ABSTRACT
Cataract is a leading ocular disease causing global blindness. The mechanism of cataractogenesis has not been well defined. Here, we demonstrate that the heat shock protein 90ß (HSP90ß) plays a fundamental role in suppressing cataractogenesis. HSP90ß is the most dominant HSP in normal lens, and its constitutive high level of expression is largely derived from regulation by Sp1 family transcription factors. More importantly, HSP90ß is significantly down-regulated in human cataract patients and in aging mouse lenses, whereas HSP90ß silencing in zebrafish causes cataractogenesis, which can only be rescued by itself but not other HSP90 genes. Mechanistically, HSP90ß can directly interact with CHMP4B, a newly-found client protein involved in control of cytokinesis. HSP90ß silencing causes upregulation of CHMP4B and another client protein, the tumor suppressor p53. CHMP4B upregulation or overexpression induces excessive division of lens epithelial cells without proper differentiation. As a result, these cells were triggered to undergo apoptosis due to activation of the p53/Bak-Bim pathway, leading to cataractogenesis and microphthalmia. Silence of both HSP90ß and CHMP4B restored normal phenotype of zebrafish eye. Together, our results reveal that HSP90ß is a critical inhibitor of cataractogenesis through negative regulation of CHMP4B and the p53-Bak/Bim pathway.
Subject(s)
Cataract , HSP90 Heat-Shock Proteins , Tumor Suppressor Protein p53 , Animals , Humans , Mice , Aging/genetics , Cataract/genetics , Endosomal Sorting Complexes Required for Transport/metabolism , HSP90 Heat-Shock Proteins/metabolism , Multivesicular Bodies/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Zebrafish/genetics , Zebrafish/metabolismABSTRACT
Cataracts are a disease that reduces vision due to opacity formation of the lens. Diabetic cataracts occur at young age and progress relatively quickly, so the development of effective treatment has been awaited. Several studies have shown that pyruvate inhibits oxidative stress and glycation of lens proteins, which contribute to onset of diabetic cataracts. However, detailed molecular mechanisms have not been revealed. In this study, we attempted to reduce galactose-induced opacity by pyruvate with rat ex vivo model. Rat lenses were extracted and cultured in galactose-containing medium to induce lens opacity. After opacity had developed, continued culturing with pyruvate in the medium resulted in a reduction of lens opacity. Subsequently, we conducted microarray analysis to investigate the genes that contribute to the therapeutic effect. We performed quantitative expression measurements using RT-qPCR for extracted genes that were upregulated in cataract-induced lenses and downregulated in pyruvate-treated lenses, resulting in the identification of 34 candidate genes. Functional analysis using the STRING database suggests that metallothionein-related factors (Mt1a, Mt1m, and Mt2A) and epithelial-mesenchymal transition-related factors (Acta2, Anxa1, Cd81, Mki67, Timp1, and Tyms) contribute to the therapeutic effect of cataracts.
ABSTRACT
Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98-2.27; OR, 2.03; 95% CI, 1.86-2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.
Subject(s)
Cataract , Hearing Loss , Aged , Middle Aged , Humans , Genome-Wide Association Study/methods , Quality of Life , Hearing , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Genetic Loci , Protein Serine-Threonine Kinases , Apoptosis Regulatory ProteinsABSTRACT
This study aims to investigate the hypothesis that Yes-associated protein (YAP) significantly regulates antioxidant potential and anti-apoptosis in UVB-induced cataract by exploring the underlying molecular mechanisms. To investigate the association between YAP and cataract, various experimental techniques were employed, including cell viability assessment, Annexin V FITC/PI assay, measurement of ROS production, RT-PCR, Western blot assay, and Immunoprecipitation. UVB exposure on human lens epithelium cells (HLECs) reduced total and nuclear YAP protein expression, increased cleaved/pro-caspase 3 ratios, decreased cell viability, and elevated ROS levels compared to controls. Similar Western blot results were observed in in vivo experiments involving UVB-treated mice. YAP knockdown in vitro demonstrated a decrease in the protein expression of FOXM1, Nrf2, and HO-1, which correlated with the mRNA expression, accompanied by an increase in cell apoptosis, caspase 3 activation, and the release of ROS. Conversely, YAP overexpression mitigated these effects induced by UVB irradiation. Immunoprecipitation revealed a FOXM1-YAP interaction. Notably, inhibiting FOXM1 decreased Nrf2 and HO-1, activating caspase 3. Additionally, administering the ROS inhibitor N-acetyl-L-cysteine (NAC) effectively mitigated the apoptotic effects induced by oxidative stress from UVB irradiation, rescuing the protein expression levels of YAP, FOXM1, Nrf2, and HO-1. The initial findings of our study demonstrate the existence of a feedback loop involving YAP, FOXM1, Nrf2, and ROS that significantly influences the cell apoptosis in HLECs under UVB-induced oxidative stress.
