Dichloroacetate ameliorates apoptosis, EMT and oxidative stress in diabetic cataract via inhibiting the IDO1-dependent p38 MAPK pathway.

As an oral antidiabetic agent, dichloroacetate (DCA) has been proven to improve diabetes and related complications. However, its functional role in diabetic cataract (DC) remains to be elucidated. This study was to define the role of DCA and its underlying molecular mechanism in DC in vitro and in vivo. In this study, it was shown that DCA dose-dependently ameliorated DC formation and development in DM rats. In addition, DCA significantly increased cell viability, reduced apoptosis, and inhibited EMT and oxidative stress of high glucose (HG)-treated SRA-01/04 cells in a concentration-dependent manner. Besides, it was revealed that Indoleamine 2,3-dioxygenase 1 (IDO1) expression was upregulated in lenses of DM rats and HG-treated SRA-01/04 cells, which was reversed by DCA. In addition, DCA abrogated the activation of the p38 MAPK signaling in the lenses of DM rats and HG-treated SRA-01/04 cells. Further experiments showed that IDO1 upregulation activated the p38 MAPK signaling in HG-challenged SRA-01/04 cells. Moreover, IDO1 overexpression partially reversed DCA-mediated inactivation of p38 MAPK signaling and suppression of HG-induced damage to SRA-01/04 cells. To sum up, our findings showed that DCA prevented DC-related apoptosis, EMT, and oxidative stress via inactivating IDO1-dependent p38 MAPK signaling.

HIF-1 inhibition reverses opacity in a rat model of galactose-induced cataract.

Cataract is an eye disease, in which the lens becomes opaque, causing vision loss and blindness. The detailed mechanism of cataract development has not been characterized, and effective drug therapies remain unavailable. Here, we investigated the effects of Hypoxia-inducible factor 1 (HIF-1) inhibitors using an ex vivo model, in which rat lenses were cultured in galactose-containing medium to induce opacity formation. We found that treatment with the HIF-1 inhibitors 2-Methoxyestradiol (2ME2), YC-1, and Bavachinin decreased lens opacity. Microarray analysis on 2ME2-treated samples, in which opacity was decreased, identified genes upregulated by galactose and downregulated by inhibitor treatment. Subsequent STRING analysis on genes that showed expression change by RT-qPCR identified two clusters. First cluster related to the cytoskeleton and epithelial-mesenchymal transition (EMT). Second cluster related to the oxidative stress, and apoptosis. ACTA2, a known marker for EMT, and TXNIP, a suppressor of cell proliferation and activator of apoptosis, were present in each cluster. Thus, suppression of EMT and apoptosis, as well as activation of cell proliferation, appear to underlie the decrease in lens opacity.

Mitigation of lens opacification by a functional food in a diabetic rodent model.

The current study was designed to test a functional food (FF) mixture containing aldose reductase inhibitors and antiglycation bioactive compounds for suppressing the onset and progression of cataracts in a diabetic rat model. Two-month-old Sprague Dawley rats were grouped as control (C), diabetes untreated (D), and diabetic rats treated with FF at two doses (FF1 = 1.35 g and FF2 = 6.25 g/100g of diet). Diabetes was induced by a single injection of streptozotocin. The FF is a mixture of amla, turmeric, black pepper, cinnamon, ginger, and fenugreek added to the rodent diet. The status of cataracts was monitored weekly by a slit lamp examination for 20 weeks, after which animals were sacrificed to collect eye lenses. Feeding FF1 and FF2 to diabetic rats yielded a significant anti-hyperglycaemic effect and marginally prevented body weight loss. FF delayed cataract progression, and FF2 showed better efficacy than FF1. FF prevented the loss of lens crystallins and their insolubilization in diabetic rats. The antioxidant potential of FF was evident with the lowered protein carbonyls, lipid peroxidation, and prevention of altered antioxidant enzyme activities induced by diabetes. These studies demonstrate the efficacy of plant-derived dietary supplements against the onset and progression of cataracts in a well-established rat model of diabetic eye disease.

