Trehalose & Eye Care Trehalose & Eye Care A Molecule Poised to Revolutionize Ocular Surface Care By Marguerite McDonald, MD, FACS cular surface disease and dry eye disease are prevalent and What is Trehalose? pervasive diseases impacting the eye health of patients. The Dry Eye Workshop II (DEWS II) and current research offer new Oinsights on the characteristics of pathophysiology of Dry Eye Disease (DED), as well as best practices for treatment and management. Therapeutic strategies that support the ocular surface, counteract hy- Trehalose—a bisacetal, non- perosmolarity and restore the tear fi lm can aid in rehabilitating the eye’s reducing homodisaccharide in structures. This knowledge offers an opportunity to introduce new ways to which two glucose units are linked together in a α-1,1-glycosidic stabilize the tear fi lm and improve patient comfort through rehydration, re- linkage (α-d-glucopyranosyl- duction of surface infl ammation, and protection against future dessication. α-d-glucopyranoside; mycose, An expanding pool of clinical data is supporting the benefi ts and sus- mushroom sugar)1—is found tained effi cacy of therapies that include bioprotectants such as trehalose abundantly in nature and in the biological world. The “extraordi- to protect cells against hyperosmolarity and promote exit of the vicious nary” properties of trehalose are cycle of DED physiopathology.1 responsible for this molecule’s As such, lubricant eye drops enhanced with trehalose can provide bioprotective role.1 1. Jain NK, Roy I. Effect of trehalose on protein patients with a new, successful way to rehabilitate the tear film in structure. Protein Sci. 2009 Jan;18(1):24-36. Ocular Surface Disease (OSD) and DED. OSD & DED Prevalence From a pathophysiological stand- significant quality-of-life impacts. A & Impact point, DED amplifi es hyperosmolarity number of studies have reported mea- The 2017 Gallup Study of Dry Eye in an unforgiving cycle either directly surable negative effects of DED on dai- (conducted by Multi-sponsor Surveys, or by inducing a cascade of inflam- ly-living tasks such as reading, carrying Inc.) revealed that 56% of adults re- matory events, contributing to a loss out professional tasks and driving. port experiencing dry eyes frequently of epithelial and goblet cells that de- (14%) or occasionally (42%).2 Projected creases surface wettability and pro- Insights on Addressing to the U.S. population, this translates motes early tear fi lm breakup.3 the Problem to a staggering 140 million dry eye In addition to the physical toll this The Tear Film & Ocular Surface sufferers.2 disease takes on patients, it also has Society (TFOS) published the Dry Eye Sponsored by 18 | REVIEW OF OPHTHALMOLOGY | MAY 2018 000_rp0518_theraMD_v4.indd 18 4/13/18 2:35 PM ADVERTORIAL Trehalose – Enhancing junctiva, which may have suffered the Clinical Support as an Excipient sequelae of dry eye. for Trehalose New research shows that recent Studies have shown that trehalose offers Excipient—an inactive substance attempts to counteract tear hyper- the following ocular surface benefi ts: that serves as the vehicle or medium osmolarity in DED have included • Protection of human corneal epithelial for a drug or other active substance. It bioprotectant features and small or- cells from desiccation-induced death confers a therapeutic enhancement on ganic molecules used in many cell in culture.7 One trehalose-containing the active component in the form of, for types throughout the natural world to solution was found to be “effective example, additional absorption, solubility restore cell volume and stabilize pro- and safe” for treatment of moderate to or strength. tein function.1 These molecules may severe dry eye syndrome. directly protect cells against hyperos- • Increased tear fi lm thickness after Essentially, an excipient serves to molarity and promote exit from the vi- instillation of one trehalose-containing enhance the effectiveness of an active cious circle of DED physiopathology.1 drop up to 240 minutes compared with drops without trehalose.8 ingredient. There is an expanding pool of clinical • Better patient satisfaction and a data on the efficacy of DED thera- therapeutic advancement in treat- pies that include trehalose, whose ment