Enhancing Ocular Surface in Dry Eye Disease Patients: A Clinical Evaluation of a Topical Formulation Containing Sesquiterpene Lactone Helenalin

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 17; no. 2; p. 175
• Main Authors: Ng, Dalia, Altamirano-Vallejo, Juan Carlos, Navarro-Partida, Jose, Sanchez-Aguilar, Oscar Eduardo, Inzunza, Andres, Valdez-Garcia, Jorge Eugenio, Gonzalez-de-la-Rosa, Alejandro, Bustamante-Arias, Andres, Armendariz-Borunda, Juan, Santos, Arturo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.01.2024; MDPI
• Subjects: Arnica; Chemical properties; conjunctival impression cytology; Cytokines; Diagnosis; Dosage and administration; Drug therapy; Dry eye syndromes; Eye diseases; Inflammation; meibomiography; MMP-9; ocular tolerability; Ophthalmic drugs; Oxidative stress; Testing; Tumor necrosis factor-TNF; Mexico; United States > US; conjunctival impression cytology; ocular tolerability; meibomiography; MMP-9; Arnica
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph17020175

The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 ( < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores ( < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer's test scores ( < 0.001), whereas Group 2 did not ( > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate.