Search Results (719)

Oculomics uses ocular images, ocular biofluids and functional ocular tests to extract diagnostic information on local or systemic biological states. Most current evidence is cross-sectional: one retinal photograph, OCT scan, OCTA examination or tear sample is compared with a reference population, or converted into a diagnostic or prognostic score. This approach is useful for screening and risk enrichment, but it does not show whether the same patient is changing over time. In this review, dynamic oculomics, or oculomic kinetics, is presented as a diagnostic-monitoring approach based on repeated ocular measurements within the same individual. Its object is the personal trajectory: baseline level, short-term variability, long-term drift, response to stimulus, recovery and modification by treatment. We discuss the biological basis of ocular trajectories, the limits imposed by local ocular regulation and disease, and the technical constraints of fundus photography, structural OCT, OCTA, functional challenge tests, tear analysis, aqueous humour analysis, continuous intraocular pressure monitoring and home-based imaging. We also examine artificial intelligence, validation, governance, health-economic considerations and practical implementation. The available evidence does not support a universal ocular surrogate for systemic disease. More realistic applications include detection of unexpectedly rapid tissue change, individualised risk stratification, treatment-response assessment and recognition of discordance between systemic markers and ocular tissue behaviour. Full article

Nicotinamide adenine dinucleotide (NAD⁺) is a fundamental metabolic cofactor and signaling molecule that supports redox reactions, DNA repair, chromatin regulation, stress adaptation, inflammation, and neuronal maintenance. Age-associated NAD⁺ decline has been implicated in brain aging and neurodegenerative disorders, but the causal node and limiting compartment differ across tissues and disease states. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) catalyzes the final step in NAD⁺ biosynthesis and represents the major nuclear isoform of the mammalian NMNAT family. Direct human genetic evidence establishes NMNAT-1 as a causal gene in inherited retinal degeneration, whereas evidence linking endogenous NMNAT-1 to broader brain aging or sporadic neurodegeneration is mainly convergent preclinical, preliminary, or indirect. Beyond NAD⁺ synthesis, biochemical and Drosophila studies suggest possible chaperone-like and proteostasis-supporting functions, but a separable NAD⁺-independent function of endogenous mammalian NMNAT-1 has not yet been established in vivo. Here, we review the molecular structure, localization, and regulation of NMNAT-1, emphasizing calibrated distinctions among catalytic nuclear NAD⁺ supply, engineered axonal protection, pathway-adjacent NAD⁺ interventions, and putative non-catalytic protection. We further discuss how NMNAT-1 dysfunction may contribute to aging-associated genomic instability, neuroinflammation, synaptic impairment, retinal degeneration, selected neurodegenerative models, and glioma biology. Finally, we evaluate therapeutic strategies targeting NMNAT-1 and NAD⁺ pathways, noting that no human trial has yet established efficacy for an NMNAT-1-directed neurological therapy. A compartment-aware and evidence-stratified view is therefore essential for translating NMNAT-1 biology into interventions for age-related neural disease. Full article

The global prevalence of myopia is increasing, and the combination of myopia and glaucoma is widely expected to become an important clinical and public health issue. Myopic eyes undergo axial elongation and posterior pole remodeling, leading to optic disc tilt, peripapillary deformation, choroidal thinning, and altered spatial relationships between the optic nerve head and its vascular supply. Glaucomatous optic neuropathy is associated with retinal ganglion cell damage, lamina cribrosa deformation, and ocular blood flow impairment. Recent advances in optical coherence tomography angiography and laser speckle flowgraphy have enabled noninvasive assessment of retinal, peripapillary, choroidal, and optic nerve head circulation. These modalities have revealed reduced radial peripapillary capillary density, choroidal microvasculature dropout, and reduced optic nerve head tissue blood-flow signal in glaucomatous eyes. In eyes with myopia and glaucoma, myopia-related structural deformation and glaucoma-associated perfusion abnormalities may coexist and show sectoral correspondence with neural damage, particularly in regions related to the central visual field. This review summarizes the anatomical background of ocular blood flow, myopia-induced structural and vascular changes, glaucoma-associated blood flow impairment, and their interaction in eyes with myopia and glaucoma. Potential therapeutic approaches targeting ocular blood flow are also discussed, although evidence beyond intraocular pressure reduction remains limited. Full article

