Association of CUL4B with the pathogenesis of age-related cataract.

PURPOSE: Age-related cataract (ARC) is the most common cause of visual impairment and blindness in older adults. However, the role of CUL4B in the ARC remains unclear. Therefore, we investigated CUL4B expression and its effects on apoptosis. MATERIALS AND METHODS: CUL4B expression levels were detected by a quantitative real-time polymerase chain reaction from the anterior lens capsules of patients with ARC and HLE-B3 cells treated with different concentrations of H2O2. CUL4B expression was silenced by siRNA transfection to evaluate apoptosis. CUL4B and apoptotic proteins B cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), caspase-3, cleaved caspase-3, Bax, Bak, and Bid were assessed using western blot analysis. Apoptosis was monitored using the TUNEL assay. RESULTS: CUL4B expression was downregulated in the anterior lens capsules (P < 0.0001) and H2O2-treated HLE-B3 cells (P = 0.0405). CUL4B protein levels were significantly lower in 100 µmol/L (P = 0.0012) and 200 µmol/L (P = 0.0041) H2O2-treated HLE-B3 cells than in the untreated cells. CUL4B expression was significantly knocked down at the mRNA (P = 0.0043) and protein levels (P = 0.0002) in HLE-B3 cells. Bcl-2 (P = 0.0199), Mcl-1 (P = 0.0042), and caspase-3 (P = 0.0142) were significantly downregulated, whereas cleaved caspase-3 (P = 0.0089) and Bak (P = 0.009) were significantly upregulated in the knockdown group. The TUNEL assay showed a greater induction of apoptosis. CONCLUSIONS: CUL4B downregulation promotes the apoptosis of lens epithelial cells. Our study may help in understanding the role of CUL4B in ARC pathogenesis.

Rare micropupil secondary to congenital cataract surgery favoring the development of the affected eye: a case report.

BACKGROUND: Congenital microcoria has been extensively reported and usually leads to visual dysfunction or blindness. However, micropupil development secondary to cataract surgery has never been reported. Here, we describe a rare case of micropupil development in infancy that occurred secondary to combined cataract extraction and intraocular lens implantation for treatment of congenital cataract. When the patient reached adulthood, the affected eye not only gained good vision but also showed better ocular development and refractive status than the fellow eye. CASE PRESENTATION: A 17-year-old boy presented to our outpatient clinic with decreased vision in his left eye related to congenital cataract surgery at 6 months of age. The affected eye had exhibited a pinhole pupil since the third month postoperatively. The condition had been managed with observation and regular monocular occlusion treatment. Upon presentation to our clinic, the best-corrected visual acuity (BCVA) in his fellow eye was 0.0 logMAR(20/20) with a refraction of - 5.75 diopters cylinder/-2.25 diopters sphere, and the BCVA in his affected eye was 0.5 logMAR(20/40) with a refraction of 0.00 diopters. Ophthalmic examination of the affected eye revealed a pinhole pupil (approximately 0.5 mm) with high light reflex sensitivity but no response to pupil-dilating drugs. The patient underwent pupilloplasty of the affected eye under corneal surface anesthesia. Postoperative examination revealed better ocular development in the affected eye than in the fellow eye (axial length: 24.21 vs. 27.02 mm, respectively) as well as better refractive status in the affected eye (BCVA of 0.0 logMAR(20/20) with a refraction of - 2.23 diopters cylinder/-3.00 diopters sphere vs. 0logMAR(20/20) with a refraction of -5.75 diopters cylinder/-2.25 diopters sphere). CONCLUSIONS: We have reported a rare case of micropupil development secondary to congenital cataract surgery, which is an uncommon complication, especially in children. However, unlike congenital microcoria, the secondary pinhole pupil may have reduced imaging haze and halos, possibly favoring the development of the affected eye. This case provides further insight into the treatment of congenital cataract.

Myopia and Nutrient Associations with Age-Related Eye Diseases in Korean Adults: A Cross-Sectional KNHANES Study.

