Search Results (297)

Background/Objectives: Vernal keratoconjunctivitis (VKC) is a chronic, recurrent allergic disease with the risk of permanent injury or visual disabilities. Tacrolimus (FK506) is a potent immunosuppressant with insoluble ability and a high molecular weight. Methods: To address this disease, we successfully prepared FK506-loaded polymeric micelles (0.01%, FK506-MS) by a simple, organic solvent-free method. The physicochemical properties of FK506-MS were characterized. Corneal permeability, biocompatibility, and bioavailability were evaluated in vitro and in vivo in comparison with a commercially available FK506 suspension (0.1%, FK506-Susp). Therapeutic efficacy was also assessed in a murine model of VKC. Results: FK506-MS exhibited a small, homogeneous particle size with near-neutral surface charge. FK506-MS displayed a rapid and sustained release, along with excellent biocompatibility and stability. Ocular pharmacokinetic studies in rabbits revealed that FK506-MS, despite being only one-tenth the concentration of FK506-Susp, could achieve sufficient concentration in the conjunctiva with a prolonged half-life (T1/2) while systemic exposure in blood was markedly reduced. FK506-MS elicited comparable therapeutic responses across evaluated parameters: clinical symptoms, molecular biomarkers of inflammation, and histopathological findings. Conclusions: The dose-sparing advantage of FK506-MS suggests that the conventional paradigm of concentration-dependent therapeutic efficacy may require further refinement. The nanomicellar delivery system not only overcomes the solubility limitation of FK506 but also exhibits a potential therapeutic paradigm: achieving comparable clinical efficacy with a lower dose and reduced systemic exposure. These results provide a promising preclinical basis for the potential development of a topical tacrolimus therapy that may offer improved safety, cost-effectiveness, and patient adherence. Full article

Aristotelia chilensis (maqui berry) is a Chilean native fruit rich in anthocyanins with potential antioxidant, glycemic, cardiometabolic, and ocular benefits, but its clinical efficacy remains unclear. This systematic review synthesized and critically appraised human trials evaluating oral maqui supplementation in adults. Following PRISMA 2020 and a PROSPERO-registered protocol, five databases were searched, and risk of bias and certainty of evidence were assessed using RoB 2/ROBINS-I and GRADE. Twelve clinical trials published between 2014 and 2023 were included. Acute studies consistently showed reduced postprandial glucose and modulation of insulin response, whereas chronic interventions showed modest and inconsistent effects on HbA1c, lipid profile, and other cardiometabolic markers. Favorable changes were also reported for oxidative stress biomarkers and autonomic parameters, although these findings were mainly based on surrogate endpoints. The most consistent evidence was observed in the ocular domain, where maqui supplementation improved tear production, dry eye symptoms, and tear inflammatory markers. The overall certainty of evidence ranged from moderate to very low because of methodological heterogeneity, small sample sizes, and short intervention duration. Maqui berry supplementation shows promise, particularly for acute glycemic control and ocular surface health, but larger long-term randomized trials using standardized formulations are needed before definitive clinical recommendations can be made. Full article

Background: Retinal and optic nerve disorders remain major causes of visual morbidity worldwide. Ocular fundus flavoprotein fluorescence (FPF) imaging has emerged as a potential noninvasive biomarker of mitochondrial dysfunction for earlier detection and evaluation of disease severity. Methods: We conducted a Systematic Scoping Review of the diagnostic and correlational utility of quantitative FPF parameters in retinal and optic nerve diseases compared with healthy controls. Following PRISMA-ScR guidelines, we searched MEDLINE, Web of Science, Scopus, and CENTRAL for peer-reviewed human studies available online before 31 December 2025. Results: Seventeen studies were included, encompassing 1914 eyes and 1339 participants, and were predominantly cross-sectional. In healthy eyes, mean macular and optic nerve head FPF intensity were reported as 24.1 ± 12.2 gsu and 30.6 ± 14.6 gsu, respectively. Higher signals were reported in several disorders, including diabetes mellitus (76.0 [67.0–92.0] gsu), neovascular age-related macular degeneration (67.47 ± 17.77 gsu), and retinitis pigmentosa (50.5 ± 12.2 gsu). However, lower, unchanged, or stage-dependent signals were also observed within the same disease categories. Interpretation across studies was limited by substantial heterogeneity in patient selection, disease definitions, imaging protocols, control groups, and FPF outcome metrics. The precise cellular and sublayer origin of the detected signal also remains challenging to determine. Conclusions: Ocular fundus FPF imaging provides promising metabolic insight into retinal and optic nerve diseases. However, current evidence remains heterogeneous and largely cross-sectional, limiting clinical interpretability and generalizability. Longitudinal studies, technical standardization, and multimodal integration are needed to define reproducible disease-specific FPF profiles and improve translational applicability. Full article

