Universal artificial intelligence platform for collaborative management of cataracts.
ABSTRACT: PURPOSE:To establish and validate a universal artificial intelligence (AI) platform for collaborative management of cataracts involving multilevel clinical scenarios and explored an AI-based medical referral pattern to improve collaborative efficiency and resource coverage. METHODS:The training and validation datasets were derived from the Chinese Medical Alliance for Artificial Intelligence, covering multilevel healthcare facilities and capture modes. The datasets were labelled using a three-step strategy: (1) capture mode recognition; (2) cataract diagnosis as a normal lens, cataract or a postoperative eye and (3) detection of referable cataracts with respect to aetiology and severity. Moreover, we integrated the cataract AI agent with a real-world multilevel referral pattern involving self-monitoring at home, primary healthcare and specialised hospital services. RESULTS:The universal AI platform and multilevel collaborative pattern showed robust diagnostic performance in three-step tasks: (1) capture mode recognition (area under the curve (AUC) 99.28%-99.71%), (2) cataract diagnosis (normal lens, cataract or postoperative eye with AUCs of 99.82%, 99.96% and 99.93% for mydriatic-slit lamp mode and AUCs >99% for other capture modes) and (3) detection of referable cataracts (AUCs >91% in all tests). In the real-world tertiary referral pattern, the agent suggested 30.3% of people be 'referred', substantially increasing the ophthalmologist-to-population service ratio by 10.2-fold compared with the traditional pattern. CONCLUSIONS:The universal AI platform and multilevel collaborative pattern showed robust diagnostic performance and effective service for cataracts. The context of our AI-based medical referral pattern will be extended to other common disease conditions and resource-intensive situations.
Project description:PURPOSE:To determine the incidence and natural history of cataracts in children with congenital toxoplasmosis. METHODS:Children referred to the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981 and 2005 were examined by ophthalmologists at predetermined times according to a specific protocol. The clinical course and treatment of patients who developed cataracts were reviewed. RESULTS:In the first year of life, 134 of 173 children examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present at birth and 13 developed postnatally. Locations of the cataracts included anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen cataracts were partial, nine total, and five with unknown complexity. Twelve cataracts remained stable, 12 progressed, and progression was not known for 3. Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma. Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with cataracts had additional ocular lesions. CONCLUSIONS:In the NCCCTS cohort, 11.6% of patients were diagnosed with cataracts. There was considerable variability in the presentation, morphology, and progression of the cataracts. Associated intraocular pathology was an important cause of morbidity.
Project description:Histone acetylation plays key roles in gene expression, but its effects on superoxide dismutase 1 (SOD1) expression in senile cataract remains unknown. To address this problem, the study was to investigate the influence of histone acetylation on SOD1 expression and its effects in the pathogenesis of senile cataract. Senile cataract was classified into three types-nuclear cataract (NC), cortical cataract (CC), and posterior subcapsular cataract (SC)-using the Lens Opacities Classification System III. In senile cataracts, SOD1 expression decreased significantly. Both H3 and H4 were deacetylated at -600?bp of the SOD1 promoter of cataract lenses, and hypoacetylated at -1500, -1200, and -900?bp. In hypoacetylated histones, the hypoacetylation pattern differed among the cataracts. In vitro, anacardic acid (AA) significantly reduced H3 and H4 acetylation at the SOD1 promoter, decreased protein expression, and induced cataract formation in rabbits. AA also inhibited HLEC viability and increased cell apoptosis. In contrast, trichostatin A (TSA) was able to efficaciously stop AA's effects on both rabbit lenses and HLECs. Decreased histone acetylation at the SOD1 promoter is associated with declined SOD1 expression in senile cataracts. Histone acetylation plays an essential role in the regulation of SOD1 expression and in the pathogenesis of senile cataracts.
Project description:PURPOSE:To understand how we might improve the provision of medical care for children with cataracts. DESIGN:A phenomenological design was employed. Semi-structured interviews were conducted to capture rich descriptions of the phenomena. Our goal in the interview and the analysis was to understand the sources of distress associated with treatment for cataract and deprivation amblyopia which (1) could be addressed by the medical community and (2) related to treatment adherence. SETTING:Interviews were conducted by a non-clinician researcher in New Zealand (NZ) in a location chosen by informants. In NZ, the red reflex screening test is performed shortly after birth, and surgery to remove paediatric cataracts is publicly funded. PARTICIPANTS:Families of children who had a history of cataract in Auckland, NZ were posted an invitation to participate. Twenty families were interviewed. RESULTS:Our analysis illustrated that informants described a wide range of experiences, from declined cataract surgery to full adherence to medical advice including years of patching for more than 4 hours a day. Across these experiences, we identified three relevant themes; timing of diagnosis, communication between the parent and clinician, and parental social support networks. CONCLUSION:The medical community may be better placed to support families dealing with childhood cataract by improving detection of childhood cataract, building appropriate communication pathways and promoting social support, with an emphasis on empathetic, individualised care.