Review on the potential roles of traditional Chinese medicines in the prevention, treatment, and postoperative recovery of age-related cataract.

ETHNIC PHARMACOLOGICAL RELEVANCE: Cataract is the most common cause of blindness worldwide, a visual disorder caused by a clouded lens that seriously affects People's Daily lives. Age-related cataract (ARC) is the most common type of cataract due to long-term combined effects of many factors, and its pathogenesis is varied. At present, the surgery is the main treatment for cataracts, but it is still limited to the prevention, treatment of early cataracts and the postoperative complications care. While, its drug treatments are still in the stage of exploration and research. Traditional Chinese Medicine (TCM), a unique resource in China, is conceived under the guidance of traditional Chinese medicine theory and has little toxicity and side effects, but it has made great progress in the treatment and prevention of ARC. AIM OF THIS REVIEW: This review presents an overview of the pathogenesis of ARC in both traditional and modern medicines and summarizes the history and therapeutic effect of TCM on ARC including their formula, crude drugs and active components, and also the other auxiliary methods. METHODS: A number of recognized databases like SciFinder, PubMed, Science Direct, Google Scholar, and China National Knowledge Infrastructure (CNKI) were extensively explored by using keywords and phrases such as "cataract", "age-related cataract", "traditional medicine", "ethnopharmacology", "herbs", "medicinal plants", or other relevant terms, and the plants/phytoconstituents that are evaluated in the models of age-related cataract. As well as the current TCM adjuvant therapy used in the clinical treatment were summarized. RESULTS: TCM revealed to plays an active role in treating age-related cataract, via multi-pathway and multi-target, and can treat or delay ARC by inhibiting abnormal glucose metabolism, antioxidant damage, inhibiting LEC apoptosis, and so on, which is in concordance with the good effects of the global use of TCM in clinical application. Concerning the early prevention and treatment of cataract and postoperative complications, TCM and auxiliary methods remain to achieve better clinical effects. CONCLUSION: ARC belongs to the category of "Yuan Yi Nei Zhang" in TCM theory, showing that there are many causes of ARC including aging, and kidney-yang, spleen, sperm and blood deficiencies. At the same time, the viscera gradually decline, as well as yin or yang progressively become weak, especially in the elder people. So, TCM could be mainly based on liver, kidney, and spleen syndrome differentiation, personalizing diagnosis and treatment, following multiple targets, regulating fundamentally yin and yang, and thus justifying the advantages of Chinese medicine in the prevention and treatment of ARC.

Influence of Endogenous Substances on Site-II to Site-I Displacement of Diclofenac Bound to Albumin in the Aqueous Humor of Patients with Cataract.

Diclofenac instillation is useful in preventing intraoperative miosis and macular edema caused by postoperative inflammation in cataract surgery; however, optimum efficacy is not attained when the instilled diclofenac strongly binds to albumin in patients' aqueous humor. Therefore, a method that inhibits diclofenac binding and increases the concentration of its free fraction is needed. We conducted a basic study regarding the effects of inhibitors on the binding of instilled diclofenac to albumin and endogenous substances in aqueous humor. Aqueous humor samples from 16 patients were pooled together for analysis. The free fraction of diclofenac was measured using ultrafiltration methods in various experiments with pooled and mimic aqueous humor. Free fraction of diclofenac, a site II drug, in pooled aqueous humor was 0.363 ± 0.013. The binding of diclofenac in the presence of phenylbutazone (PB), a site I inhibitor, was significantly inhibited (free fraction = 0.496 ± 0.013); however, no significant inhibition by ibuprofen, a site II inhibitor, (free fraction = 0.379 ± 0.004), was observed. The unexpected result was due to free fatty acids (FFAs; palmitic acid (PA)) and L-tryptophan (Trp). The inhibition of diclofenac binding by PB in the mimic aqueous humor containing these endogenous substances revealed significant binding inhibition in the presence of PA and Trp. Diclofenac is strongly rebound from site II to site I in the presence of FFAs and Trp in the aqueous humor because FFAs and Trp induce a conformational change in albumin. Therefore, PB significantly inhibits the binding of diclofenac to albumin.