Background: Dry eye disease (DED) is a multifactorial disease. Numerous risk factors might cause DED, including indoor air pollution, such as incense. Incense (Bakhoor) is widely used in many cultures, including Saudi Arabia, although its smoke contains toxic chemicals that pose serious health hazards. This research investigates the link between the Schirmer II test and tear fluid proteins in DED patients. The study focuses on identifying the ocular examinations, hypothesizing that incense smoke, particularly from synthetic types, exacerbates DED. Methods: This pilot cross-sectional study was conducted at King Abdulaziz Medical City (KAMC) in Jeddah, Saudi Arabia. Participants were recruited from the Cornea and Ophthalmology Clinics. Eye assessments analyzed tear protein concentrations, including tear collection using Schirmer II test strips and tear break-up time (TBUT). The study included DED patients who used incense. Tear fluid from the Schirmer test of 20 randomly selected patients was used for protein analysis of total protein, lactoferrin, and Immunoglobulin E. Inclusion criteria were male and female subjects aged 18 years or older, diagnosed with DED, and using incense. The sample size was 55 participants, selected via convenience sampling. Subjective data were collected through questionnaires, as well as objective data from the tear test and the sample and analyzed with SPSS. Descriptive and inferential statistics were used, with statistical significance set at p-value < 0.05. Results: The Ocular Comfort Index (OCI) categories showed that 21.8% had no symptoms, 40.0% had low symptoms, 30.9% had moderate symptoms, and 7.3% reported high symptoms. TBUT values and Schirmer test scores decreased with increasing OCI severity, with no statistical significance. The mean (SD) of total protein in the right and left eyes for high OCI was 7.19 (1.39) and 7.42 (0.91), respectively, with no statistical significance. The immunoglobulin E levels in the right and left eyes for high OCI were 301.71 (55.97) and 301.71 (47.14), respectively, with no statistical significance. The mean (SD) of lactoferrin in the right and left eyes for high OCI was 163.77 (10.42) and 159.43 (1.68), respectively, with no statistical significance. Conclusions: The study findings demonstrate alignment in incense-using patients between subjective OCI symptom scores and objective clinical diagnostic measures. Specifically, higher OCI scores are associated with lower TBUT and Schirmer II test values, as well as changes in tear biomarkers such as IgE and lactoferrin. These findings emphasize the potential of using simple screening methods combined with bioanalytical markers for early detection of ocular surface disease. This highlights the potential health risks associated with incense exposure, particularly for individuals predisposed to DED. The urgency for further research to explore the long-term effects of incense on ocular health and to raise awareness about its potential impact on populations with high incense usage cannot be overstated. Full article

Aberrant pathogenic immune responses drive autoimmune uveitides; however, comprehensive leukocyte profiling in the conditions remains limited. Here, this exploratory pilot study aimed to elucidate the immunodynamics of ocular sarcoidosis (OS) and Vogt–Koyanagi–Harada disease (VKH) to identify blood diagnostic biomarkers during their acute phases. We performed a prospective observational analysis of ten newly diagnosed, treatment-naïve OS patients and seven VKH patients during their acute phases, along with eight healthy controls (HCs). Mass cytometry was utilized to quantify the proportions of 37 distinct leukocyte subsets. In OS group, the proportion of CD8⁺ naive was lower than in both VKH and control groups. Furthermore, the proportions of CD8⁺ central memory and γδ T cells were decreased compared to HC group. Hierarchical cluster analysis categorized the leukocyte subsets into four principal clusters: Cluster A (Th17-like, monocytes, neutrophils, etc.), Cluster B (Tregs, B cells, NK cells, basophils, etc.), Cluster C (CD8⁺ T cells, Th1-like, Th2-like, DCs, etc.), and Cluster D (CD4⁺ terminal effector, CD8⁺ terminal effector, and CD66b⁻ neutrophils). Compared to HC group, the abundance of Cluster A was relatively high in OS group, and the abundance of cluster B was relatively high in VKH group. In OS group, the proportions of CD8⁺ T cells and CD8⁺ terminal effector correlated negatively with serum ACE and sIL-2R levels. ROC curve analysis estimated that CD4⁺/CD8⁺ ratio (cut-off value: ≥3.46), the proportion of monocytes (≥9.41%), and the decreased proportions of CD3⁺ T cells (≤43.9%) and CD8⁺ T cells (≤10.0%) in peripheral blood may serve as potential blood biomarkers for diagnosing OS. The exploratory pilot study provides a comprehensive and simultaneous data of leukocyte subset proportions in the acute phase of OS and VKH, and our preliminary findings suggest that the proportions of specific leukocyte subsets may represent potential candidates for blood-based biomarkers in the diagnosis of OS. Full article

