the right eye was: 20/13 × IOL = sph-0.25D and that for the left eye was: 20/13 × IOL = sph -1.75D D/cyl -0.50D/Ax170°. Although the exotropia was complicated by dissociated horizontal deviation and dissociated vertical deviation, there were no significant changes in ocular position before and after surgery. The patient was satisfied with achieving independence from spectacles and SCLs. Conclusion: The use of the crossed monovision method with monofocal IOLs in this patient and defective binocular function created a visual environment with no inconvenience in everyday life after secondary IOL implantation. In terms of secondary implant after amblyopia treatment, the IOL type or postoperative targeted refraction must be chosen to maintain or improve the visual environment obtained with the amblyopia treatment.

A Case Report of a Filipino Boy with Childhood Cataract and Clinically Diagnosed Roberts Syndrome.

Childhood cataract is a common cause of visual impairment. Familial types are uncommon among Filipinos. Furthermore, it is not common to have one that follows an autosomal dominant pattern of inheritance but with associated syndromic presentation like Roberts syndrome which is an autosomal recessive disorder. This is a case of a 9-year-old Filipino boy with cataract in the left eye associated with low-set ears, facial asymmetry, underdeveloped nasal ala, cleft lip and palate, macroglossia, micrognathia, short right shin, and absent feet. Patient was clinically diagnosed with Roberts syndrome. We present a clinically diagnosed Roberts syndrome (RS), the first reported RS in a Filipino in local and international literature to our knowledge with an autosomal dominant childhood cataract. Genetic testing can assist in the confirmation of this case.

IOL calculation using six formulas in children undergoing lens extraction and primary IOL implantation with and without posterior optic capture.

PURPOSE: To evaluate formulas for intraocular lens (IOL) calculation in children undergoing lens extraction and IOL implantation. METHODS: Retrospective, consecutive case series at the Department of Ophthalmology, Goethe University Frankfurt, Germany. We included eyes that received lens extraction and IOL implantation (SN60AT, Alcon, Fort Worth, TX) due to congenital or juvenile cataract. Preoperative assessments included biometry (IOLMaster 500/700, Carl Zeiss Meditec, Germany). To evaluate the measurements, we compared the mean prediction error (MPE), mean and median absolute prediction error (MAE, MedAE) of six different formulas, and number of eyes within ± 0.5, ± 1.0, ± 2.0D of target refraction. Postoperative spherical equivalent was measured by retinoscopy 4-12 weeks after surgery. RESULTS: 66 eyes matched our inclusion criteria with a mean age of 6.3 years ± 3.2. MedAE was lowest in SRK/T (0.55D ± 1.08) followed by Holladay I (0.75D ± 1.00), EVO 2.0 (0.80D ± 0.89), Barrett Universal II (BUII, 0.86D ± 1.00), Hoffer Q (0.97 D ± 0.94), and Haigis (1.10D ± 0.95). Regarding eyes within ± 0.5D SRK/T (45.5.%, 30 eyes) performed best, followed by Holladay I (36.4%, 24 eyes), EVO 2.0 and BUII (each 34.8%, 23 eyes). There was a myopic shift seen in all formulas (MPE: -0.21 to -0.90D). CONCLUSION: Using modern formulas, or even AI formulas, for IOL calculation in children's eyes does barely improve predictability of the postoperative refraction. A myopic shift can be found for all formulas. However, specific formulas like SRK/T seem to better anticipate this.

Novel molecular, structural and clinical findings in an Italian cohort of congenital cataract.