Background: Chronic kidney disease (CKD) is characterized by persistent inflammation, metabolic dysregulation, and mineral and bone disorder (CKD-MBD), all of which may affect ocular tissues. While retinal manifestations of CKD have been increasingly investigated, data regarding clinical anterior segment modifications and their relationship with systemic biochemical parameters remain limited. Methods: We performed a cross-sectional study including 130 participants: 53 non-CKD subjects, 29 patients undergoing maintenance hemodialysis (HD), and 48 kidney transplant recipients (KTRs). All participants underwent comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement using Goldmann applanation tonometry, Schirmer I test, tear break-up time (TBUT) and assessment of cataract and blepharitis prevalence. Serum creatinine estimated glomerular filtration rate (eGFR), calcium, phosphate, parathyroid hormone (PTH), magnesium, 25-hydroxyvitamin D, and Activin A were recorded. Associations between ocular and systemic parameters were evaluated using correlation and regression analyses. Results: TBUT, Schirmer I and IOP did not differ significantly among groups (all p > 0.05). After adjustment for age, sex, BMI and diabetes mellitus (DM), HD patients showed worse visual acuity than the non-CKD reference group, reflected by higher logMAR BCVA values (adjusted B = +0.128, p = 0.024). In KTRs, higher corrected calcium was independently associated with reduced tear film parameters, correlating with both shorter TBUT (B = −0.903, p = 0.037) and lower Schirmer I values (B = −5.947, p = 0.008). Circulating Activin A increased progressively from controls to KTR to HD patients (median 189.5 vs. 273.0 vs. 314.0 pg/mL, p < 0.001) but showed no independent association with any anterior segment parameter; it was instead associated with cumulative glucocorticoid exposure (B = +1.602, p = 0.024). Conclusions: In CKD, clinical anterior segment and ocular surface differences were largely explained by age, sex, and comorbidity rather than renal replacement modality, with visual acuity deficit persisting in HD after adjusting for these covariates. At the individual level, corrected calcium was the parameter most consistently associated with tear film parameters in KTRs, whereas elevated Activin A was not independently associated with ocular involvement and likely reflects systemic disease activity. Full article

Ocular ischemic syndrome (OIS) is a vision-threatening disorder characterized by retinal ischemia, oxidative stress, and inflammation. In this study, the protective effects of anakinra, an interleukin-1 receptor antagonist, were investigated and compared with those of tocilizumab, an interleukin-6 receptor antagonist. Twenty-four male Wistar rats were randomly assigned to four groups (n = 6 per group): sham-operated (SG), carotid artery clamping/unclamping (CUG), anakinra-treated carotid artery clamping/unclamping (ACUG), and tocilizumab-treated carotid artery clamping/unclamping (TCUG). An experimental ocular ischemic injury model induced by transient bilateral common carotid artery occlusion was established by transient bilateral common carotid artery clamping followed by reperfusion. Retinal tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels, and histopathological examinations were performed. OIS markedly increased MDA, TNF-α, IL-1β, and IL-6 levels while significantly decreasing tGSH, SOD, and CAT activities. Both anakinra and tocilizumab attenuated oxidative stress and inflammatory responses; however, anakinra produced notably greater improvements in MDA, tGSH, SOD, and CAT levels. Histopathological evaluation demonstrated that both treatments reduced retinal injury, edema, vascular congestion, and inflammatory cell infiltration. Although retinal architecture appeared slightly better preserved in the anakinra-treated group, histopathological scores were comparable between the treatment groups. These findings suggest that anakinra may attenuate oxidative and inflammatory retinal damage in this experimental ocular ischemic injury model and may provide greater biochemical protection than tocilizumab, whereas histopathological protection was comparable between treatments. Nevertheless, further experimental and clinical studies are required to confirm these findings. Full article