Background: The photopic negative response (PhNR) of the full-field electroretinogram is a retinal ganglion cell-weighted functional signal increasingly proposed as a clinical biomarker. Despite extensive study across ocular and systemic diseases, its precise clinical role and incremental value remain incompletely established. Methods: This narrative review synthesizes key human studies of the photopic negative response, with emphasis on physiological basis, recording methodology, and clinical contexts in which PhNR may provide added functional insight. Results: In glaucoma, PhNR provides an objective measure of retinal ganglion cell dysfunction that correlates moderately with optical coherence tomography (OCT)-derived structural loss and visual field indices, but with substantial inter-individual variability. Its greatest clinical utility lies in early disease detection, cross-sectional functional assessment, and documenting short-term functional changes following intraocular pressure reduction, rather than longitudinal progression monitoring. Beyond glaucoma, PhNR reveals inner retinal dysfunction in systemic and genetic conditions, particularly idiopathic intracranial hypertension and diabetes, where retinal ganglion cells may reflect broader neurological or metabolic stress. Conclusions: PhNR is best viewed not as a standalone diagnostic or progression tool, but as a complementary functional biomarker that adds objective insight when structural imaging or psychophysical testing is limited or discordant. Its role aligns closely with the retina’s emerging function as a mirror of systemic and genetic disease, provided recordings are standardized and results interpreted cautiously. Full article

Fixation instability (FI) and vergence instability (VI) in amblyopia and strabismus are associated with disrupted physiologic fixation eye movements (FEMs). This study examined how viewing conditions affect FEM patterns in strabismic subjects with and without amblyopia. FEMs of the non-dominant/amblyopic and dominant/fellow eyes were recorded using video-oculography during both-eye viewing (BEV), fellow/dominant-eye viewing (FEV/DEV), and amblyopic/non-dominant-eye viewing (AEV/NDEV) in strabismic subjects with amblyopia (SA, n = 56), without amblyopia (S, n = 19), and controls (C, n = 25). FI, VI, fast FEM amplitudes, slow FEM velocities, and time-based control of eye deviation were analyzed. The SA group showed the greatest FI in the amblyopic eye during AEV compared with the fellow eye during FEV, whereas minimal inter-ocular FI differences were observed in the S group and controls. Under monocular viewing, both SA and S groups exhibited increased FI in the non-viewing eye and higher VI than controls. Regression analyses indicated that visual acuity deficits primarily influenced viewing-eye FI and FEM dynamics, while strabismus mainly affected non-viewing-eye FI and slow FEMs. C and S groups showed the least eye deviation during BEV, whereas the SA group showed the least eye deviation—but the highest VI—during AEV, indicating a distinct pattern of incomitance. Distinct FEM patterns shaped by viewing conditions may reflect underlying visuomotor control mechanisms and serve as biomarkers for AI (artificial intelligence)-based classification. Full article

Antibody–drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of action, clinical efficacy, safety profiles, biomarker strategies, and emerging resistance mechanisms. Key safety concerns, including interstitial lung disease (ILD), ocular toxicity, and peripheral neuropathy, are emphasized alongside approaches for re-challenge following toxicity. We further discuss next-generation ADC platforms, including bispecific and conditionally activated constructs, as well as combination strategies with immunotherapy. Collectively, ADCs beyond HER2 are poised to reshape treatment paradigms in NSCLC, offering hope for patients with limited therapeutic options. This review identifies current gaps, highlights ongoing research priorities, and proposes practical considerations for integrating these therapies into clinical practice. Full article

