Clinical Evidence of a Photoreceptor Origin in Diabetic Retinal Disease.

Clinical Relevance: Although diabetes is associated with a classic microvascular disease of the retina, it is also increasingly being recognized as a cause of retinal neuropathy. Preclinical evidence suggests that retinal neuropathy in diabetes manifests in part as photoreceptor dysfunction, preceding the development of vascular features in experimental models. It remains unknown whether such findings are relevant to patients with diabetes. Methods: Here, we review 4 lines of clinical evidence suggesting that diabetes-associated photoreceptor pathology is linked to the development of retinal microvascular disease. Results: First, a major population-based investigation of susceptibility loci for diabetic retinopathy (DR) implicated a photoreceptor protein product as a protective factor. Next, electroretinography and other studies of visual function collectively show that rod and/or cone-derived abnormalities occur decades before the development of vascular features of DR. Third, protection from DR seemingly develops in patients with coincident retinitis pigmentosa, as suggested by several case series. Finally, based on anatomic features, we propose that the beneficial effect of macular laser in DR occurs via ablation of diseased photoreceptors. Conclusions: The evidence we present is limited due to the small patient populations used in the studies we cite and due to the lack of methodologies that allow causative relationships to be inferred. Collectively, however, these clinical observations suggest that photoreceptors are involved in early diabetic retinal disease and may in fact give rise to the classic features of DR. Financial Disclosures: Proprietary or commercial disclosures may be found in the Footnotes and Disclosures at the end of this article.

Exploring aldose reductase inhibitors as promising therapeutic targets for diabetes-linked disabilities.

Diabetes mellitus significantly increases mortality and morbidity rates due to complications like neuropathy and nephropathy. It also leads to retinopathy and cataract formation, which is a leading cause of vision disability. The polyol pathway emerges as a promising therapeutic target among the various pathways associated with diabetic complications. This review focuses on the development of natural and synthetic aldose reductase inhibitors (ARIs), along with recent discoveries in diabetic complication treatment. AR, pivotal in the polyol pathway converting glucose to sorbitol, plays a key role in secondary diabetes complications' pathophysiology. Understanding AR's function and structure lays the groundwork for improving ARIs to mitigate diabetic complications. New developments in ARIs open up exciting possibilities for treating diabetes-related complications. However, it is still challenging to get preclinical successes to clinical effectiveness because of things like differences in how the disease starts, drug specificity, and the complexity of the AR's structure. Addressing these challenges is crucial for developing targeted and efficient ARIs. Continued research into AR's structural features and specific ARIs is essential. Overcoming these challenges could revolutionize diabetic complication treatment, enhance patient outcomes, and reduce the global burden of diabetes-related mortality and morbidity.

Chronic myeloid leukemia diagnosed from the course of diabetic retinopathy.

We report a case of chronic myeloid leukemia (CML), which was diagnosed during the management of proliferative retinopathy (PR) in a patient with type I diabetes mellitus due to the fulminant nature of the PR. This case highlights the importance of vigilance on the part of the ophthalmologist in the diagnosis of co-existing systemic disorders, notably hematological malignancy, which aggravates the posterior segment vasculopathy of the eye and the management of which is crucial for the patient. We also describe a short literature review on the clinical features, mechanism of the posterior segment vasculopathy of the eye, and management of PR co-existing in a patient with CML.

A spectral domain optical coherence tomography (SD-OCT) study of intraretinal hyperreflective foci and its relationship with visual acuity and grades of retinopathy among patients of diabetes mellitus in Indian population.

Background: Hyperreflective foci (HRF) are biomarkers in detection of diabetic retinopathy (DR). Presence of HRF on spectral domain optical coherence tomography (SD-OCT) can give a correlation with visual acuity change and grades of DR. Purpose of this study is to determine the presence, location, and role of HRF in the retina of DM patients with and without retinopathy. Methods: A total of 192 eyes of patients suffering from type II DM were evaluated. Patients were divided into 2 groups, with Group A having diabetes without retinopathy (20 patients) and group B (76 patients) having diabetes and various grades of retinopathy. SD-OCT was performed in all patients, passing through the center of fovea. On OCT, presence and absence of HRF were noted. Characteristics of the hyper-reflective spots were evaluated: location, shape, size, back shadowing and association with central macular thickness (CMT), visual acuity, and grades of retinopathy. Results: HRF were present in 169 eyes (88%) out of 192 eyes. The shape and location of HRF tend to change with disease progression. HRF were significantly associated with increasing grades of retinopathy (χ2 = 57.586, p < 0.01) Association of macular edema was significant with both retinopathy (χ2 = 8.895, p < 0.05) and HRF (χ2 = 34.720, p < 0.01). Association of best-corrected visual acuity with HRF (χ2 = 21.232, p < 0.01), macular edema (χ2 = 86.960, p < 0.01), and CMT (χ2 = 47.959, p< 0 .01) was significant. Conclusion: HRF is a great indicator for early diagnosis of subclinical retinopathy and can be used to monitor the progression of disease and development of macular edema. Significant difference is present in HRF distribution and morphology.

