What does this recent artificial tear additive do?

OTC artificial tears are arguably the most common first-line treatment for dry eye disease (DED). Over the last few years, we have seen new artificial tears come to market with additives to help stabilize the tear film and replace missing components. These include emollients, hydroxypropyl-guar, and sodium hyaluronate. Additionally, more preservative-free (PF) options have become available, both in single-use vials and in multi-dose bottles. The additive trehalose has been used in Europe and elsewhere in the world for several years in OTC DED treatments. Within the United States, we have only just recently noted this in some OTC tears. So, what is it, and what does it do?

WHAT IS IT?

Trehalose is a disaccharide bioprotectant that stabilizes protein and membranes. It is found in plants, microorganisms, and insects.^1,2

WHAT DOES IT DO?

In relation to DED, trehalose helps aid in osmoprotection by suppressing hyperosmolarity-induced inflammatory reaction.³ Tear hyperosmolarity triggers an inflammatory cascade, which leads to desiccation and cellular apoptosis of epithelial and goblet cells. Trehalose helps to halt this cascade. The current understanding is that it preserves cell integrity by stabilizing membrane lipids, protecting proteins, and renewing cell material, which allows the cells to adapt and survive dehydration and poor environmental conditions.^4,3,5,6

Protecting the corneal cells from desiccation, apoptosis, and impending inflammation creates an environment for accelerated healing. This leads to restoration and maintenance of the osmotic balance of the eye’s front surface. Studies have found a decrease in specific inflammatory cytokine levels and ocular surface damage, including conjunctival epithelial metaplasia, in patients who used a trehalose/hyaluronic acid tear substitute.⁷ More importantly, both corneal staining, as well as TBUT are shown to improve in two weeks and maintained at four weeks with use of trehalose dissolved in saline when compared to control of saline alone.⁸

CURRENT OPTIONS

The current options for trehalose-containing artificial tears on the U.S. market are Thera-Tears EXTRA Dry Eye Therapy, Allergan’s Refresh Optive Mega-3, Thea Pharmaceuticals’ iVizia, and Scope’s Optase MGD Advanced Dry Eye Drops. Are more coming? OM

REFERENCES

1. Hernandez, E, Taisne C, Lussignol M, Esclatine A, Labetoulle M. Commercially Available Eye Drops Containing Trehalose Protect Against Dry Conditions via Autophagy Induction. J Ocul Pharmacol Ther. 2021;37(7):386-393. doi: 10.1089/jop.2020.0119.
2. Pinto-Bonilla, JC, Del Olmo-Jimeno A, Llovet-Osuna F, Hernandez-Gaililea. A randomized crossover study comparing trehalose/hyaluronate eyedrops and standard treatment: patient satisfaction in the treatment of dry eye syndrome. Ther Clin Risk Manag. 2015;11:595-603. doi: 10.2147/TCRM.S77091.
3. Liu Z, Chen D, Chen X, et al. Trehalose Induces Autophagy Against Inflammation by Activating TFEB Signaling Pathway in Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress. Invest Ophthalmol Vis Sci. 2020;61(10):26. doi: 10.1167/iovs.61.10.26.
4. Luyckx J, Baudouin C. Trehalose: an intriguing disaccharide with potential for medical application in ophthalmology. Clin Ophthalmol. 2011;5:577-81. doi: 10.2147/OPTH.S18827.
5. Hill-Bator, A., Misiuk-Hojło, M., Marycz, K., Grzesiak, J. Trehalose-based eye drops preserve viability and functionality of cultured human corneal epithelial cells during desiccation. Biomed Res Int. 2014;2014:292139. doi: 10.1155/2014/292139.
6. Hovakimyan M, Ramoth T, Lobler M, et al. Evaluation of protective effects of trehalose on desiccation of epithelial cells in three-dimensional reconstructed human corneal epithelium. Curr Eye Res. 2012;37(11):982-9. doi: 10.3109/02713683.2012.700754.
7. Fariselli, C, Giannaccare G, Fresina M, Versura P. Trehalose/hyaluronate eyedrop effects on ocular surface inflammatory markers and mucin expression in dry eye patients. Clin Ophthalmol. 2018;12:1293-1300. doi: 10.2147/OPTH.S174290.
8. Matsuo T, Tsuchida Y, Morimoto N. Trehalose eye drops in the treatment of dry eye syndrome. Ophthalmology. 2002 ;109(11):2024-9. doi: 10.1016/s0161-6420(02)01219-8.

DR. KOETTING practices at Hines-Sight in Denver, Colo. She is a fellow of the American Academy of Optometry, diplomate of the American Board of Optometry, an active member of AOA, and a speaker and consultant for multiple companies. Follow her on Instagram at Dr_Jazz_Hands, or email her at Dr.CeceliaKoetting@gmail.com.