Subject(s)
Apoptosis , Cataract , Forkhead Box Protein M1 , NF-E2-Related Factor 2 , Oxidative Stress , Ultraviolet Rays , YAP-Signaling Proteins , Apoptosis/radiation effects , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Ultraviolet Rays/adverse effects , Humans , Animals , Forkhead Box Protein M1/metabolism , Forkhead Box Protein M1/genetics , Mice , Cataract/etiology , Cataract/metabolism , Cataract/pathology , YAP-Signaling Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Lens, Crystalline/metabolism , Lens, Crystalline/radiation effects , Transcription Factors/metabolism , Transcription Factors/genetics , Reactive Oxygen Species/metabolism , Male , Signal Transduction , Mice, Inbred C57BLABSTRACT
Gaze understandinga suggested precursor for understanding others' intentionsrequires recovery of gaze direction from the observed person's head and eye position. This challenging computation is naturally acquired at infancy without explicit external guidance, but can it be learned later if vision is extremely poor throughout early childhood? We addressed this question by studying gaze following in Ethiopian patients with early bilateral congenital cataracts diagnosed and treated by us only at late childhood. This sight restoration provided a unique opportunity to directly address basic issues on the roles of "nature" and "nurture" in development, as it caused a selective perturbation to the natural process, eliminating some gaze-direction cues while leaving others still available. Following surgery, the patients' visual acuity typically improved substantially, allowing discrimination of pupil position in the eye. Yet, the patients failed to show eye gaze-following effects and fixated less than controls on the eyestwo spontaneous behaviors typically seen in controls. Our model for unsupervised learning of gaze direction explains how head-based gaze following can develop under severe image blur, resembling preoperative conditions. It also suggests why, despite acquiring sufficient resolution to extract eye position, automatic eye gaze following is not established after surgery due to lack of detailed early visual experience. We suggest that visual skills acquired in infancy in an unsupervised manner will be difficult or impossible to acquire when internal guidance is no longer available, even when sufficient image resolution for the task is restored. This creates fundamental barriers to spontaneous vision recovery following prolonged deprivation in early age.
Subject(s)
Fixation, Ocular , Vision, Ocular , Attention , Blindness , Child , Humans , Visual AcuityABSTRACT
Crystallin proteins are a class of main structural proteins of the vertebrate eye lens, and their solubility and stability directly determine transparency and refractive power of the lens. Mutation in genes that encode these crystallin proteins is the most common cause for congenital cataracts. Despite extensive studies, the pathogenic and molecular mechanisms that effect congenital cataracts remain unclear. In this study, we identified a novel mutation in CRYBB1 from a congenital cataract family, and demonstrated that this mutation led to an early termination of mRNA translation, resulting in a 49-residue C-terminally truncated CRYßB1 protein. We show this mutant is susceptible to proteolysis, which allowed us to determine a 1.2-Å resolution crystal structure of CRYßB1 without the entire C-terminal domain. In this crystal lattice, we observed that two N-terminal domain monomers form a dimer that structurally resembles the WT monomer, but with different surface characteristics. Biochemical analyses and cell-based data also suggested that this mutant is significantly more liable to aggregate and degrade compared to WT CRYßB1. Taken together, our results provide an insight into the mechanism regarding how a mutant crystalin contributes to the development of congenital cataract possibly through alteration of inter-protein interactions that result in protein aggregation.
Subject(s)
Cataract , Crystallins , Lens, Crystalline , Humans , Cataract/metabolism , Crystallins/genetics , Lens, Crystalline/metabolism , Mutation , Protein AggregatesABSTRACT
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 (Crygcdup). 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 Crygcdup 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.