The Effect of Pan-Retinal Photocoagulation on Central Macular Thickness in a Sample of Iraqi Patients With Proliferative Diabetic Retinopathy.

OBJECTIVE: To evaluate the effect of pan-retinal photocoagulation (PRP) on central macular thickness (CMT) in a sample of Iraqi patients with proliferative diabetic retinopathy (PDR). METHODS: This prospective study was conducted at Ghazi Al-Hariri for Surgical Specialties Hospital, Baghdad, from March 2024 to May 2024. A total of 24 eyes from 18 treatment-naive PDR patients with no previous diabetic macular edema (DME) were enrolled. Each eye received PRP in two sessions, one week apart, using the Nidek GYC 500 laser system. CMT was measured at baseline and four weeks after the second PRP session using the Topcon DRI Triton Plus optical coherence tomography (OCT). Statistical analyses, including paired t-tests and Shapiro-Wilk tests for normality, were performed to evaluate changes in CMT. RESULTS: The mean CMT increased from 258.4 ± 30.7 microns at baseline to 269.9 ± 36.8 microns post PRP, with a mean increase of 11.5 ± 26.3 microns. This increase was statistically significant (p = 0.042). The Shapiro-Wilk test confirmed that the data were approximately normally distributed both before (W = 0.960, p = 0.445) and after (W = 0.931, p = 0.103) PRP treatment. CONCLUSION: PRP significantly increases CMT in PDR patients, although no additional treatment for macular edema was necessary. These findings align with previous studies, suggesting that PRP-induced macular thickening is a common outcome. Further research is recommended to explore long-term effects and potential mitigation strategies.

Case reports: Intraoperative migratory retinal venous thrombus in proliferative diabetic retinopathy.

Purpose: This study aimed to study the characteristics, possible causes, and clinical implications of intraoperative migratory retinal venous thrombus in proliferative diabetic retinopathy (PDR). Cases: Two middle-aged Chinese patients with diabetes mellitus presented with blurred vision and were diagnosed with PDR and tractional retinal detachment (TRD). An interesting phenomenon was observed during pars plana vitrectomy in both patients. Movement of tiny white thrombi and interruption of blood flow were observed in a branch of the central retinal vein when the vein was pulled at the time of fibrovascular membrane delamination and disappeared with the elimination of retinal traction after finishing the process of delamination. Laboratory studies revealed abnormal erythrocyte sedimentation rate, fibrinogen, D-dimer, international normalized ratio, and IgA anti-ß2-glycoprotein I in one patient and elevated fibrinogen and IgA anticardiolipin in the other. Follow-up examinations at 1 week, 1, 3, and 6 months postoperatively showed good prognosis. Fluorescein fundus angiography at 1 month postoperatively showed neither embolus sign nor prolonged venous filling time in both patients. Discussion: Local blood stasis of the retinal vein persistently dragged by the fibrovascular membrane may result in thrombogenesis, and traction of the retina during the delamination process may lead to the movement of thrombi. On the other hand, endothelial injury and disordered local blood stasis during delamination may also activate the biological coagulation process and instant thrombus formation. As well, antiphospholipid antibodies may also be a risk factor of ocular thrombogenesis. Conclusion: This study provides the first videos recording migratory thrombus in terminal vessels, which indicates that fibrovascular membrane in PDR can lead to thrombogenesis due to dragging and hemostasis of the involved retinal vein. PDR patients with fibrovascular membranes may benefit from early relief of vascular traction through fibrovascular membrane delamination.

