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

David A. Semp, Debarun Dutta, James S. Wolffsohn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number102568
Number of pages6
JournalContact Lens and Anterior Eye
Volume49
Issue number1
Early online date15 Nov 2025
DOIs
Publication statusE-pub ahead of print - 15 Nov 2025

Bibliographical note

Copyright © 2025 The Authors. Published by Elsevier Ltd on behalf of British Contact Lens Association. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Keywords

  • Hyaluronic acid
  • Tear film
  • Dry eye
  • Artificial tear
  • Ocular symptoms
  • molecular weight
  • concentration

Fingerprint

Dive into the research topics of 'Clinical impact of varying the molecular weight of hyaluronic acid in artificial tears – A randomised controlled crossover trial'. Together they form a unique fingerprint.

Cite this