This study assessed the prevalence of myopia, cataracts, glaucoma, and macular degeneration among Koreans over 40, utilizing data from the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII, 2018). We analyzed 204,973 adults (44% men, 56% women; mean age 58.70 ± 10.75 years), exploring the association between myopia and these eye diseases through multivariate logistic regression, adjusting for confounders and calculating adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results showed a myopia prevalence of 44.6%, cataracts at 19.4%, macular degeneration at 16.2%, and glaucoma at 2.3%, with significant differences across ages and genders. A potential link was found between myopia and an increased risk of cataracts and macular degeneration, but not with glaucoma. Additionally, a higher dietary intake of carbohydrates, polyunsaturated and n-6 fatty acids, vitamins, and minerals correlated with lower risks of these diseases, underscoring the importance of the diet in managing and preventing age-related eye conditions. These findings highlight the need for dietary considerations in public health strategies and confirm myopia as a significant risk factor for specific eye diseases in the aging Korean population.

Clinical Experience of Using a Combination of Dexamethasone and Levofloxacin After Cataract Surgery.

Background: Where routine prophylactic antibiotics have been adopted following cataract surgery, rates of endophthalmitis have been decreasing. Intracameral and topical antibiotics are currently used to prevent endophthalmitis after cataract surgery. When applying topical antibiotics, there are different recommendations on the frequency and duration of therapy. The development of bacterial resistance to the excessive and long-term use of antibiotics is a growing problem worldwide. The goal is to achieve a good antibiotic effect with the shortest possible use of antibiotics. Objective: The aim of this study was to compare the effectiveness of a new combination therapy of dexamethasone and levofloxacin for seven days after cataract surgery with the previous regimen of dexamethasone, neomycin sulfate, and polymyxin B, which was given for 21 days. Methods: A retrospective analysis of medical records and administered a questionnaire was conducted to assess the effectiveness of postoperative therapy in our cataract surgery patients. The study involved 52 patients who underwent surgery within the last year, performed by a single surgeon at our institution. The findings can help us improve the quality of care we provide and optimize our patients' overall quality of life. Results: We conducted an in-depth study on 52 individuals who underwent cataract surgery at our institution. The prescribed therapeutic regimen for the participants included administering Ducressa solution four times daily for the first seven days and Maxidex solution three times daily for the subsequent 14 days. The study found that none of the participants experienced complications after surgery, and all found it easy to instill the medication. The prescribed regimen effectively managed the postoperative recovery of the participants, and the medication was well-tolerated. Conclusion: Our research found that a new combination of levofloxacin and dexamethasone, when used topically, may require a shorter treatment period, reducing the risk of antibiotic resistance and providing a safe alternative for endophthalmitis prevention.

A grape-supplemented diet prevented ultraviolet (UV) radiation-induced cataract by regulating Nrf2 and XIAP pathways.

The purpose of this study is to investigate if grape consumption, in the form of grape powder (GP), could protect against ultraviolet (UV)-induced cataract. Mice were fed with the regular diet, sugar placebo diet, or a grape diet (regular diet supplemented with 5%, 10%, and 15% GP) for 3 months. The mice were then exposed to UV radiation to induce cataract. The results showed that the GP diet dose-dependently inhibited UV-induced cataract and preserved glutathione pools. Interestingly, UV-induced Nrf2 activation was abolished in the groups on the GP diet, suggesting GP consumption may improve redox homeostasis in the lens, making Nrf2 activation unnecessary. For molecular target prediction, a total of 471 proteins regulated by GP were identified using Agilent Literature Search (ALS) software. Among these targets, the X-linked inhibitor of apoptosis (XIAP) was correlated with all of the main active ingredients of GP, including resveratrol, catechin, quercetin, and anthocyanins. Our data confirmed that GP prevented UV-induced suppression of XIAP, indicating that XIAP might be one of the critical molecular targets of GP. In conclusion, this study demonstrated that GP protected the lens from UV-induced cataract development in mice. The protective effects of GP may be attributed to its ability to improve redox homeostasis and activate the XIAP-mediated antiapoptotic pathway.

Body mass index influences age-related cataracts: an updated meta-analysis and systemic review.