Diabetic retinopathy (DR) is a leading cause of vision loss worldwide and represents a complex neurovascular complication of diabetes mellitus driven by chronic hyperglycemia. Increasing evidence identifies oxidative stress—defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defenses—as a central pathogenic mechanism linking metabolic dysregulation to retinal injury. The retina is particularly vulnerable to oxidative damage due to its high metabolic demand, elevated oxygen consumption, and abundance of polyunsaturated fatty acids. Hyperglycemia activates multiple interconnected biochemical pathways, including the polyol and hexosamine pathways, protein kinase C signaling, advanced glycation end-product formation, and lipid peroxidation, all of which converge on excessive ROS production and mitochondrial dysfunction. Growing attention has focused on oxidative stress biomarkers as tools to characterize DR severity and progression. Elevated systemic markers of lipid, protein, and DNA oxidation, together with impaired antioxidant capacity, correlate with disease stage, while oxidative biomarkers detected in aqueous and vitreous humor reflect localized retinal injury. Importantly, oxidative stress biomarkers are also associated with functional outcomes, including best-corrected visual acuity and diabetic macular edema. Integration of systemic and ocular oxidative biomarkers with clinical staging may improve risk stratification and support personalized therapeutic strategies in DR. Full article

Background/Objectives: Presbyopia is an age-related decline in near vision associated with lens stiffening and neuroretinal changes, while evidence for the effects of berry-derived phytochemicals remains limited. We investigated whether AKB, a double-standardised berry extract (anthocyanins ≥ 25%, iridoids ≥ 4.5%) from Aronia melanocarpa, Lonicera caerulea, and Vaccinium myrtillus, influences visual performance and circulating biomarkers potentially relevant to ocular homeostasis. Methods: In a randomised, double-blind, placebo-controlled, two-period crossover trial, 23 adults aged >50 years received AKB (400 mg twice daily) or placebo for 6 weeks, separated by a 5-week washout. Results: Compared with placebo, AKB was associated with improvements in selected visual-function outcomes, including near contrast sensitivity and visual-field parameters, together with directionally favourable changes in VEP and OCT readouts. AKB supplementation was also associated with lower circulating αA-/αB-crystallin and ALDH1A1 levels and higher circulating TRPV4 levels, whereas systemic antioxidant enzymes and advanced glycation end-products remained unchanged. Given the small sample size and the indirect nature of the biomarker assessment, these findings should be considered preliminary. Conclusions: Overall, short-term AKB supplementation was associated with modest, exploratory changes in selected functional and systemic biomarker outcomes, but larger and longer-term studies are needed to confirm clinical relevance and clarify underlying mechanisms. Full article

Background/Objectives: Anterior segment optical coherence tomography (AS-OCT) and optical coherence tomography angiography (AS-OCTA) have enhanced the evaluation of the cornea, ocular surface, and ocular surface diseases (OSD), offering high-resolution structural and anterior segment vascular imaging. This review summarizes recent advances in these modalities and their clinical applications. Methods: A comprehensive literature search was conducted using PubMed, Web of Science, and Google Scholar with the terms OCT, OCTA, anterior segment, and ocular surface disease. Studies published in the past five years were included, emphasizing more recent developments such as ultra-high-resolution AS-OCT (UHR-AS-OCT) and swept-source AS-OCTA technologies. Results: UHR-AS-OCT provides non-invasive, sub-micron imaging of the cornea and the ocular surface, including tear film morphology and epithelial thickness to correlate with clinical tests such as tear break-up time, and fluorescein staining. Advances in AS-OCTA allow dye-free, depth-resolved imaging of corneal and conjunctival vasculature. These vascular biomarkers have shown promising utility in conditions such as limbal stem cell deficiency, chemical ocular injury, and ocular surface squamous neoplasia. Improvements in image acquisition, motion correction, and segmentation algorithms have enhanced accuracy and repeatability, supporting broader clinical translation. Conclusions: AS-OCT and AS-OCTA have become useful adjunctive imaging tools for the cornea and ocular surface evaluation. Their non-invasive, quantitative, and reproducible metrics may enable earlier diagnosis, objective staging, and longitudinal monitoring of OSD. Integration of OCT-based imaging with artificial intelligence and multimodal data, including tear proteomics and meibography, may optimize personalized treatment for ocular surface disorders. Full article

Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, typically characterized by muscle weakness due to autoantibodies targeting acetylcholine receptors (AChR) or muscle-specific kinase (MuSK). Generalized MG is a more severe form of the condition than ocular MG. Although MG can strike at any age, young adult women are typically affected, especially in their reproductive years. MG is rare during pregnancy, with the first trimester and the postpartum period being the most common times for exacerbations. The influence of MG on pregnancy outcomes remains ambiguous, with some studies finding larger prevalence of issues such as preterm birth and small-for-gestational-age babies, while others indicate results similar to the general population. Management of MG during pregnancy necessitates careful monitoring and drug adjustments. Teratogenic concerns make several immunosuppressive drugs, such mycophenolate mofetil and methotrexate, contraindicated. In contrast, medications like prednisolone and pyridostigmine are generally recognized as safe. Women with MG may have flare-ups after giving birth, and infants may have transient neonatal myasthenia gravis. Comprehensive prenatal treatment and multidisciplinary assistance are crucial for promoting maternal and fetal health during pregnancy in women with MG. This paper examines the relevance of immunological biomarkers, RNAs, and other novel biomarkers in myasthenia gravis (MG). It emphasizes the need for more investigation to determine their role in the pathogenesis of MG, evaluate biomarker profiles across subgroups, and look at changes after treatment. The study also underlines the significance of high-throughput investigations to detect new biomarkers and reveal genetic variables impacting MG pathogenesis. Full article

