Search Results (531)

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

Topical drug administration is a common method of delivering medications to the eye to treat various ocular conditions, including glaucoma, dry eye, and inflammation. Drug efficacy following topical administration, including the drug’s distribution within the eye, absorption and elimination rates, and physiological responses can be predicted using physiologically based pharmacokinetic (PBPK) modeling. High-resolution computational models of the eye are desirable to improve simulations of drug delivery; however, these approaches can have long run times. In this study, a fast-running computational quasi-3D (Q3D) model of the human tear film was developed to account for absorption, blinking, drainage, and evaporation. Visualization of blinking mechanics and flow distributions throughout the tear film were enabled using this Q3D approach. Average drug absorption throughout the tear film subregions was quantified using a high-resolution compartment model based on a system of ordinary differential equations (ODEs). Simulations were validated by comparing them with experimental data from topical administration of 0.1% dexamethasone suspension in the tear film (R² = 0.76, RMSE = 8.7, AARD = 28.8%). Overall, the Q3D tear film model accounts for critical mechanistic factors (e.g., blinking and drainage) not previously included in fast-running models. Further, this work demonstrated methods toward improved computational efficiency, where central processing unit (CPU) time was decreased while maintaining accuracy. Building upon this work, this Q3D approach applied to the tear film will allow for more seamless integration into full-body models, which will be an extremely valuable tool in the development of treatments for ocular conditions. Full article

Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved in eye diseases, this study examined the effects of HIF-PHIs on metabolism and gene expression in retinal pigment epithelium (RPE) cells. Results revealed that PHIs differentially induced angiogenic (VEGFA, ANG) and glycolytic (PDK1, GLUT1) gene expression, with Roxadustat causing the strongest transcriptional changes. However, Roxadustat-induced angiogenic signals did not promote endothelial tube formation. Moreover, it did not induce oxidative stress, inflammation, or significant antioxidant gene responses in ARPE-19 cells. Roxadustat also reduced the inflammatory cytokine response to tumor necrosis factor-α, including IL-6, IL-8, and MCP-1, and did not exacerbate VEGF expression under high-glucose conditions. Overall, Roxadustat triggered complex gene expression changes without promoting inflammation or oxidative stress in RPE cells. Despite these findings, ophthalmologic monitoring is advised during PHI treatment in CKD patients receiving HIF-PHIs. Full article

Background and Clinical Significance: Ocular cicatricial pemphigoid (OCP) is a rare autoimmune disease affecting the conjunctiva and oral mucosa. Chronic inflammation causes conjunctival scarring, leading to symblepharon, trichiasis, corneal damage, and possible blindness. Diagnosis is clinical, supported by biopsy and immunofluorescence. Treatment includes systemic corticosteroids, immunosuppressants, and biologics in refractory cases. Case Presentation: A 64-year-old male presented with ocular irritation, trichiasis, and counting fingers (CF) visual acuity in the left eye. Slit-lamp examination revealed conjunctival inflammation, corneal epithelial defect, and symblepharon in the left eye. Biopsy confirmed ocular cicatricial pemphigoid (OCP). He was treated with topical steroids, cyclosporine, subconjunctival injections, and systemic corticosteroids, followed by surgery, which improved BCVA to 0.10 logMAR. Two years later, disease progression resulted in severe inflammation and visual decline in both eyes. Systemic azathioprine and corticosteroids achieved partial control. Due to insufficient response, rituximab therapy was initiated, leading to significant reduction in inflammation and stabilization of disease. Right eye BCVA improved to 0.16 logMAR; the left remained at CF. The patient continues to receive rituximab during exacerbations and is under regular follow-up. Conclusions: Early diagnosis and timely systemic treatment are essential in preventing vision loss in OCP. In refractory cases, biologic agents like rituximab may offer effective disease control. Full article