ROS-Responsive Nanoparticles with Antioxidative Effect for the treatment of Diabetic Retinopathy.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes necessitating early intervention to impede progression, despite current clinical treatments focusing on advanced stages. Essential oils from Fructus Alpiniae zerumbet (EOFAZ) have demonstrated efficacy in protecting against high glucose (HG)-induced Müller cell activation and DR development. This study introduced a reactive oxidative species (ROS)-responsive drug delivery system (NPSPHE@EOFAZ) targeting early DR stages and oxidative stress. Our engineered nanoparticles effectively deliver EOFAZ into HG-exposed Müller cells by detecting and responding to elevated oxidative stress levels. The NPSPHE@EOFAZ significantly inhibited abnormal cell growth, reduced oxidative stress, and alleviated inflammation in vitro. In vivo experiments on diabetic mice with DR revealed that NPSPHE@EOFAZ mitigated early pathological changes by reducing oxidative stress and inflammation while also alleviating organ damage in the heart, liver, spleen, lung, and kidney. These findings underscore the potential of NPSPHE@EOFAZ as a promising antioxidant for early intervention in DR pathogenesis.

Correlation between macular sensitivity and kidney function in patients with diabetes.

PURPOSE: The aim of this study is to investigate the correlation between kidney function in patients with diabetes and macular sensitivity at central 10° using microperimetry. METHODS: A cross-sectional study was carried out on 30 diabetic patients (58 eyes). A full-threshold microperimetry of the central 10° of retina (the macula) was performed on all subjects, consisting of 37 measurement points, using a 4-2 representation strategy. Macular sensitivity was expressed as the average threshold value in decibels for the entire field tested. The correlation between macular sensitivity and GFR, as well as microalbuminuria, blood glucose and HbA1c, was calculated using Pearson correlation rank. RESULTS: A significant positive correlation was observed between GFR and macular sensitivity among both male and female study subjects. For male participants, the correlation was measured to r([16]) = [.615], p = [<.007] and r([15]) = [.844], p = [<.001] for the left and right eyes, respectively. As for female participants, the correlation was r ([9]) = [.903], p = [<.001] and r([10]) = [.941], p = [<.001] for the left and right eyes, respectively. The correlation between macular sensitivity and the following variables was statistically insignificant: microalbuminuria, blood glucose, and HbA1c. CONCLUSION: Despite intact visual acuity measured on standard ophthalmic examination, patients with impaired kidney function had decreased macular sensitivity. This emphasizes the importance of microperimetry in preventative care and detection of early signs of diabetic retinopathy. Furthermore, we should consider the use of microperimetry as an auxiliary tool for monitoring kidney function in diabetics.

Classification of diabetic retinopathy algorithm based on a novel dual-path multi-module model.

Diabetic retinopathy is a chronic disease of the eye that is precipitated via diabetes. As the disease progresses, the blood vessels in the retina are issue to modifications such as dilation, leakage, and new blood vessel formation. Early detection and treatment of the lesions are vital for the prevention and reduction of imaginative and prescient loss. A new dual-path multi-module network algorithm for diabetic retinopathy classification is proposed in this paper, aiming to accurately classify the diabetic retinopathy stage to facilitate early diagnosis and intervention. To obtain the purpose of fact augmentation, the algorithm first enhances retinal lesion features using color correcting and multi-scale fusion algorithms. It then optimizes the local records via a multi-path multiplexing structure with convolutional kernels of exclusive sizes. Finally, a multi-feature fusion module is used to improve the accuracy of the diabetic retinopathy classification model. Two public datasets and a real hospital dataset are used to validate the algorithm. The accuracy is 98.9%, 99.3%, and 98.3%, respectively. The experimental results not only confirm the advancement and practicability of the algorithm in the field of automatic DR diagnosis, but also foretell its broad application prospects in clinical settings, which is expected to provide strong technical support for the early screening and treatment of diabetic retinopathy.

Management of Microcomplications of Diabetes Mellitus: Challenges, Current Trends, and Future Perspectives in Treatment.

Diabetes mellitus is a chronic metabolic disorder characterized by high blood sugar levels, which can lead to severe health issues if not managed effectively. Recent statistics indicate a significant global impact, with 463 million adults diagnosed worldwide and this projected to rise to 700 million by 2045. Type 1 diabetes is an autoimmune disorder where the immune system attacks pancreatic beta cells, reducing insulin production. Type 2 diabetes is primarily due to insulin resistance. Both types of diabetes are linked to severe microvascular and macrovascular complications if unmanaged. Microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy, result from damage to small blood vessels and can lead to organ and tissue dysfunction. Chronic hyperglycemia plays a central role in the onset of these complications, with prolonged high blood sugar levels causing extensive vascular damage. The emerging treatments and current research focus on various aspects, from insulin resistance to the intricate cellular damage induced by glucose toxicity. Understanding and intervening in these pathways are critical for developing effective treatments and managing diabetes long term. Furthermore, ongoing health initiatives, such as increasing awareness, encouraging early detection, and improving treatments, are in place to manage diabetes globally and mitigate its impact on health and society. These initiatives are a testament to the collective effort to combat this global health challenge.