The current genetic diagnostic workup of congenital cataract (CC) is mainly based on NGS panels, whereas exome sequencing (ES) has occasionally been employed. In this multicentre study, we investigated by ES the detection yield, mutational spectrum and genotype-phenotype correlations in a CC cohort recruited between 2020 and mid-2022. The cohort consisted of 67 affected individuals from 51 unrelated families and included both non-syndromic (75%) and syndromic (25%) phenotypes, with extra-CC ocular/visual features present in both groups (48% and 76%, respectively). The functional effect of variants was predicted by 3D modelling and hydropathy properties changes. Variant clustering was used for the in-depth assessment of genotype-phenotype correlations. A diagnostic (pathogenic or likely pathogenic) variant was identified in 19 out of 51 probands/families (~37%). In a further 14 probands/families a candidate variant was identified: in 12 families a VUS was detected, of which 9 were considered plausibly pathogenic (i.e., 4 or 5 points according to ACMG criteria), while in 2 probands ES identified a single variant in an autosomal recessive gene associated with CC. Eighteen probands/families, manifesting primarily non-syndromic CC (15/18, 83%), remained unsolved. The identified variants (8 P, 12 LP, 10 VUS-PP, and 5 VUS), half of which were unreported in the literature, affected five functional categories of genes involved in transcription/splicing, lens formation/homeostasis (i.e., crystallin genes), membrane signalling, cell-cell interaction, and immune response. A phenotype-specific variant clustering was observed in four genes (KIF1A, MAF, PAX6, SPTAN1), whereas variable expressivity and potential phenotypic expansion in two (BCOR, NHS) and five genes (CWC27, KIF1A, IFIH1, PAX6, SPTAN1), respectively. Finally, ES allowed to detect variants in six genes not commonly included in commercial CC panels. These findings broaden the genotype-phenotype correlations in one of the largest CC cohorts tested by ES, providing novel insights into the underlying pathogenetic mechanisms and emphasising the power of ES as first-tier test.

Long-term visual outcomes and ocular complications in children with Marner's hereditary cataracts operated in the period 1940-2021.

PURPOSE: To investigate visual development and long-term complications after cataract surgery in childhood. METHODS: This cross-sectional study included patients from a family with Marner's hereditary cataracts who had cataract surgery before 18 years of age. The study was conducted from 1 January 2022 until 31 December 2022. The patients contributed to their medical files and participated in an updated ophthalmologic examination. RESULTS: We included 52 patients (101 eyes, 34 females). The median age at cataract surgery was 7 years (IQR: 5-10) and the age at examination was 40 years (IQR: 21-54). Primary and secondary intraocular lens implantation had been performed in 47.5% (25 patients, 48 eyes) and 16.8% (10 patients, 17 eyes). Visual acuity was ≤0.3 logMAR in 77% (78 eyes), and <0.5 logMAR in 8% (8 eyes). Glaucoma was present in 17% (9 patients, 12 eyes), ocular hypertension in 6% (3 patients, 4 eyes), and 10% (5 patients, 5 eyes) had prior retinal detachment. Mild visual field loss (2 < mean defect (MD) ≤ 6 dB) was found in 62% (63 eyes) and moderate to advanced visual field loss (MD > 6 dB) in 24% (24 eyes). Thirty-five patients (67%) held a driver's licence, and three were not allowed to drive due to low visual function. All patients were employed. CONCLUSION: After cataract surgery in childhood, many patients achieve normal visual acuity, but mild visual field loss is common. Long-term follow-up is important due to the high risk of glaucoma.

Incidence and Risk Factors for Retinal Detachment Following Pediatric Cataract Surgery.

Background: Retinal detachment is a major postsurgical threat in pediatric cataract surgery; however, the effect of axial length remains unclear. This study aimed to assess the relationship between axial length and detachment risk in vulnerable patients. Methods: This retrospective cohort study analyzed 132 eyes of 84 pediatric cataract surgery patients aged <20 years old. Axial length was measured preoperatively, and the incidence of retinal detachment was recorded over a median follow-up of 4 years. Logistic regression analysis was used to examine the axial length-detachment relationship. Results: Twenty eyes had postoperative retinal detachments. The median axial length was longer in the detachment group (23.6 mm) than in the non-detachment group (21.6 mm). Eyes with axial length ≤23.4 mm had 0.55-fold decreased odds of detachment compared to longer eyes. Preexisting myopia and glaucoma confer heightened risk. Approximately half of the patients retained some detachment risk eight years postoperatively. Conclusion: Shorter eyes (axial length ≤23.4 mm) appear to be protected against pediatric retinal detachment after cataract surgery, whereas myopia, glaucoma, and axial elongation > 23.4 mm elevate the postoperative risk. Understanding these anatomical risk profiles requires surgical planning and follow-up care of children undergoing lensectomy.