Project description:Background:Congenital cataracts is the most common cause of childhood visual impairment and blindness worldwide. It is reported that about one quarter of congenital cataracts caused by genetic defects. Various gene mutations have been identified in hereditary cataracts so far. The purpose of the present study was to investigate the relationship between gap junction protein alpha 8 (GJA8) gene mutation and congenital cataract. Methods:A pedigree with autosomal dominant congenital cataract was investigated and the peripheral venous blood was extracted from 18 family members. After the high-throughput targeted capture and whole exome sequencing for the proband, bioinformatics analysis was performed. By combining the proband clinical symptoms, candidate variations were eliminated which were significantly not consistent with the clinical phenotype. And disease-causing variant was identified. Results:Gene sequencing revealed the heterozygous missense mutation in exon 2 of the GJA8 gene (c.178G>A), which co-segregated with the disease phenotype in the family and resulted in the substitution of glycine to serine at position 178 (p.G60S). This missense mutation was located in the hotspot mutation region, and might be harmful. Conclusions:This study reports a novel disease-causing sequence variant in the gap junctional protein encoding genes causing autosomal dominant congenital cataract in the Chinese population, caused by the missense mutation of GJA8 (c.178G>A). Our data expand the spectrum of GJA8 variants and associated phenotypes, facilitate clinical diagnosis and support the presence of relationship between genetic basis and human disease.
Project description:Cataracts are the leading cause of blindness in most countries. Although most hereditary cases appear to follow an autosomal dominant pattern of inheritance, autosomal recessive inheritance has been clearly documented and is probably underrecognized. We studied a large family-from a relatively isolated geographic region-whose members were affected by autosomal recessive adult-onset pulverulent cataracts. We mapped the disease locus to a 14-cM interval at a novel disease locus, 9q13-q22 (between markers D9S1123 and D9S257), with a LOD score of 4.7. The study of this progressive and age-related cataract phenotype may provide insight into the cause of the more common sporadic form of age-related cataracts.
Project description:BACKGROUND:Congenital nystagmus (CN) and congenital cataracts are distinct eye diseases and are usually isolated. Cases with CN and congenital cataracts caused by different genes in one family have been rarely reported. CASE PRESENTATION:A 27-year-old man presented with CN and congenital cataracts and he underwent cataract extraction 2?weeks after birth. Three years later, he had posterior chamber intraocular lens implantation. The proband's mother was only afflicted by bilateral lens opacities. Lensectomy was performed in both eyes at age 15. The proband's daughter had bilateral central cataracts and no nystagmus. She had undergone cataract extraction when she was two months old. In this family, 8 affected individuals were affected by bilateral cataracts, and three of them presented with CN. The genetic analysis was performed using a specific Hereditary Ophthalmological Disease Gene Panel on proband and his parents (one of which was a patient). PCR and Sanger sequencing verified the presence of these variants in all members of the family. The novel mutation, c.498-3C?>?T, in FRMD7 explains why X-Linked recessive inheritance of CN was found in a subset of patients. A heterozygous mutation of the GJA8 gene (c.139G?>?C), was identified in all patients and thus explains the autosomal dominant pattern of inheritance of congenital cataracts within the family. CONCLUSIONS:This is the first time that FRMD7 and GJA8 gene mutations have been linked to the pathogenesis of a family with both CN and congenital cataracts. The phenomenon of two different genetic patterns coexisting in one family is rare.
Project description:Pediatric cataracts are observed in 1-15 per 10,000 births with 10-25 % of cases attributed to genetic causes; autosomal dominant inheritance is the most commonly observed pattern. Since the specific cataract phenotype is not sufficient to predict which gene is mutated, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 23 pedigrees affected with familial dominant cataract. Review of WES data for 36 known cataract genes identified causative mutations in nine pedigrees (39 %) in CRYAA, CRYBB1, CRYBB3, CRYGC (2), CRYGD, GJA8 (2), and MIP and an additional likely causative mutation in EYA1; the CRYBB3 mutation represents the first dominant allele in this gene and demonstrates incomplete penetrance. Examination of crystallin genes not yet linked to human disease identified a novel cataract gene, CRYBA2, a member of the ??-crystallin superfamily. The p.(Val50Met) mutation in CRYBA2 cosegregated with disease phenotype in a four-generation pedigree with autosomal dominant congenital cataracts with incomplete penetrance. Expression studies detected cryba2 transcripts during early lens development in zebrafish, supporting its role in congenital disease. Our data highlight the extreme genetic heterogeneity of dominant cataract as the eleven causative/likely causative mutations affected nine different genes, and the majority of mutant alleles were novel. Furthermore, these data suggest that less than half of dominant cataract can be explained by mutations in currently known genes.
