Dry Eye Research Articles

Acne vulgaris is a common chronic inflammatory skin disease with largely unmet treatment needs. This was a multi-centre, randomized, double-blind, placebo-controlled, dose-escalation Phase 2 trial (Clinicaltrials.gov ID: NCT05104125) to evaluate the safety, tolerability and efficacy of denifanstat, a first-in-class fatty acid synthase inhibitor, in patients with moderate-to-severe acne vulgaris. Denifanstat was administered orally at 25 (n = 45), 50 (n = 44), 75 (n = 45) mg or placebo (n = 45) once daily after dinner for 12 weeks. Denifanstat was generally well-tolerated. Study drug-related TEAEs were 48.9% (22/45), 47.7% (21/44), 62.2% (28/45) and 48.9% (22/45) in the denifanstat 25, 50 and 75 mg and placebo groups, respectively. The most common TEAEs were dry eye, dry skin, urine protein positive, skin peeling and conjunctivitis (Grade 1 to 2). No serious drug-related TEAEs occurred. At Week 12, denifanstat demonstrated significantly greater median reductions in total lesion counts versus placebo (25 mg: -53.2% [Q1-Q3: -62.5% to -37.6%]; 50 mg: -61.3% [-78.2% to -29.1%]; 75 mg: -53.1% [-62.4% to -39.2%] vs. placebo: -34.2% [-53.0% to -18.4%]; all p < 0.05). The proportion of participants achieving a ≥ 2-grade reduction in Investigator's Global Assessment (IGA) for denifanstat 25, 50 and 75 mg and placebo was 31.1% (14/45), 31.8% (14/44), 22.2% (10/45) and 15.6% (7/45), respectively. The difference among the four groups was not significant (p = 0.336). Denifanstat 50 mg once daily for 12 weeks was generally well tolerated and showed potential to reduce total lesion counts in moderate-to-severe acne vulgaris. Larger and longer term studies are needed to confirm efficacy and safety.

Dry eye disease (DED) is a highly prevalent multifactorial disorder of the ocular surface that extends beyond local tear film pathology to involve systemic immune, neuroendocrine, and neurosensory mechanisms. Increasing evidence reveals a strong and bidirectional association between DED and psychiatric disorders, particularly depression, anxiety, post-traumatic stress disorder (PTSD), and sleep disturbances. This review synthesises the current knowledge on shared molecular, neuroimmune, and neuropathic pathways that underlie this comorbidity. Key mechanisms include hypothalamic–pituitary–adrenal (HPA) axis dysregulation, systemic and ocular inflammation, oxidative stress, mitochondrial dysfunction, and impaired neurotrophic signaling, especially reduced brain-derived neurotrophic factor (BDNF). Dysregulation of monoaminergic neurotransmitters such as serotonin and norepinephrine not only contributes to mood disturbances but also alters tear secretion and corneal pain perception. Corneal nerve changes and trigeminal–limbic sensitisation further reinforce the overlap between neuropathic ocular pain and affective dysregulation. Psychotropic medications, while essential for psychiatric care, may exacerbate ocular surface dysfunction through anticholinergic effects, altered neurotransmission, and tear film instability, highlighting the iatrogenic dimension of this interface. Conversely, tear-based biomarkers, including cytokines, serotonin, and BDNF, offer promising translational tools for patient stratification, diagnosis, and treatment monitoring across ocular and psychiatric domains. Recognising DED as part of a systemic, biopsychosocial continuum is critical for effective management. Multidisciplinary strategies that integrate ophthalmologic and psychiatric care, alongside novel therapies targeting shared molecular pathways, provide a framework for improving outcomes. Future research should prioritise longitudinal studies, biomarker validation, and personalised interventions to address this complex comorbidity.

Association between air pollution and dry eye: insights from network toxicology and molecular docking analysis