Subject(s)
Cataract , Crystallins , Minerals , Animals , Mice , Calcium/metabolism , Cataract/genetics , Cataract/physiopathology , Connexins/genetics , Connexins/metabolism , Crystallins/genetics , Crystallins/metabolism , Lens, Crystalline/pathology , Minerals/metabolism , X-Ray Microtomography , Disease Models, AnimalABSTRACT
Age-related cataract (ARC) is regarded as the principal cause of vision impairment among the aged. The regulatory role of long noncoding RNAs (LncRNAs) in ARC remains unclear. The lncRNA maternally expressed gene 3 (MEG3) has been reported to promote ARC progression, and the underlying mechanism was further investigated in this study. Lens epithelium samples were collected to verify the expression of MEG3. Lens epithelial cells (LECs) were treated with H2O2 to mimic microenvironment of ARC in vitro. Cell viability, reactive oxygen species, and ferroptosis were evaluated during the in viro experiments. In the present work, lncRNA MEG3 was highly expressed in ARC group, compared with normal group. MEG3 was induced, cell viability and glutathione peroxidase 4 (GPX4) level were inhibited, and ferroptosis was promoted in H2O2 treated LECs. LncRNA MEG3 silence reversed the effects of H2O2 on viability and ferroptosis in LECs. Thereafter, lncRNA MEG3 was found to bind to PTBP1 for GPX4 degradation. Silencing of GPX4 reversed the regulation of lncRNA MEG3 inhibition in H2O2-treated LECs. To sum up, lncRNA MEG3 exhibited high expression in ARC. In H2O2-induced LECs, inhibition of lncRNA MEG3 accelerated cell viability and repressed ferroptosis by interaction with PTBP1 for GPX4 messenger RNA decay. Targeting lncRNA MEG3 may be a novel treatment of ARC.
ABSTRACT
Cataract, a leading cause of blindness, is characterised by lens opacification. Type 2 diabetes is associated with a two- to fivefold higher prevalence of cataracts. The risk of cataract formation increases with the duration of diabetes and the severity of hyperglycaemia. Hydroxyapatite deposition is present in cataractous lenses that could be the consequence of osteogenic differentiation and calcification of lens epithelial cells (LECs). We hypothesised that hyperglycaemia might promote the osteogenic differentiation of human LECs (HuLECs). Osteogenic medium (OM) containing excess phosphate and calcium with normal (1 g/L) or high (4.5 g/L) glucose was used to induce HuLEC calcification. High glucose accelerated and intensified OM-induced calcification of HuLECs, which was accompanied by hyperglycaemia-induced upregulation of the osteogenic markers Runx2, Sox9, alkaline phosphatase and osteocalcin, as well as nuclear translocation of Runx2. High glucose-induced calcification was abolished in Runx2-deficient HuLECs. Additionally, high glucose stabilised the regulatory alpha subunits of hypoxia-inducible factor 1 (HIF-1), triggered nuclear translocation of HIF-1α and increased the expression of HIF-1 target genes. Gene silencing of HIF-1α or HIF-2α attenuated hyperglycaemia-induced calcification of HuLECs, while hypoxia mimetics (desferrioxamine, CoCl2) enhanced calcification of HuLECs under normal glucose conditions. Overall, this study suggests that high glucose promotes HuLEC calcification via Runx2 and the activation of the HIF-1 signalling pathway. These findings may provide new insights into the pathogenesis of diabetic cataracts, shedding light on potential factors for intervention to treat this sight-threatening condition.
