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Nature Communications Apr 2024Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and...
Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We utilize decision-analytic Markov models to evaluate the cost-effectiveness and cost-utility of different cataract screening strategies (no screening, telescreening, AI screening and DH screening). A simulated cohort of 100,000 individuals from age 50 is built through a total of 30 1-year Markov cycles. The primary outcomes are incremental cost-effectiveness ratio and incremental cost-utility ratio. The results show that DH screening dominates no screening, telescreening and AI screening in urban and rural China. Annual DH screening emerges as the most economically effective strategy with 341 (338 to 344) and 1326 (1312 to 1340) years of blindness avoided compared with telescreening, and 37 (35 to 39) and 140 (131 to 148) years compared with AI screening in urban and rural settings, respectively. The findings remain robust across all sensitivity analyses conducted. Here, we report that DH screening is cost-effective in urban and rural China, and the annual screening proves to be the most cost-effective option, providing an economic rationale for policymakers promoting public eye health in low- and middle-income countries.
Topics: Humans; Cost-Benefit Analysis; China; Cataract; Middle Aged; Mass Screening; Male; Digital Technology; Female; Markov Chains; Aged; Artificial Intelligence; Telemedicine
PubMed: 38688925
DOI: 10.1038/s41467-024-47211-w -
Journal of AAPOS : the Official... Aug 2023Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid...
Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC ≥ 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9% in enrolled patients, and 15.4% in patients who met the criteria for genetic testing.
Topics: Child, Preschool; Humans; Child; Adolescent; Young Adult; Adult; Xanthomatosis, Cerebrotendinous; Prevalence; Cholestanol; Bile Acids and Salts; Cataract
PubMed: 37321343
DOI: 10.1016/j.jaapos.2023.04.013 -
Molecular Genetics & Genomic Medicine Sep 2023To identify the mutational spectrum in a Chinese cohort with congenital cataracts.
BACKGROUND
To identify the mutational spectrum in a Chinese cohort with congenital cataracts.
METHODS
Probands (n = 164) with congenital cataracts and their affected or unaffected available family members were recruited for clinical examinations and panel-based next-generation sequencing, then classified into a cohort for further mutational analysis.
RESULTS
After recruitment (n = 442; 228 males and 214 females), 49.32% (218/442) of subjects received a clinical diagnosis of congenital cataracts, and 56.88% (124/218) of patients received a molecular diagnosis. Eighty-four distinct variants distributed among 43 different genes, including 42 previously reported variants and 42 novel variants, were detected, and 49 gene variants were causally associated with patient phenotypes; 27.37% of variants (23/84) were commonly detected in PAX6, GJA8 and CRYGD, and the three genes covered 33.06% of cases (41/124) with molecular diagnosis. The majority of genes were classified as genes involved in nonsyndromic congenital cataracts (19/43, 44.19%) and were responsible for 56.45% of cases (70/124). The majority of functional and nucleotide changes were missense variants (53/84, 63.10%) and substitution variants (74/84, 88.10%), respectively. Nine de novo variants were identified.
CONCLUSION
This study provides a reference for individualized genetic counseling and further extends the mutational spectrum of congenital cataracts.
Topics: Female; Humans; Male; Cataract; East Asian People; Mutation; Mutation, Missense; Pedigree
PubMed: 37337769
DOI: 10.1002/mgg3.2196 -
Investigative Ophthalmology & Visual... Dec 2023Oxidative stress and cellular senescence are risk factors for age-related cataract. Heme oxygenase 1 (HO-1) is a critical antioxidant enzyme and related to autophagy....
PURPOSE
Oxidative stress and cellular senescence are risk factors for age-related cataract. Heme oxygenase 1 (HO-1) is a critical antioxidant enzyme and related to autophagy. Here, we investigate the crosstalk among HO-1, oxidative stress, and cellular senescence in mouse lens epithelial cells (LECs).