Tear film alterations are commonly associated with ocular pathology. The tear film plays a vital role in maintaining the optical properties of the cornea and contains essential elements required for healing and preserving the integrity of the ocular surface. As a biological fluid, the tear film is easily collected using non-invasive techniques, making it a promising candidate for analysis and often referred to as an ideal biofluid. Several studies have attempted to identify biomarkers in the tear film that could be linked to systemic or ocular disorders, with the goal of developing tools for diagnosis or even early prevention. The quality and quantity of the tear film are influenced by hormonal status, emotional experiences related to social and familial events, and the work environment. Systemic disorders are often reflected at the ocular level through alterations in the tear film. Obesity is a well-recognized public health concern, extensively studied and investigated, much like other common systemic conditions. The presence of low-grade, chronic inflammation associated with excess body weight has been validated in several studies. The strategies for preventing obesity induced dry eye disease are based on regular physical activity, maintaining adequate hydration through sufficient fluid intake, weight loss, and the supplementation of essential fatty acids. This narrative literature review aims to highlight the tear film alterations associated with obesity. The article is intended for ophthalmologists, general practitioners, nutritionists, and researchers. Full article

Nowadays, a significant portion of the population uses eye cosmetics, a trend that is not limited to women, as men increasingly adopt stylish makeup techniques. Eye cosmetics, often termed eye makeup, include a diverse array of products such as eyelash enhancers (mascara, false eyelashes, growth serums, and dyes), eyelid products (eyeliner, kohl, eye contour cream, and eyeshadow), and eye makeup removers. There is a persistent interest among dermatologists in the influence of eye cosmetics on the skin surrounding the eye. The formulation of these cosmetics typically consists of various ingredients, some of which may present potential health risks to users. The application of eye cosmetics is linked to a range of adverse effects on the ocular surface, which may manifest as mechanical injury, tear film instability, toxicity, inflammation, and infections. Therefore, the use of cosmetics in this sensitive area is of paramount importance, necessitating a cooperative approach among eyecare professionals, dermatologists, and beauty experts. Despite the widespread use of eye makeup, its possible ocular side effects have not been sufficiently addressed. This report aims to elucidate how the use of eye cosmetics represents a lifestyle challenge that may exacerbate or initiate ocular surface and adnexal disorders. Full article

Obstructive sleep apnoea (OSA) is a prevalent condition characterised by intermittent upper airway obstruction during sleep, resulting in recurrent hypoxia and sleep fragmentation. Emerging evidence highlights the significant impact of OSA on neuro-ophthalmological health, linking it to conditions such as glaucoma, optic neuropathy, papilledema, and visual field defects. These associations emphasise the importance of understanding the mechanisms connecting OSA to neuro-ophthalmological disorders to enhance early diagnosis and management. This review explores the pathophysiological pathways, including hypoxia-induced vascular dysregulation, oxidative stress, inflammation, and intracranial pressure fluctuations, that contribute to ocular and neurological impairments in OSA patients. Advanced diagnostic tools, such as optical coherence tomography and polysomnography, offer promising avenues for detecting subclinical neuro-ophthalmological changes, enabling timely intervention. Management strategies, primarily centred on continuous positive airway pressure therapy, have shown efficacy in mitigating OSA-related neuro-ophthalmological complications. However, surgical and pharmacological interventions and lifestyle modifications remain vital components of a multidisciplinary approach to care. Despite advancements, significant research gaps persist, particularly in understanding the long-term impact of OSA treatment on neuro-ophthalmological outcomes and identifying specific biomarkers for early detection. Future research should prioritise longitudinal studies, interdisciplinary collaborations, and personalised medicine approaches to address these challenges. Recognising and treating neuro-ophthalmological disorders in OSA patients is imperative for improving quality of life and preventing irreversible visual and neurological damage. Full article

