Search Results (189)

The global healthcare system faces significant challenges posed by diabetes and its complications, highlighting the need for innovative strategies to improve early diagnosis and treatment. Machine learning models help in the early detection of diseases and recommendations for taking safety measures and treating the disease. A comparative analysis of existing machine learning (ML) models is necessary to identify the most suitable model while uniformly fixing the model parameters. Assessing risk based on biomarker measurement and computing overall risk is important for accurate prediction. Early prediction of complications that may arise, based on the risk of diabetes and biomarkers, using machine learning models, is key to helping patients. In this paper, a comparative model is presented to evaluate ML models based on common model characteristics. Additionally, a risk assessment model and a prediction model are presented to help predict the occurrence of complications. Random Forest (RF) is the best model for predicting the occurrence of Type 2 Diabetes (T2D) based on biomarker input. It has also been shown that the prediction of diabetes complications using neural networks is highly accurate, reaching a level of 98%. Full article

Cataracts remain one of the leading causes of reversible blindness in low- and middle-income countries such as Ecuador. This study assessed the efficacy of Small Incision Cataract Surgery (SICS) and analyzed sociodemographic and clinical factors associated with postoperative visual outcomes. A retrospective multicenter analysis was conducted across six ophthalmology clinics along the Ecuadorian coast between 2023 and 2024, including 558 patients aged 30 years or older. Postoperative visual acuity, measured using the LogMAR scale, improved significantly (mean improvement of 0.525 LogMAR units in the right eye (OD) and 0.489 LogMAR units in the left eye; p < 0.001). Ages between 60 and 69 years were associated with better outcomes in the right eye, while male sex was a protective factor against poor visual acuity in the left eye. Although diabetes mellitus and hypertension were prevalent, neither condition showed a significant association with postoperative visual outcomes. The findings confirm that SICS is a safe, effective, and cost-efficient surgical approach for restoring vision in resource-limited settings, supporting its inclusion in national public health strategies to reduce avoidable blindness in developing countries. Full article

Cataract surgery, while commonly considered a routine, highly effective, and generally low-risk ophthalmic procedure, has been associated with corneal endothelial cell loss (ECL), a phenomenon particularly pronounced in patients with type 2 diabetes mellitus (DM2). This increased susceptibility in diabetic patients is often attributed to pre-existing corneal abnormalities, including compromised structural integrity and reduced endothelial cell density. Additionally, metabolic stress factors inherent to diabetes, such as chronic hyperglycemia and associated oxidative stress, further exacerbate endothelial vulnerability. Consequently, diabetic patients may experience significantly greater endothelial cell loss during and after cataract surgery, necessitating targeted surgical strategies and careful perioperative management to preserve corneal health and visual outcomes. This paper aims to conduct an extensive and detailed review of the existing scientific literature to thoroughly investigate the relationship between ECL and cataract surgery in patients diagnosed with DM2. This study conducts a critical evaluation to elucidate the mechanisms contributing to high endothelial vulnerability in individuals with diabetes. It systematically compares the rates of ECL observed in diabetic and non-diabetic populations undergoing cataract surgery, examines molecular alterations following the procedure in patients with and without DM2, identifies key risk factors influencing surgical outcomes, evaluates the impact of various surgical techniques, discusses preventative measures, and examines the long-term consequences of ECL in this specific population. Furthermore, this review analyzes the existing research to identify gaps in knowledge and suggest potential directions for future investigations. Full article

Background: Epiretinal membrane (ERM) and proliferative diabetic retinopathy (PDR) belong to the group of vitreoretinal diseases, characterized by impairments at both the retina and the vitreous. The non-diabetic and diabetic forms of ERM (no-dERM and dERM) as well as the PDR are caused by microvascular disorder, which frequently occurs in association with inflammation and oxidative stress. To better characterize no-dERM, dERM, and PDR at the biomolecular level, we compared the expression of inflammatory, oxidative, lipidic peroxidation products, and complement receptors. Methods: Twenty-seven ocular fluids from patients who underwent phaco-vitrectomy were categorized as no-dERM (9, 4M/5F; 70.4 ± 6.4), dERM (6, 3M/3F; 73.2 ± 4.9), and PDR (6, 5M/1F; 63.7 ± 7.4). Six cataracts (CTR; 3M/3F; 77.7 ± 9.0) were collected for internal control of aqueous cells. Results: In aqueous cells, p65NFkB, iNOS, Nox1/Nox4, and Nrf2 were significantly upregulated, and Keap1 was downregulated in dERM compared with PDR and no-dERM. In aqueous cells, a significant upregulation for C3aR1mRNA, C5aR1mRNA, and CFHmRNA were observed in dERM. In vitreous, C3a, C5b9, and MDA levels were significantly increased in dERM compared with PDR and no-dERM. Conclusions: Inflammatory and ROS products, as well as C3aR1/C5aR1 and soluble MDA, appear of great interest, as their expression in aqueous and vitreous might have potential prognostic and therapeutic values. Full article

