Treatment with Hyaluronic acid for dry eyes

Hyaluronic acid is a common constituent in over-the-counter artificial tear drops that are used to treat dry eyes.

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SBU Enquiry Service

Consists of structured literature searches to highlight studies that can address questions received by the SBU Enquiry Service from Swedish healthcare or social service providers. We assess the risk of bias in systematic reviews and when needed also quality and transferability of results in health economic studies. Relevant references are compiled by an SBU staff member, in consultation with an external expert when needed.

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Published: Report no: ut202416 Registration no: SBU 2024/573

Question

What scientific studies have been published regarding the effect of hyaluronic acid in the treatment of dry eyes?

Method

A systematic literature search was performed using the following databases: Medline (via Ovid) and Scopus.
Two authors independently assessed the abstracts of all identified studies.
Risk of bias in relevant systematic reviews was assessed using an assessment tool based on AMSTAR.

Identified literature

One relevant systematic review with low risk of bias were identified [1]. The results and conclusions are presented in Table 1. In seven relevant systematic reviews [2-8], the risk of bias was considered to be high, therefore the results and conclusions are not reported. In addition, 28 relevant primary studies were identified [9-36]. These studies were published after the last date (January of 2016) of literature search in the included systematic review. Primary studies are not assessed for risk for bias.

Table 1 Systematic reviews with low/moderate risk of bias.
Included studies Population, Intervention, Control Outcome and Results
Pucker et al, 2016 [5]
Over the counter (OTC) artificial tear drops for dry eye syndrome
43 RCT 

Relevant studies according to PICO:
8 RCT 

Setting:
France: 2 studies
Italy: 2 studies
South Korea:
1 study
United Kingdom:
1 study
United States:
1 study
France & United Kingdom:
1 study		 Population:
Individuals with dry eye syndrome 

Intervention:
Hyaluronic acid

Comparisons:
0.5% carbo­xymethyl­celluose: 3 studies
(2 studies included in meta-analysis)

Carbomer opthalmic gel:
2 studies
1% carbo­xymethyl­celluose:
1 study

Hydro­xypropyl methyl­cellulose:
1 studyPolyvinyl alcohol:
1 study		 0.5% carbo­xymethyl­cellulose eye drop vs sodium hyaluronate (subjective symptoms)
Mean Difference: 0.93
(95% CI, –1.39 to 3.25)
(2 studies, n=135)

Grade:
Fyra cirklar där två är markerade med plus
Low
Authors' conclusion:
“Dry eye symptom scores showed signifi­cant improve­ment from baseline in both treat­ment groups at weeks four and eight in Lee 2011 and at month three in Baudouin 2012, but meta-analysis found uncertainty in the between-group difference [...]”