Subject(s)
Calcinosis , Cataract , Core Binding Factor Alpha 1 Subunit , Glucose , Hyperglycemia , Hypoxia-Inducible Factor 1 , Lens, Crystalline , Humans , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/genetics , Calcinosis/etiology , Calcinosis/metabolism , Calcinosis/pathology , Cataract/etiology , Cataract/metabolism , Cataract/pathology , Cell Differentiation/drug effects , Cells, Cultured , Core Binding Factor Alpha 1 Subunit/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Epithelial Cells/pathology , Glucose/metabolism , Hyperglycemia/complications , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Lens, Crystalline/metabolism , Lens, Crystalline/pathology , Osteocalcin/metabolism , Osteocalcin/genetics , Signal Transduction , SOX9 Transcription Factor/metabolism , SOX9 Transcription Factor/genetics , Hypoxia-Inducible Factor 1/genetics , Hypoxia-Inducible Factor 1/metabolismABSTRACT
Congenital cataract is one of the most common causes of childhood blindness, typically resulting from genetic mutations. Over a hundred gene mutations associated with congenital cataract have been identified, with approximately half occurring in the Crystallin genes. In this study, we identified a novel γA-crystallin pathogenic mutation (c. 29G > C, p. Arg10Pro (R10P)), from a four-generation Chinese family with congenital cataract, and investigated its potential molecular mechanisms underlying congenital cataracts. We compared the protein structure and stability of purified the wild type (WT) and R10P under physiological conditions and environmental stresses (UV irradiation, pH imbalance, heat shock, and chemical denaturation) using spectroscopic experiments, SEC analysis, and the UNcle protein analysis system. The results demonstrate that γA-R10P has no significant impact on the structure of γA-crystallin on normal condition. However, it is more sensitive to UV irradiation at high concentrations and prone to aggregation at high temperatures. Therefore, our study reveals the crucial role of the conserved site mutation R10P in maintaining protein structure and stability, providing new insights into the mechanisms of cataract formation.
ABSTRACT
TOPIC: This systematic review and meta-analysis aims to clarify the association of cataract surgery with cognitive impairment and dementia. CLINICAL RELEVANCE: The association between vision impairment and cognitive decline is well-established. However, the cognitive benefits of cataract surgery are less clear. Given the lack of cure for dementia, identifying modifiable risk factors is key in caring for patients with cognitive deficits. METHODS: The study was conducted following Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. PubMed, Embase, and Cochrane Library were searched from inception through October 11, 2022, for studies reporting the effect of cataract surgery on cognitive impairment and dementia. We pooled maximally adjusted hazard ratios (HRs) for dichotomous outcomes and ratio of means (RoM) for continuous outcomes using a random-effects model. Heterogeneity was examined using sensitivity and subgroup analyses. The quality of evidence was evaluated using the Newcastle-Ottawa scale, Cochrane risk-of-bias tool for randomized trials, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: This review included 24 articles comprising 558 276 participants, of which 19 articles were analyzed qualitatively. The bias of studies ranged from low to moderate, and GRADE extended from very low to low. Cataract surgery was associated with a 25% reduced risk of long-term cognitive decline compared with those with uncorrected cataracts (HR, 0.75; 95% confidence interval [CI], 0.72-0.78). This cognitive benefit was seen across various cognitive outcomes and remained robust to sensitivity analyses. Participants who underwent cataract surgery showed a similar risk of long-term cognitive decline as healthy controls without cataracts (HR, 0.84; 95% CI, 0.66-1.06). Additionally, cataract surgery was associated with a 4% improvement in short-term cognitive test scores among participants with normal cognition (RoM, 0.96; 95% CI, 0.94-0.99), but no significant association was observed among participants with preexisting cognitive impairment. DISCUSSION: Cataract surgery may be associated with a lower risk of cognitive impairment and dementia, and cataract-associated vision impairment may be a modifiable risk factor for cognitive decline. Physicians should be aware of the cognitive sequelae of cataracts and the possible benefits of surgery. The cognitive benefits of cataract surgery should be investigated further in randomized trials. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Subject(s)
Cataract Extraction , Cognitive Dysfunction , Humans , Aged , Cataract/complications , Cognition/physiology , Dementia , Risk FactorsABSTRACT