Type 2 diabetes mellitus (T2DM) is a major public health concern that significantly increases the risk of diabetic retinopathy (DR), a leading cause of visual impairment worldwide. This study aimed to identify molecular markers of inflammation (INF) and angiogenesis (ANG) in the aqueous humor (AH) of patients with non-proliferative diabetic retinopathy (NPDR). We conducted an observational, multicenter, case–control study including 116 participants classified into T2DM with NPDR, T2DM without DR, and non-diabetic controls (SCG) undergoing cataract surgery. AH samples were collected intraoperatively and analyzed for 27 cytokines using multiplex immunoassay. Eighteen immune mediators were detected in AH samples, and several were significantly elevated in the NPDR group, including the interleukins (IL) -1β, -6, -8, -15, -17, as well as the granulocyte–macrophage colony stimulating factor (GM-CSF), basic fibroblast growth factor (bFGF), interferon gamma-induced protein (IP-10), macrophage inflammatory protein 1 beta (MIP-1b), monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell-expressed and -secreted protein (RANTES), and the vascular endothelial growth factor (VEGF). These molecules are involved in retinal INF, blood–retinal barrier breakdown, and pathological neovascularization. Our findings reveal a distinct pro-INF and pro-ANG profile in the AH of NPDR patients, suggesting that these cytokines may serve as early diagnostic/prognostic biomarkers for DR. Targeting these molecules could provide novel therapeutic strategies to mitigate retinal damage and vision loss in diabetic patients. Full article

Background: The advent of newer pharmacological agents, particularly proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors, in combination with conventional lipid-lowering treatments, has allowed for the significant lowering of low-density lipoprotein cholesterol (LDL-C). However, it is unclear if very low LDL-C levels achieved with the use of PCSK-9 inhibitors are associated with increased adverse events that may outweigh potential benefits. Methods: A systematic search of PubMed, Medline, and Cochrane databases was conducted from their inception to 21 February 2025, for randomized controlled trials (RCTs) reporting clinical outcomes with intensive lipid-lowering treatment with PCSK-9 inhibitors leading to very low (<40 mg/dL) LDL-C levels vs. a control group with higher LDL-C levels. The outcomes of interest included the incidence of major adverse cardiovascular events (MACEs), neurocognitive disorders, diabetes mellitus, muscle disorders, any adverse events, events leading to drug discontinuation, cataract, hepatobiliary disorders, and cancer. Random effects meta-analysis models were used to calculate the pooled incidence and odds ratio (OR) with 95% confidence intervals (Cis). Results: A total of six RCTs with 52,951 patients (11,209 very low LDL-C, and 41,742 control) met the inclusion criteria. Compared with patients in the control arm, very low LDL-C was associated with a reduction in MACEs (OR = 0.76, 95% CI: 0.64, 0.89; p < 0.01; I² = 44.8%). The incidence of most safety outcomes including neurocognitive disorders, diabetes mellitus, muscle disorders, any adverse events, events leading to drug discontinuation, cataract, hepatobiliary disorders, and cancer were comparable between the very low LDL-C and control groups. Conclusions: Very low LDL-C values following intensive lipid-lowering with PCSK-9 inhibitors are associated with a major reduction in cardiovascular events without any significant increase in serious side effects. Full article

Purpose: To investigate the role of the kynurenine pathway (KP) in ocular diseases by evaluating the activity of key enzymes—kynurenine aminotransferase (KAT) and kynurenine monooxygenase (KMO)—and the 3-hydroxykynurenine to kynurenic acid (3-HK/KYNA) ratio in relation to cataract severity, diabetes, glaucoma, and pseudoexfoliation syndrome (PEXS). Methods: Tryptophan metabolite levels were measured in patients undergoing cataract surgery and stratified by SPONCS grading and comorbid conditions. KAT and KMO activities were estimated using metabolite ratios (KYNA/KYN and 3-HK/KYN, respectively). Statistical analyses included Kruskal–Wallis tests with post hoc comparisons and Mann–Whitney U tests. Results: KAT activity declined significantly with increasing SPONCS grade (p = 0.014), suggesting a progressive loss of KYNA production and antioxidative capacity in advanced cataracts. Diabetic patients exhibited higher KMO activity (p = 0.039) and elevated 3-HK/KYNA ratios (p = 0.013), indicating a metabolic shift toward oxidative stress and neurotoxicity. Similarly, glaucoma patients had significantly increased KMO activity (p = 0.032), consistent with enhanced 3-HK-mediated retinal ganglion cell damage. In contrast, PEXS showed no significant alterations in KP markers. Conclusions: The kynurenine pathway is differentially modulated in ocular diseases. A decline in KAT activity correlates with cataract severity, while upregulation of KMO is prominent in diabetes and glaucoma, revealing disease-specific metabolic dysregulation. Targeting KMO to reduce toxic metabolite accumulation or enhancing KYNA synthesis may offer novel therapeutic avenues. These findings also support the potential of KP metabolites as biomarkers for disease monitoring and progression. Full article