This study investigated the protective role of a shorter axial length in preventing retinal detachment after pediatric cataract surgery. This highlights the correlation between smaller eye sizes and reduced detachment risk, emphasizing the need for careful consideration of anatomical factors in surgical planning and patient monitoring, particularly for patients with preexisting myopia or postoperative glaucoma.

Genetics of bilateral pediatric cataract in the Israeli and Palestinian populations.

PURPOSE: Bilateral pediatric cataract (BPC) is one of the most common causes of childhood visual impairment and blindness worldwide. A significant percentage of pediatric cataracts are caused by genetic alterations. We aim to characterize the set of genes and variants that cause BPC in the Israeli and Palestinian populations and to assess genotype-phenotype correlation. METHODS: Retrospective study in a multidisciplinary center for visual impairment, located in a tertiary medical center. Medical charts of families who underwent genetic counseling because of BPC in a family member were reviewed. Clinical characteristics and genetic tests results were obtained from medical records of affected subjects. RESULTS: Twenty-two families (47 patients) underwent genetic counseling and completed genetic testing. Causative variants were identified in 18/22 (81.8%) of the families, including 3 novel variants. Genetic testing used included mainly panel for congenital cataracts and whole exome sequencing. Eleven families performed genetic testing with the intention of future pregnancy planning. Main causative genes identified were crystalline genes followed by transcription factor genes. BCOR gene variants were associated with persistent fetal vasculature (PFV) cataract in two of three families. CONCLUSIONS: Combined molecular techniques are useful in identifying variants causing pediatric cataracts and showed a high detection rate in our population. BCOR gene variants might be associated with PFV type of cataracts. The study of pathogenic variants may aid in family planning and prevention of pediatric cataracts in future pregnancies. Additionally, in certain cases, it assists in diagnosing non-suspected syndromic types of pediatric cataracts.

Comparison of Congenital Rubella Syndrome Cases at a Philippine Tertiary Hospital from 2009-2012 to 2019-2022.

Background and Objective: The Philippines does not have a national congenital rubella syndrome (CRS) surveillance or registry. Regular monitoring of CRS cases in hospitals, including in a Philippine tertiary hospital, helped in the past to provide clinico-epidemiologic data on CRS. This study aimed to continue providing clinico-epidemiologic data on CRS cases seen in the Philippine tertiary hospital from 2009-2012 and 2019-2022 and compare the cases seen from said timelines. Methods: A cross-sectional study was used, employing chart review of patients newly diagnosed with CRS from 2009-2012 and 2019-2022 in the Department of Ophthalmology and Visual Sciences at the Philippine tertiary hospital. Results: Forty-two patients newly diagnosed with CRS from 2009-2012 and 2019-2022 were included. Only 14 (33%) were serologically-confirmed cases (albeit qualitatively). Median age (first and third interquartile ranges) at consult was 1 year (0.4, 2.5). Twenty-four (57%) patients had maternal history of rashes and/or fever. Trimester of pregnancy when mother became symptomatic was not significantly correlated with chief complaint (p=0.20) and numbers of ophthalmic (p=0.68) and systemic manifestations (p=0.32). Cataract was the most common ophthalmic manifestation present in 40 (95%) patients. Twenty-six (62%) patients had other associated systemic findings of which hearing loss was the most common. Only 29 of 40 patients with cataract underwent lensectomy, with 23 patients having poor visual prognosis prior to surgery (5 with nystagmus alone, 10 with nystagmus and strabismus, and 8 with strabismus alone). Discussion: Using ophthalmic manifestations as primary indicator, this study provided an update on the CRS cases in the country. Laboratory confirmation remains a challenge in diagnosing CRS as the tests are costly and not widely available. There was increase from 2009-2012 compared to 2019-2022 in number of patients who underwent surgical treatment for cataract but visual outcomes were suboptimal due to delay in consultation. Although there was a decrease in number of CRS cases seen in the Philippine tertiary hospital, this cannot be attributed to increased rubella-containing vaccine (RCV) coverage alone. Conclusion: Provision of data from individual hospital-based studies similar to this highlights the need for a national CRS surveillance system or registry. This can better gauge the burden of CRS and identify the gap in RCV coverage.

