Search Results (169)

Chronic diseases such as cardiovascular disorders, diabetes, neurological conditions, and kidney disease continue to rise worldwide. These conditions create a growing demand for continuous, non-invasive, and personalized health monitoring technologies. Wearable biosensors meet this need by enabling real-time physiological and biochemical measurements outside traditional clinical settings. Among wearable biosensors, those based on biofluids like sweat, tears, and saliva provide a painless alternative to blood sampling. These fluids also grant access to metabolites, electrolytes, hormones, proteins, and disease related biomarkers that reflect systemic health status. Advanced sensing technology allow us to continuously track health status by analyzing key biomarkers in these accessible biofluids. This review summarizes recent advances in non-invasive wearable biosensors and focuses on their sensing principles which includes biorecognition elements, signal transduction mechanisms, and data acquisition strategies. We also discussed key sensing modalities, including electrochemical, optical, thermal, and piezoelectric approaches, highlighting their advantages for wearable integration and performance in biofluid sensing. Finally the review also outlines recent developments and applications of these systems in biofluid sensing. In the end we highlights existing challenges, potential solutions, and future directions toward clinically deployable, AI-assisted precision healthcare systems. Full article

Alzheimer’s disease is characterized by a chronic, long-term neurodegenerative process and an increasing need for easily accessible biomarkers that enable early diagnosis and disease monitoring. For this reason, tears have attracted growing interest as a potential source of such biomarkers, and prolactin-inducible protein is a candidate tear protein of mechanistic interest whose clinical value remains to be established as a biomarker of Alzheimer’s disease. The literature indicates that prolactin-inducible protein is physiologically present in the lacrimal apparatus. Proteomic studies in patients with Alzheimer’s disease have repeatedly demonstrated decreased levels of prolactin-inducible protein in tears, typically accompanied by reduced concentrations of other proteins associated with normal lacrimal gland function. Although the evidence remains inconclusive, these findings suggest that alterations in prolactin-inducible protein levels may reflect lacrimal gland dysfunction related to neurodegenerative processes, autonomic dysregulation, and inflammation. Nevertheless, the lack of specificity of prolactin-inducible protein for Alzheimer’s disease, as well as the influence of various factors on its concentration, limit its value as a standalone biomarker. The most plausible approach is the incorporation of prolactin-inducible protein into multimarker panels, which could enable improved patient stratification and assessment of lacrimal gland dysfunction in Alzheimer’s disease. 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: 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

Craniofacial and corneal neuropathic pain are disabling conditions characterized by persistent pain that is frequently refractory to conventional pharmacologic and interventional therapies. These disorders arise from complex interactions between peripheral nerve injury, neuroinflammation, and maladaptive central sensitization within trigeminal pathways, features that span neuropathic and nociplastic pain mechanisms as defined by the International Association for the Study of Pain, thus emphasizing the need for mechanism-based, patient-stratified treatment strategies. Regenerative medicine offers a paradigm shift from symptom suppression toward structural nerve repair and functional restoration. This narrative review examines the pathophysiological mechanisms underlying craniofacial and corneal neuropathic pain and critically evaluates emerging regenerative therapies, including autologous biologics (autologous serum tears and platelet-rich plasma), mesenchymal stem cells and their derivatives, exosomes and extracellular vesicles, and neurotrophic peptides. Particular emphasis is placed on corneal neuropathic pain as a translational model, given the cornea’s dense sensory innervation and the ability to non-invasively quantify nerve regeneration using in vivo confocal microscopy as an objective biomarker of treatment response. Clinical evidence across regenerative modalities varies by indication: cenegermin has demonstrated robust efficacy and regulatory approval for neurotrophic keratitis, while platelet-rich plasma shows growing evidence in temporomandibular disorders, myofascial pain, and occipital neuralgia. Cell-based and cell-free therapies demonstrate strong preclinical promise but remain limited by heterogeneous protocols and a paucity of large-scale randomized trials. Key barriers to translation include regulatory uncertainty, lack of standardized outcome measures, and workforce and implementation challenges. Advancing regenerative therapies for craniofacial and corneal neuropathic pain will require rigorous clinical trials, biomarker-driven patient selection, and multidisciplinary collaboration. Sex as a biological variable remains underexplored across all regenerative modalities and represents a priority for future research. Full article