Project description:AIM:To identify mutations in the genes of a four-generation Chinese family with congenital membranous cataracts and investigate the morphologic changes and possible functional damage underlying the role of the mutant gene. METHODS:Whole exome analysis of thirteen members of a four-generation pedigree affected with congenital membranous cataracts was performed; co-segregation analysis of identified variants was validated by Sanger sequencing. All members underwent detailed physical and complete eye examinations. The physical changes caused by the mutation were analyzed in silico through homology modeling. The lens fiber block from a patient was observed under a scanning electron microscope (SEM). Cell membrane proteins and cytoplasmic proteins from the human lenses donated by one patient with cataract in this family and from the dislocated lens resulted from the penetrating ocular trauma of a patient unrelated with this family were extracted, and the expression and localization of MP20 and Cx46 were detected by Western blot (WB) assay in these proteins. RESULTS:A novel LIM2 heterozygous mutation (c.388C>T, p.R130C) was identified with congenital membranous cataracts inherited by an autosomal dominant (AD) pattern. Nystagmus and amblyopia were observed in all patients of this family, and exotropia and long axial length were observed in most patients. A/B ultrasound scan and ultrasound biomicroscopy revealed obvious thin crystalline lenses from 1.7 to 2.7 mm in central thickness in all cataract eyes. The bioinformatic analysis showed that the mutation was deleterious to the physiological function of LIM2-encoded MP20. Furthermore, by SEM, ultrastructure of the cataract nucleus showed that lens fiber cells (LFCs) remained morphologic characteristics of immature fiber cells, including flap cell surface with straight edges and lacking normal ball-and-socket joint boundaries, which implied that the differentiation of LFCs might be inhibited. Accumulation of MP20 and Cx46 in the cytoplasm was observed in the cytoplasm of the LFCs in human cataract lens. CONCLUSION:We identify a novel heterozygous LIM2 (c.388C>T, p.R130C) mutation inherited by an AD pattern. This LIM2 mutation causes the abnormal sub-localization of MP20 and Cx46 in LFCs resulting in membranous cataracts.
Project description:<h4>Purpose</h4>Cataracts are the leading cause of visual impairment and blindness, and therefore early identification and modification of the risk factors for cataracts are meaningful. This study aimed to investigate the relationship between socioeconomic status (SES) and lifestyle factors, and age-related cataracts in South Korea.<h4>Methods</h4>This cross-sectional study was based on data collected in the 2008-2011 Korea National Health and Nutrition Examination Survey. A total of 15?866 subjects, aged ?40 years, were included. SES was defined using household income and education level. Sociodemographic, lifestyle, and other associated factors were assessed by health interviews and examinations. Cataracts were diagnosed via slit-lamp examination using the Lens Opacities Classification System III.<h4>Results</h4>The prevalence of any cataract was 38.9% in men and 42.3% in women (P<0.001). In women, the risk of cataracts increased with decreases in household income (P-value for trend=0.016 and 0.041 in any, and cortical cataract, respectively) and education level (P-value for trend=0.009, 0.027, and 0.016 in any, nuclear, and cortical cataract, respectively) after adjusting for confounding factors. Current smoking was correlated with nuclear cataracts in men (OR 1.21; 95% CI: 1.00, 1.46 in age-adjusted analysis) and cataract surgery in women (OR 2.25; 95% CI: 1.00, 5.04 in multivariate-adjusted analysis).<h4>Conclusions</h4>Socioeconomic disparities in cataract prevalence were observed in women; current smoking increased the risk of nuclear cataracts in men and surgery in women. Public health interventions focusing on gender differences are warranted to prevent and treat cataracts.
Project description:Cataracts or clouding of the lens is the leading cause of blindness in the world. Age and diabetes are major risk factors, and with an increasing aging and diabetic population, the burden of cataracts will grow. Cataract surgery is an effective way to restore vision; however, alternatives to cataract surgery are required to reduce the looming cataract epidemic. Since it is well established that oxidative damage plays a major role in the etiology of cataracts, antioxidants have been promoted as therapies to delay and/or prevent cataracts. However, many antioxidant interventions including vitamin C have produced mixed results as anti-cataract therapies. Progress has been made towards our understanding of lens physiology and the mechanisms involved in the delivery and uptake of antioxidants to the lens which may guide future studies aimed at addressing some of the inconsistencies seen in previous animal and human studies. Of interest is the potential for vitamin C based supplements in delaying the onset of cataracts post vitrectomy which occurs in up to 80% of patients within two years. These targeted approaches are required to reduce the burden of cataract on hospitals and improve the quality of life of our aging and diabetic population.