Background: Systemic arterial stiffness and atherosclerosis have been increasingly recognized as potential contributors to the pathogenesis of glaucoma. Several studies have reported associations between glaucoma and various surrogate markers of vascular stiffness. However, despite the growing interest in the vascular components of glaucoma, no previous studies have specifically explored the relationship between the indices derived from acceleration plethysmography (APG) and glaucoma. This study seeks to address this gap by investigating the potential association between APG parameters and the presence of glaucoma. Methods: The subjects were 701 patients (mean age 68.6 years, 54% male) with open-angle glaucoma (primary open-angle glaucoma [POAG] or exfoliation glaucoma [EXG]), and 94 control subjects (mean age 60.1 years, 57% male) who had no eye diseases other than cataracts. The subjects were all cases in which APG was measured using a sphygmograph (TAS9 Pulse Analyzer Plus View; YKC Corp., Tokyo, Japan). The amplitude of waveform types (a, b, c, d, and e-waves) and derived vascular types (A, B, and C) of the accelerated pulse wave components were statistically compared between the cases and controls. Results: The accelerated pulse wave components (mean ± standard deviation) of the control and glaucoma groups were a-wave 785 ± 99 and 776 ± 93 (p = 0.40), b-wave −522 ± 161 and −491 ± 143 (p = 0.050), c-wave −142 ± 108 and −156 ± 105 (p = 0.24), d-wave −288 ± 144 and −322 ± 122 (p = 0.014), and e-wave 103 ± 79 and 90 ± 58 (p = 0.059), with differences between the groups being observed in the b and d-waves. For derived vascular types, compared with the controls and POAG, patients with EXG had a lower frequency of Type A and a higher frequency of Type C than the other groups (p = 0.044). Multivariate analysis showed that factors significantly associated with vascular type included age (p < 0.0001), sex (p < 0.0001), diastolic blood pressure (p = 0.021), and pulse rate (p < 0.0001), while BMI, systolic blood pressure, history of hypertension, history of diabetes, presence or absence of glaucoma, and presence or absence of pseudoexfoliation material were not significant. Conclusions: This is the first study to investigate the relationship between APG and glaucoma with a large sample size. In elderly glaucoma patients, particularly those with EXG, systemic vascular changes are often present. APG parameters may reflect vascular alterations in glaucoma. Full article

Advanced glycation end-products (AGEs) and oxidative stress are recognized as central contributors to the pathogenesis of age-related or diabetic cataracts, diabetic retinopathy (DR), and age-related macular degeneration (AMD). These glycation-related diseases are characterized by impaired redox balance and decreased glutathione (GSH) levels. This review aims to examine the mechanistic links between AGEs and GSH depletion across ocular tissues by integrating in vitro, ex vivo, in vivo, and clinical studies relevant to this topic. The multiple levels of evidence highlight GSH homeostasis as both a biomarker and therapeutic target in glycation-related ocular disorders. Therapeutic strategies aimed at restoring GSH homeostasis under glycation stress are categorized into four mechanistic domains: (I) promoting GSH supply and synthesis, (II) enhancing GSH recycling, (III) mitigating glycation stress, and (IV) reducing oxidative and nitrosative stress. Most of these strategies have been explored via different approaches, and experimental findings with various interventions have shown promise in restoring GSH balance and mitigating AGE-induced damage. A pathological link between GSH depletion and vascular endothelial growth factor (VEGF) overexpression is observed in DR and wet AMD. GSH-centered interventions act upstream to modulate redox homeostasis while anti-VEGF therapies target downstream angiogenesis. This study supports the rationale for a dual-targeting strategy that combines redox-based interventions with VEGF inhibition in glycation-related ocular diseases. Full article