Characterizing Vascular Wall and Lumen Caliber in Eyes with Diabetic Retinopathy Based on Adaptive Optics Scanning Laser Ophthalmoscopy.

(200/200) Purpose: Our aim was to evaluate structural alterations of retinal arterioles due to type 1 diabetes (T1D) and/or diabetic retinopathy (DR) under AOSLO imaging. METHODS: Each study eye underwent mydriasis and AOSLO imaging in a single-visit study. The instrument's arrangement of four offset aperture images provided two orthogonal split-detector images and enabled isotropic analysis of the arteriolar boundaries. For each arteriole, we calculated the wall-to-lumen ratio (WLR), mean wall thickness, and luminal and external diameters. RESULTS: In total, we enrolled 5 (20.8%) healthy control eyes and 19 eyes of patients with T1D. The DR distribution was: four (16.7%) no-DR, nine (37.5%%) mild or moderate nonproliferative DR (NPDR), and six (25%) severe NPDR or proliferative DR. Mean wall thickness increased significantly in eyes with T1D compared to healthy controls (p = 0.0006) and in eyes with more advanced DR (p = 0.0004). The WLR was significantly higher in eyes with T1D (p = 0.002) or more severe DR (p = 0.004). There was no significant relationship between T1D status or DR severity and any of the arteriolar diameters. CONCLUSIONS: In this preliminary study, there appeared to be increases in the WLR and mean wall thickness in eyes with T1D and more severe DR than in the controls and eyes with no/less severe DR. Future studies may further elucidate the relationship between the retinal arteriolar structure and physiologic alterations in DR.

Laser Treatment for Diabetic Retinopathy: History, Mechanism, and Novel Technologies.

Background: Diabetic retinopathy (DR), as a complication of diabetes mellitus (DM), remains a significant contributor to preventable vision impairment in the working-age population. Laser photocoagulation is essential in treating DR in conjunction with anti-vascular endothelial growth factor (VEGF) injection, steroids, and vitrectomy. This review summarizes the history of laser photocoagulation and highlights its current role and long-term effectiveness in real-world conditions. Methods: The National Clinical Trial (NCT), PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases were searched utilizing combined or individual keywords, and a total of 121 articles were reviewed by the authors. Results: Several novel laser photocoagulation technologies, such as patterned scanning laser, subthreshold micropulse laser, navigated laser, multimodal imaging-guided laser, and retina rejuvenation therapy, substantially decrease the adverse effects and improve the accuracy and security of laser therapy. Numerous studies have demonstrated the outstanding clinical efficacy of combination therapies with pharmacologic treatments like anti-VEGF in treating DR and diabetic macular edema (DME). A 20-year follow-up retrospective study in our center preliminarily demonstrated the long-term effectiveness of conventional laser photocoagulation. Conclusions: More clinical trials are required to confirm the clinical effectiveness of novel laser technologies. Better treatment protocols for the combination therapy may be detailed. Anti-VEGF treatment has better effects, especially for DME and in a short period. But in real-world conditions, given the long-term effectiveness and economic advantages of conventional laser treatment, it should be prioritized over anti-VEGF injection in certain situations.

α-Klotho prevents diabetic retinopathy by reversing the senescence of macrophages.