Inhibitory effect of Nifedipine on aldose reductase delays cataract progression.

Aldose reductase (ALR2) is a rate-limiting component of the polyol pathway, which is essential for the NADPH-mediated conversion from glucose to sorbitol. ALR2 dysregulation has been linked to α-crystallin aggregation, increased oxidative stress, and calcium inflow, all of which contribute to a diabetic cataract. Given its crucial role in occular pathologies, ALR2 has emerged as a promising target to treat oxidative stress and hyperglycaemic condition which form the underlying cause of diabetic cataracts. However, several of them had issues with sensitivity and specificity to ALR2, despite being screened as effective ALR2 inhibitors from a wide range of structurally varied molecules. The current study investigates the inhibitory potential of Nifedipine, an analog of the dihydro nicotinamide class of compounds against ALR2 activity. The enzyme inhibition studies were supported by in vitro biomolecular interactions, molecular modeling approaches, and in vivo validation in diabetic rat models. Nifedipine demonstrated appreciable inhibitory potential with the purified recombinant hAR (human aldose reductase; with an IC50 value of 2.5 µM), which was further supported by Nifedipine-hAR binding affinity (Kd = 2.91 ± 1.87 × 10-4 M) by ITC and fluorescence quenching assays. In the in vivo models of STZ-induced diabetic rats, Nifedipine delayed the onset progression of cataracts by preserving the antioxidant enzyme activity (SOD, CAT, and GPX GSH, TBARS, and protein carbonyls) and was shown to retain the α-crystallin chaperone activity by reducing the calcium levels in the diabetic rat lens. In conclusion, our results demonstrate effective inhibition of ALR2 by Nifedipine, resulting in amelioration of diabetic cataract conditions by lowering oxidative and osmotic stress while retaining the chaperone activity of α-crystallins. The present study could be envisaged to improve the eye condition in older adults upon Nifedipine treatment.

Evaluating the utility of inflammation score in post-cataract surgery endophthalmitis. Results from a prospective study in India. EMS Report #4.

PURPOSE: To investigate if inflammation score (IS), calculated from the cornea, anterior chamber, iris, and vitreous, indicates endophthalmitis severity. METHODS: In a prospective study, consecutive adults with a clinical diagnosis of post-cataract endophthalmitis within 6 weeks of surgery were recruited. Patients were allocated to IS-based primary treatment (IS < 10: intravitreal injection and IS ≥ 10: vitrectomy) and randomized to two intravitreal antibiotics combinations (vancomycin + ceftazidime and vancomycin + imipenem). Undiluted vitreous microbiology work-up included culture susceptibility, polymerase chain reaction, Sanger sequencing, and targeted next-generation sequencing. RESULTS: The average age of 175 people was 63.4 ± 10.7 years and included 52.6% small incision cataract surgery and 47.4% phacoemulsification surgery. Severe endophthalmitis (IS ≥ 20), diagnosed in 27.4% of people, had a shorter time to symptoms (average 5.4 vs 8.7 days; P = 0.018), poorer presenting vision (all ≤ hand motion), higher culture positivity (50% vs 30.7%; P = 0.032), and higher Gram-negative bacterial infection (70.8% vs 46.2%; P = 0.042). For IS ≥ 20 discriminant and Gram-negative infection, Spearman's coefficient was 0.7 [P < 0.0001, 95% confidence interval (CI) 0.59-0.82], with an area under the receiver operating characteristic curve of 0.9 (95% CI 0.85-0.94, P < 0.0001), a Youden index J of 0.74, a sensitivity of 87.2%, and a specificity of 87.5%. The final vision of >20/400 and >20/100 was regained in 50.2% and 29.1% of people, respectively. The susceptibility of common Gram-positive cocci and Gram-negative bacilli was the highest for vancomycin (95.0%) and colistin (88.6%), respectively. NGS detected polymicrobial infection in 88.5% of culture-negative endophthalmitis. CONCLUSIONS: Higher inflammation scores indicated severe disease and Gram-negative infection in post-cataract endophthalmitis.