Age-related cognitive impairment represents a critical stage in the continuum of neurodegenerative disorders, including Alzheimer’s disease (AD), highlighting the need for objective and non-invasive physiological indicators of early neurological change. This study investigates the simultaneous analysis of microsaccadic eye movements and pupil size variations as ocular biomarkers associated with age-related cognitive impairment using eye-tracking technology. A total of 70 participants were recruited and categorized into three age groups: individuals in their 20s, 60s, and 70s. Participants in their 70s were further categorized based on MMSE-K scores into cognitively normal (≥24) and impaired (≤23) subgroups. Quantitative analyses showed a significant age-related increase in microsaccade frequency along both axes, with significantly higher microsaccade frequencies (p < 0.01) among individuals with lower cognitive scores within the same age group. Pupil size variation, including constriction and dilation rates, declined with age, while response speed remained relatively unchanged across all age groups. These findings highlight a clear association between age related-cognitive decline and involuntary ocular responses. The proposed dual-biomarker method offers a non-invasive and quantitative framework that may complement traditional cognitive screening tools. Future studies involving larger cohorts and clinically diagnosed AD populations are required to determine the diagnostic utility of these ocular biomarkers. Full article

Diabetic retinopathy (DR) is a major complication of both Type 1 and Type 2 diabetes mellitus (T1DM and T2DM). Disease progression can result in visual impairment, primarily due to diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). Although several ocular treatments are available for DME, a subset of patients fails to respond, reflecting the multifactorial, complex, and systemic nature of DR. Inflammatory biomarkers can be classified according to different characteristics, including imaging biomarkers—most commonly assessed using optical coherence tomography (OCT)—and molecular biomarkers, which are defined by their biochemical and biophysical properties. Pro- and anti-inflammatory cytokines, chemokines, adipokines, and inflammation-related enzymes are recognized as key inflammatory biomarkers and can be detected in the vitreous humour, aqueous humour, tears, serum, and other biological tissues. The identification and characterization of reliable biomarkers may help determine disease severity, monitor disease progression, and predict the risk of specific outcomes, thereby aiding in the prevention of end-stage disease (prognostic biomarkers). In addition, biomarkers may serve as predictive tools for therapeutic response, guiding personalized treatment strategies and enabling ongoing monitoring. This review provides a comprehensive overview of the role of inflammatory biomarkers in the diagnosis and management of DR and DME. Full article

Background: Marinesco–Sjögren syndrome (MSS, MIM #248800) is a condition that is characterized by biallelic pathogenic variants in the SIL1 gene. Manifestations include congenital cataracts, cerebellar ataxia, progressive muscle weakness and skeletal deformities, delay in psychomotor development, hypergonadotropic hypogonadism and short stature. Muscular involvement has been extensively discussed as a clinical finding but there is little literature on muscle imaging. The aim of this paper is to systematically review muscular imaging techniques in MSS reported in the literature, and to describe the clinical and imaging features of two pediatric subjects with MSS. Methods: Having searched through three electronic databases (PubMed, Scopus and Web of Science) two articles, written in English, describing twelve patients with MSS mutations on whom muscle MRI imaging was performed, were selected. In addition, two paediatric cases (brother and sister) with Marinesco–Sjögren syndrome (MSS) and MRI muscle findings were added. Data on type of study, cohort characteristics, type of mutation, neuromuscular signs and symptoms, imaging assessment, electrophysiological findings, biopsies, CNS symptoms, ocular signs and muscle imaging data were collected and stored in a table. Results: Of the 239 articles examined, only 3 used a muscle imaging technique to describe myopathy in MSS; one used a CT while another a muscle MRI. All 14 patients showed signs of fatty replacement. The infiltration mainly affected the lower limbs, but involvement in the upper limb was described in some adult patients. Conclusions: Performing a muscle MRI in MSS can lead to the early identification of muscle involvement and may be a useful biomarker to monitor disease progression. Full article