Clinical features, radiological imaging, and treatment strategies of nonmetallic intraorbital foreign bodies: a retrospective analysis.

AIM: To provide comprehensive data on nonmetallic intraorbital foreign bodies (IOFBs) by summarizing and analyzing material types, clinical manifestations, imaging features, and treatment strategies. METHODS: Totally 28 nonmetallic IOFB cases treated at Shengjing Hospital of China Medical University from 2012 to 2020 were retrospectively reviewed. The types of foreign bodies, clinical features, imaging manifestations, and treatment outcomes were analyzed. RESULTS: Among all cases, 67.8% (19/28) of the foreign bodies were organic. The top three entrances were the upper eyelid skin (7/28), lower fornix conjunctiva (6/28), and lower eyelid skin (4/28). In most cases (11/28, 39.3%), foreign bodies remained in the medial orbits. The major clinical manifestations included eyelid redness and swelling (20/28, 71.4%), conjunctival congestion and edema (17/28, 60.7%), and ophthalmoptosis (15/28, 53.6%). Infection was the main complication, which occurred in 57.1% (16/28) of all cases. Computerized tomography (CT) values differed for different foreign bodies and varied in the different periods after injury. The plant- and grease-derived foreign bodies and the surrounding pus cysts showed different signals on magnetic resonance imaging (MRI). The prognosis varied with different foreign body types, surgery timing, and intraoperative management. CONCLUSION: The majority of nonmetallic IOFBs are organic and often remain in the superior, medial, and inferior areas of the orbit. Clinical manifestations vary owing to their different textures. CT and MRI facilitate the identification of foreign body materials. Plant-derived foreign bodies should be completely removed, and surgical treatment is a complicated process.

Clinical and genetic findings in patients with congenital cataract and heart diseases.

BACKGROUND: Congenital cataract (CC) and congenital heart disease (CHD) are significant birth defects. In clinical practice, the concurrence of CC and CHD is frequently observed in patients. Additionally, some monogenic diseases, copy number variation (CNV) syndromes, and diseases associated with intrauterine infection involve both cataract and heart defects. However, little is known about the association between CC and CHD. Here, we characterised the demographic, clinical, and genetic features of patients with CC and heart defects. METHODS: Medical records for 334 hospitalised patients diagnosed with CC were reviewed. Demographic and clinical features of patients with CC with and without CHD were compared. Clinical and genomic information for patients with 'cataract' and 'cardiac defects' were reviewed from Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER). Microarray-based comparative genomic hybridisation and whole-exome sequencing were performed in 10 trio families with CC and CHD to detect de novo genomic alterations, including copy number variants and single nucleotide changes. RESULTS: In a retrospective analysis of 334 patients with CC over the past 10 years at our hospital, we observed a high proportion of patients (41.13%) with CHD (including innocent CHD, which reported as left-to-right shunt in echocardiography test). The CC with CHD group had higher incidences of preterm birth and Down's syndrome than the CC without CHD group. Atrial septal defect was the most frequent heart defect. A total of 44 cases with cataracts and heart diseases were retrieved from Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER). In total, 52 genomic alterations were reported, 44% of which were de novo germline variants. In the 10 trio families with CC and CHD, we found de novo CNVs responsible for two well-known chromosomal disorders and identified a novel pathogenic mutation in GJA8 responsible for CC. CONCLUSIONS: We observed significant associations between CHD and CC in our 10-year patient cohort. Based on the cohort and data from DECIPHER, developmental syndromes in some patients were due to genetic defects, thus explaining the concurrence of CC and CHD. Additionally, we detected de novo mutations as an independent cause of cataracts. Our findings suggest that developmental syndromes in patients with CC deserve more attention in clinical practice by ophthalmologists.

Outcomes of Bilateral Congenital and Developmental Cataracts Following IOL Implantation in Preschool Children.