On January 17, 2025, the FDA approved datopotamab deruxtecan-dlnk (DATROWAY; Dato-DXd), a Trop-2-directed antibody and topoisomerase inhibitor conjugate, for the treatment of adults with unresectable or metastatic, hormone receptor-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. Approval was based on results from TROPION-Breast01 (TB01), a multicenter, randomized, open-label trial comparing Dato-DXd with investigator's choice of chemotherapy (ICC). The trial was designed with dual primary endpoints: progression-free survival assessed by blinded independent central review according to RECIST v1.1 and overall survival (OS). TB01 demonstrated a 2-month improvement in median progression-free survival for Dato-DXd compared with ICC (6.9 vs. 4.9 months, respectively; stratified HR, 0.63; 95% confidence interval, 0.52-0.76; P < 0.0001). The OS endpoint was not met; at the final analysis of OS, the median OS was 18.6 months in the Dato-DXd arm and 18.3 months in the ICC arm (HR, 1.01; 95% confidence interval, 0.83-1.22). Although there was no OS improvement, Dato-DXd was also not associated with a clear trend toward potential detriment compared with ICC. The most commonly reported adverse reactions (≥20%) with Dato-DXd were stomatitis, nausea, fatigue, alopecia, constipation, dry eye, keratitis, and vomiting. Overall, the favorable benefit-risk profile for Dato-DXd supported its approval for the intended indication.

Itaconate-functionalized tetrahedral framework nucleic acids break the dry eye vicious cycle through dual antioxidant and anti-inflammatory actions

TFOS DEWS III: Digest.

Targeting the NLRP3 inflammasome: Pharmacological mechanisms for the treatment of dry eye disease.

TRPA1inhibition reduces ocular pain and corneal neurogenic inflammation in a mouse model of dry eye disease.

Ocular bacterial microbiome analysis by next-generation sequencing in patients with Stevens-Johnson syndrome and Sjögren's disease: associations with dry eye indices.

TFOS DEWS III: Management and Therapy.

Characterizing inflammatory, nerve innervation, and immune alterations in three dry eye disease animal models.

Effects of curcumin-liposome formulation on inflammatory cascade activated by oxidative stress in primary human corneal epithelial cells.

Imbalanced mitochondrial homeostasis in ocular diseases: unique pathogenesis and targeted therapy.

Approaching ocular risks during spaceflight with 3D printing: Technical strategies to protect astronaut vision.

Differential chemokine profiles between lacrimal and salivary glands in a murine model of primary Sjögren disease.

Clinical and Genetic Profiling of Fibromyalgia-Associated Dry Eye: A Multifactorial Approach.

This study aimed to assess the efficacy of two formulations of lubricant eye drops, containing a gelling agent or not, compared to normal saline. This was a prospective, randomized, double-blinded, three-group, parallel, interventional single-site clinical study. Forty-five Gazan participants with moderate to severe dry eye disease (DED) were randomized into three groups of 15 participants each. Each group received either normal saline eye drops or lubricant eye drops. For each group, one drop was applied three times a day for six weeks. All participants applied the normal saline solution for the first week. The outcomes assessed were the Arab-ocular surface disease index (Arab-OSDI) scores and clinical tests including tear break-up time test (TBUT), corneal fluorescein staining (CFS), and lissamine green conjunctival staining (LGS) at weeks 1, 3, and 6. Both formulations exhibited a significant improvement in Arab-OSDI scores from visit 2 at follow-up time points (p < 0.001). TBUT, CFS, and LGS showed an improvement in both the SH 0.15% and SH 0.38% groups (p < 0.05). SH 0.38% had a greater improvement in the proportion of evaporative dry eye from visit 2 to visit 5 (p = 0.001). Lubricant eye drops are beneficial for alleviating the symptoms of dry eye. There was no noticeable difference in the effectiveness of these formulations in relieving symptoms and changing any of the objective signs that were assessed. Improved EDE outcomes occurred with SH 0.38% eye drops, observed between visit 2 and visit 5.

Abnormalities in the tear film lipid layer, which plays a critical role in preventing water evaporation and protecting the corneal surface, lead to dry eye disease. The lipids in this layer include both meibum lipids (from the meibomian glands) and phospholipids of other origins. Meibum lipids include cholesteryl esters, wax monoesters, wax diesters (WdiEs), (O-acyl)-ω-hydroxy fatty acids (OAHFAs), and cholesteryl OAHFAs. Nonetheless, the exact composition of these lipid classes remains largely unclear. Here, we analyze the composition of cholesteryl esters, wax monoesters, WdiEs, OAHFAs, cholesteryl OAHFAs, phosphatidylcholines, and sphingomyelins in human meibum and tears using multiple reaction monitoring mode liquid chromatography-tandem mass spectrometry, which is highly sensitive, selective, and quantitative. This revealed that the WdiEs in meibum and tears fall within the type 1ω and 2ω classes. Among the lipids examined, the type 1ω WdiEs in particular comprised diverse species. The lipid composition of most of the lipid classes, except for the phosphatidylcholines, was similar in meibum and tears. The findings of this comprehensive lipid analysis contribute to elucidating the overall composition of human meibum and tear lipids.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-23048-1.