Safety and efficacy profile of intravitreal ranibizumab vs dexamethasone in treatment of naïve diabetic macular edema.

PURPOSE: To compare the safety and efficacy parameters of intravitreal ranibizumab vs intravitreal dexamethasone (IVD) in the treatment of patients with naïve diabetic macular edema (DME) in terms of best-corrected visual acuity (BCVA), central macular thickness (CMT), and possible complications like intraocular pressure (IOP) rise and cataract progression. METHODS: A hospital-based prospective and comparative study of naïve DME patients was conducted between November 2020 and October 2021 with a minimum follow-up (F/U) period of 6 months. Thirty phakic patients received one dose of IVD implant (Group A) and the other 30 (Group B) received three consecutive monthly doses of ranibizumab. The main exclusion criteria were steroid responders and the presence of ocular inflammation. RESULTS: The mean pre-injection CMT in Group A was 405µ and reduced to 297.07µ at 3 months and 278.35µ at 6 months. Mean increase in logMAR BCVA was 0.55. The mean pre-injection IOP was 16.28 and 17.64 mm of Hg at 6 months. In Group B, the mean pre-injection CMT was 401.07µ and reduced to 276.1µ at 3 months and 292.9µ at 6 months. Mean BCVA increased to 0.37. The mean pre-injection IOP was 17.28 mm Hg and 16.42 mm Hg at 6 months. There was no significant progression of cataract in both groups. CONCLUSION: The mean decrease in CMT was comparable in both the groups at 6 months F/U with an improvement of BCVA with no significant IOP fluctuation or cataract progression. Hence, IVD appears to be noninferior to ranibizumab in the treatment of naïve DME.

Epigallocatechin gallate delays age-related cataract development via the RASSF2/AKT pathway.

Age-related cataract (ARC) is a common eye disease, the main cause of which is oxidative stress-mediated apoptosis of lens epithelial cells (LECs). Epigallocatechin gallate (EGCG) is the most potent antioxidant in green tea. Our results demonstrated that EGCG could effectively reduce apoptosis of LECs and retard lens clouding in aged mice. By comparing transcriptome sequencing results of three groups of mice (young control, untreated aged, and EGCG-treated) and screening using GO and KEGG analyses, we selected RASSF2 as the effector gene of EGCG for mechanistic exploration. We verified that the differential expression of RASSF2 was associated with the occurrence of ARC in clinical samples and mouse tissues by immunohistochemistry and western blotting, respectively. We showed that high RASSF2 expression plays a crucial role in the oxidative induction of apoptosis in LECs, as revealed by overexpression and interference experiments. Further studies showed that RASSF2 mediates the inhibitory effect of EGCG on apoptosis and ARCogenesis in LECs by regulating AKT (Ser473) phosphorylation. In this study, we found for the first time the retarding effect of EGCG on lens clouding in mice and revealed the mechanism of action of RASSF2/AKT in it, which provides a theoretical basis for the targeted treatment of EGCG.

Comparison of the outcomes of phacoemulsification versus topical medication alone in canine diabetic cataracts: a retrospective study.

BACKGROUND: Long-term comparisons of phacoemulsification with topical medication are limited in canine diabetic cataracts. OBJECTIVES: To compare outcomes of eyes submitted to phacoemulsification with those of topical medication for canine diabetic cataracts and identify risk factors for complications. METHODS: Through medical records review, 150 eyes (76 dogs) with diabetic cataracts were included; 58 eyes (31 dogs) underwent phacoemulsification (phaco-group) and 92 eyes (48 dogs) received ophthalmic solution alone (medication-group). The medication-group was divided into owner-led and vet-led groups depending on who elected not to perform surgery. Comparisons involved time-to-complications, vision, and the number and type of ophthalmic solutions administered. The association between complications and pretreatment clinical findings was investigated. RESULTS: No difference was found in complication risk between the phaco and owner-led medication groups. Conversely, the vet-led medication-group had a higher complication risk than the other groups. At the last follow-up, 94.8% of the phaco-group had vision, whereas 7.6% of the medication-group restored some visual axis. Poor glycemic control in the medication-group and younger age in the phaco-group increased complication risk. At 1-year post-treatment, the average number of ophthalmic solutions administered was 1.7 and 2.6 in the phaco and medication groups, respectively. The medication-group used anti-inflammatories the most throughout the follow-up, whereas the phaco-group used anti-inflammatories the most until 1-year post-treatment and lacrimostimulants at 1.5-year post-treatment. CONCLUSIONS: For canine diabetic cataracts, phacoemulsification is recommended because it is superior to topical management alone in terms of maintaining vision and reducing the number of ophthalmic solutions required in the long term.