PURPOSE: To assess the web accessibility and readability of patient-oriented educational websites for cataract surgery. DESIGN: Cross-sectional electronic survey. PARTICIPANTS: Websites with information dedicated to educating patients about cataract surgery. METHODS: An incognito search for "cataract surgery" was performed using a popular search engine. The top 100 patient-oriented cataract surgery websites that came up were included and categorized as institutional, private practice, or medical organization according to authorship. Each site was assessed for readability using 4 standardized reading grade-level formulas. Accessibility was assessed through multilingual availability, accessibility menu availability, complementary educational video availability, and conformance and adherence to the Web Content Accessibility Guidelines (WCAG) 2.0. A standard t test and chi-square analysis were performed to assess the significance of differences with regard to readability and accessibility among the 3 authorship categories. MAIN OUTCOME MEASURES: The main outcome measures were the website's average reading grade level, number of accessibility violations, multilingual availability, accessibility menu availability, complementary educational video availability, accessibility conformance level, and violation of the perceivable, operable, understandable, and robust (POUR) principles according to the WCAG 2.0. RESULTS: A total of 32, 55, and 13 sites were affiliated with institutions, private practice, and other medical organizations, respectively. The overall mean reading grade was 11.8 ± 1.6, with higher reading levels observed in private practice websites compared with institutions and medical organizations combined (12.1 vs. 11.4; P = 0.03). Fewer private practice websites had multiple language options compared with institutional and medical organization websites combined (5.5% vs. 20.0%; P = 0.03). More private practice websites had accessibility menus than institutions and medical organizations combined (27.3% vs. 8.9%; P = 0.038). The overall mean number of WCAG 2.0 POUR principle violations was 17.1 ± 23.1 with no significant difference among groups. Eighty-five percent of websites violated the perceivable principle. CONCLUSIONS: Available patient-oriented online information for cataract surgery may not be comprehensible to the general public. Readability and accessibility aspects should be considered when designing these resources. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Subject(s)
Cataract Extraction , Cataract , Humans , Cross-Sectional Studies , Patient Education as Topic , Comprehension , InternetABSTRACT
TOPIC: Review of the efficacy and safety of standard versus soft topical steroid application after cataract surgery. CLINICAL RELEVANCE: The control of postoperative inflammation is the mainstay of treatment after cataract surgery. However, no consensus exists regarding the postoperative steroid of choice. Basing the choice of topical postoperative steroidal treatment on high-quality data regarding both risks and benefits of various drugs would be advantageous for both patients and clinicians. METHODS: A systematic search of the PubMed, Scopus, and Embase electronic databases for all peer-reviewed published randomized control trials that included clinical outcomes of topical steroidal treatment after uneventful cataract surgery was performed. Individual study data were extracted and evaluated in a weighted pooled analysis including grading of total anterior chamber (AC) inflammation, AC cells, AC flare, postoperative visual acuity (VA), intraocular pressure (IOP), and rate of adverse events (AEs). RESULTS: Overall, 508 studies were found, of which 7 were eligible for the systematic review and ultimately were included for analysis, reporting on 593 patients from 5 countries. Age of included patients, when available, ranged between 3.7 and 73.4 years. Follow-up data were available for analysis at 1, 7, and 28 days after surgery. Except for a significantly lower grade of AC flare in the standard steroid group at day 7 (standardized mean difference, 0.26; 95% confidence interval, 0.05-0.47; I2 = 0%), inflammatory activity measurements displayed insignificant differences at every other follow-up (days 1 and 28 after surgery). Pooled analysis of IOP at each follow-up demonstrated a higher IOP at the 7-day visit in the standard steroid group, whereas IOP at other time points was comparable among the groups. Qualitative analysis of ocular AEs showed similarities among the groups. DISCUSSION: The findings of this study suggest that for the average patient, both groups produce a comparable effect on both AC inflammation and postoperative IOP and VA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
ABSTRACT
PURPOSE: To report the cumulative incidence of complications and to describe refractive error and visual acuity (VA) outcomes in children undergoing secondary intraocular lens (IOL) implantation after previous surgery for nontraumatic cataract. DESIGN: Pediatric cataract registry. PARTICIPANTS: Eighty children (108 eyes: 60 bilateral, 48 unilateral) undergoing lensectomy at younger than 13 years of age. METHODS: Annual data collection from medical record review through 5 years after lensectomy. MAIN OUTCOME MEASURES: Cumulative incidence of newly emergent complications after secondary IOL implantation; refractive error and VA by 5 years after lensectomy. RESULTS: Median follow-up after secondary IOL implantation was 2.7 years (interquartile range [IQR], 0.8-3.3 years; range, 0.6-5.0 years) for bilateral and 2.1 years (range, 0.5-6.4 years) for unilateral cases. A common complication after secondary IOL implantation was a glaucoma-related adverse event (GRAE; glaucoma or glaucoma suspect); the cumulative incidence was 17% (95% confidence interval [CI], 3%-29%) in bilateral cases and 12% (95% CI, 0%-23%) in unilateral cases. The cumulative incidence of surgery for visual axis opacification was 2% (95% CI, 0%-7%) for bilateral cases and 4% (95% CI, 0%-10%) for unilateral cases. The median prediction error within 90 days of implantation was 0.88 diopter (D; IQR, -0.50 to +3.00 D) less hyperopic than intended among 21 eyes for bilateral cases and 1.50 D (IQR, -0.25 to +2.38 D) less among 19 unilateral cases. The median spherical equivalent refractive error at 5 years (at a median of 5.1 years of age) in eyes receiving a secondary IOL was +0.50 D (IQR, -2.38 to +2.94 D) for 48 bilateral cases and +0.06 D (IQR, -2.25 to +0.75 D) for 22 unilateral cases. Median monocular VA at 5 years was 20/63 (IQR, 20/50-20/100) for bilateral cases (n = 42) and 20/400 (IQR, 20/160-20/800) for unilateral cases (n = 33). CONCLUSIONS: Eyes with secondary IOL implantation have a risk of developing new GRAEs. Five years after lensectomy (approximately 2.5 years after secondary IOL implantation), the average refractive error was less hyperopic than desired given the anticipated further myopic shift before refraction stabilizes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