METHODS
The gene expression of HO-1, p21, LC3, and p62 was measured in human samples. The protective properties of HO-1 were examined in hydrogen peroxide (H2O2)-damaged LECs. Autophagic flux was examined by Western blot and mRFP-GFP-LC3 assay. Western blotting and lysotracker staining were used to analyze lysosomal function. Flow cytometry was used to detect intracellular reactive oxygen species and analyze cell cycle. Senescence-associated β-galactosidase assay was used to determine cellular senescence. The crosstalk between HO-1 and transcription factor EB (TFEB) was further observed in TFEB-knockdown cells. The TFEB binding site in the promoter region of Hmox1 was predicted by the Jasper website and was confirmed by chromatin immunoprecipitation assay.
RESULTS
HO-1 gene expression decreased in LECs of patients with age-related nuclear cataract, whereas mRNA expression levels of p21, LC3, and p62 increased. Upon H2O2-induced oxidative stress, LECs showed the characteristics of autophagic flux blockade, lysosomal dysfunction, and premature senescence. Interestingly, HO-1 significantly restored the impaired autophagic flux and lysosomal function and delayed cellular senescence. TFEB gene silencing greatly reduced the HO-1-mediated autophagic restoration, leading to a failure to prevent LECs from oxidative stress and premature senescence.
CONCLUSIONS
We demonstrated HO-1 effects on restoring autophagic flux and delaying cellular senescence under oxidative stress in LECs, which are dependent on TFEB.
Topics: Animals; Humans; Mice; Autophagy; Cataract; Cellular Senescence; Epithelial Cells; Heme Oxygenase-1; Hydrogen Peroxide; Oxidative Stress
PubMed: 38051262
DOI: 10.1167/iovs.64.15.6 -
The British Journal of Ophthalmology Dec 2023There is accumulating evidence of the associations between age-related eye diseases (AREDs) and smoking or dietary factors. We aimed to provide an umbrella review of the... (Review)
Review
BACKGROUND
There is accumulating evidence of the associations between age-related eye diseases (AREDs) and smoking or dietary factors. We aimed to provide an umbrella review of the published literature pertaining to smoking or dietary intake as risk factors for major AREDs including cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy.
METHODS
We searched for pertinent systematic reviews or meta-analyses in PubMed and Web of Science until 16 April 2022. We reperformed the meta-analysis of each association using random effects models. The heterogeneity and 95% prediction interval were calculated. The presence of small-study effect or excess significance bias was also assessed.
RESULTS
In total, 64 associations from 25 meta-analyses and 41 associations from 10 qualitative systematic reviews were evaluated. There was convincing (class I) evidence for only one association, namely current smoking and cataract. Two factors had highly suggestive (class II) evidence, namely ever smoking associated with cataract and fish consumption associated with AMD. We also found suggestive (class III) evidence for associations between the dietary intake of omega-3 polyunsaturated fatty acid, lutein, zeaxanthin, vitamin C and the risk of cataract.
CONCLUSIONS
Smoking as a risk factor for cataract was the most robust association we identified. We also identified several dietary elements associated with AREDs. Large prospective studies are warranted to further examine the associations discussed in this review.
PROSPERO REGISTRATION NUMBER
CRD42022339082.
Topics: Humans; Cataract; Diet; Macular Degeneration; Smoking; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 36575624
DOI: 10.1136/bjo-2022-322325 -
The British Journal of Ophthalmology Feb 2024To report the incidence and associated risk factors for developing suspected and definitive glaucoma after bilateral congenital cataract (CC) removal with a 5-year...
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.
