Clinical impact of varying the molecular weight of hyaluronic acid in artificial tears – A randomised controlled crossover trial

Abstract

Purpose: To assess the impact of molecular weight of hyaluronic acid, of the same concentration, in artificial tears. Methods: A size exclusion high-performance liquid chromatography system with ultraviolet detection was used to measure hyaluronic acid content and establish a relative molecular weight, based on standardised hyaluronic acid samples. The rheology of HydraMed®, Evolve® and Hylo-Forte® eye drops, which all report containing 0.2 % hyaluronic acid as the principal constituent, was assessed at shear rates of relevance to blink conditions in-vitro, using a research rheometer fitted with a 60 mm aluminium flat plate measuring system at 31 °C. Twenty-five participants (aged 23.6 ± 9.2 years) meeting the TFOS DEWS II criteria for a diagnosis of dry eye disease were randomised to receive one double-masked application of each drop, on separate days. Dry eye symptom severity, non-invasive breakup time, tear meniscus height and ocular redness were assessed at baseline and 5, 15, 30, 45, 60 and 90 min after application. Results: Rheology demonstrated Hylo-Forte (2.5 M Da, 0.16 % hyaluronic acid) had a more non-linear (non-Newtonian) relationship between viscosity and sheer force (r2 = 0.295) compared to HydraMed (0.8 M Da, 0.26 % hyaluronic acid; r2 = 0.485) and Evolve (1.3 M Da, 0.24 % hyaluronic acid; r2 = 0.521). Dry eye symptoms rapidly reduced and tear stability improved with drop instillation and the effect slowly declined with time (p < 0.001), with all drops following a similar profile (p > 0.05). Hylo-Forte demonstrated the greatest reduction in dry eye symptoms and sustained improvement in tear stability. Tear meniscus height increased with drop instillation and then declined with time (F = 18.643, p < 0.001), with Evolve having a reduced initial effect compared to HydraMed and Hylo-Forte (F = 4.045, p < 0.001). Average bulbar redness was low (0.63 ± 0.44 Efron grade) and did not change with drop application (F = 1.721, p = 0.120). Conclusions: Artificial tear formulation impacts its rheology, leading to differences in clinical effectiveness, even from a single application. Higher molecular weight hyaluronic acid in Hylo-Forte demonstrated more non-Newtonian behaviour, which is more aligned with the rheology of the natural tear film.