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Investigative Ophthalmology & Visual... Jul 2023To investigate the association of genetically determined primary open-angle glaucoma (POAG), myopic refractive error (RE), type 2 diabetes (T2D), blood pressure (BP),...
PURPOSE
To investigate the association of genetically determined primary open-angle glaucoma (POAG), myopic refractive error (RE), type 2 diabetes (T2D), blood pressure (BP), body mass index (BMI), cigarette smoking, and alcohol consumption with the risk of age-related cataract.
METHODS
To assess potential causal effects of clinical or behavioral factors on cataract risk, we conducted two-sample Mendelian randomization analyses. Genetic instruments, based on common genetic variants associated with risk factors at genome-wide significance (P < 5 × 10-8), were derived from published genome-wide association studies (GWAS). For age-related cataract, we used GWAS summary statistics from our previous GWAS conducted in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (28,092 cataract cases and 50,487 controls; all non-Hispanic whites) or in the UK Biobank (31,852 cataract cases and 428,084 controls; all European-descent individuals). We used the inverse-variance weighted (IVW) method as our primary source of Mendelian randomization estimates and conducted common sensitivity analyses.
RESULTS
We found that genetically determined POAG and mean spherical equivalent RE were significantly associated with cataract risk (IVW model: odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.01-1.08; P = 0.018; per diopter more hyperopic: OR = 0.92; 95% CI, 0.89-0.93; P = 6.51 × 10-13, respectively). In contrast, genetically determined T2D, BP, BMI, cigarette smoking, or alcohol consumption were not associated with cataract risk (P > 0.05).
CONCLUSIONS
Our results provide evidence that genetic risks for POAG and myopia may be causal risk factors for age-related cataract. These results are consistent with previous observational studies reporting associations of myopia with cataract risk. This information may support population cataract risk stratification and screening strategies.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Mendelian Randomization Analysis; Genome-Wide Association Study; Glaucoma, Open-Angle; Risk Factors; Myopia; Cataract; Polymorphism, Single Nucleotide
PubMed: 37459064
DOI: 10.1167/iovs.64.10.19 -
Indian Journal of Ophthalmology May 2024
Topics: Humans; Cataract Extraction; Cataract
PubMed: 38648429
DOI: 10.4103/IJO.IJO_888_24 -
Turkish Journal of Ophthalmology Aug 2023Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular... (Review)
Review
Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular pressure (IOP) at diagnosis, and a wider range of IOP fluctuation compared to primary open-angle glaucoma. Patients with this syndrome have a ten-fold higher risk of developing glaucoma than the normal population. A definite diagnosis can be made by the observation of pseudoexfoliation material (PEM) on the anterior lens surface, ciliary processes, zonules, and iris. PEM deposits on the zonules may explain the clinically observed zonular weakness and lens subluxation or dislocation. An increased incidence of cataract development is also associated with PES. There is growing evidence for systemic associations of PES with peripheral, cardiovascular, and cerebrovascular system diseases, Alzheimer's disease, hearing loss, and increased plasma homocysteine levels. Indications for surgery are markedly more common in patients with pseudoexfoliation glaucoma than primary open-angle glaucoma. The goal of this article is to review the latest perspectives on the clinical features, therapy, and systemic associations of this clinically and biologically challenging disease.
Topics: Humans; Cataract; Exfoliation Syndrome; Glaucoma; Glaucoma, Open-Angle; Lens Subluxation
PubMed: 37602651
DOI: 10.4274/tjo.galenos.2023.76300 -
Indian Journal of Ophthalmology Nov 2023
Topics: Humans; Infant, Newborn; Cataract; Eye; Iatrogenic Disease; Retinopathy of Prematurity; Gestational Age; Retrospective Studies; Laser Coagulation
PubMed: 37869997
DOI: 10.4103/IJO.IJO_2744_23 -
Current Opinion in Ophthalmology Jan 2024This review aims to clarify the advantages and disadvantages of immediately sequential bilateral cataract surgery (ISBCS) based on recent studies, illustrate the safety... (Review)
Review
PURPOSE OF REVIEW
This review aims to clarify the advantages and disadvantages of immediately sequential bilateral cataract surgery (ISBCS) based on recent studies, illustrate the safety of this approach, the cost-effectiveness, and present the importance of inclusion protocols for the best results.
RECENT FINDINGS
In recent studies, the authors found no evidence of an increased risk of bilateral devastating complications such as endophthalmitis with ISBCS based on descriptive evidence compared to delayed sequential bilateral cataract surgery (DSBCS). Furthermore, recent studies on cost analyses showed that ISBCS resulted in fewer costs and significant cost savings to third-party payers, patients, and society compared to DSBCS.
