Search Results (220)

Background: Radiation maculopathy (RM) is a delayed, sight-threatening complication of ocular radiotherapy. Traditionally regarded as a pure microvascular disease, emerging evidence points to the central role played by retinal neuroinflammation, driven by microglial activation and cytokine dysregulation affecting both the retina and the choroid. Hyperreflective retinal foci, neuroinflammatory in origin (I-HRF), visualized through advanced imaging modalities such as spectral domain optical coherence tomography (OCT), have been identified as early and critical biomarkers of both preclinical and clinical retinal neuroinflammation. Materials and Methods: This review synthesizes findings from experimental and clinical studies to explore the pathophysiology of neuroinflammation and the associated imaging parameters in RM. Results: The integration of experimental and clinical evidence specifically underscores the significance of I-HRF as an early indicator of neuroinflammation in RM. OCT enables the identification and quantification of these biomarkers, which are linked to microglial activation and cytokine dysregulation. Conclusions: The pathophysiology of RM has evolved from a predominantly vascular condition to one strongly secondary to neuroinflammatory mechanisms involving the retina and choroid. In particular, I-HRF, as early biomarkers, offers the potential for preclinical diagnosis and therapeutic intervention, paving the way for improved management of this sight-threatening complication. 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

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

Background: Type 2 diabetes mellitus (T2DM) is an epidemic chronic disease that affects millions of people worldwide. This study aims to explore the impact of T2DM on the tear proteome, specifically investigating whether alterations occur before the development of diabetic retinopathy. Methods: Flush tear samples were collected from healthy subjects and subjects with preDM and T2DM. Tear proteins were processed and analyzed by mass spectrometry-based shotgun proteomics using a data-independent acquisition parallel acquisition serial fragmentation (diaPASEF) approach. Machine learning algorithms, including random forest, lasso regression, and support vector machine, and statistical tools were used to identify potential biomarkers. Results: Machine learning models identified 17 proteins with high importance in classification. Among these, five proteins (cystatin-S, S100-A11, submaxillary gland androgen-regulated protein 3B, immunoglobulin lambda variable 3–25, and lambda constant 3) exhibited differential abundance across these three groups. No correlations were identified between proteins and clinical assessments of the ocular surface. Notably, the 17 important proteins showed superior prediction accuracy in distinguishing all three groups (healthy, preDM, and T2DM) compared to the five proteins that were statistically significant. Conclusions: Alterations in the tear proteome profile were observed in adults with preDM and T2DM before the clinical diagnosis of ocular abnormality, including retinopathy. Full article

This pilot study explored whether the ceruloplasmin (CP) and ferritin (FT) levels in ocular fluids could serve as biomarkers for early neurodegenerative diseases (Alzheimer’s, Parkinson’s, and other dementias). CP and FT are known to modulate neurodegenerative tissue responses. We analysed aqueous and vitreous samples from 26 patients (8M/18F, aged 60–85) who were undergoing elective vitreoretinal (VR) surgery. Of these, 14 had idiopathic epiretinal membranes (ERMs), 6 had idiopathic macular holes (MH), and 6 were patients with Alzheimer’s disease (AD) who presented with VR disorders (VRDs). CP, FT, and selected neuroinflammatory mediators such as interferon γ (IFN-γ), interleukin (IL-6), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were quantified. Odds ratio analysis was applied to assess the CP/FT ratio’s association with subretinal drusen. We found distinct CP and FT profiles in VRD samples. In aqueous fluid, the CP increased and the FT decreased in early-stage ERM, which reduced the CP/FT ratio. Similar patterns were observed in vitreous fluid. The CP levels correlated with the VEGF (aqueous), IL-4 (vitreous), NGF, and BDNF levels; FT correlated with IL-6 and NGF. A higher CP/FT ratio was associated with increased risk for neurodegenerative conditions. Our findings support the quantification of CP and FT in ocular fluids as a promising approach for identifying early neurodegenerative changes and suggest that the CP/FT ratio may be linked to drusen imaging and clinical neurodegenerative history. 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