References

  1. Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016;2(2):CD009729. Available from: https://doi.org/10.1002/14651858.CD009729.pub2.
  2. Doughty MJ, Glavin S. Efficacy of different dry eye treatments with artificial tears or ocular lubricants: a systematic review. Ophthalmic Physiol Opt. 2009;29(6):573-83. Available from: https://doi.org/10.1111/j.1475-1313.2009.00683.x.
  3. Hynnekleiv L, Magno M, Moschowits E, Tonseth KA, Vehof J, Utheim TP. A comparison between hyaluronic acid and other single ingredient eye drops for dry eye, a review. Acta Ophthalmol. 2024;102(1):25-37. Available from: https://doi.org/10.1111/aos.15675.
  4. Hynnekleiv L, Magno M, Vernhardsdottir RR, Moschowits E, Tonseth KA, Dartt DA, et al. Hyaluronic acid in the treatment of dry eye disease. Acta Ophthalmol. 2022;100(8):844-60. Available from: https://doi.org/10.1111/aos.15159.
  5. Liu S, Yang G, Li Q, Tang S. Safety and efficacy of topical diquafosol for the treatment of dry eye disease: An updated meta-analysis of randomized controlled trials. Indian J Ophthalmol. 2023;71(4):1304-15. Available from: https://doi.org/10.4103/IJO.IJO_268_23.
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  14. Gross D, Childs M, Piaton JM. Comparative study of 0.1% hyaluronic acid versus 0.5% carboxymethylcellulose in patients with dry eye associated with moderate keratitis or keratoconjunctivitis. Clin Ophthalmol. 2018;12:1081-8. Available from: https://doi.org/10.2147/OPTH.S161578.
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  16. Jun JH, Bang SP, Park HS, Yoon D, Ahn JY, Kim SJ, et al. A randomized multicenter clinical evaluation of sequential application of 0.3% and 0.15% hyaluronic acid for treatment of dry eye. Jpn J Ophthalmol. 2022;66(1):58-67. Available from: https://doi.org/10.1007/s10384-021-00885-x.
  17. Labetoulle M, Chiambaretta F, Shirlaw A, Leaback R, Baudouin C. Osmoprotectants, carboxymethylcellulose and hyaluronic acid multi-ingredient eye drop: a randomised controlled trial in moderate to severe dry eye. Eye (Lond). 2017;31(10):1409-16. Available from: https://doi.org/10.1038/eye.2017.73.
  18. Labetoulle M, Mortemousque B, Group CBLS. Performance and Safety of a Sodium Hyaluronate Tear Substitute with Polyethylene Glycol in Dry Eye Disease: A Multicenter, Investigator-Masked, Randomized, Noninferiority Trial. J Ocul Pharmacol Ther. 2022;38(9):607-16. Available from: https://doi.org/10.1089/jop.2022.0048.
  19. Laihia J, Jarvinen R, Wylegala E, Kaarniranta K. Disease aetiology-based design of multifunctional microemulsion eye drops for moderate or severe dry eye: a randomized, quadruple-masked and active-controlled clinical trial. Acta Ophthalmol. 2020;98(3):244-54. Available from: https://doi.org/10.1111/aos.14252.
  20. Lambiase A, Sullivan BD, Schmidt TA, Sullivan DA, Jay GD, Truitt ER, 3rd, et al. A Two-Week, Randomized, Double-masked Study to Evaluate Safety and Efficacy of Lubricin (150 mug/mL) Eye Drops Versus Sodium Hyaluronate (HA) 0.18% Eye Drops (Vismed(R)) in Patients with Moderate Dry Eye Disease. Ocul Surf. 2017;15(1):77-87. Available from: https://doi.org/10.1016/j.jtos.2016.08.004.
  21. Lee JE, Kim S, Lee HK, Chung TY, Kim JY, Choi CY, et al. A randomized multicenter evaluation of the efficacy of 0.15% hyaluronic acid versus 0.05% cyclosporine A in dry eye syndrome. Sci Rep. 2022;12(1):18737. Available from: https://doi.org/10.1038/s41598-022-21330-0.
  22. Lopez-de la Rosa A, Pinto-Fraga J, Blazquez Arauzo F, Urbano Rodriguez R, Gonzalez-Garcia MJ. Safety and Efficacy of an Artificial Tear Containing 0.3% Hyaluronic Acid in the Management of Moderate-to-Severe Dry Eye Disease. Eye Contact Lens. 2017;43(6):383-8. Available from: https://doi.org/10.1097/ICL.0000000000000284.
  23. Mihaltz K, Faschinger EM, Vecsei-Marlovits PV. Effects of Lipid- Versus Sodium Hyaluronate-Containing Eye Drops on Optical Quality and Ocular Surface Parameters as a Function of the Meibomian Gland Dropout Rate. Cornea. 2018;37(7):886-92. Available from: https://doi.org/10.1097/ICO.0000000000001523.
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  27. Park Y, Song JS, Choi CY, Yoon KC, Lee HK, Kim HS. A Randomized Multicenter Study Comparing 0.1%, 0.15%, and 0.3% Sodium Hyaluronate with 0.05% Cyclosporine in the Treatment of Dry Eye. J Ocul Pharmacol Ther. 2017;33(2):66-72. Available from: https://doi.org/10.1089/jop.2016.0086.
  28. Pinto-Fraga J, Lopez-de la Rosa A, Blazquez Arauzo F, Urbano Rodriguez R, Gonzalez-Garcia MJ. Efficacy and Safety of 0.2% Hyaluronic Acid in the Management of Dry Eye Disease. Eye Contact Lens. 2017;43(1):57-63. Available from: https://doi.org/10.1097/ICL.0000000000000236.
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  32. Salim S, Kamath SJ, Jeganathan S, Pai SG, Mendonca TM, Kamath AR. Comparing the efficacy of sodium hyaluronate eye drops and carboxymethylcellulose eye drops in treating mild to moderate dry eye disease. Indian J Ophthalmol. 2023;71(4):1593-7. Available from: https://doi.org/10.4103/IJO.IJO_2666_22.
  33. Sanchez-Gonzalez JM, De-Hita-Cantalejo C, Gonzalez-Rodriguez ML, Fernandez-Trueba-Fagundez A, Ballesteros-Sanchez A, Martinez-Perez C, et al. Efficacy assessment of liposome crosslinked hyaluronic acid and standard hyaluronic acid eye drops for dry eye disease management: a comparative study employing the ocular surface analyzer and subjective questionnaires. Front Med (Lausanne). 2024;11:1264695. Available from: https://doi.org/10.3389/fmed.2024.1264695.
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