ABSTRACT
PURPOSE: Examine the frequency and cost of procedural clearance tests and examinations in preparation for low-risk cataract surgery among members of a commercial healthcare organization in the United States. Determine what characteristics most strongly predict receipt of preoperative care and the probability that preoperative care impacts postsurgical adverse events. DESIGN: Retrospective healthcare claims analysis and medical records review from a large, blended-health organization headquartered in Western Pennsylvania. PARTICIPANTS: Members aged ≥ 65 years who were continuously enrolled 6 months before and after undergoing cataract surgery from 2018 to 2021 and had approved surgery claims. METHODS: Preoperative exams or tests occurring in the 30 days before surgery were identified via procedural and diagnosis codes on claims of eligible members (e.g., Current Procedural Terminology codes for blood panels and preprocedural International Classification of Diseases, 10th Revision, Clinical Modification codes). Prevalence and cost were directly estimated from claims; variables predictive of preoperative care receipt and adverse events were tested using mixed effects modeling. MAIN OUTCOME MEASURES: Total costs, prevalence, and strength of association as indicated by odds ratios. RESULTS: Up to 42% of members undergoing cataract surgery had a physician office visit for surgical clearance, and up to 23% of members had testing performed in isolation or along with clearance visits. The combined costs for the preoperative visits and tests were $4.3 million (approximately $107-$114 per impacted member). There was little difference in member characteristics between those receiving and not receiving preoperative testing or exams. Mixed effects models showed that the most impactful determinants of preoperative care were the surgical facility and member's care teams; for preoperative testing, facilities were a stronger predictor than care teams. Adverse events were rare and unassociated with receipt of preoperative testing, exams, or a combination of the two. CONCLUSIONS: Rates of routine preoperative testing before cataract surgery appear similar to those prior to the implementation of the Choosing Wisely campaign, which was meant to reduce this use. Additionally, preoperative evaluations, many likely unnecessary, were common. Further attention to and reconsideration of current policies and practice for preoperative care may be warranted, especially at the facility level. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
ABSTRACT
OBJECTIVE: To investigate the incidence and outcomes of retinal tear (RT) and retinal detachment (RD) after cataract extraction in patients with a history of previous phakic RT. DESIGN: Retrospective case series. SUBJECTS: Phakic eyes with RT that were successfully treated with laser photocoagulation or cryotherapy and subsequently underwent cataract surgery. METHOD: A retrospective review of phakic eyes treated for RTs between April 1, 2012 and May 31, 2023 was performed. Exclusions included prior vitreoretinal surgery before cataract removal and follow-up of less than 6 months post-cataract surgery. MAIN OUTCOME MEASURES: The incidence of RTs and RDs after cataract surgery, along with visual and anatomic outcomes. RESULTS: Of 12,109 phakic eyes treated for RTs, 1039 (8.6%) eyes underwent cataract surgery. After exclusions, 713 eyes of 660 patients were studied. The mean (standard deviation, SD) follow-up period post-cataract surgery was 34.8 (24.6) months with a median of 239 and 246 days to a new RT or RD development. The overall incidence for diagnosis of post-cataract surgery RT and RD was 7.3% (52/713) (2.9% and 4.3%, respectively), with a one-year incidence of 5.6% (2.2% and 3.4%, respectively). Multivariable regression analysis identified a higher risk of RT/RD among younger individuals (odds ratio [OR] 1.034; 95% confidence interval [CI] 1.004-1.065, P=0.028), males (OR 2.058; 95% CI 1.110-3.816, P=0.022), and those with shorter interval between laser treatment and cataract surgery (OR 1.001; 95% CI 1.001-1.001, P=0.011). Single surgery anatomic success for the RD repair was achieved in 25 eyes (80.6%) at 3 months, with a 100% final reattachment rate. The median final logMAR visual acuity was 0.10 (20/25) for RT, showing no significant change from post-cataract surgery, and 0.18 (20/30) for RD, a significant worsening from after cataract surgery. CONCLUSION: One year post-cataract surgery, the rate of diagnosed RT and RD in patients with previously treated RTs was relatively high, occurring in nearly 1 in 18 eyes. Higher risk was noted among younger individuals, males, and patients with a shorter interval between initial treatment for RT and cataract surgery. RD repair achieved good anatomical results, but vision declined.