The covalent conjugation of pharmaceutical compounds to polymeric carriers represents an effective strategy for enhancing drug properties, including improved bioavailability, targeted delivery, and sustained release, while reducing systemic toxicity and adverse effects. By exploiting the physicochemical characteristics of biopolymers—particularly molecular charge and weight—we engineered a polymeric platform for glucocorticoid delivery with precisely controlled parameters including particle size, surface charge, targeting capability, and release kinetics. This study reports a linker-free synthesis of hyaluronic acid-dexamethasone (HA-DEX) conjugates through Steglich esterification, catalyzed by 4-dimethylaminopyridine (DMAP), which facilitates the acylation of sterically hindered alcohols. The reaction specifically couples carboxyl groups of hyaluronic acid with the C21 hydroxyl group of dexamethasone. Incorporation of hydrophobic dexamethasone moieties induced self-assembly into nanoparticles featuring a hydrophobic core and negatively charged hydrophilic shell (−20 to −25 mV ζ-potential). In vitro characterization revealed pH-dependent release profiles, with 80–90% dexamethasone liberated in mildly acidic phosphate buffer (pH 5.2) versus 50–60% in phosphate-buffered saline (pH 7.4) over 35 days, demonstrating both sustained release and inflammation-responsive behavior. The conjugates exhibited potent anti-inflammatory activity in a human tumor necrosis factor-α (TNFα)-induced inflammation model. These findings position HA-DEX conjugates as promising candidates for targeted glucocorticoid delivery to specific anatomical sites including ocular, articular, and tympanic tissues, where their combination of CD44-targeting capability, enhanced permeability and retention effects, and stimulus-responsive release can optimize therapeutic outcomes while minimizing off-target effects. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is known to affect multiple organ systems, including the respiratory tract and nervous and ocular systems. This retrospective study aimed to characterize the spatiotemporal distribution of viral antigen and associated pathological changes in the nose, lungs, brain, and eyes of K18-hACE2 mice intranasally infected with SARS-CoV-2. Using histology and immunohistochemistry, tissues were examined at 3, 6, and 7/8 days post-infection (dpi). In addition, lung and brain tissues were analyzed by means of RT-qPCR to determine viral RNA titers. Viral antigen was most pronounced in the nose, brain, and lung at 3, 6, and 7/8 dpi, respectively, whereas viral antigen was detected at 6 and 7/8 dpi in the retina. Quantitative PCR confirmed increasing viral RNA levels in both lung and brain, peaking at 7/8 dpi. Nasal and lung inflammation mirrored viral antigen distribution and localization. In the brain, the predominantly basal viral spread correlated with lymphohistiocytic meningoencephalitis, neuronal vacuolation, and altered neurofilament immunoreactivity. Retinal ganglion cells showed viral antigen expression without associated lesions. Microglial activation was evident in both the optic chiasm and the brain. These findings highlight the K18-hACE2 model’s utility for studying extrapulmonary SARS-CoV-2 pathogenesis. Understanding the temporal and spatial dynamics of viral spread enhances insights into SARS-CoV-2 neurotropism and its clinical manifestations. 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

Background/Objectives: Dry eye disease (DED) is a multifactorial condition with complex pathophysiology involving tear film instability, ocular surface inflammation, and nerve dysfunction. This review summarizes current evidence on the different available therapies targeting these mechanisms. Methods: A review of clinical studies evaluating treatment outcomes for therapies targeting aqueous tear deficiency, Meibomian gland dysfunction, ocular surface inflammation, and ocular pain was conducted, with an emphasis on randomized controlled trials and meta-analyses where available. Results: Artificial tears provide symptomatic relief with limited impact on tear film stability. Punctal plugs improve tear retention but show variable efficacy across studies. Treatments targeting MGD—such as lipid-based lubricants, eyelid hygiene, thermal pulsation (LipiFlow, iLux), and intense pulsed light (IPL)—demonstrate improvements in gland function, though outcomes vary. Anti-inflammatory agents including cyclosporine, lifitegrast, and short-term corticosteroids improve ocular surface signs, with mixed symptom relief. Biologic therapies like autologous serum tears and platelet-rich plasma show promise for both signs and symptoms, but data remain inconsistent. Nerve-targeted therapies, including oral neuromodulators (gabapentin, antidepressants), botulinum toxin, and transcutaneous nerve stimulation, have shown potential for managing neuropathic ocular pain, although randomized data are limited. Overall, variability in study designs, patient populations, and outcome measures highlights the need for more rigorous research. Conclusions: Personalized, mechanism-based treatment strategies are essential for optimizing outcomes in DED. Future research should prioritize well-designed, controlled studies to clarify the role of emerging therapies and guide the individualized management of this heterogeneous condition. Full article

Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily affecting the lacrimal and salivary glands, characterized by ocular and oral dryness. Beyond exocrine dysfunction, SS may also involve multiple organs and systems, contributing to systemic complications that impair a patient’s quality of life. Among these, ocular inflammation represents a significant clinical challenge, manifesting as dry eye disease and other vision-affecting complexities. Despite advances in SS understanding, the inflammatory mechanisms driving ocular manifestations remain incompletely elucidated. This review aims to clarify the key inflammatory pathways underlying ocular complications in SS and the clinical implications. Additionally, it discusses both conventional and novel therapeutic strategies focusing on mitigating SS-associated ocular inflammation, including targeted immunomodulatory agents, regenerative medicine, and innovative drug delivery systems. By integrating current knowledge from recent studies, this review attempts to provide researchers and clinicians with a comprehensive resource for optimizing SS treatment approaches. The advancement of targeted therapies and emerging mitigation strategies holds promise for improving patient outcomes and enhancing SS management. Full article

The therapeutic potential of exosomes (Exos), a subpopulation of extracellular vesicles (EVs) secreted by various cell types, has been broadly emphasized. Exos are endosome-derived membrane-bound vesicles 50–150 nm in size. Exos can be general or cell type-specific. Their contents enable them to function as multi-signaling and vectorized vehicles. Exos are important for maintaining cellular homeostasis. They are released into extracellular spaces, leading to uptake by neighboring or distant cells and delivering their contents to modulate cell signaling. Exos influence tissue responses to injury, infection, and disease by fusion with the target cells and transferring their cargo, including cytokines, growth and angiogenic factors, signaling molecules, lipids, DNA, mRNAs, and non-coding RNAs. They are implicated in various physiological and pathological conditions, including ocular surface events, such as corneal scarring, wound healing, and inflammation. Their biocompatibility, stability, low immunogenicity, and easy detectability in bodily fluids (blood, tears, saliva, and urine) make them promising tools for diagnosing and treating ocular diseases. The potential to engineer specific Exo cargos makes them outstanding therapeutic delivery vehicles. The objective of this review is to provide novel insights into the functions of Exo cargos and their applications as biomarkers and therapeutics, or targets in the cornea. Full article

Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the integrity of the blood–retinal barrier, and contribute to angiogenesis. Recent advancements in molecular and cellular biology have revealed the heterogeneity of pericytes and their critical involvement in ocular physiology and pathology. This review provides a comprehensive analysis of pericyte functions in ocular health and their implications in diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusion. Pericyte dysfunction is implicated in vascular instability, neurovascular coupling failure, inflammation, and pathological neovascularization, contributing to vision-threatening disorders. The review further explores recent findings on pericyte-targeted therapies, including pharmacological agents, gene therapy, and cell-based approaches, aiming to restore pericyte function and preserve ocular health. Full article

Background/Objectives: Chronic neuropathic ocular pain (NOP) can manifest concurrently with dry eye (DE) symptoms following ocular surgical procedures. Due to its low prevalence, NOP remains an underrecognized and underdiagnosed postoperative complication, leading to suboptimal management. This study evaluated the long-term evolution of symptoms, signs, and tear biomarkers in patients with NOP and DE after corneal refractive surgery (RS). Methods: Patients with chronic NOP and persistent DE-related symptoms after corneal RS were assessed in two visits (V1 and V2), at least two years apart. Symptoms (DE, pain, anxiety, and depression) were measured with specific questionnaires. Clinical examination included a slit-lamp ocular surface evaluation, corneal sensitivity measurement, and subbasal corneal nerve plexus evaluation. Basal tear samples were collected, and a 20-plex cytokine panel and Substance P (SP) were assayed. Results: Twenty-three patients (35.57 ± 8.43 years) were included, with a mean time between visits of 4.83 ± 1.10 years. DE symptoms, measured with the Ocular Surface Disease Index questionnaire, improved at V2 (p < 0.001), along with a reduction in anxiety and depression levels, measured with the Hospital Anxiety and Depression Scale (p = 0.027). Corneal staining also decreased (p < 0.001), while subbasal nerve plexus parameters and corneal sensitivity remained unchanged. Tear analysis revealed increased concentrations of fractalkine/CX3CL1 (p = 0.039), interleukin (IL)-1 receptor antagonist (Ra) (p = 0.025), IL-10 (p = 0.002), and SP (p < 0.001). Conclusions: Symptom improvement may result from better control of underlying pathologies or natural disease progression. However, the increased levels of SP and fractalkine/CX3CL1 suggest sustained neurogenic inflammation, while elevated IL-1Ra and IL-10 indicate a potential compensatory anti-inflammatory response. Full article