Background: Regional heterogeneity of the macula and peripheral retinas contributes to the differences in retinal physiology, metabolic demand and susceptibility to macular diseases such as age-related macular degeneration (AMD), diabetic macular oedema (DME) and Macular telangiectasia type 2 (MacTel). Extracellular vesicles (EVs) released from the retinal pigment epithelium (RPE)-choroid are increasingly recognised as mediators of extracellular communication and correlate with the molecular biological states of their tissue of origin. However, regional variation in EV composition in human RPE-Choroid tissues remains poorly characterised. Methods: Human macular and peripheral RPE-choroid explants from non-diseased donor eyes (n = 4) were cultured ex vivo using a transwell system. EV and EV-depleted conditioned media were collected by differential ultracentrifugation, respectively. EVs were characterised by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Proteomic profiling was performed using LC-MS/MS followed by multivariate, pathway, and differential expression analyses. Results: TEM and NTA confirmed the presence of vesicle-like particles in a 119–140 nm size range, indicating small EVs in both regions. Proteomic analysis demonstrated a region-associated separation between the macular and peripheral samples in both EV proteome and EV-depleted soluble secretome datasets. GO enrichment analysis revealed that macular EV proteomes were enriched for wound healing, cell–substrate adhesion, and focal adhesion-related terms with a high abundance of integrin and annexin family members, whereas peripheral EV proteomes were enriched for retinoid- and vitamin-binding terms. In the EV-depleted soluble secretome, macular-enriched proteins were associated with actin binding and extracellular matrix-related terms, while peripheral-enriched proteins were correlated with RNA localisation and nuclear compartment terms. Comparative analysis identified EV-specific, secretome-specific, and shared extracellular protein pools. Several EV-specific markers and membrane proteins such as annexins and integrins, showed a relatively high enrichment in macular EV proteomes, whereas CD63 is more abundant in peripheral EV proteomes. In contrast, EV-depleted soluble secretome contains cytokine- and ligand-associated proteins, including MIF, SPP1, and IL6, which may suggest that EVs and soluble secreted proteins represent partially distinct extracellular signalling compartments. Conclusions: Human macular and peripheral RPE-choroid explants released secretory proteins in a regional differentiated manner, supported by PLS-DA and GO enrichment analyses of both EV proteomes and EV-depleted soluble secretome. Further analysis of the EV proteomes may show that such differences were also able to be reflected in protein categories such as EV-specific markers, mitochondrial and membrane proteins. These findings provide a foundation for future investigations into the role of EV-mediated communication in macular diseases and may support the development of region-specific extracellular biomarkers and therapeutic targets. Full article

Neurodegenerative diseases represent a major and growing global health burden characterized by progressive neuronal dysfunction, axonal degeneration, and irreversible neural tissue loss. Increasing evidence identifies oxidative stress as one of several interacting pathogenic mechanisms in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and several optic neuropathies. Interest has increasingly focused on the brain-retina axis, as the retina and optic nerve share structural, metabolic, and molecular features with the central nervous system and may provide accessible insights into neurodegeneration. This scoping review mapped current evidence on oxidative stress in neurodegeneration, emphasizing cranial nerve involvement, optic nerve vulnerability, retinal ganglion cell degeneration, visual dysfunction, oxidative biomarkers, and emerging therapeutic strategies. The review followed established methodological frameworks and PRISMA-ScR recommendations; no formal risk-of-bias appraisal was undertaken, consistent with scoping-review methodology. The literature shows that oxidative stress interacts with mitochondrial dysfunction, neuroinflammation, impaired mitophagy, ferroptosis, and altered bioenergetics, contributing to neuronal injury in cerebral and retinal disorders. Retinal ganglion cells appear particularly vulnerable because of their high metabolic demands and reliance on oxidative phosphorylation. Glaucoma and other optic neuropathies share molecular signatures with central neurodegenerative diseases. Retinal imaging and oxidative biomarkers show promise for diagnosis, monitoring, and stratification. The evidence base is nonetheless dominated by preclinical work; biomarker performance is inconsistent across matrices and assay platforms and most antioxidant clinical trials have been negative. Oxidative stress is therefore best regarded as one interacting node of a broader pathogenic network rather than a universal or predominant driver and the brain-retina continuum as a mechanistically plausible but not yet clinically validated framework for biomarker-guided neuroprotection. Full article

Cocaine-induced ocular toxicity is an increasingly acknowledged but often underestimated clinical condition that includes a wide range of eye-related symptoms. The extensive recreational use of cocaine, together with its powerful sympathomimetic and vasoconstrictive effects, leads to various ocular problems that can impact all anatomical components of the eye. This narrative review aims to deliver a thorough and current synthesis of the existing research on the epidemiology, pathophysiology, clinical symptoms, and therapy of cocaine-related ocular illness. Evidence suggests that cocaine-induced ocular damage involves vascular, local toxic, neuronal, and immunological processes. Reported manifestations in the literature include the ocular surface, optic nerve, posterior segment, orbit, and adnexal tissues. Novel imaging techniques have revealed subclinical retinal microvascular changes in chronic users, suggesting a continuum from initial vascular dysregulation to manifest ischemic injury. Notwithstanding increased awareness, the existing evidence is constrained by heterogeneity, small sample sizes, and a prevalence of case reports. A comprehensive understanding of the pathophysiological mechanisms and long-term ocular effects is crucial for enhancing diagnostic precision, directing management, and informing preventive measures. Enhanced multidisciplinary collaboration between ophthalmologists and addiction experts is essential to tackle this intricate and dynamic clinical dilemma. Full article