ABSTRACT
PURPOSE: To compare the associations of race/ethnicity and socioeconomic status (SES) with visual impairment (VI) prior to surgical removal of cataracts across two large health systems in the U.S. Mid-Atlantic region. DESIGN: Multi-institutional cross-sectional data study. PARTICIPANTS: Patients aged 65 and older who underwent cataract surgery at Johns Hopkins Hospital (JHH) and Kaiser Permanente (KP) between January 1, 2017 and December 31, 2019. METHODS: Covariates included patient age, sex, smoking status, surgery laterality, Charlson Comorbidity Index (CCI), and ocular comorbidities. Multivariable generalized estimating equation models were used to examine the association of race/ethnicity and area deprivation index (ADI) with visual acuity. MAIN OUTCOME MEASURES: Visual acuity prior to cataract surgery was assessed using Log of Minimum Angle of Resolution (logMAR). Race/ethnicity and ADI were the main exposures of interest. RESULTS: At JHH, 11,509 patients (17,731 eyes) were included, while KP had 7,143 patients (10,542 eyes). After adjusting for covariates, Black (ß, 0.49), Asian (ß, 0.83), and Hispanic patients (ß, 0.95) were more likely to have worse visual acuity secondary to cataracts at JHH (P < 0.001 for all) compared to White patients. Similarly, at KP, Black (ß, 0.56), Asian (ß, 0.70), and Hispanic patients (ß, 0.89) were more likely to have worse visual acuity (P < 0.001 for all) compared to White patients. Compared to those living in the least disadvantaged neighborhoods (Quartile [Q]1 ADI) at JHH, higher ADI quartiles (more deprived) were more likely to have worse visual acuity (ß, 0.27; P = 0.001 for Q2, ß, 0.40; P = 0.001 for Q3, ß, 0.95; P < 0.001 for Q4). There was no significant association found between ADI and VI secondary to cataracts at KP. CONCLUSIONS: Among older adults, non-White race/ethnicity was independently associated with VI secondary to cataracts in two large health systems in the U.S. Mid-Atlantic region, after adjustment for ADI. Area deprivation was also associated with VI but only in the JHH system. Our study suggests that non-White patients and those with lower SES are at greater risk of VI secondary to cataracts possibly due to social, structural and institutional barriers.