Ocular manifestations of HIV infection at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.

BACKGROUND: The pattern of HIV-associated eye disease has changed with ongoing advancements in highly active antiretroviral therapy (HAART). HIV-infected individuals now live longer, enabling us to observe the long-term effects of HIV and HAART on the eye. There are few recent studies on HIV-related ocular disease in sub-Saharan Africa. OBJECTIVES: To describe the ocular manifestations of HIV in patients attending the Nthabiseng HIV clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. METHODS: A cross-sectional study was conducted in 2021 and 2022 using convenience sampling of patients at the HIV clinic. The participants' clinical history was taken, their files were reviewed, and they underwent ocular examination. Correlation between eyes was managed by taking disease in one eye as the presence of disease in the participant. Descriptive statistics were used to summarise participant characteristics. Univariate and multivariate logistic regression models were used to assess the odds ratio (OR) of developing HIV-associated ocular diseases, and a p-value of <0.05 was used to define statistical significance. RESULTS: There were 182 participants (139 females and 43 males), with a mean (standard deviation) age of 48.9 (10.6) years. The most common anterior segment diagnoses were conjunctival microangiopathy (34.6%), pinguecula (31.3%) and cataracts (30.2%), while the most common posterior segment finding was peripheral retinal scarring with features in keeping of previous cytomegalovirus retinitis (24.2%). Notably, only 1.1% of patients had HIV retinopathy. A CD4 count <200 cells/µL showed an increased OR for cataracts (OR 4.24; p=0.003) and any anterior segment diagnoses (OR 10.05; p=0.029), while a CD4 count ≥200 cells/µL showed an increased risk of conjunctival microangiopathy (OR 2.14; p=0.017). CONCLUSION: With the advent of HAART, ocular manifestations of HIV are changing and the incidence of severe ocular opportunistic infections and HIV retinopathy has decreased precipitously. Although this study has shown that patients with a CD4 count <200 cells/µL are at increased risk of developing anterior ocular manifestations of HIV, including cataracts, these diseases are relatively innocuous or easily treatable. Routine ocular screening of HIV patients seems to be substantially less important now than it was in the pre-HAART era.

Attenuation of epithelial-mesenchymal transition via SGLT2 inhibition and diabetic cataract suppression by dapagliflozin nanoparticles treatment.

AIMS: Chronic hyperglycemia triggers overproduction of AKR1B1 (aldo-keto reductase family 1 member B) and receptor for advanced glycation end product (RAGE), which causes epithelial-mesenchymal transition (EMT) in the lens epithelial cells (LECs) of diabetic mellitus (DM) cataracts. However, it is unclear whether EMT in LECs is related to abnormal increase of SGLT2. Sodium glucose cotransporter 2 (SGLT2) inhibitor, also known as dapagliflozin (Dapa) can be used to treat diabetes. Here, we examined how Dapa or nano eye-drops (DapaN) reduce EMT in LECs of DM cataracts. The nano eye-drop provides an ophthalmic treatment that suppressed diabetic cataract progression and improved potency with reduced side effects. MAIN METHODS: SD rats were injected with streptozocin (STZ) (65 mg/kg, ip), nano-Dapa drops (0.456 mg/10 ml/eye) or Dapa (1.2 mg/kg/day) treatment for 6-12 weeks. Immunofluorescence staining was used for protein quantification of RAGE, SGLT2, N-cadherin and E-cadherin in the LECs of rats. KEY FINDINGS: In this study, Dapa applies nanotechnology-based delivery system and it contains polyvinylpyrrolidone (PVP) and HPBCD. Dapa showed therapeutic effect on DM cataracts, wherein it targeted EMT biomarker, E-cadherin. The nano-Dapa drops or oral Dapa inhibited SGLT2, suppressed AKR1B1 expression, decreased AcSOD2- and RAGE-induced EMT in diabetic cataracts. Our findings suggest that nanotechnology-based Dapa eye drops (Dapa-PVP-HPBCD) can effectively improve solubility of Dapa in aqueous solution. SIGNIFICANCE: Taken together, results suggest that the SGLT2-mediated DM cataract therapy may involve the AKR1B1-RAGE-AcSOD2-EMT pathway. The nano eye drops and Dapa show potential beneficial effects for cataract prevention. This study conveys new insights into cataract treatment and supplementation of nano-Dapa drops shows promising result in preventing diabetic cataracts.