Topics: Child; Humans; Infant; Incidence; Follow-Up Studies; Longitudinal Studies; Prospective Studies; Visual Acuity; Postoperative Complications; Cataract; Cataract Extraction; Glaucoma; Ocular Hypertension; Risk Factors
PubMed: 36828619
DOI: 10.1136/bjo-2022-322589 -
Progress in Retinal and Eye Research Jul 2023The lens is an important determinant of overall vision quality whose refractive and transparent properties change throughout life. Alterations to the refractive... (Review)
Review
The lens is an important determinant of overall vision quality whose refractive and transparent properties change throughout life. Alterations to the refractive properties of the lens contribute to the process of emmetropisation in early childhood, and then the gradual loss in lens power that occurs throughout adulthood. In parallel to these changes to lens refractive power, age-dependent increases in lens stiffness and light scattering result in presbyopia and cataract, respectively. In recent years it has been confirmed that the lens operates an internal microcirculation system that generates circulating fluxes of ions, water and nutrients that maintain the refractive properties and transparency of the lens. By actively regulating lens water content, the microcirculation system controls two key parameters, lens geometry and the gradient of refractive index, which together determine the refractive properties of the lens. Furthermore, by delivering nutrients and antioxidants to the lens nucleus, the microcirculation system maintains lens transparency by preventing crystallin aggregation. Interestingly, the solubility, intramolecular packing and refractive index increment of crystallin proteins can be modulated by the ability of crystallin proteins to dynamically bind water, a processed called syneresis. In a series of previous studies it has been shown that the application of external pressure to the lens can induce syneresis. Since it is now known that lens water transport generates a substantial internal hydrostatic pressure gradient, we speculate that the microcirculation is capable of regulating crystallin function by altering the amount of water bound to lens proteins in the nucleus, where the pressure gradient and protein concentrations are the highest. Here we present evidence for the links between lens transport, pressure, syneresis and protein function. Furthermore, because the lens pressure gradient can be regulated by intrinsic and extrinsic stimuli, we suggest mechanisms via which this integrative system can be used to effect the changes to the refractive and transparent properties of the lens that are observed across our lifetime.
Topics: Child, Preschool; Humans; Adult; Lens, Crystalline; Cataract; Crystallins; Refraction, Ocular
PubMed: 36470825
DOI: 10.1016/j.preteyeres.2022.101152 -
The Journal of Biological Chemistry Aug 2023Connexin mutant mice develop cataracts containing calcium precipitates. To test whether pathologic mineralization is a general mechanism contributing to the disease, we...
Connexin mutant mice develop cataracts containing calcium precipitates. To test whether pathologic mineralization is a general mechanism contributing to the disease, we characterized the lenses from a nonconnexin mutant mouse cataract model. By cosegregation of the phenotype with a satellite marker and genomic sequencing, we identified the mutant as a 5-bp duplication in the γC-crystallin gene (Crygc). Homozygous mice developed severe cataracts early, and heterozygous animals developed small cataracts later in life. Immunoblotting studies showed that the mutant lenses contained decreased levels of crystallins, connexin46, and connexin50 but increased levels of resident proteins of the nucleus, endoplasmic reticulum, and mitochondria. The reductions in fiber cell connexins were associated with a scarcity of gap junction punctae as detected by immunofluorescence and significant reductions in gap junction-mediated coupling between fiber cells in Crygc lenses. Particles that stained with the calcium deposit dye, Alizarin red, were abundant in the insoluble fraction from homozygous lenses but nearly absent in wild-type and heterozygous lens preparations. Whole-mount homozygous lenses were stained with Alizarin red in the cataract region. Mineralized material with a regional distribution similar to the cataract was detected in homozygous lenses (but not wild-type lenses) by micro-computed tomography. Attenuated total internal reflection Fourier-transform infrared microspectroscopy identified the mineral as apatite. These results are consistent with previous findings that loss of lens fiber cell gap junctional coupling leads to the formation of calcium precipitates. They also support the hypothesis that pathologic mineralization contributes to the formation of cataracts of different etiologies.
Topics: Animals; Mice; Calcium; Cataract; Connexins; Crystallins; Lens, Crystalline; Minerals; X-Ray Microtomography; Disease Models, Animal
PubMed: 37331601
DOI: 10.1016/j.jbc.2023.104935 -
JAMA Ophthalmology Feb 2024Three leading disease causes of age-related visual loss are cataract, age-related macular degeneration (AMD), and glaucoma. Although all 3 eye diseases have been...
IMPORTANCE
Three leading disease causes of age-related visual loss are cataract, age-related macular degeneration (AMD), and glaucoma. Although all 3 eye diseases have been implicated with falls and fracture risk, evidence is mixed, with the contribution of different eye diseases being uncertain.