PURPOSE: To evaluate the different ocular outcomes and the potential factors affecting visual acuity in bilateral congenital cataracts and developmental cataracts after intraocular lens implantation in preschool children. METHODS: In a retrospective study, 86 eyes (51 congenital and 35 developmental cataract cases) of 43 children aged 6 years and younger who were diagnosed as having bilateral cataracts and underwent cataract aspiration combined with primary or secondary foldable intraocular lens implantation between 2003 and 2018 were reviewed. A minimum of 1 year of follow-up was required. The best corrected visual acuity (BCVA) and the factors associated with visual results were explored. RESULTS: The postoperative BCVA in the developmental cataract group (0.20 ± 0.19 logarithm of the minimum angle of resolution [logMAR]) was significantly better than that in the congenital cataract group (0.57 ± 0.31 logMAR) (P < .001). The mean refractive error was 3.61 ± 3.03 diopters in the congenital cataract group and 2.15 ± 1.82 diopters in the developmental cataract group. All cases of strabismus and nystagmus were found in the congenital cataract group. In the congenital cataract group, the variables age at cataract extraction and refractive error were significantly associated with BCVA (P < .001, P = .001, respectively). These variables had little effect on the developmental cataract group (P = .971, P = .576, respectively). Postoperative complications were recorded in 18 eyes: 4 in the developmental cataract group and 14 in the congenital cataract group. CONCLUSIONS: The BCVA in the developmental cataract group was significantly better than that in the congenital cataract group. The therapeutic effects of patients with congenital cataracts and developmental cataracts should be evaluated separately. [J Pediatr Ophthalmol Strabismus. 2021;58(3):180-187.].

A novel MAF missense mutation leads to congenital nuclear cataract by impacting the transactivation of crystallin and noncrystallin genes.

The transcription factor v-maf avain musculoaponeurotic fibrosarcoma oncogene homolog (MAF) plays an important role in lens development. It contains a unique extended homology region (EHR) in the DNA binding domain. MAF mutations are associated with phenotypically distinct forms of congenital cataract and show different effects on the transactivation of target genes. Mutations in the MAF EHR region were rarely reported and their corresponding phenotype and impact on target genes' transactivation were not evaluated. A three- generation Chinese family with congenital cataract was recruited. The patients in the family present non-syndromic congenital nuclear and lamellar opacities. A novel MAF mutation (c.812 T > A, p.Val271Glu) was identified by targeted next-generation sequencing. The mutation is in highly conserved EHR region of MAF and co-segregates with the cataract in the family. It is predicted to be pathogenic by multiple algorithms and is absent in a control population. Dual luciferase activity assay shows the mutation significantly impair the transcriptional activity of four crystallin genes (CRYAA, CRYBA4, CRYBA1, and CRYGA) and two non-crystallin genes (HMOX1 and KDELR2). Herein, we report a novel missense mutation in the MAF EHR region of the DNA binding domain in a family with congenital cataract. The mutation is associated with non-syndromic bilateral nuclear cataract and impacts the transactivation of cataract associated genes involved in lens structure and stress response.

A novel mutation in the CRYAA gene associated with congenital cataract and microphthalmia in a Chinese family.

BACKGROUND: Congenital cataract is the leading cause of blindness in children worldwide. Approximately half of all congenital cataracts have a genetic basis. Protein aggregation is the single most important factor in cataract formation. METHODS: A four-generation Chinese family diagnosed with autosomal dominant congenital cataracts and microphthalmia was recruited at the Shengjing Hospital of China Medical University. Genomic DNA was extracted from the peripheral blood of the participants. All coding exons and flanking regions of seven candidate genes (CRYAA, CRYBA4, CRYBB2, CRYGC, GJA8, MAF, and PITX3) were amplified and sequenced. Restriction fragment length polymorphism (RFLP) assays were performed to confirm the candidate causative variant, c.35G > T in the CRYAA gene. We constructed pcDNA3.1(+)-CRYAA expression plasmids containing either the wild-type or the R12L mutant alleles and respectively transfected them into HEK293T cells and into HeLa cells. Western blotting was performed to determine protein expression levels and protein solubility. Immunofluorescence was performed to determine protein sub-cellular localization. RESULTS: A heterozygous variant c.35G > T was identified in exon 1 of CRYAA, which resulted in a substitution of arginine to leucine at codon 12 (p.R12L). The nucleotide substitution c.35G > T was co-segregated with the disease phenotype in the family. The mutant R12L-CRYAA in HEK293T cells showed a significant increase in the expression level of the CRYAA protein compared with the wild-type cells. Moreover, a large amount of the mutant protein aggregated in the precipitate where the wild-type protein was not detected. Immunofluorescence studies showed that the overexpressed mutant CRYAA in HeLa cells formed large cytoplasmic aggregates and aggresomes. CONCLUSIONS: In summary, we described a case of human congenital cataract and microphthalmia caused by a novel mutation in the CRYAA gene, which substituted an arginine at position 12 in the N-terminal region of αA-crystallin. The molecular mechanisms that underlie the pathogenesis of human congenital cataract may be characterized by the prominent effects of the p.R12L mutation on αA-crystallin aggregation and solubility. Our study also expands the spectrum of known CRYAA mutations.

A Novel Insertion Variant of CRYGD Is Associated with Congenital Nuclear Cataract in a Chinese Family.