Platelet-rich plasma (PRP) is widely used as a second-line treatment for chronic tendinopathy that persists despite structured conservative care, yet outcomes and imaging correlates remain heterogeneous. This review outlines PRP biology and preparation, summarises quantitative imaging techniques for monitoring tendon response, and presents the experience of a single centre integrating these methods into routine supraspinatus and lateral elbow PRP workflows. PRP is described as an autologous platelet concentrate with variable leukocyte and fibrin content, with leukocyte-rich formulations commonly selected for chronic tendinopathy. Quantitative approaches—including ultrasound shear-wave elastography and radiomics, MRI T2/T2* mapping, CT-based bone metrics, PET/CT, and optical techniques—offer numerical biomarkers of tendon structure, mechanics, and inflammation but are rarely implemented in PRP trials. At the authors’ centre, leukocyte-rich PRP is injected under ultrasound guidance after failed physiotherapy, and follow-up combines validated questionnaires with grey-level run-length matrix texture analysis of ultrasound and 3.0 T MRI T2 distribution profiling. A pilot ultrasound study in supraspinatus and common extensor tendinosis showed uniform short-term clinical improvement and significant changes in most texture features, with selected parameters correlating with symptom relief. A prospective supraspinatus cohort demonstrated significant six-month clinical gains in both tendinosis and small partial-thickness tears, whereas only the tendinosis group exhibited T2 profile convergence toward asymptomatic patterns. These data indicate that quantitative ultrasound radiomics and whole-length T2 profiling are feasible imaging biomarkers that capture PRP-induced tendon remodelling beyond qualitative imaging and may help tailor PRP protocols to specific tendon phenotypes. 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

Cognitive dysfunction and neurodegenerative disorders represent an increasing clinical challenge in aging dogs and cats, while objective and minimally invasive biomarkers for early detection and disease monitoring remain limited. Tear film is a biologically active fluid reflecting both local and systemic processes and offers a practical, non-invasive source of potential biomarkers in geriatric veterinary patients. Proteomic analyses of canine and feline tear film have revealed a complex protein composition, including molecules involved in inflammation, oxidative stress, immune regulation, and cellular homeostasis—processes implicated in neurodegeneration. However, growing evidence from human and veterinary research emphasizes the importance of CNS-specific and mechanistically informative biomarkers, such as markers of axonal injury, synaptic degeneration, and glial activation, which may provide a more precise framework for interpreting peripheral proteomic alterations. This review summarizes current knowledge on tear film proteomics in dogs and cats and discusses its potential relevance to cognitive dysfunction and neurodegenerative processes. Particular attention is given to the integration of tear-derived proteins with validated blood and cerebrospinal fluid biomarkers, as well as to methodological challenges and future research priorities. With appropriate standardization and clinical validation, tear film proteomics may contribute to the development of novel diagnostic and monitoring strategies for neurodegenerative disorders in companion animals. 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

Dry eye disease (DED) has increasingly been linked to oxidative stress; however, the specific redox mechanisms underlying different clinical phenotypes remain incompletely understood. This study aimed to evaluate tear film oxidative stress profiles in patients with primary DED and sarcoidosis-associated DED (S-DED) by assessing lipid peroxidation, antioxidant enzyme activity, and total tear protein content, and to explore their relationship with clinical tear film dysfunction. Tear samples were analyzed for superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, as well as for malondialdehyde (MDA) and total protein levels, alongside standard clinical tests of tear film stability and secretion. Both DED groups exhibited significant oxidative alterations compared to controls, but with distinct redox signatures. Primary DED was characterized by markedly increased tear MDA levels, indicating predominant lipid peroxidation, whereas S-DED showed a more pronounced impairment of antioxidant defense, reflected by preserved or increased SOD activity in the context of significantly reduced GPx activity. Total tear protein levels were reduced in both groups, with evidence suggesting qualitative protein alterations in S-DED. The tear collection method significantly influenced the measured levels of several oxidative stress markers, underscoring the importance of sampling technique when interpreting tear-based redox profiles. Oxidative stress markers correlated with clinical measures of tear film dysfunction, supporting their physiological relevance. These findings demonstrate that DED encompasses heterogeneous oxidative stress mechanisms and that sarcoidosis acts as a modifier of ocular surface redox homeostasis. Distinct tear-based redox profiles differentiate primary from sarcoidosis-associated dry eye, highlighting the potential value of oxidative biomarkers for phenotyping DED beyond tear deficiency alone. Full article

Autoimmune ocular surface diseases represent a complex group of disorders in which systemic immune dysregulation triggers chronic inflammation, epithelial dysfunction, and progressive tissue fibrosis. Systemic lupus erythematosus, primary Sjögren’s syndrome, and ocular cicatricial pemphigoid are the principal entities linking systemic autoimmunity to ocular surface pathology. These conditions share convergent mechanisms—including dysregulated cytokine signaling (IFN-I, IL-6, and IL-17), complement activation, and epithelial–mesenchymal transition—culminating in tear film instability and visual impairment. Recent advances in molecular immunology and omics profiling have elucidated disease-specific pathways and identified actionable therapeutic targets. Conventional immunosuppressants such as corticosteroids and cyclosporine remain fundamental, yet emerging biologics targeting BAFF, IFNAR, and JAK/STAT signaling—alongside regenerative strategies employing mesenchymal and induced pluripotent stem cells—are transforming disease management. Parallel innovations in amniotic membrane transplantation, keratoprosthesis, and bioengineered corneal scaffolds integrate structural reconstruction with immune modulation. Furthermore, the convergence of multi-omics analytics, artificial intelligence-assisted diagnostics, and microbiome-based immunomodulation heralds a new era of precision ophthalmology. This review synthesizes current molecular insights, clinical observations, and translational advances that collectively redefine autoimmune ocular surface diseases—from chronic inflammatory disorders into a targetable, regenerative, and potentially reversible spectrum of conditions. Full article