SUMMARY
The ISBCS surgical approach decreases hospital visits, reduces costs, and provides rapid visual rehabilitation and neuro adaptation. The risk of bilateral simultaneous complications is now recognized to be very rare with intracameral antibiotics and compliance with correct protocols. With new generations of optical biometry and lens calculation formulas, refractive surprises are occasional for normal eyes. However, refractive surprise is controversial, especially in the implantation of presbyopia correction intra-ocular lenses, which must be evaluated carefully in the ISBCS approach.
Topics: Humans; Phacoemulsification; Lens Implantation, Intraocular; Cataract Extraction; Visual Acuity; Cataract
PubMed: 38390776
DOI: 10.1097/ICU.0000000000001003 -
JAMA Ophthalmology Aug 2023Lensectomy with primary intraocular lens (IOL) implantation is often used in the management of nontraumatic pediatric cataract, but long-term data evaluating the...
IMPORTANCE
Lensectomy with primary intraocular lens (IOL) implantation is often used in the management of nontraumatic pediatric cataract, but long-term data evaluating the association of age and IOL location with the incidence of complications are limited.
OBJECTIVE
To describe the incidence of complications and additional eye surgeries through 5 years following pediatric lensectomy with primary IOL implantation and association with age at surgery and IOL location.
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study used Pediatric Eye Disease Investigator Group cataract registry data from 61 institution- and community-based practices over 3 years (June 2012 to July 2015). Participants were children younger than 13 years without baseline glaucoma who had primary IOL implantation (345 bilateral and 264 unilateral) for nontraumatic cataract. Data analysis was performed between September 2021 and January 2023.
EXPOSURES
Lensectomy with primary IOL implantation.
MAIN OUTCOME AND MEASURES
Five-year cumulative incidence of complications by age at surgery (<2 years, 2 to <4 years, 4 to <7 years, and 7 to <13 years) and by IOL location (sulcus vs capsular bag) were estimated using Cox proportional hazards models.
RESULTS
The cohort included 609 eyes from 491 children (mean [SD] age, 5.6 [3.3] years; 261 [53%] male and 230 [47%] female). Following cataract extraction with primary IOL implantation, a frequent complication was surgery for visual axis opacification (VAO) (cumulative incidence, 32%; 95% CI, 27%-36%). Cumulative incidence was lower with anterior vitrectomy at the time of IOL placement (12%; 95% CI, 8%-16%) vs without (58%; 95% CI, 50%-65%), and the risk of undergoing surgery for VAO was associated with not performing anterior vitrectomy (hazard ratio [HR], 6.19; 95% CI, 3.70-10.34; P < .001). After adjusting for anterior vitrectomy at lens surgery, there were no differences in incidence of surgery for VAO by age at surgery (<2 years, HR, 1.35 [95% CI, 0.63-2.87], 2 to <4 years, HR, 0.86 [95% CI, 0.44-1.68], 4 to <7 years, HR, 1.06 [95% CI, 0.72-1.56]; P = .74) or by capsular bag vs sulcus IOL fixation (HR, 1.22; 95% CI, 0.36-4.17; P = .75). Cumulative incidence of glaucoma plus glaucoma suspect by 5 years was 7% (95% CI, 4%-9%), which did not differ by age after controlling for IOL location and laterality.
CONCLUSIONS AND RELEVANCE
In this cohort study, a frequent complication following pediatric lensectomy with primary IOL was surgery for VAO, which was associated with primary anterior vitrectomy not being performed but was not associated with age at surgery or IOL location. The risk of glaucoma development across all ages at surgery suggests a need for long-term monitoring.
Topics: Child; Humans; Male; Female; Child, Preschool; Lens Implantation, Intraocular; Cohort Studies; Prospective Studies; Visual Acuity; Cataract Extraction; Cataract; Glaucoma; Ocular Hypertension
PubMed: 37347490
DOI: 10.1001/jamaophthalmol.2023.2335 -
Klinische Monatsblatter Fur... Jan 2024Cataract is among the leading causes of visual impairment worldwide. Innovations in treatment have drastically improved patient outcomes, but to be properly implemented,... (Review)
Review
Cataract is among the leading causes of visual impairment worldwide. Innovations in treatment have drastically improved patient outcomes, but to be properly implemented, it is necessary to have the right diagnostic tools. This review explores the cataract grading systems developed by researchers in recent decades and provides insight into both merits and limitations. To this day, the gold standard for cataract classification is the Lens Opacity Classification System III. Different cataract features are graded according to standard photographs during slit lamp examination. Although widely used in research, its clinical application is rare, and it is limited by its subjective nature. Meanwhile, recent advancements in imaging technology, notably Scheimpflug imaging and optical coherence tomography, have opened the possibility of objective assessment of lens structure. With the use of automatic lens anatomy detection software, researchers demonstrated a good correlation to functional and surgical metrics such as visual acuity, phacoemulsification energy, and surgical time. The development of deep learning networks has further increased the capability of these grading systems by improving interpretability and increasing robustness when applied to norm-deviating cases. These classification systems, which can be used for both screening and preoperative diagnostics, are of value for targeted prospective studies, but still require implementation and validation in everyday clinical practice.