OBJECTIVE: To investigate a novel insertion variant of CRYGD identified in a Chinese family with nuclear congenital cataract. METHODS: A Chinese family with congenital nuclear cataract was recruited for the mutational screening of candidate genes by direct sequencing. Recombinant N-terminal Myc tagged wildtype or mutant CRYGD was expressed in HEK293T cells. The expression pattern, protein solubility and subcellular distribution were analyzed by western blotting and immunofluorescence. PRINCIPAL FINDINGS: A novel insertion variant, c.451_452insGACT, in CRYGD was identified in the patients. It causes a frameshift and a premature termination of the polypeptide to become Y151*. A significantly reduced solubility was observed for this mutant. Unlike wildtype CRYGD, which existed mainly in the cytoplasm, Y151* was mis-located in the nucleus. CONCLUSIONS: We have identified a novel mutation, c.451_452insGACT, in CRYGD, which is associated with nuclear cataract. This is the first insertion mutation of CRYGD found to cause autosomal dominant congenital cataract. The mutant protein, with loss of solubility and localization to the nucleus, is hypothesized to be the major cause of cataract in these patients.

A novel nonsense mutation in the MIP gene linked to congenital posterior polar cataracts in a Chinese family.

PURPOSE: To detect the causative mutation for congenital posterior polar cataracts in a five-generation Chinese family and further explore the potential pathogenesis of this disease. METHODS: Coding exons, with flanking sequences of five candidate genes, were screened using direct DNA sequencing. The identified mutations were confirmed by restriction fragment length polymorphism (RFLP) analysis. A full-length wild-type or an Y219* mutant aquaporin0 (AQP0) fused with an N-terminal FLAG tag, was transfected into HEK293T cells. For co-localization studies, FLAG-WT-AQP0 and Myc-Y219*-AQP0 constructs were co-transfected. Quantitative real-time RT-PCR, western blotting and immunofluorescence studies were performed to determine protein expression levels and sub-cellular localization, respectively. RESULTS: We identified a novel nonsense mutation in MIP (c.657 C>G; p.Y219*) (major intrinsic protein gene) that segregates with congenital posterior polar cataract in a Chinese family. This mutation altered a highly conserved tyrosine to a stop codon (Y219*) within AQP0.When FLAG-WT-AQP0 and FLAG-Y219*-AQP0 expression constructs were singly transfected into HEK 293T cells, mRNA expression showed no significant difference between the wild-type and the mutant, while Y219*-AQP0 protein expression was significantly lower than that of wild-type AQP0. Wild-type AQP0 predominantly localized to the plasma membrane, while the mutated protein was abundant within the cytoplasm of HEK293T cells. However, when FLAG-WT-AQP0 andMyc-MU-AQP0were co-expressed, both proteins showed high fluorescence in the cytoplasm. CONCLUSIONS: The novel nonsense mutation in the MIP gene (c.657 C>G) identified in a Chinese family may cause posterior polar cataracts. The dominant negative effect of the mutated protein on the wild-type protein interfered with the trafficking of wild-type protein to the cell membrane and both the mutant and wild-type protein were trapped in the cytoplasm. Consequently, both wild-type and mutant protein lost their function as a water channel on the cell membrane, and may result in a cataract phenotype. Our data also expands the spectrum of known MIP mutations.

Ten-year etiologic review of Chinese children hospitalized for pediatric cataracts.

PURPOSE: Our aim was to obtain a better understanding of the etiologies and characteristics of pediatric cataracts treated at a single facility in China. METHODS: Medical records accrued over a 10-year period (from August, 2003 to July, 2013) at Shengjing Hospital of China Medical University were reviewed retrospectively, identifying all patients treated for various subtypes of pediatric cataract. A database with 367 subjects under 14 years of age (598, including second-round surgeries) was generated. RESULTS: Of this cohort (n = 367; males: 232, 63.2%; females: 135, 36.8%), 200 patients (54.5%) had bilateral cataracts, and 258 (70.3%) were under 3 years of age. In all age groups and in all subtypes of pediatric cataract, males were most commonly affected. Congenital cataract was the most prevalent subtype, accounting for 296 patients (80.7%). Most congenital cataracts were associated with other ocular or systemic abnormalities; and in 48 patients (16.22%), they were hereditary. Traumatic cataract was the most common subtype (85.92%) of acquired cataract. The few instances of cataracts due to steroids (n = 3) or to metabolic disorders (n = 2) occurred in males and involved both eyes. CONCLUSION: The majority of pediatric cataracts in this patient population were congenital in nature. A significant lag in ophthalmologic evaluation of Chinese infants was evident and should be addressed by educating both children and parents on risk factors for cataract development. Regular assessments are especially important in children subjected to long-term systemic steroid treatments.