Comparison of biometric methods in young children with congenital cataracts in their eyes

BACKGROUND: Relevant keratometric and biometric indicators are necessary for intraocular lens (IOL) power calculation, which is difficult to verify in young children. AIM: Evaluation of the accuracy of various ultrasound methods and optical biometry for axial length measurement in young children with congenital cataracts. MATERIAL AND METHODS: Forty-six children (74 eyes) with congenital cataracts (43 eyes) and pseudophakia (31 eyes) at the age of 6 months to 4 years were examined. Various methods measured the axial length: ultrasound A-scan under general anesthesia by US-4000, ultrasound B-scan without general anesthesia by Voluson E8, and optical biometry by AL-Scan in cases of transparent optics. RESULTS: The greater axial length difference was observed between A-scan and optical biometry (less by 0,78 mm) than between B-scan and optical biometry (more by 0,27 mm). The median axial length difference between A-scan and B-scan was equal for infants and young children with congenital cataracts (0,525 mm and 0,535 mm, respectively). CONCLUSION: Axial length should be measured by different methods in young children with their further comparison to obtaining more accurate biometric indicators for IOL power calculation. The decrease of 12 mm in axial length, which occurs during the A-scan, can lead to errors in the IOL calculation of 36 diopters and unplanned refraction in the long-term period.

Karakteristik Katarak Kongenital di RSUD Provinsi NTB Periode 2018-2019

Congenital cataracts are the leading cause of blindness in children. Lens opacity in early life has the potential to cause permanent visual impairment if not treated promptly. Cataract surgery performed at the right time can prevent children from amblyopia (lazy eye). This study aims to determine the characteristics of congenital cataracts at the West Nusa Tenggara Provincial General Hospital in the 2018-2019 period. This research uses descriptive method. The data used is secondary data from medical records of congenital cataract patients at the West Nusa Tenggara Provincial General Hospital in the 2018-2019 period. In the 2018-2019 period, 40 children had congenital cataracts. Most of the cataract sufferers were women (52.5%); living outside the city of Mataram (92.5%) with an age distribution of under 12 months (95%) and the rest over 12 months. For infants under 12 months, 53 percent have been diagnosing at the age of 1-2 months. The characteristics of congenital cataracts found were generally bilateral (52.5%), had standard birth weight (52.5%), history of natural birth delivery (67.5%), and had other extraocular congenital abnormalities (72.5%). Most patients with congenital cataracts in the West Nusa Tenggara Provincial General Hospital have been diagnosing at a (pretty/moderately) early age of 1-2 months at the beginning of their lives. So, with appropriate and prompt therapy, hoping that it can reduce the risk of amblyopia.

Novel PAX6 variant in a family with ophthalmologic, pancreatic, and olfactory features

Variants in the PAX6 gene have been associated with ophthalmologic, neurologic, and pancreatic differences. We report on a proband, mother, and affected brother who presented with congenital cataracts and glaucoma at a young age. Non-ocular findings are also reported among these family members. After a congenital cataracts next generation sequencing (NGS) gene panel was found to be non-diagnostic in 2016, a more expanded panel in 2020 revealed a novel variant: c.178T>A; p.Tyr60Asn in exon 6 of the PAX6 gene in the proband. The variant is also present in the affected mother and affected brother; it is absent in an unaffected brother. The clinical findings of these three relatives, in conjunction with their genetic testing and the associated PAX6 features reported in the literature, suggest that this novel familial variant may be an underlying etiology for these individuals' ophthalmologic, pancreatic, and olfactory symptoms.

Defect of LSS Disrupts Lens Development in Cataractogenesis

Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts.

Brief Postnatal Visual Deprivation Triggers Long-Lasting Interactive Structural and Functional Reorganization of the Human Cortex

Patients treated for bilateral congenital cataracts provide a unique model to test the role of early visual input in shaping the development of the human cortex. Previous studies showed that brief early visual deprivation triggers long-lasting changes in the human visual cortex. However, it remains unknown if such changes interact with the development of other parts of the cortex. With high-resolution structural and resting-state fMRI images, we found changes in cortical thickness within, but not limited to, the visual cortex in adult patients, who experienced transient visual deprivation early in life as a result of congenital cataracts. Importantly, the covariation of cortical thickness across regions was also altered in the patients. The areas with altered cortical thickness in patients also showed differences in functional connectivity between patients and normally sighted controls. Together, the current findings suggest an impact of early visual deprivation on the interactive development of the human cortex.