Ocular diseases are a significant public health problem worldwide and represent one of the leading causes of disability. The prevalence of visual impairment is steadily increasing, largely driven by the ageing population. Oxidative stress, chronic inflammation and neurodegenerative processes underlie the pathogenesis of many eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and cataracts, contributing to progressive vision loss and functional impairment. Carotenoids such as lutein, zeaxanthin, meso-zeaxanthin, β-carotene, lycopene, and astaxanthin exhibit multidirectional biological effects, including antioxidant, anti-inflammatory, and neuroprotective properties. These compounds are selectively accumulated in the tissues of the eye, especially in the retina and macula, where they neutralise reactive oxygen species, modulate inflammatory pathways, stabilise mitochondrial function and support the survival and function of retinal ganglion cells and photoreceptors. The aim of our review was to provide a comprehensive review of current data regarding the mechanisms of action of carotenoids and their potential clinical significance in the prevention and treatment of retinal, optic nerve, lens, and eye surface diseases, including dry eye syndrome and Meibomian gland dysfunction. We identified results of available experimental and clinical research and outlined that an adequate supply of carotenoids in the diet or in the form of supplementation may support the protection of eye structures against oxidative and inflammatory damage, improve visual performance and potentially slow disease progression. However, high-quality prospective clinical trials are necessary to conclusively assess their therapeutic efficacy and establish evidence-based recommendations for clinical practice. Full article

Ocular toxicity induced by cisplatin appears to be almost irreversible, while trace elements have been shown to be protective in retinal angiopathies, degenerative or inflammatory conditions. A total of 60 Wistar rats were used in which administration of cisplatin intraperitoneally and of selenium and zinc nanoparticles, both per os and intraperitoneally, were performed. Retinal tissues were studied with TEM and optical microscopy. The results showed reduced tissue lesions in the trace element administration groups compared to the cisplatin administration group concluding that trace elements in the form of nanoparticles can achieve better tissue penetration for the treatment of cisplatin-induced ocular toxicity. Full article

Optical coherence tomography (OCT) is widely used in biomedical imaging and ophthalmology. However, OCT images are frequently corrupted by speckle noise from coherent light interference. This degradation hampers clinical diagnosis of retinal lesions and identification of tissue layers. We propose a speckle noise reduction algorithm based on a Multi-Scale Self-Attention Generative Adversarial Network combined with a Siamese network (SA-Siamese-GAN). To address the limited receptive fields of traditional convolutional neural networks (CNNs), which can cause broken or blurred retinal layers, a self-attention mechanism is integrated into the bottleneck layer of the generator to capture global pixel dependencies. A Siamese network enforces structural consistency, and a joint loss function combining Wasserstein distance, perceptual loss, and structural similarity (SSIM) is used. Experiments on 11,103 pairs of clinical OCT retinal images show that SA-Siamese-GAN outperforms BM3D, NLM, Wavelet, and GAN-ResNet. It removes speckle noise while preserving retinal layer structure and fine textures, and achieves the highest Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index (SSIM). Full article

Purpose: To describe the morphological and functional features of two patients phenotypically and genotypically diagnosed with Best disease and autosomal dominant drusen (BD-ADD) using multimodal imaging. It is hypothesized that the concurrent presence of pathogenic mutations in both BEST1 and EFEMP1 genes is associated with a phenotype that may exhibit characteristic features of both diseases potentially revealing further additive effects on retinal function or structure. The data are compared with those from a patient with genetically confirmed ADD. Methods: The patients received a full ophthalmological investigation, including fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT) and polarization-sensitive optical coherence tomography (PS-OCT). Genetic analysis of DNA samples was performed by targeted whole-exome sequencing. Results: Macular SD-OCT demonstrated a thickened retinal pigment epithelium (RPE)-Bruch’s membrane complex corresponding to macular drusen-like deposits in both ADD and BD-ADD cases. In contrast to isolated ADD, BD-ADD showed small hyperautofluorescent dots originating in hyperreflective photoreceptor debris at or above the RPE on FAF imaging. FAF further showed large hyperautofluorescent spots corresponding to sub-RPE drusen in both ADD and BD-ADD. The tissue-specific contrast of PS-OCT imaging allowed identification of the RPE within the macular lesion, structural changes of the subretinal material and incipient scar formation. Genetic analysis identified pathogenic mutations in both the BEST1 and the EFEMP1 gene in both BD-ADD cases. Conclusions: The characteristic morphological and functional features of both diseases are evident in the patients with the BD-ADD dual genotype. The coexistence of two independent autosomal dominant disorders provides an illustrative opportunity to inform our understanding of BEST1- and EFEMP1-mediated retinal disease. Full article

