The Effect of Sodium Hyaluronate Eye Drops 2, 4 or 6 Times a Day on Signs and Symptoms of Dry Eye Disease

Abstract

Purpose

A randomized clinical trial was run to evaluate the effectiveness of a preservative-free 0.4% sodium hyaluronate eye drop (LOF) in different dosage schemes to alleviate signs and symptoms of dry eye disease (DED).

Methods

A total of 116 subjects with mild-to-moderate DED were included, and 111 completed the study (from which 67.6% were female and 65.3% were users of oral contraceptives). Patients were randomly assigned to instill a drop of LOF either 2 (BID), 4 (QID) or 6 (6TD) times a day (at least 3 hours apart) for 30 days. The clinical parameters and symptom endpoints were Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), ocular surface staining, and conjunctival hyperemia. Other parameters evaluated were chemosis, best corrected visual acuity, and the incidence of adverse events (AE).

Results

There was a significant reduction in OSDI scores by day 30 in all groups. The recovery of the OSDI score back to normal values was observed in 51.4% of patients treated (50%, 48.6%, and 55.6% in BID, QID, and 6TD, respectively, p = 0.822). Similar improvement was observed for TBUT, 50.5% of patients increased this variable to >10 seconds (39.5%, 51.4%, and 61.1%, p = 0.175), and for ocular surface staining, ≥72% showed Grade 0. There were no significant differences among posology groups regarding ocular surface staining, conjunctival hyperemia, or any safety parameters. No overall improvement in OSDI and TBUT to normal values was noted for 31 patients (21 were female and 71.4% users of contraceptive drugs).

Conclusion

The ophthalmic use of preservative free LOF, 2, 4 or 6 times a day, may alleviate clinical parameters and symptoms in 50% of patients with mild-to-moderate DED after a one-month treatment. This improvement seemed to be less ubiquitous in patients within reproductive age and using oral contraceptives.

Trial Registration

This trial is registered at clinicaltrials.gov (NCT0704531).

Keywords:

• contraceptives
• dry eye disease
• ocular surface disease index
• sodium hyaluronate
• tear break-up time

Abbreviations

6TD, 6 times a day; AE, adverse events; BCVA, best-corrected visual acuity; BID, 2 times a day; CFS, corneal fluorescein staining; CLGS, conjunctival lissamine green staining; DED, dry eye disease; FPFV, first patient first visit; LPLV, last patient last visit; OSDI, ocular surface disease index; QID, 4 times a day; TBUT, tear break-up time.

Data Sharing Statement

The dataset generated during and/or analyzed for the current study is available in the Open Science Framework (https://osf.io) repository as DOI 10.17605/OSF.IO/YDRZQ.

Acknowledgments

Phase II clinical study to evaluate the efficacy of multidose Lagricel^® Ofteno ophthalmic solution applied in three different dosage schemes as treatment to mild-to-moderate dry eye (NCT0704531) was conducted in six centers in Mexico (Jalisco, Mexico City, Veracruz, and Yucatan). The study protocol and informed consent form were approved by their respective Institutional Review Boards as follows: Instituto Tecnológico de Estudios Superiores de Monterrey, Comité de ética en investigación de la escuela de medicina del Instituto Tecnológico y de Estudios Superiores de Monterrey, Centro de Investigación Clínica Acelerada S.C., Hospital la Misión, Sociedad Administradora de Servicios de Salud S.C., and Comité de Clínica Bajío CLINBA S.C.

We thank the participants in the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was sponsored by Laboratorios Sophia, S.A. de C.V. (Zapopan, Jalisco, Mexico). MVP, SRA, and OMO are employees of Laboratorios Sophia, S.A. de C.V. The sponsor provided support in the form of salaries for authors (MVP, SRA, and OMO), this does not alter our adherence to the Good Publication Practice guidelines for pharmaceutical companies (GPP3) policies on sharing data and materials. The authors report no other conflicts of interest in this work.