Effectiveness of rb-bFGF Eye Drops for Post-Cataract Surgery Dry Eye and Observation of Changes in Tear Secretion and Corneal Damage in Patients.

Objective: Dry eye syndrome after cataract surgery is a common complication that may affect the patient's visual comfort and quality of life. Because the surgery may affect the secretion and quality of tears in the eye, resulting in dry and uncomfortable eyes.This study aimed to investigate the therapeutic effects of recombinant bovine basic fibroblast growth factor (rb-bFGF) eye drops on dry eye syndrome after cataract surgery and to analyze its impact on tear secretion and corneal injury. Methods: This is a retrospective study. A total of 126 patients (126 eyes) with dry eye syndrome after cataract surgery were treated between January 2021 and October 2022. patients were randomly divided into a study group (64 patients, 64 eyes) and a control group (62 patients, 62 eyes). Both groups were treated with sodium hyaluronate eye drops, while the study group received rb-bFGF eye drops for four weeks in addition to the sodium hyaluronate eye drops. The clinical efficacy, results of tear secretion test (SIT), tear film break-up time (BUT), corneal fluorescein staining, corneal topography examination, oxidative stress indicators, ocular surface disease index (OSDI) score, and drug adverse reactions were compared between the two groups. Results: The study group exhibited a significantly higher total effective treatment rate (96.88%) compared to the control group (85.48%), suggesting the enhanced efficacy of rb-bFGF eye drops. Moreover, the study group demonstrated extended tear secretion length and tear film break-up time, indicating improved tear film stability and ocular surface health. Additionally, the study group showed reduced corneal fluorescein staining score and improved corneal surface regularity index, indicative of enhanced corneal integrity and smoothness. Notably, tear superoxide dismutase levels were elevated, while lipid peroxide levels were lowered in the study group, underscoring the potential antioxidative effects of rb-bFGF. The study group also exhibited a lower OSDI score, suggesting reduced ocular discomfort and improved quality of life. Although the study group had a slightly higher incidence of adverse reactions (9.38%) compared to the control group (8.06%), the difference was not statistically significant. Particularly significant is the statistical significance highlighting the heightened total effective treatment rate in the study group, indicating the potential of rb-bFGF eye drops in promoting favorable therapeutic outcomes. Conclusion: rb-bFGF eye drops are safe and effective in treating dry eye syndrome after cataract surgery. They can help regulate tear secretion, repair corneal damage, and improve dry eye symptoms. Despite the retrospective design and relatively small sample size of this study, further randomized controlled trials and larger sample size may be needed to verify the robustness of the results, but this study is important for guiding the treatment strategy and optimizing patient care for dry eye after cataract surgery.

Astaxanthin ameliorates oxidative stress in lens epithelial cells by regulating GPX4 and ferroptosis.