Glycation is known as an important factor inducing human diseases, including diabetic complications. As oxidative stress contributes to procedures of glycation, antioxidants may inhibit glycation and delay the progression of diabetic complications. Our previous investigation of human aqueous humor after the intake of a lutein-containing supplement demonstrated increases in antioxidative activities and decreases in peroxidative products. This study enrolled 25 patients with diabetes (DM group) and 100 age-matched controls. Aqueous humor samples were collected during cataract surgery before and after 6 weeks of oral intake of the lutein-containing antioxidant supplement, Ocuvite + Lutein^®. The carboxymethyl-lysine level (CML) was measured as an indicator of glycation. Levels of superoxide dismutase activities (SOD) and total hydroperoxide (TH) were measured as indicators of oxidation. Changes after intake and the differences between age-matched controls and the DM group were evaluated. CML decreased after intake among the DM group, while there were no changes among the age-matched controls. SOD was significantly lower and TH was significantly higher in the DM group as compared to the age-matched controls, both before and after intake. In line with the decreases in glycation, the intake of lutein-containing antioxidant supplements may inhibit diabetic complications in diabetic patients. Full article

Cataracts, characterized by the opacification of the eye lens, remain a leading cause of reversible blindness globally. Age and diabetes are key risk factors, and with the increasing aging and diabetic population, the global burden of cataracts is projected to rise significantly. Current treatment is predominantly surgical; however, pharmacological strategies could offer a non-invasive alternative with the potential to delay, prevent, or even reverse cataract progression. Recent research has enhanced our understanding of cataractogenesis, emphasizing oxidative stress as a key underlying mechanism, but also including other processes such as calcium dysregulation and altered lens homeostasis or specific events induced by hyperglycemia in diabetic cataracts. New therapeutic approaches have emerged considering the molecular mechanisms involved in cataracts, most of which focus on pharmacological agents with antioxidant properties. Additionally, small-molecule chaperones, aldose reductase inhibitors, and protein aggregation inhibitors have also demonstrated potential in stabilizing or restoring lens protein structure and transparency. While experimental results have shown encouraging results, further research is needed to optimize drug delivery systems to the lens, assess long-term safety, and confirm the clinical efficacy of these treatments. This article reviews current progress in pharmacological treatments for cataracts, outlining challenges and prospects for future integration into clinical practice. Full article

Cataract formation remains a significant cause of global visual impairment. Increasing attention has been directed toward antioxidant-based interventions as potential non-surgical strategies to delay or prevent cataractogenesis, particularly in the age-related and diabetic contexts. This review summarizes recent preclinical evidence on nutritional antioxidants for the prevention of age-related and diabetic cataracts. Agents such as trimetazidine, Moringa oleifera stem extract, ginsenoside Rg1, lanosterol nanoparticles, β-casomorphin-7, and cerium oxide-based nanotherapies have been shown to mitigate oxidative damage, modulate redox signaling pathways, and preserve lens clarity. Advances in drug delivery, including topical formulations, nanoparticle carriers, and intravitreal injections, have been proposed to overcome the anatomical and pharmacokinetic barriers associated with the avascular lens. The new data support ongoing translational research to maximize the clinical use of antioxidants and highlight their therapeutic potential in the prevention of age-related and diabetic cataracts. Full article

The process of aging exerts profound effects on various physiological systems, leading to the progression of chronic degenerative disorders and pathologies associated with advancing age. Cellular senescence plays a central role in the aging process and the onset of various eye conditions associated with advancing age, including age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, cataracts, and ocular surface disorders. The accumulation of senescent cells (SnCs) and their secretion of pro-inflammatory and tissue-remodeling factors, collectively known as the senescence-associated secretory phenotype (SASP), exacerbate chronic inflammation, oxidative stress, and tissue dysfunction, contributing to disease progression. This study is the first to systematically integrate the multifaceted mechanisms of cellular senescence in ocular diseases, revealing differential regulatory mechanisms of specific signaling pathways across different ocular pathologies, thereby providing novel insights into the pathogenesis of these disorders. SnC-targeted therapies such as senolytics, senomorphics, SASP modulators, mitochondrial-targeted antioxidants, and epigenetic reprogramming are emerging as regenerative therapies, demonstrating potent anti-inflammatory effects, restoration of normal tissue physiology, and successful regeneration of ocular defects in preclinical models and clinical trials, while slowing senescence-associated disease progression. This review not only summarizes the role of cellular senescence in ocular diseases but also delves into potential therapeutic strategies, particularly highlighting novel perspectives for root-cause-targeted therapies from the unique angle of senescence biology, which may pioneer new directions for the treatment of ocular pathologies. Full article