Diabetic retinopathy (DR) reflects retinal microvascular injury and systemic immune-metabolic stress, and most public DR transcriptomic datasets lack paired microbiome/metabolomic profiles. We used gutMGene v2.0 as a curated microbe/metabolite–host gene prior and integrated it with peripheral blood transcriptomics from GSE221521. Candidate genes were refined by weighted gene co-expression network analysis (WGCNA), repeated resampling, cross-dataset assessment, mechanism scoring, peripheral blood mononuclear cell (PBMC) single-cell localization and filamin A (FLNA)-centered single-cell gene regulatory network (GRN) virtual knockout. The gutMGene prior contained 238 host genes; 15 DR-associated genes overlapped this prior, and WGCNA retained ten candidate gut microbe and microbial metabolite-related genes (GMMRGs): FLNA, AKT1, IRAK1, BCL10, CDK6, CTSD, JUP, CXCL1, CXCR2 and IL4R. Resampling prioritized FLNA as the most consistent candidate. Cross-dataset assessment localized the strongest signal to type 2 diabetes (T2D) PBMCs, retinal endothelial cells and advanced proliferative diabetic retinopathy with diabetic macular edema (PDR + DME) retinal tissue, with weaker separation in whole blood, broad retinal tissue and six-donor type 1 diabetes (T1D) PBMCs. FLNA virtual knockout predicted cell-context-dependent perturbation of immune-related transcriptional programs, including IL4R in DR B cells and CTSD in DR monocytes/NK cells. This prior-guided study identifies FLNA within a ten-gene GMMRG set as a circulating host-response signal that links curated microbe/metabolite–host records to immune-vascular and cytoskeletal remodeling in DR. Full article

Oxidative stress contributes to retinal neurovascular injury through inflammation, mitochondrial dysfunction, blood–retinal barrier (BRB) disruption, microcirculatory impairment, and regulated cell death. Hydroxysafflor yellow A (HSYA), a water-soluble quinochalcone C-glycoside derived from safflower (Carthamus tinctorius L.), modulates oxidative and inflammatory signaling, apoptosis, mitochondrial injury, endothelial barrier dysfunction, and neurovascular damage in experimental ischemic, inflammatory, and metabolic disorders. This review critically evaluates the direct ocular evidence for HSYA in diabetic retinopathy and examines the systemic-to-ocular pharmacokinetic and delivery barriers that constrain its ophthalmic translation. Current ocular evidence is limited and concentrated mainly in DR models, in which HSYA attenuates oxidative stress, inflammation, BRB disruption, and apoptosis, potentially through Nrf2/HO-1 signaling. Evidence in retinal photic injury is limited, whereas the proposed relevance of HSYA to retinal ischemia–reperfusion injury, glaucoma, and AMD remains largely hypothesis-generating. The principal translational challenge is whether HSYA can achieve pharmacologically relevant exposure in ocular target tissues. Future studies should integrate dose, plasma and ocular exposure, target engagement, retinal structure, local safety, and visual function in disease-specific models. Accordingly, evidence from non-DR models is discussed primarily to define mechanistic hypotheses and experimental priorities rather than to establish ophthalmic efficacy. Full article

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by restoring anti-tumor immunity, but immune activation can disrupt ocular immune homeostasis and induce ophthalmic immune-related adverse events (OirAEs). Although uncommon, OirAEs may involve nearly all ocular compartments and can cause irreversible visual impairment or interruption of effective anticancer therapy. The 2025 international consensus criteria now provide a standardized framework for defining and classifying OirAEs. This review integrates current evidence on ICI-associated ocular toxicity, with emphasis on tissue-specific immune mechanisms and their clinical implications. Blockade of the PD-1/PD-L1 and CTLA-4 pathways may impair ocular immune privilege, expand autoreactive T-cell subsets, alter cytokine and chemokine networks, and amplify autoantibody-mediated retinal injury. These processes provide a plausible framework for understanding diverse phenotypes, including uveitis, ocular surface disease, optic neuritis, orbital inflammation, ocular myopathy, and retinopathy. We also outline a mechanism-informed management approach that balances visual preservation with maintenance of systemic anti-tumor immunity. Local corticosteroid therapy, cautious systemic immunosuppression, and selected steroid-sparing biologics should be individualized according to severity, anatomical involvement, and the oncologic context. Together, these insights support a consensus-based and mechanism-informed framework for recognizing and managing OirAEs while preserving systemic anti-tumor immunity. Full article