Novel Likely Pathogenic Variants Identified by Panel-Based Exome Sequencing in Congenital Cataract Patients

Purpose. To identify likely pathogenic variants in three families with congenital cataracts via panel-based exome sequencing. Methods. A panel containing 153 genes associated with congenital cataracts was designed. Genes were selected through reference to databases including the Human Gene Mutation Database (HGMD), Online Mendelian Inheritance in Man (OMIM), Genetic Home Reference, and the latest peer-reviewed publications on the genetics of hereditary cataracts. Panel-based exome sequencing was performed with the Illumina HiSeq X-Ten platform, and then the identified variants were confirmed with Sanger sequencing and evaluated according to the American College of Medical Genetics and Genomics (ACMG) criteria. Results. Three likely pathogenic variants were found. A novel CRYBB2: c.230G > T p.G77V variant was identified in family A, a novel CRYBB2: c.230G > A p.G77D variant was identified in family B, and a novel CRYGD: c.475delG p.A159Pfs∗9 variant was identified in family C. Conclusion. Panel-based exome sequencing revealed three likely pathogenic variants in three unrelated Chinese families with congenital cataracts. These data expand the genetic spectrum associated with congenital cataracts.

Congenital cataract and spherophakia leading to starvation in a free-ranging muskox neonate from the Northwest Territories, Canada

A muskox neonate ( Ovibos moschatus) that died of starvation was diagnosed with congenital lenticular anomalies that included spherophakia and hypermature cataract associated with probable lens-induced lymphocytic uveitis and neutrophilic keratitis. Impaired sight as a result of cataract and associated inflammation likely contributed to abandonment and starvation, although maternal death cannot be excluded definitively. Ocular lesions, such as congenital cataracts and spherophakia in neonates, may be important factors affecting survival in free-ranging animals.

Broadening the Mutation Spectrum in GJA8 and CHMP4B: Novel Missense Variants and the Associated Phenotypes in Six Chinese Han Congenital Cataracts Families

Purpose: To broaden the mutation and phenotype spectrum of the GJA8 and CHMP4B genes and to reveal genotype-phenotype correlations in a cohort of Chinese patients with congenital cataracts (CCs).Methods: Six Chinese Han families with CCs inherited in an autosomal dominant (AD) pattern were recruited for this study. All patients underwent full ocular examinations. Genomic DNA was extracted from the leukocytes of peripheral blood collected from all available patients and their unaffected family members. Whole-exome sequencing (WES) was performed on all probands and at least one of their parents. Candidate variants were further confirmed by Sanger sequencing. Bioinformatic analysis with several computational predictive programs was performed to assess the impacts of the candidate variants on the structure and function of the proteins.Results: Four heterozygous candidate variants in three different genes (CRYBB2, GJA8, and CHMP4B) were identified in affected individuals from the six families, including two novel missense variants (GJA8: c.64G > C/p. G22R, and CHMP4B: c.587C > G/p. S196C), one missense mutation (CRYBB2: c.562C > T/p. R188C), and one small deletion (GJA8: c.426_440delGCTGGAGGGGACCCT/p.143_147delLEGTL). The three missense mutations were predicted as deleterious in all four computational prediction programs. In the homologous model, the GJA8: p.143_147delLEGTL mutation showed a sequence deletion of five amino acids at the cytoplasmic loop of the Cx50 protein, close to the third transmembrane domain. Patients carrying mutations in the same gene showed similar cataract phenotypes at a young age, including total cataracts, Y-sutural with fetal nuclear cataracts, and subcapsular cataracts.Conclusion: This study further expands the mutation spectrum and genotype-phenotype correlation of CRYBB2, GJA8, and CHMP4B underlying CCs. This study sheds light on the importance of comparing congenital cataract phenotypes in patients at the same age stage. It offers clues for the pathogenesis of CCs and allows for an early prenatal diagnosis for families carrying these genetic variants.