Purpose To prospectively evaluate the safety and efficacy of cultivated oral mucosal epithelial transplantation (COMET) for the treatment of severe ocular surface disorders (OSDs). Methods This phase II, nonrandomized clinical trial involved patients with severe OSDs (i.e., Stevens-Johnson syndrome, ocular cicatricial pemphigoid, or severe chemical/thermal injury) who underwent COMET at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Patients were assigned to three groups according to the purpose of the surgery: visual improvement (VI) group, epithelial repair (ER) group, or release of adhesion (RA) group. The primary outcomes (i.e., from before surgery to 24-weeks post COMET) were change in distance vision, change in epithelial abnormality score, and change in fornix shortening score, respectively. The secondary outcomes included any change in Ocular Surface Grading Score (OSGS) and subjective symptoms evaluated by National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) findings. All intra- and postoperative adverse events were recorded. Results Of the 27 registered patients in this study, 22 (i.e., 14 SJS cases, 5 OCP cases, and 3 severe chemical/thermal injury cases) underwent COMET. At 24-weeks postoperative, logMAR visual acuity and the fornix shortening score were significantly improved in the VI group (11 cases, 2.2 to 1.5, p = 0.0060) and RA group (5 cases, 4.7 to 1.2, p = 0.0010), respectively. The total epithelial abnormality score improved in 50% of the ER-group patients (4 cases). All OSGS and NEI-VFQ scores improved, and no serious adverse events were observed. Conclusion COMET is safe and effective for treating severe OSDs.
PURPOSE:Herpes simplex keratitis (HSK) is a leading cause of infectious corneal blindness, yet local host-response programs underlying active disease, recurrence, and stromal involvement remain incompletely understood. This study aimed to establish a deep tear proteomic atlas of HSK and characterize phenotype-associated local host-response states. METHODS:Data-independent acquisition mass spectrometry was used to profile tear proteins from HSK-affected eyes (n = 20), contralateral unaffected eyes (n = 12), and healthy control eyes (n = 25). Differential abundance testing, co-expression network analysis, functional enrichment, and exploratory analyses of recurrence status and clinical phenotypes were performed. Bootstrap LASSO prioritized candidate tear host-response signatures, and cross-omic concordance was examined using an independent RNA-seq dataset. RESULTS:We quantified 4656 proteins, with 480 upregulated and 267 downregulated in HSK-affected eyes versus controls. HSK-affected eyes showed immune-metabolic remodeling, with activated humoral immunity/coagulation pathways and suppressed glycoprotein metabolism and mitochondrial energy homeostasis. Co-expression networks identified HSK-associated modules enriched in immune activation and oxidative stress, alongside negatively associated modules linked to structural maintenance. Recurrent HSK showed distinct proteomic programs involving epidermal development and actin cytoskeleton regulation. Stromal HSK showed enrichment of extracellular matrix organization and wound healing programs, whereas epithelial/mixed subtypes were enriched for translational and post-transcriptional regulatory processes. KRT12 and SNRPD3 were prioritized as tissue-concordant candidate tear host-response signatures showing consistent upregulation in an independent corneal-tissue RNA-seq dataset. CONCLUSIONS:This comprehensive tear proteomic atlas provides a molecular resource for investigating local host-response heterogeneity in HSK and prioritizes candidate tear markers for future prospective and independent validation.
TOPIC:To estimate the global incidence trends of OSSN. CLINICAL RELEVANCE:Despite recognized associations and regional differences, there is an absence of a comprehensive global analysis of OSSN's epidemiological burden across diverse geographic and socioeconomic settings. METHODS:A systematic review and meta-analysis was conducted using Medline, Embase, and Scopus databases up to June 2025, including all age groups, sexes, and geographic regions. Pooled incidence and prevalence were estimated using random-effects models, with heterogeneity assessed by χ2 and I2 statistics. Risk of bias was conducted using the Joanna Briggs Institute Critical Appraisal Tools. RESULTS:Twenty-four studies published between 1992 and 2025, were included, encompassing 33,615 incident OSSN cases (52.9% female; mean age 57.3 years). The incidence of broad OSSN across ten studies ranged from 0.03 to 36.72 per 1,000,000 person-years. The global incidence of conjunctival squamous cell carcinoma (SCC) was 0.70 per 1,000,000 person-years (95% CI, 0.24-1.99; I2 = 100.0%), with pooled incidence of 1.05 per 1,000,000 person-years (95% CI 0.04-27.8; I2 = 99.1%) in individuals aged younger than 60 and 4.18 per 1,000,000 person-years in individuals aged above 60 (95% CI 0.77-22.7; I2 = 98.8%). Conjunctival SCC incidence was highest in Africa (5.04 per 1,000,000 person-years; 95% CI 2.72-9.34; I2 = 99.4%), followed by North America (1.29; 95% CI 0.10-17.33; I2 = 100.0%), and lowest in Asia (0.06; 95% CI 0.01-0.40; I2 = 97.5%). Incidence increased with age and was generally higher in males. Corneal SCC incidence was low (0.04 per 1,000,000 person-years; 95% CI 0.0-122.36; I2 = 100.0%), and only one study reported on corneal limbal SCC (0.82 per 1,000,000 person-years). No large studies reported prevalence. Overall, incidence estimates varied widely by region, sex, age, and anatomical site. Most studies used ICD codes or pathology-confirmed diagnoses, though few stratified by HIV status, age group, or anatomical site. There was a lack of data in South American countries. CONCLUSION:Available population-level data highlighted geographic variation in reported OSSN incidence, and a single incidence estimate cannot be reliably established due to inconsistent definitions and capture of OSSN subtypes. Conjunctival SCC demonstrated the highest reported incidence in African populations. There is an urgent need for standardized subtype-specific OSSN surveillance and reporting. OSSN is a rare but regionally concentrated ocular surface malignancy.
