Hyaluronic acid in the treatment of dry eye disease

Abstract

Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan commonly used in the treatment of DED. This review aims to critically evaluate the literature on the safety and efficacy of artificial tears containing HA used in DED treatment. Literature searches were conducted in PubMed, including MEDLINE, and in Embase via Ovid with the search term: "(hyaluronic acid OR hyaluronan OR hyaluronate) AND (dry eye OR sicca)". A total of 53 clinical trials are included in this review, including eight placebo-controlled trials. Hyaluronic acid concentrations ranged from 0.1% to 0.4%. Studies lasted up to 3 months. A broad spectrum of DED types and severities was represented in the reviewed literature. No major complications or adverse events were reported. Artificial tears containing 0.1% to 0.4% HA were effective at improving both signs and symptoms of DED. Two major gaps in the literature have been identified: 1. no study investigated the ideal drop frequency for HA-containing eyedrops, and 2. insufficient evidence was presented to recommend any specific HA formulation over another. Future investigations assessing the optimal drop frequency for different concentrations and molecular weights of HA, different drop formulations, including tonicity, and accounting for DED severity and aetiology are essential for an evidence-based, individualized approach to DED treatment.

Keywords: artificial tears; dry eye disease; dry eye treatment; hyaluronate; hyaluronic acid.

Fig. 1

Illustration of the pre‐corneal tear film containing hyaluronic acid. Hyaluronic acid attracts surrounding water molecules with its numerous hydroxyl groups, thickening and stabilizing the mucoaqueous layer of the tear film. Illustration by Emily Moschowits.

Fig. 2

The hyaluronic acid molecule made up of repeating N‐acetyl‐glucosamine and glucuronic acid linked together via alternating β‐1,3 and β‐1,4 glycosidic bonds. Illustration by Emily Moschowits.

Fig. 3

Hyaluronic acid increases tear film stability. (A, 1–4) Cross section of a thin tear film in dry eye disease with short tear film break up time (TBUT). (B, 1–4) After application of hyaluronic acid, the tear film increases in viscosity and thickness and allows for even distribution across the ocular surface. Proportions are exaggerated for illustrative purposes. Illustration by Emily Moschowits.

Fig. 4

Timeline of the discovery and development of HA in ophthalmology. DED = dry eye disease, HA = Hyaluronic acid. Illustration by Emily Moschowits. [Correction added on 14‐May‐2022, after first online publication: Figure 4 was corrected in this version.]

Fig. 5

Methodology for determining studies of relevance for the present review.

Fig. 6

Number of included studies conducted in each country. Generated by Bing in Excel by Emily Moschowits.

Fig. 7

Modified Vicious Circle of Dry Eye Disease inspired by Bron et al. Hyaluronic acid treatment attempts to break the circle. Blue drops illustrate action‐points where hyaluronic acid contributes. Illustration by Emily Moschowits, using elements from Sara Nøland with permission.