OBJECTIVE
To examine whether people with cataract, AMD, or glaucoma have higher risks of falls or fractures than those without.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was a population-based study in England using routinely collected electronic health records from the Clinical Practice Research Datalink (CPRD) GOLD and Aurum primary care databases with linked hospitalization and mortality records from 2007 to 2020. Participants were people with cataract, AMD, or glaucoma matched to comparators (1:5) by age, sex, and general practice. Data were analyzed from May 2021 to June 2023.
EXPOSURES
For each eye disease, we estimated the risk of falls or fractures using separate multivariable Cox proportional hazards regression models.
MAIN OUTCOMES
Two primary outcomes were incident falls and incident fractures derived from general practice, hospital, and mortality records. Secondary outcomes were incident fractures of specific body sites.
RESULTS
A total of 410 476 people with cataract, 75 622 with AMD, and 90 177 with glaucoma were matched (1:5) to 2 034 194 (no cataract), 375 548 (no AMD), and 448 179 (no glaucoma) comparators. The mean (SD) age was 73.8 (11.0) years, 79.4 (9.4) years, and 69.8 (13.1) years for participants with cataract, AMD, or glaucoma, respectively. Compared with comparators, there was an increased risk of falls in those with cataract (adjusted hazard ratio [HR], 1.36; 95% CI, 1.35-1.38), AMD (HR, 1.25; 95% CI, 1.23-1.27), and glaucoma (HR, 1.38; 95% CI, 1.35-1.41). Likewise for fractures, there were increased risks in all eye diseases, with an HR of 1.28 (95% CI, 1.27-1.30) in the cataract cohort, an HR of 1.18 (95% CI, 1.15-1.21) for AMD, and an HR of 1.31 (95% CI, 1.27-1.35) for glaucoma. Site-specific fracture analyses revealed increases in almost all body sites (including hip, spine, forearm, skull or facial bones, pelvis, ribs or sternum, and lower leg fractures) compared with matched comparators.
CONCLUSIONS AND RELEVANCE
The results of this study support recognition that people with 1 or more of these eye diseases are at increased risk of both falls and fractures. They may benefit from improved advice, access, and referrals to falls prevention services.
Topics: Humans; Aged; Cohort Studies; Cataract; Glaucoma; Macular Degeneration
PubMed: 38153708
DOI: 10.1001/jamaophthalmol.2023.5858 -
Environmental Science & Technology Aug 2023Cataract is one key cause of visual disability and blindness. Ambient particulate matter is more likely to increase cataract risk due to eye continuous exposure to the...
Cataract is one key cause of visual disability and blindness. Ambient particulate matter is more likely to increase cataract risk due to eye continuous exposure to the environment. However, less is known about whether long-term exposure to particulate matter 2.5 (PM) is related to age-related cataracts. We conducted a population-based study among 22,298 adults from two multicenter cohort studies [China Family Panel Studies (CFPS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS)]. The associations between PM and age-related cataracts were analyzed by Cox proportional hazard regression models, which were also stratified according to demographic characteristics. The restricted cubic spline (RCS) model was used to explore the dose-response relationships between PM and age-related cataracts. The population attributable fraction (PAF) was calculated to assess the burden of age-related cataracts that can be attributed to PM. In the final analysis, 1897 participants reported age-related cataracts during follow-up. Long-term exposure to PM was associated with age-related cataracts, with HRs of 1.165 (1.130, 1.201), 1.138 (1.103, 1.173), and 1.091 (1.057, 1.126) for per 10 μg/m increase at one-, two-, and three-year before the end of follow-up, respectively. Furthermore, associations between PM and age-related cataracts were also demonstrated in RCS models. The PAF of age-related cataracts to PM in the total participants was 24.63%. Our research found that long-term exposure to PM may increase the risk of age-related cataracts, and age-related cataracts should be considered as an important public health issue due to air pollution.
Topics: Middle Aged; Humans; Aged; Air Pollutants; East Asian People; Particulate Matter; Air Pollution; Cohort Studies; China; Cataract; Environmental Exposure
PubMed: 37534997
DOI: 10.1021/acs.est.3c02646