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) and a significant cause of acquired blindness in the working-age population worldwide. Aging is considered as an important risk factor for DR development. Macrophages in aged mice bear typical M2 marker proteins but simultaneously express a pro-inflammatory factor profile. This may explain why the level of intraocular inflammation does not decrease during proliferative diabetic retinopathy (PDR) despite the occurrence of neovascularization and fibrosis (M2 activation). α-Klotho (KL) was originally discovered as a soluble anti-aging factor, which is mainly expressed in kidney tubular epithelium, choroid plexus in the brain and secreted in the blood. However, the role of KL in DR pathophysiology has not been previously reported. METHODS: Type 1 (streptozotocin [STZ]-induced) and type 2 (a high-fat diet along with a low dose of STZ) diabetic mouse models were established and injected with or without KL adenovirus via the tail vein for 12 weeks. Vldlr-/- mice were injected intravitreally with or without soluble KL protein from P8 to P15. The retinal structure and function were analyzed by electroretinogram and optical coherence tomography. The neovascular lesions were analyzed by retinal flat mount and RPE flat mount. The senescence markers, macrophage morphology, and KL expression levels were detected by immunofluorescence staining. A cell model was constructed using RAW264.7 cells stimulated by 4-hydroxynonenal (4HNE) and transfected with or without KL adenovirus. The senescence-associated secretory phenotypes were detected by qRT-PCR. Senescence was detected by SA-ß-Gal staining. Serum, aqueous humor, and vitreous humor KL levels of proliferative diabetic retinopathy (PDR) patients were measured by enzyme-linked immunosorbent assay. Quantitative proteomics and bioinformatics were applied to predict the change of proteins and biological function after overexpression of KL in macrophages. The effects of KL on the HECTD1 binding to IRS1 were analyzed by bioinformatics, molecular docking, and Western Blot. RESULTS: Serum, aqueous humor, and vitreous humor KL levels were lower in patients with PDR than in those with cataracts. KL relieved the retinal structure damage, improved retina function, and inhibited retinal senescence in diabetic mice. KL administration attenuated the neovascular lesions in VLDLR-/- mice by decreasing the secretion of VEGFA and FGF2 from macrophages. KL also protected RAW264.7 cells from 4HNE-induced senescence. Additionally, it inhibited E3 ubiquitin ligase HECTD1 expression in both diabetic mouse peripheral blood mononuclear cells and 4HNE-treated RAW264.7 cells. KL inhibited HECTD1 binding to IRS1 and reduced the ubiquitination of IRS1. CONCLUSIONS: Macrophage aging is involved in DM-induced retinopathy. KL alleviates DM-induced retinal macrophage senescence by downregulating HECTD1 and decreasing IRS1 ubiquitination and degradation. Meanwhile, KL administration attenuated the neovascular lesions by altering the activation state of macrophages and decreasing the expression of VEGFA and FGF2.

Ambulatory blood pressure monitoring and vascular complications in patients with type 1 diabetes mellitus - Systematic review and meta-analysis of observational studies.

AIMS: This study aimed to evaluate the role of the 24-Hour Ambulatory Blood Pressure Monitoring (ABPM) as a possible predictor of vascular outcomes in office normotensive people with type 1 diabetes mellitus (T1DM). METHODS: This is a systematic review including cohort studies from the Embase, PubMed/Medline, and Web of Science databases on people with T1DM undergoing ABPM and subsequent evaluation of vascular complications. Measurements of difference (MD) were obtained using random effect model meta-analysis. RESULTS: We found 364 articles and 49 duplicates. Seven studies were included, comprising 635 participants aged 25.8 ±â€¯6.2 years. Most (57.5 %) were men, mean duration of diabetes was 11.8 ±â€¯5.3 years, mean glycated hemoglobin level among participants was 8.5 % ± 1.6 %, and mean follow-up time was 4.2 years. Lower night systolic blood pressure MD - 4.37 mmHg (p = 0.0009) and night diastolic blood pressure MD - 3.97 mmHg (p < 0.0001) were associated with lower incidence of albuminuria. People withT1DM who presented no beginning or progression of retinopathy were those with lower night diastolic blood pressure MD - 3.62 mmHg (p = 0.042), diurnal diastolic blood pressure MD - 2.69 mmHg (p = 0.0138), and 24-hour diastolic blood pressure MD - 3.65 mmHg (p = 0.037). CONCLUSION: Small mean differences in blood pressure parameters, as measured by ABPM, between people with T1DM are associated with a lower incidence or risk of progression of nephropathy and retinopathy.

The influence of insulin on diabetic retinopathy and retinal vessel parameters in diabetes.