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article

Objectives: The study examined tear and serum alterations using the ferning test and quantified the number of branches formed during the controlled drying of these biological fluids (tears and serum), in order to identify a potential diagnostic patterning test in individuals with obesity. Methods: A total of 61 patients aged between 25 and 72 years were enrolled (median age [interquartile range] = 39.0 [26] years). BMI values ranged from 19.1 to 47.5 kg/m², with a median BMI (interquartile range) of 29.3 (12.1) kg/m². Results: The Kruskal–Wallis test showed statistically significant differences among at least two Schirmer classes with respect to the number of branches observed in dried tears at a brightness threshold of 220 (H(2) = 8.485, p = 0.014). According to the Dunn post hoc test, Schirmer Class 1 showed a markedly lower number of branches compared with Classes 2 and 3 (p < 0.031 and p < 0.021), whereas no significant difference was found between Classes 2 and 3. The Kruskal–Wallis test further suggested the presence of statistically significant differences in the number of branches in dried serum, quantified using ImageJ2 at a brightness threshold of 190, across visceral fat classes (H(2) = 9.583, p = 0.008). Dunn’s post hoc tests revealed that the number of branches in serum analyzed at a brightness threshold of 190 was significantly higher in visceral fat class 3 compared to class 1 (p_holm = 0.006), while no statistically significant differences were observed between classes 1 and 2 or between classes 2 and 3 (p_holm > 0.05). Conclusions: In addition to other obesity-specific complications patients with obesity exhibit an increased risk of developing dry eye syndrome. The combined assessment of DPT in both the tear film and serum may represent a new method for analyzing obesity-associated biomarkers. Further studies are required to determine the sensitivity and specificity of these approaches in diagnosing systemic alterations induced by excess adipose tissue. Full article

Ocular allergy (OA) is a subtype of seasonal allergy that causes symptoms of itchiness, redness, swelling and irritation of the ocular surface and eyelids, often triggering allergy-induced eye rubbing and sustained inflammation for up to six months of the year during peak allergy season. These symptoms, coupled with reduced sleep quality, impaired daily productivity and decreased mood, highlight a significant yet underrepresented disease burden. Recent advances in tear-based multi-omics have enabled detailed characterisation of OA-associated biochemical changes on the ocular surface, highlighting human tears as a promising biospecimen for diagnostic biomarker and therapeutic target research. This review discusses emerging proteomic, lipidomic, metabolomic and miRNA findings comparing OA sufferers with healthy controls, and, where relevant, with comorbid conditions such as dry eye disease and keratoconus. Differential expression patterns across these analytes implicate key pathways involved in immune response, wound healing, angiogenesis, inflammation, oxidative stress and return to homeostasis on the ocular surface. By integrating these data into a stepwise model of OA biopathway activation, this review outlines candidate biomarkers and highlights methodological advances that may support translation of tear multi-omics into clinical tools for OA management. Full article

Keratoconjunctivitis sicca (KCS) in dogs is an immune-mediated disorder characterized by aqueous tear deficiency, ocular surface inflammation, and risk of vision loss. Although tear quantity is routinely evaluated using the Schirmer tear test (STT), the accompanying qualitative alterations in tear protein composition remain poorly understood. In this exploratory study, we identified and characterized qualitatively differentially expressed tear proteins in samples collected from seven Beagle dogs with KCS and five healthy Beagles. Samples were collected using filter paper, extracted in phosphate-buffered saline, concentrated by trichloroacetic acid precipitation, and then separated via two-dimensional electrophoresis. Differential protein spots were identified by MALDI-TOF-MS-based peptide mass fingerprinting. Total protein concentrations were determined by measuring UV absorbance at 280 nm and were found to be significantly higher in dogs with KCS (30.7 ± 13.5 mg/mL) than in healthy dogs (11.5 ± 1.8 mg/mL, p < 0.05). Five proteins were identified as differentially expressed: serum albumin, lactotransferrin isoform 1, immunoglobulin gamma heavy chain C, major allergen Can f 1, and lysozyme C. High-molecular-weight proteins were upregulated in KCS, whereas low-molecular-weight proteins (<10 kDa, proline-rich protein-like components) were markedly reduced or absent. These compositional shifts suggest that KCS alters both the quantity and qualitative integrity of the tear proteosome, reflecting impaired tear film homeostasis and diminished ocular surface defense. The results support the potential utility of the tear proteome as a source of diagnostic and therapeutic biomarkers in canine KCS. Full article