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

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

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

Dry eye disease (DED) is a common, multifactorial disorder of the ocular surface. Although DED can affect individuals at any age, its prevalence, clinical manifestations, underlying mechanisms, and optimal management strategies differ considerably across the lifespan. In children, symptoms are frequently associated with atopy and allergic disorders and environmental factors, whereas in young adults, digital device usage and contact lens wear are the predominant contributors. In older adults, systemic diseases and polypharmacy significantly elevate the risk of DED. Across all age groups, tear film instability, decreased tear production, and chronic inflammation are central pathogenic features. Key tear biomarkers, such as pro-inflammatory cytokines, have been widely linked to disease development. Cathepsin S and tumor necrosis factor-alpha have recently been implicated in age-related DED. A nuanced understanding of these age-related differences is crucial for improving diagnostic accuracy and tailoring interventions to specific patient populations. This review synthesizes current evidence on DED across age groups, focusing on prevalence, risk factors, pathophysiology, molecular mechanisms, coexisting conditions, biomarkers, and treatment options. Finally, it highlights critical unmet clinical needs in the management of age-related DED. Full article

Background: This study explored the diagnostic potential of image-processing analysis in optical coherence tomography (OCT) images to detect systemic vascular changes in individuals with systemic diseases. Methods: Ocular OCT images from two cohorts diabetic patients and healthy control subjects were analyzed. A novel Superpixel Segmentation (SpS) algorithm was used to process these images and extract optical image density information from ocular vascular tissue. The algorithm was applied to isolate the choroid layer for analysis of its optical properties. The procedure was performed by separate examiners, and both inter- and intra-observer repeatability were assessed. Choroidal area (CA) and choroidal optical image density (COID) metrics were used to assess structural changes in the vascular tissue and predict alterations in the choroidal parameters. Results: A total of 110 diabetic patient eye images and 92 healthy control images were processed. The results showed significant differences in CA and COID between diabetic and healthy eyes, indicating that these parameters could serve as valuable biomarkers for early vascular damage. Conclusions: The use of the SpS algorithm on OCT B-scan images allows for the identification of new parameters linked to ocular vascular damage. These findings suggest that digital image-processing techniques can reveal differences in vascular tissue, offering potential new indicators of pathology. Full article

Objective: This study aimed to investigate the structural, vascular, and biochemical alterations in patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PXG) and to evaluate the associations between serum biomarkers, the retinal nerve fiber layer (RNFL), choroidal thickness (CT), and vessel density (VD) in these groups. Methods: All subjects underwent spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) to assess RNFL thickness, CT, and VD. Serum levels of inflammatory and oxidative stress biomarkers—including malondialdehyde (MDA), glutathione (GSH), interleukin-6 (IL-6), nitric oxide (NO), inducible NO synthase (iNOS), galectin-3, and SCUBE-1—were analyzed, and regression and ROC curve analyses were performed to evaluate predictive value and diagnostic performance. Results: A total of 80 patients were included and are listed as follows: 25 controls, 30 with PES, and 25 with PXG. There were no significant differences among groups in terms of age or gender. RNFL thickness, CT, and VD were significantly reduced in the PXG group compared to the PES and control groups (p < 0.001). PXG patients showed the most pronounced reductions in both peripapillary and macular CT, as well as superficial and deep VD. Serum iNOS, SCUBE-1, galectin-3, and MDA levels were significantly elevated in PXG, while GSH levels were lower (p < 0.001); NO levels showed no significant differences. In the PES and PXG groups, several ocular parameters correlated significantly with serum biomarkers, particularly iNOS, MDA, and GSH. Regression analysis in PXG patients identified iNOS and MDA as significant predictors of RNFL thickness and VD. ROC analysis demonstrated that MDA and GSH exhibited the highest diagnostic accuracy among the tested biomarkers for distinguishing PXG patients from controls. Conclusions: PXG is associated with significant structural, vascular, and biochemical alterations, including reduced RNFL thickness, choroidal thinning, and decreased VD. Altered serum levels of MDA and GSH were significantly associated with these ocular changes and demonstrated the highest diagnostic accuracy among the biomarkers evaluated. These findings support their potential utility as non-invasive biomarkers for distinguishing PXG from PES and healthy controls and for monitoring disease progression. Full article