AIM: To investigate the associations between insulin use and diabetic retinopathy (DR), and retinal vascular parameters in type 2 diabetes (T2DM). METHODS: A total of 6,374 T2DM patients, consisting of 2,231 patients receiving insulin alone and 4143 patients without any hypoglycemic medication, were included in cross-sectional analyses. Among those without DR at baseline, 791 patients were followed for three years in longitudinal analyses. Fundus photography was taken to diagnose DR and calculate central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), and vascular tortuosity. Inverse probability treatment-weighted analyses were performed. RESULTS: After adjusting for gender, age, body mass index, blood pressure, blood glucose, T2DM duration, smoking, and alcohol use, insulin users showed a higher risk of DR (odds ratio (OR) = 2.27, 95% confidence interval (95%CI) = 2.08-2.48, P < 0.001), larger CRVE (ß = 3.92, 95%CI = 2.46-5.37, P < 0.001), smaller AVR (ß=-0.0083, 95%CI=-0.0121- -0.0046, P < 0.001), and larger vascular curvature (ß = 0.19, 95%CI = 0.05-0.33, P = 0.008). After 3 years, insulin users had a higher risk of developing DR (OR = 1.94; 95% CI = 1.37-2.73, P = 0.002), and greater change in CRVE (ß = 3.92, 95%CI = 0.96-6.88, P = 0.009). CONCLUSIONS: The impact of insulin on the retinal microvasculature provides support for linking insulin to the increased risk of DR, as well as cardiovascular events in T2DM.

Characterization and Automatic Discrimination between Predominant Hypoperfusion and Hyperperfusion Stages of NPDR.

BACKGROUND/OBJECTIVES: Diabetic retinopathy (DR) is a common diabetes complication that can lead to blindness through vision-threatening complications like clinically significant macular edema and proliferative retinopathy. Identifying eyes at risk of progression using non-invasive methods could help develop targeted therapies to halt diabetic retinal disease progression. METHODS: A set of 82 imaging and systemic features was used to characterize the progression of nonproliferative diabetic retinopathy (NPDR). These features include baseline measurements (static features) and those capturing the temporal dynamic behavior of these static features within one year (dynamic features). Interpretable models were trained to distinguish between eyes with Early Treatment Diabetic Retinopathy Study (ETDRS) level 35 and eyes with ETDRS levels 43-47. The data used in this research were collected from 109 diabetic type 2 patients (67.26 ± 2.70 years; diabetes duration 19.6 ± 7.26 years) and acquired over 2 years. RESULTS: The characterization of the data indicates that NPDR progresses from an initial stage of hypoperfusion to a hyperperfusion response. The performance of the classification model using static features achieved an area under the curve (AUC) of the receiver operating characteristics equal to 0.84 ± 0.07, while the model using both static and dynamic features achieved an AUC of 0.91 ± 0.05. CONCLUSION: NPDR progresses through an initial hypoperfusion stage followed by a hyperperfusion response. Characterizing and automatically identifying this disease progression stage is valuable and necessary. The results indicate that achieving this goal is feasible, paving the way for the improved evaluation of progression risk and the development of better-targeted therapies to prevent vision-threatening complications.

Comparative Efficacy of Low-Carbohydrate and Ketogenic Diets on Diabetic Retinopathy and Oxidative Stress in High-Fat Diet-Induced Diabetic Rats.

This study examined the effect of a low-carbohydrate diet (LCD) and a low-carbohydrate ketogenic diet (LCKD) on diabetic retinopathy in high-fat diet-induced diabetes mellitus in rats and studied the mechanisms of action. Rats were divided into four groups: the Control group, which was fed a normal diet for 16 weeks; the HFD group, which was fed a high-fat diet (HFD) for the first 8 weeks and then switched to a normal diet for 8 weeks; the HFD+LCD group, fed a HFD for 8 weeks followed by an LCD for 8 weeks, and the HFD+LCKD group, which was fed a HFD for 8 weeks followed by an LCKD for 8 more weeks. Both the LCD and the LCKD effectively reduced the final body and total fat weights and decreased fasting serum levels of glucose, insulin, hemoglobin A1 (HbA1C), triglycerides, cholesterol, and LDL-c. They also reduced the levels of malondialdehyde (MDA), tumor necrosis factor-α, vascular endothelial factor, caspapse-3, and bax. In the HFD rats, we found increased serum levels of ß-Hydroxybutyrate and upregulated expression of Bcl2, glutathione, superoxide dismutase, and hemeoxygenase-1. Moreover, the LCD and LCKD significantly reduced mRNA levels of Kelch-like ECH-associated protein 1 (Keap1) and enhanced mRNA and nuclear concentrations of nuclear factor erythroid factor 2 (Nrf2). All these effects were associated with improved layers of the retina in the HFD - LCD and HFD + LCKD rats but not in HFD animals. The impact of the LCKD was always more profound on all measured parameters and on improving the structure of the retina compared to the LCD. In conclusion, the LCKD is superior to the LCD in preventing diabetic retinopathy in HFD-fed rats. Mechanistically, our results suggest that the hypoglycemic and hypolipidemic conditions and the Nrf2-dependent antioxidant and anti-inflammatory effects may be involved in the preventative effects of the LCD and LCKD.