Rare micropupil secondary to congenital cataract surgery favoring the development of the affected eye: a case report.

BACKGROUND: Congenital microcoria has been extensively reported and usually leads to visual dysfunction or blindness. However, micropupil development secondary to cataract surgery has never been reported. Here, we describe a rare case of micropupil development in infancy that occurred secondary to combined cataract extraction and intraocular lens implantation for treatment of congenital cataract. When the patient reached adulthood, the affected eye not only gained good vision but also showed better ocular development and refractive status than the fellow eye. CASE PRESENTATION: A 17-year-old boy presented to our outpatient clinic with decreased vision in his left eye related to congenital cataract surgery at 6 months of age. The affected eye had exhibited a pinhole pupil since the third month postoperatively. The condition had been managed with observation and regular monocular occlusion treatment. Upon presentation to our clinic, the best-corrected visual acuity (BCVA) in his fellow eye was 0.0 logMAR(20/20) with a refraction of - 5.75 diopters cylinder/-2.25 diopters sphere, and the BCVA in his affected eye was 0.5 logMAR(20/40) with a refraction of 0.00 diopters. Ophthalmic examination of the affected eye revealed a pinhole pupil (approximately 0.5 mm) with high light reflex sensitivity but no response to pupil-dilating drugs. The patient underwent pupilloplasty of the affected eye under corneal surface anesthesia. Postoperative examination revealed better ocular development in the affected eye than in the fellow eye (axial length: 24.21 vs. 27.02 mm, respectively) as well as better refractive status in the affected eye (BCVA of 0.0 logMAR(20/20) with a refraction of - 2.23 diopters cylinder/-3.00 diopters sphere vs. 0logMAR(20/20) with a refraction of -5.75 diopters cylinder/-2.25 diopters sphere). CONCLUSIONS: We have reported a rare case of micropupil development secondary to congenital cataract surgery, which is an uncommon complication, especially in children. However, unlike congenital microcoria, the secondary pinhole pupil may have reduced imaging haze and halos, possibly favoring the development of the affected eye. This case provides further insight into the treatment of congenital cataract.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract.

AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

Development of a postoperative visual function rehabilitation compliance assessment scale for children with congenital cataract: a reliability and validity study.

OBJECTIVE: To develop a comprehensive compliance assessment scale for postoperative visual function rehabilitation in children with congenital cataracts and to assess its reliability and validity. METHOD: Drawing on the Interactive Model of Health Behavior, we conducted a literature review and semi-structured interviews to create a pool of 36 items. The items underwent rigorous evaluation through the Delphi method, face validity checks, and item analysis, leading to a reduction to 18 items. To assess the scale's reliability and validity, we collected data from 225 parents of children with congenital cataracts. We employed SPSS version 25.0 for data analysis and evaluated construct validity using exploratory factor analysis, content validity, internal consistency reliability, and test-retest reliability. RESULTS: The compliance scale for postoperative visual function rehabilitation in children with congenital cataracts comprises 5 dimensions and 18 items. Exploratory factor analysis extracted 5 common factors, with a cumulative variance contribution rate of 68.178%. Item-level content validity index ranged from 0.730 to 1.000, and the content validity index of the scale was 0.963. The total Cronbach's alpha coefficient, split-half reliability, and test-retest reliability of the scale were 0.855, 0.778, and 0.859, respectively. CONCLUSIONS: The compliance assessment scale for postoperative visual function rehabilitation in children with congenital cataracts demonstrates acceptable reliability and validity. It serves as a valuable reference for developing standardized nursing programs for these children in clinical practice.

A novel base substitution mutation of the CRYBA2 gene is associated with autosomal dominant congenital cataract.

Congenital cataract is one of the leading causes of vision loss in children, and a large proportion of cases are related to genetics. In a Chinese family, we reported a new missense mutation in CRYBA2 (c.223T>C: p.Tyr75His), which can cause autosomal dominant congenital bilateral cataract. We collected blood samples from family members (mother and two sons) and extracted DNA. Through whole-exome sequencing, we discovered a novel unreported mutation. According to relevant ACMG guidelines, this mutation was determined to be a variant of unknown clinical significance. This article further expands the site information on the CRYBA2 mutations.