PurposeThis study investigated the efficacy of automated ocular thermography metrics for the screening of dry eye disease (DED).MethodsThis was a prospective study that enrolled 20 participants with DED, sex- and age-matched to 20 non-DED controls. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire-5 (DEQ5), noninvasive tear-break-up time (NITBUT), tear meniscus height (TMH), meibomian gland dysfunction (MGD) score, and corneal staining were measured in a screening visit. The DED group was defined as: OSDI score of ≥13 or DEQ-5 score of ≥6, and DED signs in at least one eye (corneal/conjunctival/lid margin staining, NITBUT <5 seconds, tear film osmolarity ≥308 miliosmoles [mOsm]/L). Thermography recording of the ocular surface (natural blinking over a period of 30 seconds) was conducted the next day, and the thermal cooling rate and thermal interblink interval (IBI) were derived.ResultsThermal IBI was significantly shorter in the DED group compared to the non-DED group (P = 0.034). The thermal cooling rate was significantly faster in the DED group (P = 0.047). Thermal IBI significantly correlated with DEQ5 (r = −0.37, P = 0.025) and OSDI (r = −0.37, P = 0.026). The thermal cooling rate significantly correlated with DEQ5 (r = −0.39, P = 0.022) and OSDI (r = −0.36, P = 0.036). The best discrimination was achieved by combining the thermal cooling rate and TMH, with an area under the curve (AUC) = 0.80 (sensitivity = 0.87 and specificity = 0.63).ConclusionsThe thermal IBI and thermal cooling rate were significant predictors of DED, suggesting the utility of ocular thermography for DED screening.Translational RelevanceAutomated ocular thermography may help to assess ocular dryness in a noninvasive, quantifiable, and real-time manner.

BackgroundSjögren’s syndrome (SS) is a chronic autoimmune disorder marked by lymphocytic infiltration of exocrine glands, leading to xerostomia, keratoconjunctivitis sicca, and systemic involvement including fatigue, arthralgia, and visceral organ impairment. Its pathogenesis reflects a multifactorial interaction of genetic, environmental, and hormonal influences that collectively disrupt immune homeostasis and drive tissue injury. Extensive investigations remain essential to clarify molecular pathways and establish reliable biomarkers that can enable early detection and precision therapy in SS. Detailed characterization of metabolic and molecular disturbances associated with SS is indispensable for advancing both pathophysiological insight and clinical management.Material and methodsRigorous quality control, batch adjustment, and data normalization were applied to untargeted metabolomics to ensure consistency and analytical reliability. Serum metabolite profiling in SS was assessed through unsupervised principal component analysis (PCA) to distinguish intergroup variations. Quantitative evaluation of metabolite abundance, machine learning–based metabolite selection, and functional enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to identify candidate biomarkers. Differential gene expression and enrichment analyses, construction of protein–protein interaction (PPI) networks in the SS group, and orthogonal partial least squares discriminant analysis (OPLS-DA) were subsequently performed to investigate underlying molecular mechanisms. Correlations among metabolites, key genes, and immune cell subsets were also examined.ResultsQuality control confirmed the reliability and precision of the untargeted metabolomics data. Differential metabolite analysis highlighted significant alterations, with PC O-36:5, 4-Aminobutyric acid, and PC 16:0_16:1 exhibiting the most marked changes. Machine learning algorithms further identified metabolites including PC O-36:5, Prostaglandin B1, and L-Ergothioneine as candidates with diagnostic potential for SS. Functional enrichment revealed altered KEGG pathways including arginine and proline metabolism, pyrimidine metabolism, and nucleotide metabolism. Sequencing data analysis indicated enriched GO terms related to viral response, KEGG pathways such as Influenza A, and Gene Set Enrichment Analysis (GSEA) pathways including HUNTINGTONS_DISEASE. Two-way orthogonal partial least squares (O2PLS) delineated metabolites central to metabolic networks, such as PC O-36:5, along with genes critical to gene interaction networks, including GZMA. Correlation analysis demonstrated tight associations between metabolites, genes, and immune cell subsets in SS.ConclusionThis integrative analysis identified molecular markers with diagnostic relevance for SS and advanced the understanding of metabolic and molecular alterations underlying the disease.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12920-025-02256-8.