PURPOSE: Visual impairment and blindness caused by cataracts are major public health problems. Several factors are associated with an increased risk of age-related cataracts, such as age, smoking, alcohol consumption, and ultraviolet radiation. This meta-analysis aimed to assess the association between body mass index and age-related cataracts. METHODS: Studies on weight and age-related cataracts published from January 2011 to July 2020 were reviewed by searching PubMed, Medline, and Web of Science databases. The random-effects and fixed-effects models were used for the meta-analysis, and the results were reported as odd ratios. RESULTS: A total of nine studies were included in the meta-analysis. No correlation was found between underweight and nuclear cataracts (OR=1.31, 95% CI [-0.50 to 3.12], p=0.156). The results of the random-effects model showed that overweight was significantly associated with age-related cataracts and reduced the risk of age-related cataracts (OR=0.91, 95% CI [0.80-1.02], p<0.0001; I2=62.3%, p<0.0001). Significant correlations were found between overweight and cortical, nuclear, and posterior subcapsular cataracts (OR=0.95, 95% CI [0.66-1.24], p<0.0001; OR=0.92, 95% CI (0.76-1.08), p<0.0001; OR=0.87, 95% CI [0.38-1.02], p<0.0001). Significant correlations were found between obesity and cortical, nuclear, and posterior subcapsular cataracts (OR=1.00, 95% CI [0.82-1.17], p<0.0001; OR=1.07, 95% CI [0.92-1.22], p<0.0001; OR=1.14, 95% CI [0.91-1.37], p<0.0001). CONCLUSION: This finding suggested a significant correlation between body mass index and age-related cataracts, with overweight and obesity reducing or increasing the risk of age-related cataracts, respectively.

Long-term complications of permanent hypoparathyroidism in adults: prevalence and associated factors.

INTRODUCTION: Patients with Chronic hypoparathyroidism (CHPT) receiving conventional treatment are exposed to several long-term complications including basal ganglia calcifications, posterior subcapsular cataract, kidney stones, and renal insufficiency. The aim of this study was to assess the prevalence and the associated factors of these complications in patients with CHPT. METHODS: We conducted a cross-sectional study including 58 patients with CHPT. All participants underwent physical examination, biochemical assessment (total serum calcium, serum phosphorus, serum albumin, intact-PTH, serum magnesium, 25-hydroxy-vitamin D, serum creatinine, thyroid stimulating hormone (TSH), and 24-hour urinary calcium), slit lamp examination, brain computed tomography scan (CT-scan), and renal ultrasound. RESULTS: Participants had a mean age of 52.6 ± 16.4 years and a gender ratio (women/men) of 3.5. Fahr syndrome, cataract, urolithiasis, and renal failure were found in 55%, 62%, 12%, and 17% of cases, respectively. CHPT duration >15 years (Adjusted-OR = 43.1, 95-CI: 2.63-703.06, p = 0.008) and poor adherence to treatment (Adjusted-OR = 8.04, 95%-CI: 1.52-42.42, p = 0.014) were independently associated with the risk of Fahr syndrome. Age >55 years (adjusted-OR = 5.07, 95-CI: 1.10-23.42, p = 0.037), disease duration >15 years (adjusted-OR = 20.21, 95-CI: 1.54-265.84, p = 0.022), and magnesium level <0.8 mmol/l (adjusted-OR = 36.46, 95-CI: 3.75-354.08, p = 0.002) were independently associated with the risk of subcapsular cataract. Only hypercalciuria (Adjusted-OR = 21.27, 95-CI: 2.31-195.91, p = 0.007) was an independent risk factor for kidney stones. Renal failure was not associated with kidney stones (p = 1). However, creatinine clearance was negatively correlated with age (r = -0.784; p < 10-3) and disease duration (r = -0.352; p = 0.007). CONCLUSION: Our results revealed high prevalences of neurological, ocular, and renal complications in patients with CHPT and emphasized the importance of regular biological monitoring, therapeutic adjustments, screening, and adherence to treatment in the prevention of these complications.

All about traumatic cataracts: narrative review.