A Case of Non-Syndromic Congenital Cataracts Caused by a Novel MAF Variant in the C-Terminal DNA-Binding Domain-Case Report and Literature Review.

The MAF gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the MAF variants in the C-terminal DNA-binding domain associated with non-syndromic congenital cataracts and describe a patient with a novel, disease-causing de novo missense variant. Published reports of C-terminal MAF variants and their associated congenital cataracts and ophthalmic findings were reviewed. The patient we present and his biological parents had genetic testing via a targeted gene panel followed by trio-based whole exome sequencing. A 4-year-old patient with a history of bilateral nuclear and cortical cataracts was found to have a novel, likely pathogenic de novo variant in MAF, NM_005360.5:c.922A>G (p.Lys308Glu). No syndromic findings or anterior segment abnormalities were identified. We report the novel missense variant, c.922A>G (p.Lys308Glu), in the C-terminal DNA-binding domain of MAF classified as likely pathogenic and associated with non-syndromic bilateral congenital cataracts.

Four mutations identified in Chinese families with autosomal dominant congenital cataracts by next-generation sequencing.

BACKGROUND: Congenital cataracts, which can arise due to a combination of factors like environmental influences and genetic predisposition, significantly impact children's visual health globally. The occurrence rate of congenital cataracts varies from 0. 63 to 9.74 per 10,000 births. There are 7.4 instances per 10,000 children, with the highest occurrence seen in Asia. Symptoms of the disease include clouding of the lens and visual impairment. Timely identification of the condition plays a crucial role in the management and outlook of pediatric patients. OBJECTIVE: This investigation aimed to discover causative mutations in four separate Chinese family lineages. METHODS: The detailed clinical data and family history of four Chinese families with autosomal dominant congenital cataracts were carefully documented. Examination of the Whole Exome Sequencing was utilized to identify the genetic anomalies present in the familial cases. Subsequent validation of the identified mutations was carried out using PCR and Sanger sequencing. Following this, various computational predictive programs were utilized to evaluate how the mutations impact the structure and function of the protein. RESULTS: The sequencing results reveal four potential disease-causing mutations: c.436G > A (p.V146M) of CRYBB2 Family 1, c.26G > T (p.R9I) of GJA3 in family 2, c.227G > A (p.R76H) of GJA8 in family 3, c.-168G > T of FTL in family 4. Among them, the causative mutation in Family GJA3 is novel, and Family FTL is a rare cataract syndrome. These familial mutations showed complete co-segregation with the affected individuals, with no presence in unaffected family members or the 100 controls. Several bioinformatic prediction tools also support the likely pathogenicity of these mutations. CONCLUSION: Our findings expand the mutational and phenotypic spectrum of genes associated with congenital cataracts and provide clues to the pathogenesis of congenital cataracts. These data also demonstrate the importance of NGS technology for the molecular diagnosis of congenital cataract patients.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes.

AIM: To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes. METHODS: Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited. Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients' medical records. A hierarchical cluster analysis was performed. The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts. RESULTS: A total of 164 children (299 eyes) were divided into two clusters based on their ocular features. Cluster 1 (96 eyes) had a shorter axial length (mean±SD, 19.44±1.68 mm), a low prevalence of macular abnormalities (1.04%), and no retinal abnormalities or posterior cataracts. Cluster 2 (203 eyes) had a greater axial length (mean±SD, 20.42±2.10 mm) and a higher prevalence of macular abnormalities (8.37%), retinal abnormalities (98.52%), and posterior cataracts (4.93%). Compared with the eyes in Cluster 2 (57.14%), those in Cluster 1 (71.88%) had a 2.2 times higher chance of good best-corrected visual acuity [<0.7 logMAR; OR (95%CI), 2.20 (1.25-3.81); P=0.006]. CONCLUSION: This retrospective study categorizes congenital cataracts into two distinct clusters, each associated with a different likelihood of visual outcomes. This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit, thereby making strides toward precision medicine in the field of congenital cataracts.

Novel MIP gene mutation causes autosomal-dominant congenital cataract.

AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.