Ferroptosis is a form of regulated cell death closely associated with oxidative stress and mitochondrial dysfunction and is characterised by the accumulation of reactive oxygen species (ROS) and lipid species and iron overload. Damage to human lens epithelial cells (LECs) is associated with age-related cataract progression. Astaxanthin (ATX), a carotenoid with natural antioxidant properties, counteracts ferroptosis in the treatment of various degenerative diseases. However, this mechanism has not been reported with respect to cataract treatment. In this study, the differential expression levels of glutathione peroxidase 4 (GPX4) in the lens of young and aged mice were analysed. Continuous ATX supplementation for 8 months upregulated GPX4 expression in the mouse LECs and delayed the progression of ferroptosis. Upon treatment with erastin, ROS and malondialdehyde accumulated and the mitochondrial membrane potential decreased. At the same time, the expressions of GPX4, SLC7A11, and ferritin were suppressed in human LECs. All of these phenomena were partially reversed by ATX and Fer-1, a ferroptosis inhibitor. This study confirmed that the ATX-mediated targeting of GPX4 might alleviate human LECs damage by inhibiting ferroptosis and ameliorating oxidative stress and that this could represent a promising therapeutic approach for age-related cataract.

Carbon Monoxide Releasing Molecule-3 Alleviates Oxidative Stress and Apoptosis in Selenite-Induced Cataract in Rats via Activating Nrf2/HO-1 Pathway.

PURPOSE: This study investigated the protective effect of carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide, on selenite-induced cataract in rats and explore its possible mechanism. METHODS: Sprague-Dawley rat pups treated with sodium selenite (Na2SeO3) were chosen as the cataract model. Fifty rat pups were randomly divided into 5 groups: Control group, Na2SeO3 (3.46 mg/kg) group, low-dose CORM-3 (8 mg/kg/d) + Na2SeO3 group, high-dose CORM-3 (16 mg/kg/d) + Na2SeO3 group, and inactivated CORM-3 (iCORM-3) (8 mg/kg/d) + Na2SeO3 group. The protective effect of CORM-3 was tested by lens opacity scores, hematoxylin and eosin staining, TdT-mediated dUTP nick-end labeling assay, and enzyme-linked immunosorbent assay. Besides, quantitative real-time PCR and western blotting were used for mechanism validation. RESULTS: Na2SeO3 induced nuclear cataract rapidly and stably, and the achievement ratio of Na2SeO3 group was 100%. CORM-3 alleviated lens opacity of selenite-induced cataract and attenuated the morphological changes of the rat lens. The levels of antioxidant enzymes GSH and SOD in rat lens were also increased by CORM-3 treatment. CORM-3 significantly reduced the ratio of apoptotic lens epithelial cells, besides, CORM-3 decreased the expression of Cleaved Caspase-3 and Bax induced by selenite and increased the expression of Bcl-2 in rat lens inhibited by selenite. Moreover, Nrf-2 and HO-1 were upregulated and Keap1 was downregulated after CORM-3 treatment. While iCORM-3 did not exert the same effect as CORM-3. CONCLUSIONS: Exogenous CO released from CORM-3 alleviates oxidative stress and apoptosis in selenite-induced rat cataract via activating Nrf2/HO-1 pathway. CORM-3 may serve as a promising preventive and therapeutic strategy for cataract.

Effect of alirocumab on cataracts in patients with acute coronary syndromes.

BACKGROUND: Some data suggest that low levels of low-density lipoprotein cholesterol (LDL-C) are associated with risk of cataracts. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors reduce LDL-C below levels achieved with statins alone. We determined whether the incidence of cataracts was influenced by treatment with the PCSK9 inhibitor alirocumab versus placebo, and whether that incidence was affected by achieved LDL-C levels. METHODS: The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome receiving high-intensity or maximum-tolerated statin. Incident cataracts were pre-specified events of interest. In multivariable analysis using propensity score-matching on characteristics including cataract risk factors, incident cataracts were compared in the alirocumab and placebo groups according to LDL-C levels achieved with alirocumab. RESULTS: Over median follow-up of 2.8 years (interquartile range 2.3 - 3.4), the incidence of cataracts was similar with alirocumab (127/9462 [1.3%]) versus placebo (134/9462 [1.4%]); hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74 - 1.20). In patients treated with alirocumab with ≥ 2 LDL-C values < 25 mg/dL (0.65 mmol/L), the incidence of cataracts was 71/4305 (1.6%), versus 60/4305 (1.4%) in propensity score-matched patients from the placebo group (HR 1.10, CI 95% 0.78 - 1.55). In patients treated with alirocumab with ≥ 2 LDL-C values < 15 mg/dL (0.39 mmol/L), the incidence of cataracts was 13/782 (1.7%), versus 36/2346 (1.5%) in matched patients from the placebo group (HR 1.03, CI 95% 0.54 - 1.94). CONCLUSION: Treatment with alirocumab versus placebo, added to statin, did not influence the incidence of cataracts, even when achieved LDL-C levels on alirocumab were very low. Longer follow-up studies might be necessary to exclude the long-term effects on the incidence or progression of cataracts. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01663402 .

