Published in Ocular Surface

How Hyaluronic Acid Eyedrops Fit into Dry Eye Treatment

This is editorially independent content
6 min read

With all the hyaluronic acid eyedrops available, it can become a daunting task trying to determine which of these specific products are the right fit for your patient’s dry eye needs.

How Hyaluronic Acid Eyedrops Fit into Dry Eye Treatment
With all the hyaluronic acid eyedrops available, it can become a daunting task in trying to determine which of these specific products are the right fit for your patient’s dry eye needs. Based on the questions I hear most often, here is an overview of what hyaluronic acid eyedrops are all about and what is currently offered over the counter.

First, a couple of important reminders:

  • TFOS DEWS II defines dry eye disease (DED) as a multi-factorial disease characterized by the loss of homeostasis of the tear film by tear film instability, hyperosmolarity, and ocular surface inflammation.
  • Preservative-free (PF) eyedrops are strongly recommended over eyedrops containing preservatives because studies have shown particular additives like benzalkonium chloride (BAK) and polyquaternium (Polyquad) can act as pro-inflammatory agents where they work as a detergent and break up the lipid layer of the natural tear film, causing tear film instability and toxicities to the corneal surface.1

The deal with hyaluronic acid (HA)

HA is a glycosaminoglycan (GAG) that is already naturally found in the aqueous humor and vitreous of the eye.2
HA is commonly found in PF eyedrops because:
  • HA has a strong affinity for water molecules, allowing for a high ability to bind and retain water molecules, increasing ocular surface wettability and reducing tear evaporation.2
  • HA has high viscoelasticity, which reduces the friction between the cornea and eyelids during blinking thus reducing mechanical stress and damage to the cornea.2
  • Clinical studies have shown that HA promotes healing of corneal epithelial abrasions by stimulating epithelial cell adhesion, proliferation, migration, and overall epithelial healing.2

Factors that need to be considered in HA eyedrops


It is already known that tear hyperosmolarity significantly contributes to DED. Clinical studies have shown that eyedrops with hypotonicity showed better effects on corneal and conjunctival epithelium than isotonic eyedrops. Treatment with hypotonic sodium hyaluronate eye drops gave a statistically significantly better improvement in clinical and cytological signs of DED, compared with isotonic sodium hyaluronate at the same concentration because the overall osmolarity of the tear film was reduced.3
Examples of hypotonic HA formulations include Hyabak and Thealoz Duo eyedrops and Hylo eyedrops.4

Molecular weight

The molecular weight of HA depends on the length of the chain of each molecule and the HA concentration does not always reflect the molecular weight. High molecular weight HA (HMWHA) has been shown to have a higher therapeutic effect in DED than low molecular weight HA (LMWHA) due to two main functions:
  1. HMWHA allows for higher retention of water and secretory mucin in the aqueous layer of the tear film due to having a larger chain length. This reduces friction between the eyelids and ocular surface and reduces ocular surface damage and inflammation.5
  2. HMWHA has anti-inflammatory effects while LMWHA elicits inflammatory effects. Due to HMWHA being a larger polymer, it is able to maintain secretory mucin expression, and protect the lacrimal glands and goblet cells against pro-inflammatory markers which stabilizes the tear film.
Examples of high molecular weight HA eyedrops include Hylo, Hylo Gel, and Hylo Dual eyedrops.4

HA concentration

And, of course, last but not least, concentration. The more HA, the better! A 2018 study revealed that all concentrations helped improve overall DED symptoms, and specifically reported that 0.3% HA is more effective in improving tear film instability by increasing the number of conjunctival goblet cells, and in decreasing corneal epithelial apoptosis.6
Keep in mind that eyedrops with HA can have different viscosities due to the different concentrations of hyaluronate. The higher the concentration of HA, the more viscous the eyedrop will be. The viscosity of eyedrops is important to consider because ocular contact time and bioavailability of the eyedrops can be enhanced by increasing the drop viscosity.6

How HA compares to other common artificial tear ingredients known to alleviate DED

Carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (HPMC), polyethylene glycol, polyvinyl alcohol are very common polymers that are used to mimic mucins to protect inflamed tissues and increase viscosity, and emollients are common agents used to protect evaporation by sealing in existing moisture. The main difference is that HA is already present in the natural tears and has a higher retention time on the ocular surface that promotes more epithelial cell migration, thereby supporting more epithelial healing and alleviating severe dry eye symptoms.7
Through numerous clinical studies, choosing preservative-free HA eyedrops has been shown to be beneficial for the treatment of many patients’ moderate to severe dry eye symptoms. By considering other factors such as HA concentration, molecular weight, and osmolarity, you can better clinically determine which specific preservative-free HA eyedrop products will best fit your patients individualized dry eye treatment plan.
Preservative-Free Eye DropsKey IngredientsExpiry After Opening
Hyabak0.15% sodium hyaluronate: natural hypotonic solution3 months
Thealoz DUO0.15% sodium hyaluronate: natural hypotonic solution, 3% trehalose3 months
Thealoz DUO GEL0.15% sodium hyaluronate: natural hypotonic solution, 0.25% carbomer, 3% trehalose3 months
HYLO0.10% sodium hyaluronate6 months
HYLO DUAL0.05% sodium hyaluronate, 2% ectoine (acts as an osmolyte), a borate buffer, and water6 months
HYLO GEL0.20% sodium hyaluronate, a citrate buffer, sorbitol, and water6 months
iDROP PUR0.18% viscoadaptive hyaluronan (hyaluronic acid and glycerin)12 months
iDROP PUR0.18% viscoadaptive hyaluronan (hyaluronic acid and glycerin)12 months
iDROP GEL0.30% hyaluronic acid, glycerin12 months
iDROP MGD0.20% hyaluronic acid with added glycerin, osmoprotectants12 months
Evolve Daily Intensive0.2% sodium hyaluronate, sodium chloride, borate acid, water3 months
Evolve Intensive Gel0.2% sodium hyaluronate, 0.2% carbomer, glycerol, sorbitol, sodium chloride, water3 months
HydraSense0.15% hyaluronic acid, sodium chloride, sodium citrate dihydrate, citric acid anhydrous, water12 months
HydraSense Advanced0.15% hyaluronic acid, Provitamin B5, sodium chloride, sodium citrate dihydrate, citric acid anhydrous, water12 months
HydraSense Night Therapy0.30% hyaluronic acid, sodium chloride, sodium citrate dihydrate, citric acid anhydrous, water12 months

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  1. Steven DW, Alaghband P, Lim KS. Preservatives in glaucoma medication. Br J Ophthalmol. 2018 Nov;102(11):1497-1503.
  2. HA: No Laughing Matter (2018):
  3. Aragona P, Di Stefano G, Ferreri F, et al Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjögren's syndrome patients.British Journal of Ophthalmology 2002;86:879-884.
  4. Comparing preservative free eyedrop products in Canada and looking beyond (2020):
  5. Kojima T, Nagata T, Kudo H, et al. The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice. Int J Mol Sci. 2020;21(10):3516.
  6. You IC, Li Y, Jin R, Ahn M, Choi W, Yoon KC. Comparison of 0.1%, 0.18%, and 0.3% Hyaluronic Acid Eye Drops in the Treatment of Experimental Dry Eye. J Ocul Pharmacol Ther. 2018;34(8):557-564.
  7. GOMES, J.A.P. et al. Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro British journal of ophthalmology, v.88, n.6, p.821-825, 2004.
  8. Aequus Eye Care (2021):
Deepon Kar, OD
About Deepon Kar, OD

Dr. Kar is from Calgary, Alberta. She started her healthcare career in academic research by successfully completing a Master’s degree in Neuroscience at the Cumming School of Medicine in Calgary in 2012. She then graduated from the Illinois College of Optometry in 2019 with a special interest in dry eye disease management and specialty contact lenses.

Dr. Kar moved to Lethbridge, Alberta to provide optometric care to the rural community. When she’s not looking after her patient’s eye care needs or joining her co-hosts on the Four Eyes Podcast, you can find her exploring the local trails and eateries in Lethbridge, and searching for a rescue dog to add to her family!

Deepon Kar, OD
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