Topics: Humans; Prospective Studies; Photography; Cataract; Lens, Crystalline; Visual Acuity; Phacoemulsification
PubMed: 38242135
DOI: 10.1055/a-2003-2369 -
Die Ophthalmologie Jun 2024
Topics: Humans; Cataract; Cataract Extraction; Infant, Newborn; Female
PubMed: 38396077
DOI: 10.1007/s00347-024-02001-z -
Free Radical Biology & Medicine Aug 2023Oxidative stress-induced lens epithelial cells (LECs) death plays a pivotal role in age-related cataract (ARC) with severe visual impairment, in which ferroptosis is...
Oxidative stress-induced lens epithelial cells (LECs) death plays a pivotal role in age-related cataract (ARC) with severe visual impairment, in which ferroptosis is gradually receiving numerous attention resulting from lipid peroxide accumulation and reactive oxygen species (ROS) overproduction. However, the essential pathogenic factors and the targeted medical strategies still remain skeptical and indistinct. In this work, by transmission electron microscopy (TEM) analysis, the major pathological courses in the LECs of ARC patients have been identified as ferroptosis, which was manifested with remarkable mitochondrial alterations, and similar results were found in aged mice (24-month-old). Furthermore, the primary pathological processes in the NaIO3-induced mice and HLE-B3 cell model have also been verified to be ferroptosis with an irreplaceable function of Nrf2, proved by the increased sensitivity to ferroptosis when Nrf2 was blocked in Nrf2-KO mice and si-Nrf2-treated HLE-B3 cells. Importantly, it has been found that an increased expression of GSK-3β was indicated in low-Nrf2-expressed tissues and cells. Subsequently, the contributions of abnormal GSK-3β expression to NaIO3-induced mice and HLE-B3 cell model were further evaluated, inhibition of GSK-3β utilizing SB216763 significantly alleviated LECs ferroptosis with less iron accumulation and ROS generation, as well as reversed expression alterations of ferroptosis markers, including GPX4, SLC7A11, SLC40A1, FTH1 and TfR1, in vitro and in vivo. Collectively, our findings conclude that targeting GSK-3β/Nrf2 balance might be a promising therapeutic strategy to mitigate LECs ferroptosis and thus probably delay the pathogenesis and development of ARC.
Topics: Animals; Mice; Antioxidants; Cataract; Epithelial Cells; Ferroptosis; Glycogen Synthase Kinase 3 beta; NF-E2-Related Factor 2; Reactive Oxygen Species
PubMed: 37156294
DOI: 10.1016/j.freeradbiomed.2023.04.022 -
Current Opinion in Ophthalmology Jan 2024Oxidative stress plays a central role in cataract pathogenesis, a leading cause of global blindness. This review delves into the role of oxidative stress in cataract... (Review)
Review
PURPOSE OF REVIEW
Oxidative stress plays a central role in cataract pathogenesis, a leading cause of global blindness. This review delves into the role of oxidative stress in cataract development and key biomarkers - glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) - to clarify their functions and potential applications in predictive diagnostics and therapies.
RECENT FINDINGS
Antioxidants serve as pivotal markers in cataract pathogenesis. GSH affects the central lens due to factors such as enzyme depletion and altered connexin expression, impairing GSH diffusion. Age-related oxidative stress may hinder GSH transport via connexin channels or an internal microcirculation system. N-acetylcysteine, a GSH precursor, shows promise in mitigating lens opacity when applied topically. Additionally, SOD, particularly SOD1, correlates with increased cataract development and gel formulations have exhibited protective effects against posterior subscapular cataracts. Lastly, markers of lipid peroxidation, MDA and 4-HNE, have been shown to reflect disease severity. Studies suggest a potential link between 4-HNE and connexin channel modification, possibly contributing to reduced GSH levels.
SUMMARY
Oxidative stress is a significant contributor to cataract development, underscoring the importance of antioxidants in diagnosis and treatment. Notably, GSH depletion, SOD decline, and lipid peroxidation markers are pivotal factors in cataract pathogenesis, offering promising avenues for both diagnosis and therapeutic intervention.
Topics: Humans; Antioxidants; Oxidative Stress; Cataract; Lens, Crystalline; Glutathione; Superoxide Dismutase; Connexins
PubMed: 37882550
DOI: 10.1097/ICU.0000000000001009