Cataract surgery in neovascular AMD: impact on visual acuity and disease activity.

BACKGROUND: Cataract and neovascular age-related macular degeneration (nAMD) often co-exist and both contribute to impaired vision. It has been debated whether cataract surgery can increase nAMD activity. The purpose of this retrospective study was to investigate the impact of cataract surgery on visual acuity, treatment intensity for nAMD and macular morphology in patients with on-going treatment for nAMD. METHODS: Data was obtained from the Swedish Macular Register, the Swedish National Cataract Register, optical coherence tomography (OCT) images and patient charts. All eyes were treated at the Department of Ophthalmology at the County Hospital of Västmanland, Västerås, Sweden. Follow-up was 6 months after surgery. The study was approved by the Swedish Ethical Review Authority. RESULTS: In total, 156 patients (168 eyes) were included. The mean age at cataract surgery was 82 (standard deviation, SD 6) years. Both distance and near visual acuity improved after surgery. Distance visual acuity increased from 59 (SD 12) to 66 (SD 15) letters ETDRS (P < 0.001). Proportion of eyes with normal near visual acuity increased from 12 to 41%. The anti-vascular endothelial growth factor (VEGF) treatment intensity remained unchanged: mean of 3.4 (SD 1.9) and 3.3 (SD 1.7) treatments were given 6 months pre- and postoperatively, respectively. The prevalence of intraretinal fluid (IRF) in the macula increased from 22 to 31% postoperatively, while subretinal fluid, fluid under the pigment epithelium (sub-RPE fluid) and central retinal thickness were unaltered. In eyes with new IRF, improvement in visual acuity and number of anti-VEGF treatments were similar to eyes without new IRF. CONCLUSION: Cataract surgery improved visual acuity in patients with on-going treatment for nAMD and did not affect anti-VEGF treatment intensity. Macular morphology remained unchanged. The slight increase in intraretinal fluid after surgery was not found to affect visual acuity or anti-VEGF treatment intensity. It is hypothesized that this might indicate that it represents degenerative intraretinal cystic fluid.

Intravitreal acetazolamide implant for pseudophakic cystoid macular edema.

BACKGROUND: Pseudophakic cystoid macular edema (PCME) is the most common cause of visual acuity deterioration after uncomplicated cataract surgery. There is no consensus regarding how to manage recurrent or refractory cases. REPORT: A 54-year-old woman complained of decreased vision and central metamorphopsia in the right eye (OD) 3 months after uneventful cataract surgery. Visual acuity was 0.3 logMAR (20/40) OD and 0.1 logMAR (20/25) OS. Reduced macular brightness was seen OD on funduscopy associated with increased macular thickness on optical coherence tomography (OCT). Pseudophakic cystoid macular edema (PCME) was diagnosed, and treatment with oral acetazolamide was tried without success. The patient underwent a single intravitreal injection of an acetazolamide implant (260 µg) OD as off-label treatment. Four weeks following the injection, she reported complete resolution of her metamorphopsia and visual loss OD. Four months later, her visual acuity was 0.0 logMAR (20/20) in OD and 0.1 logMAR (20/25) in OS. The patient reported no discomfort after the injection procedure. Laboratory and ophthalmologic tests did not identify any adverse effects of the medication. CONCLUSION: We show that PCME refractory to conventional treatment improved after intravitreal acetazolamide implant injection. Further investigation is warranted to confirm these preliminary findings.