Background/Objectives: Uncontrolled or long-standing diabetes can lead to proliferative diabetic retinopathy (PDR), a condition that significantly impairs vision. A subset of patients does not respond adequately to conventional therapies, such as intravitreal injections of anti-vascular endothelial growth factor (VEGF) or laser treatment. This study aims to identify potential biomarkers for alternative treatment pathways in the vitreous and blood of patients with severe PDR. Methods: Vitreous samples were collected from PDR patients (n = 3) undergoing vitrectomy for vitreous hemorrhage and from control patients (n = 9) undergoing ocular surgery for epiretinal membrane or macular holes. Blood samples were collected from a separate group of PDR patients (n = 13) and non-diabetic control patients without retinopathy (n = 13). Medical histories were obtained. Two-stage real-time quantitative polymerase chain reaction (qPCR) was used to evaluate mRNA expression levels of genes potentially implicated in PDR, including HIF2A, PAI-1, TIE1, TIE2, ANGPT2, and VEGFA. Molecular and statistical analyses were performed to compare PDR and control vitreous and blood samples. Results: The PDR vitrectomy group included two females and one male, aged 71–77 years (mean 74 years). All participants had undergone pan-retinal photocoagulation and two had received anti-VEGF injections before vitrectomy. These participants had elevated HbA1c levels. Targeted vitreous gene analysis revealed varying levels of increased expression of all genes examined as compared to the control group. A trend for increased median expression was demonstrated for all examined genes: HIF2A by 1.44-fold (PDR = 2.50, control = 1.74, p = 0.21), PAI-1 by 1.56-fold (PDR = 3.00, control = 1.93, p = 0.37), TIE1 by 1.36-fold (PDR = 2.33, control = 1.72, p = 0.66), TIE2 by 2.06-fold (PDR = 2.81, control = 1.36, p = 0.51), ANGPT2 by 2.93-fold (PDR = 6.32, control = 2.16, p = 0.1), and VEGFA by 3.53-fold (PDR = 3.51, control = 0.99, p = 0.08). PDR blood sample analysis as compared to controls showed a trend for increased expression of VEGFA by 1.2-fold (PDR = 0.88, control = 0.74, p = 0.57), whereas the other examined genes showed a trend of reduced expression; HIF2A decreased by 0.50-fold (PDR = 0.38, control = 0.75, p = 0.07), PAI by 0.51-fold (PDR = 0.35, control = 0.69, p = 0.09), TIE-1 by 0.79-fold (PDR = 0.79, control = 1.00, p = 0.54), TIE-2 by 0.70-fold (PDR = 0.58, control = 0.82, p = 0.34), and ANGPT2 by 0.45-fold (PDR = 0.51, control = 1.15, p = 0.11). Conclusions: Vitreous sample analysis revealed a trend of increased mRNA expression of ANGPT2 and VEGFA in patients with PDR. Blood sample analysis did not show a significant increase of VEGFA mRNA expression but a decreased trend of HIF2A, PAI-1, and ANGPT2 mRNA expression. These trends warrant validation in a larger cohort to explore alternative pathways for targeted treatment. Full article

Artificial intelligence (AI) is reshaping precision medicine by revealing diagnostic links between ocular biomarkers and systemic musculoskeletal disorders. This review synthesizes clinical evidence on the associations between optical coherence tomography (OCT)-derived parameters, such as retinal nerve fiber layer (RNFL) thinning and choroidal thickness, and conditions including osteoporosis, cervical spine instability, and inflammatory arthritis. The findings, based on an analysis of studies that integrate AI with ocular and musculoskeletal imaging, highlight consistent correlations between ocular microstructural changes and systemic degenerative pathologies. These results suggest that the eye may serve as a non-invasive window into biomechanical dysfunction. This review also discusses the emerging role of AI-assisted surgical systems informed by ocular metrics. Overall, AI-driven ocular analysis offers a promising avenue for early detection and management of musculoskeletal disease, supporting its clinical relevance and interdisciplinary potential. Full article

The biomechanical and optical properties of the cornea are responsible for its functional response, structural integrity and refractive function. Corneal viscoelasticity is the cornea’s ability to absorb transient increases in intraocular pressure (IOP) and constitutes a biomarker of glaucoma. The use of silicone hydrogel soft contact lenses (SiH-SCLs) can affect both corneal viscoelasticity and IOP. However, the behavior of the pure elastic and viscous components remains hidden within viscoelastic properties, and their influence and relationship with IOP in the biomechanical changes observed with short-term SiH-SCL use remains unknown. This study investigates the effects of silicone hydrogel soft contact lenses (SiH-SCLs) on corneal elasticity and viscosity and their influence on IOP over different lens wear periods: 10 or 20 consecutive days. Ocular Response Analyzer (ORA) measurements were combined with a biomechanical Standard Linear Solid Model (SLSM) to differentiate and calculate the elastic and viscous components of the cornea. The results showed that after 10 days of lens wear, elasticity and viscosity increased, with a significant reduction in IOP. After 20 days, elasticity and viscosity decreased, with a further reduction in IOP, reflecting a time-dependent effect of SiH-SCLs on corneal biomechanics. The study indicates the potential protective role of corneal viscosity against changes in IOP, which may be used for glaucoma treatment. Full article