Ocular trauma is an important cause of monocular blindness worldwide. Injury to the lens after blunt or penetrating trauma is common and can result in vision impairment. Selecting the most appropriate therapeutic approaches depends on factors such as patients' age, mechanism of trauma, and underlying clinical conditions. Early management, especially within childhood, is essential because of the difficulties involved in examination; anatomical variations; as well as accompanying intraocular inflammation, amblyopia, or vitreoretinal adhesions. The objective of this study was to provide a comprehensive review of the epidemiology and clinical management of traumatic cataract, highlighting the significance of accurate diagnosis and selection of the optimal therapeutic approach.

Late spontaneous posterior capsule rupture with single-piece hydrophobic acrylic intraocular lens dislocation.

In this study, we described and discussed the late onset spontaneous posterior capsule rupture with intraocular lens (IOL) dislocation years after uncomplicated cataract surgery and implantation of hydrophobic acrylic IOLs. Eight patients presented with spontaneous posterior capsule rupture and IOL dislocation 5-20 years after uncomplicated phacoemulsification and IOL (AcrySof, Alcon, US) implantation. None of the patients had undergone posterior capsulotomy in the past. Four of the patients admitted habitual eye rubbing. An intact and well-centered continuous curvilinear capsulotomy edge was observed in all cases. IOLs were dislocated or displaced behind the anterior capsulotomy with a significant decrease in vision. A large rupture with a curled edge of the broken posterior capsule was visible. Dislocated IOLs were removed, and a three-piece IOL was inserted in the sulcus in six cases and suture fixated to the sclera in two cases. Improved vision was achieved in all cases. Although the mechanism underlying this late complication is unclear, habitual eye rubbing or IOL design may play a role. Further investigation is needed to prevent this complication in the future.

High glucose promotes osteogenic differentiation of human lens epithelial cells through hypoxia-inducible factor (HIF) activation.

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.

Transcriptome alterations in sf3b4-depleted zebrafish: Insights into cataract formation in retinitis pigmentosa model.

Posterior subcapsular cataract (PSC) frequently develops as a complication in patients with retinitis pigmentosa (RP). Despite numerous scientific investigations, the intricate pathomechanisms underlying cataract formation in individuals affected by RP remain elusive. Therefore, our study aims to elucidate the potential pathogenesis of cataracts in an RP model using splicing factor subunit 3b (sf3b4) mutant zebrafish. By analyzing our previously published transcriptome dataset, we identified that, in addition to RP, cataract was listed as the second condition in our transcriptomic analysis. Furthermore, we confirmed the presence of nucleus retention in the lens fiber cells, along with abnormal cytoskeleton expression in both the lens fiber cells and lens epithelial cells in sf3b4-depleted fish. Upon closer examination, we identified 20 differentially expressed genes (DEGs) that played a role in cataract formation, with 95 % of them related to the downregulation of structural lens proteins. Additionally, we also identified that among all the DEGs, 13 % were associated with fibrotic processes. It seems that the significant upregulation of inflammatory mediators, in conjunction with TGF-ß signaling, plays a central role in the cellular biology of PSC and posterior capsular opacification (PCO) in sf3b4 mutant fish. In summary, our study provides valuable insights into cataract formation in the RP model of sf3b4 mutants, highlighting its complexity driven by changes in structural lens proteins and increased cytokines/growth factors.

Radiation cataract in Heterogeneous Stock mice after γ-ray or HZE ion exposure.

Health effects of space radiation are a serious concern for astronauts on long-duration missions. The lens of the eye is one of the most radiosensitive tissues in the body and, therefore, ocular health risks for astronauts is a significant concern. Studies in humans and animals indicate that ionizing radiation exposure to the eye produces characteristic lens changes, termed "radiation cataract," that can affect visual function. Animal models of radiation cataractogenesis have previously utilized inbred mouse or rat strains. These studies were essential for determining morphological changes and dose-response relationships between radiation exposure and cataract. However, the relevance of these studies to human radiosensitivity is limited by the narrow phenotypic range of genetically homogeneous animal models. To model radiation cataract in genetically diverse populations, longitudinal cataract phenotyping was nested within a lifetime carcinogenesis study in male and female heterogeneous stock (HS/Npt) mice exposed to 0.4 Gy HZE ions (n = 609) or 3.0 Gy γ-rays (n = 602) and in unirradiated controls (n = 603). Cataractous change was quantified in each eye for up to 2 years using Merriam-Focht grading criteria by dilated slit lamp examination. Virtual Optomotry™ measurement of visual acuity and contrast sensitivity was utilized to assess visual function in a subgroup of mice. Prevalence and severity of posterior lens opacifications were 2.6-fold higher in HZE ion and 2.3-fold higher in γ-ray irradiated mice compared to unirradiated controls. Male mice were at greater risk for spontaneous and radiation associated cataracts. Risk for cataractogenesis was associated with family structure, demonstrating that HS/Npt mice are well-suited to evaluate genetic determinants of ocular radiosensitivity. Last, mice were extensively evaluated for cataract and tumor formation, which revealed an overlap between individual susceptibility to both cancer and cataract.