Background: Diabetic macular edema (DME) is the most common cause of vision loss among diabetic patients. The first-line treatments for DME are anti-vascular endothelial growth factor (VEGF)-drugs, while intravitreal steroids are generally reserved for second-line treatment. Limited data exist on the role of optical coherence tomography (OCT) biomarkers as predictors of success in non-responders to anti-VEGF treatment undergoing simultaneous cataract surgery and dexamethasone intravitreal implant (DEX-I). Methods: This study was designed as a retrospective analysis of patients with DME who were refractory to anti-VEGF treatment but underwent cataract surgery and received a DEX-I at the time of surgery. All procedures were performed between May 2021 and February 2024. The best-corrected visual acuity (BCVA) and central subfoveal thickness (CST) were recorded at baseline and at 1 week, 1 month, and 3 months. The following OCT-based biomarkers were also collected: ellipsoid zone (EZ) integrity, disorganization of the retinal inner layers (DRIL), CST, and hyperreflective foci (HRF). Correlations between the baseline biomarkers and the anatomical outcome were analyzed using linear mixed models (LMMs). Results: Eleven patients (eighteen eyes) met the inclusion criteria. The mean CST decreased significantly from 469.4 ± 53.8 µm at baseline, to 373.1 ± 34.7 µm at 1 week (p = 0.002) and 354.4 ± 24.1 µm at 1 month (p = 0.011). The mean BCVA improved significantly from 0.47 LogMAR to 0.33 LogMAR at 1 week (p = 0.001), 0.23 LogMAR at 1 month (p < 0.001), and 0.25 LogMAR at 3 months (p < 0.001). Baseline predictors significantly influencing CST included the presence of DRIL, a disrupted/absent EZ, and a higher CST. Conclusions: The administration of DEX-I for DME refractory to anti-VEGF treatment in patients undergoing cataract surgery promoted functional improvements persisting longer than the anatomical ones. Patients presenting with DRIL, disrupted EZ, and higher CST at baseline may be better candidates for the combination of DEX-I and cataract surgery. Full article

Background: The aim of this study was to evaluate corneal endothelial changes following phacoemulsification cataract surgery with intraocular lens implantation in patients with type 2 diabetes (study group) and without diabetes (control group). The study aimed to determine the extent of endothelial cell damage and the regenerative capacity of the cornea in patients with well-controlled diabetes. Methods: This study compared corneal endothelial parameters in 80 eyes (80 patients) with well-controlled type 2 diabetes and 80 eyes (80 patients) without diabetes, all of whom underwent uneventful phacoemulsification cataract surgery. Patients were examined preoperatively and at 14 days, 3 months, and 6–8 months postoperatively. Endothelial cell density (ECD), percentage of hexagonal cells (%HEX), cell size variability (CV), and central corneal thickness (CCT) were assessed using a specular microscope. Visual acuity, intraocular pressure (IOP), and cumulative dissipated energy (CDE) during phacoemulsification were also measured. Results: The study and control groups were matched for age and sex. Preoperatively, patients with type 2 diabetes had significantly lower endothelial cell density (2480.76 ± 303.48 cells/mm²) compared to the control group (2629.64 ± 304.73 cells/mm², p = 0.002). Visual acuity was also significantly lower in the study group (0.44 ± 0.18) than in the control group (0.50 ± 0.19, p = 0.049). No significant preoperative differences were observed in IOP, CV, %HEX, or CCT. Postoperatively, both groups experienced ECD decline: −18.44%, −18.77%, and −19.05% in the study group and −15.12%, −16.42%, and −16.73% in the control group at 14 days, 3 months, and 6–8 months, respectively. Differences between groups were not statistically significant (p = 0.285). A significant %HEX decrease was observed in both groups at all time points, with a greater decline in the study group at 14 days and 3 months. CV significantly increased in both groups at 14 days and 3 months postoperatively, but no significant difference was found between groups. A significant increase in CCT was observed at 14 days and 3 months postoperatively, with a greater increase in the study group at 14 days. Preoperative visual acuity negatively correlated with CDE in both groups. Additionally, CDE negatively correlated with ECD at all time points. Conclusions: Endothelial cell density is lower in patients with well-controlled type 2 diabetes than in non-diabetic individuals. Both groups are at risk of endothelial cell loss during phacoemulsification. Despite good glycemic control and comparable preoperative endothelial morphology, the cornea in diabetic patients is more vulnerable to damage, with a prolonged regeneration process. The impaired regenerative capacity of the corneal endothelium suggests the need for additional precautions during cataract surgery in diabetic patients. Despite ECD decline and delayed endothelial regeneration, the functional status of the cornea, as indicated by visual acuity and CCT, remains stable. The adequate corneal endothelial cell reserve in well-controlled type 2 diabetes patients allows for cataract surgery without significant corneal complications. Full article