ABSTRACT
PURPOSE: To compare the effectiveness and safety of a single injection of subconjunctival triamcinolone acetonide (TA) with that of postoperative topical prednisolone acetate (PA) with and without nonsteroidal anti-inflammatory drugs (NSAIDs) for cataract surgery prophylaxis. DESIGN: Retrospective, comparative effectiveness cohort study. PARTICIPANTS: Patients at Kaiser Permanente Northern California from 2018 through 2021. INTERVENTION: Exposure groups included topical PA with or without NSAID and subconjunctival injection of TA (Kenalog; Bristol-Myers-Squibb) 10 mg/ml or 40 mg/ml in a low dose (1.0-3.0 mg) or high dose (3.1-5.0 mg). MAIN OUTCOME MEASURES: The adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of postoperative macular edema (ME) and iritis diagnoses 15 to 120 days after surgery (effectiveness measures) and a glaucoma-related event (safety measure) between 15 days and 1 year after surgery. RESULTS: Of 69 832 eligible patient-eyes, postoperative ME, iritis, and a glaucoma-related event occurred on average in 1.3%, 0.8%, and 3.4% of eyes in the topical groups and 0.8%, 0.5%, and 2.8% of eyes in the injection groups, respectively. In multivariable analysis, compared with the PA reference group, the PA plus NSAID group had a lower OR of ME (OR, 0.88; 95% CI, 0.74-1.04; P = 0.135). and all injection groups had even lower odds, with the high-dose TA 10-mg/ml group reaching statistical significance (OR, 0.64; 95% CI, 0.43-0.97; P = 0.033). A trend of lower odds of a postoperative iritis diagnosis was noted in the high-strength (40 mg/ml) groups. For postoperative glaucoma-related events, compared with PA, the TA 10-mg/ml low-dose group showed lower odds (OR, 0.69; 95% CI, 0.55-0.86; P = 0.001), the TA 10-mg/ml high-dose group showed similar odds (OR, 0.90; 95% CI, 0.70-1.15; P = 0.40), and the TA 40-mg/ml low-dose and high-dose groups showed higher odds of an event occurring (OR, 1.46 [95% CI, 0.98-2.18; P = 0.062] and OR, 2.14 [95% CI, 1.36-3.37; P = 0.001], respectively). CONCLUSIONS: The TA 10-mg/ml high-dose (4 mg) group was associated with a lower risk of postoperative ME and a similar risk of glaucoma-related events compared with the topical groups. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
ABSTRACT
PURPOSE: To evaluate risk factors for intraocular pressure (IOP) spike after cataract surgery using the IRIS® Registry (Intelligent Research in Sight). DESIGN: Retrospective clinical cohort study. PARTICIPANTS: Adults with IRIS Registry data who underwent stand-alone phacoemulsification from January 1, 2013, through September 30, 2019. METHODS: Intraocular pressure spike was defined as postoperative IOP of > 30 mmHg and > 10 mmHg from the baseline within the first postoperative week. Odds ratios (ORs) for demographic and clinical characteristics were calculated with univariable and multivariable logistic regression analyses. MAIN OUTCOME MEASURES: Incidence and OR of IOP spike. RESULTS: We analyzed data from 1 191 034 eyes (patient mean age, 71.3 years; 61.2% female sex; and 24.8% with glaucoma). An IOP spike occurred in 3.7% of all eyes, 5.2% of eyes with glaucoma, and 3.2% of eyes without glaucoma (P < 0.0001). Multivariable analyses of all eyes indicated a greater risk of IOP spike with higher baseline IOP (OR, 1.57 per 3 mmHg), male sex (OR, 1.79), glaucoma (OR, 1.20), Black race (OR, 1.39 vs. Asian and 1.21 vs. Hispanic), older age (OR, 1.07 per 10 years), and complex surgery coding (OR, 1.22; all P < 0.0001). Diabetes (OR, 0.90) and aphakia after surgery (OR, 0.60) seemed to be protective against IOP spike (both P < 0.0001). Compared with glaucoma suspects, ocular hypertension (OR, 1.55), pigmentary glaucoma (OR, 1.56), and pseudoexfoliative glaucoma (OR, 1.52) showed a greater risk of IOP spike and normal-tension glaucoma (OR, 0.55), suspected primary angle closure (PAC; OR, 0.67), and PAC glaucoma (OR, 0.81) showed less risk (all P < 0.0001). Using more baseline glaucoma medications was associated with IOP spike (OR, 1.18 per medication), whereas topical ß-blocker use (OR, 0.68) was protective (both P < 0.0001). CONCLUSIONS: Higher baseline IOP, male sex, glaucoma, Black race, older age, and complex cataract coding were associated with early postoperative IOP spike, whereas diabetes and postoperative aphakia were protective against a spike after stand-alone phacoemulsification. Glaucomatous eyes demonstrated different risk profiles dependent on glaucoma subtype. The findings may help surgeons to stratify and mitigate the risk of IOP spike after cataract surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Subject(s)
Intraocular Pressure , Phacoemulsification , Registries , Humans , Male , Intraocular Pressure/physiology , Female , Aged , Retrospective Studies , Risk Factors , Middle Aged , Aged, 80 and over , Tonometry, Ocular , Incidence , Postoperative Complications , Lens Implantation, Intraocular , Ocular Hypertension/physiopathology , Ocular Hypertension/etiology , Glaucoma/physiopathology , Glaucoma/surgeryABSTRACT
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.