Practice Patterns and Sociodemographic Disparities in the Clinical Care of Anatomical Narrow Angles in the United States.

PURPOSE: To assess treatment and visit patterns among patients with newly diagnosed anatomical narrow angle (ANA) and identify sociodemographic factors associated with disparities in care. DESIGN: Retrospective practice pattern evaluation study. METHODS: A total of 263,422 patients diagnosed with ANA between 2007 and 2019 were identified in the Optum Clinformatics Data Mart. Inclusion was limited to newly diagnosed ANA, defined as (1) continuous enrollment during a 2-year lookback period and 1-year study period from first diagnosis; (2) diagnosis by an ophthalmologist or optometrist; and (3) no history of pseudophakia, ANA treatments, or prior primary angle closure glaucoma diagnosis. Outcome measures were treatment with laser peripheral iridotomy (LPI), cataract surgery, or intraocular pressure-lowering medications and number of eye care visits. Logistic and Poisson regression were performed to assess factors associated with treatment and eye care visits, respectively. RESULTS: Among 52,405 eligible cases, 27.7% received LPI, 13.9% received drops, and 15.1% received cataract surgery. Odds of LPI were higher in Asians and Hispanics (odds ratio [OR] ≥ 1.16, P < .001). Non-Whites had higher odds of drops (OR ≥ 1.19, P < .001), but Hispanics had lower odds of cataract surgery (OR = 0.79, P < .001). The mean number of eye care visits was 2.6±2.1 including the day of diagnosis. Older age and treatment were associated with higher rates of eye care visits (rate ratio > 1.15, P < .001). CONCLUSION: More than a quarter of patients with newly diagnosed ANA receive treatment with LPI. Racial minorities are more likely to receive ANA-specific treatments but less likely to receive cataract surgery. These differences may reflect racial differences in disease severity and the need for clearer practice guidelines in ANA care.

Preventing the Argentinian flag sign and managing anterior capsular tears: A review.

The Argentinian flag sign (AFS) is a feared complication during cataract extraction. Intralenticular pressures, especially excessive posterior pressure, have been identified as potential mechanisms for capsular stress and tearing associated with AFS. Capsular tension is created by positive intralenticular pressures, which cause the irido-lens diaphragm to move anteriorly once the manual capsulorhexis has been initiated. This tension can cause inadvertent tears that self-propagate to the lens equator, causing an AFS, among other intraoperative complications. Thus, this review highlights the importance of identifying intumescent cataracts as well as a combination of techniques to relieve intracapsular pressures needed to prevent AFS. However, some instances of anterior capsular tears are unavoidable. Therefore, focus will also be placed on techniques during cataract extraction used to manage anterior capsular tears, mitigating extension to the posterior capsule.

Exceeding radiation thresholds for cataract induction in diagnostic imaging: a paediatric case report.

This case report investigates the radiation dose received by a paediatric patient with a ventricular assist device who underwent four non-contrast brain computed tomography (CT) scans, two brain perfusion CT scans and two head angiographic CT scans. The total estimated absorbed dose to the lens of the eye is above the 500 mGy radiation-induced cataract threshold. It is recommended that this patient and those with similar imaging histories have routine follow-up with an ophthalmologist. It is also recommended that radiation dose tracking and an electronic medical alert program be implemented to allow the identification of patients who may exceed tissue reaction thresholds.