Effect of the Mediterranean Diet (MeDi) on the Progression of Retinal Disease: A Narrative Review.

Worldwide, the number of individuals suffering from visual impairment, as well as those affected by blindness, is about 600 million and it will further increase in the coming decades. These diseases also seriously affect the quality of life in working-age individuals. Beyond the characterization of metabolic, genetic, and environmental factors related to ocular pathologies, it is important to verify how lifestyle may participate in the induction of the molecular pathways underlying these diseases. On the other hand, scientific studies are also contributing to investigations as to whether lifestyle could intervene in modulating pathophysiological cellular responses, including the production of metabolites and neurohormonal factors, through the intake of natural compounds capable of interfering with molecular mechanisms that lead to ocular diseases. Nutraceuticals are promising in ameliorating pathophysiological complications of ocular disease such as inflammation and neurodegeneration. Moreover, it is important to characterize the nutritional patterns and/or natural compounds that may be beneficial against certain ocular diseases. The adherence to the Mediterranean diet (MeDi) is proposed as a promising intervention for the prevention and amelioration of several eye diseases. Several characteristic compounds and micronutrients of MeDi, including vitamins, carotenoids, flavonoids, and omega-3 fatty acids, are proposed as adjuvants against several ocular diseases. In this review, we focus on studies that analyze the effects of MeDi in ameliorating diabetic retinopathy, macular degeneration, and glaucoma. The analysis of knowledge in this field is requested in order to provide direction on recommendations for nutritional interventions aimed to prevent and ameliorate ocular diseases.

Occlusive retinal vasculitis associated with intravitreal Faricimab injections.

PURPOSE: We describe a case of occlusive vasculitis associated with intravitreal Faricimab (Vabysmo) injections. METHODS: A retrospective case report. RESULTS: A 52-year old man treated with monthly Faricimab injections for diabetic macula oedema presented with sudden reduced vision, new retinal hemorrhages, significant retinal vascular occlusions and ischemia. After screening for differential diagnoses was unremarkable, the patient was treated with oral and intravitreal steroid therapy under which the occlusive vasculitis was stabilized. CONCLUSION: Occlusive vasculitis, though rare, is a potential complication of Faricimab therapy. Comprehensive reporting and large-scale analyses are essential to better understand and manage this adverse event.

Therapeutic Potential of Quercetin in Diabetic Neuropathy and Retinopathy: Exploring Molecular Mechanisms.

Diabetes mellitus poses a significant health challenge globally, often leading to debilitating complications, such as neuropathy and retinopathy. Quercetin, a flavonoid prevalent in fruits and vegetables, has demonstrated potential therapeutic effects in these conditions due to its antioxidant, anti-inflammatory, and neuroprotective properties. This review summarizes and provides a comprehensive understanding of the molecular mechanisms underlying the efficacy of quercetin in ameliorating diabetic neuropathy and retinopathy. A thorough search was carried out across scientific databases, such as SciFinder, PubMed, and Google Scholar, to gather pertinent literature regarding the effect of quercetin on diabetic neuropathy and retinopathy till February 2024. Preclinical studies indicate that quercetin mitigates neuropathic pain, sensory deficits, and nerve damage associated with diabetic neuropathy by improving neuronal function, reducing DNA damage, regulating pro-inflammatory cytokines, enhancing antioxidant enzyme levels and endothelial function, as well as restoring nerve injuries. In diabetic retinopathy, quercetin shows the potential to preserve retinal structure and function, inhibiting neovascularization, preventing retinal cell death, reducing pro-inflammatory cytokines, and increasing neurotrophic factor levels. Moreover, through modulating key signaling pathways, such as AMP-activated Protein Kinase (AMPK) activation, Glucose Transporter 4 (GLUT 4) upregulation, and insulin secretion regulation, quercetin demonstrates efficacy in reducing oxidative stress and inflammation, thereby protecting nerve and retinal tissues. Despite promising preclinical findings, challenges, such as limited bioavailability, necessitate further research to optimize quercetin's clinical application in order to establish its optimal dosage, formulation, and long-term efficacy in clinical settings.