of moderate to severe DED when Workshop II report, which includes unique properties have shown ex- comparing an eyedrop containing a more comprehensive DED defini- ceptional osmotic and bioprotectant hyaluronic acid-trehalose with an HA- tion that keenly accounts for the piv- abilities enabling them to act as a wa- only eyedrop.9 otal role that tear fi lm hyperosmolarity ter replacement and prevent against • Increased tear production at day 14 of plays, often resulting in ocular surface desiccation stress.1,4,5 treatment in a dry eye mouse model.10 inflammation. As well, DEWS II, an • Decreased eye surface apoptosis at evidence-based report involving 150 How Trehalose Works day 14 of treatment in a dry eye mouse worldwide experts, further illuminates Trehalose maintains cell protein model.10 the pathophysiology of dry eye and integrity during drying and rehydra- • Improved appearance of ocular surface its central mechanism of evaporative tion, and it has been shown to protect epithelial disorders through suppression water loss leading to hyperosmolar against oxidative strain and stabilize of apoptosis and serum-like response tissue damage.3 protein function.6 upon topical application, as well as 10 When it comes to DED treatment, The mechanism by which this mem- maintained corneal health. longstanding research advocates the ber of the polyhydroxyl compound • Suppressed infl ammatory and proteo- use of lubricating eye drops as a pal- molecules works is by increasing com- lytic MMP-9 and HSP70 expression and keratinization, and restored ocular liative technique for symptom relief pactness and stability in organisms, surface integrity in mice with dry eye to rehabilitate some of the eye struc- thereby aiding in the overcoming of damaged by a desiccative model.11 tures, such as the cornea and con- stress conditions such as heat, cold Reawakening Dormant Desert Life Anastatica hierochuntica or white mustard fl ower, commonly called Rose of Jericho, is found in arid areas in the Middle East and the Sahara Desert.1 After the rainy season, the plant dries up, drops its leaves and curls its branches into a tight ball to hibernate. Once re-wetted in a subsequent rainy season, the ball uncurls and awakens from its dormant state, causing the capsular fruits to open and disperse seeds. The plant’s extraordinary ability to achieve this reawakening activity is attributed to the presence of trehalose, a disaccharide sugar involved in several mecha- nisms of cryptobiosis.2 1. Friedman J, Stein J. The Infl uence of Seed-Dispersal Mechanisms on the Dispersion of Anastatica Hierochuntica (Cruciferae) in the Negev Desert, Israel. Journal of Ecology 1980;68(1):43-50. 2. Wickens GE. Ecophysiology of Economic Plants in Arid and Semi-Arid Lands HYDRATED 1st ed. Berlin, Germany: Springer-Verlag Heidelberg; 1998. DEHYDRATED MAY 2018 | REVIEW OF OPHTHALMOLOGY | 19 000_rp0518_theraMD_v4.indd 19 4/13/18 2:29 PM Trehalose & Eye Care Trehalose Use Trehalose helps retain moisture in the tear fi lm when the in Dry Eye Disease patient is in a desiccating environment, thereby assisting in increas- Trehalose has been shown to: ing tear fi lm thickness. It decreases future irritation by protecting 1. Rehydrate Tear Film corneal epithelial cells from apoptosis after desiccation. It also sup- • Retain moisture when drying out • Help increase tear fi lm thickness8 ports homeostasis of the tear fi lm by restoring osmotic balance to 2. Protect Against Future Irritation the ocular surface.”— Marguerite McDonald, MD, FACS • Help improve corneal staining7 • Help protect corneal epithelial cells from apoptosis after desiccation3,5 3. Support Homeostasis of Tear Film lubricant eye drops enhanced with I think that trehalose will increase • Restore osmotic balance trehalose. the efficacy of artificial tears in the to ocular surface10 With dry eye, trehalose helps re- treatment of dry eye. This unique • Help maintain homeostasis tain moisture in the tear fi lm when the disaccharide offers the bioprotec- of corneal cells10 patient is in a desiccating environ- tant benefi ts that lead to comfort and ment, thereby assisting in increasing maintenance of a stable tear film, tear fi lm thickness. It decreases future which yields better and more stable irritation by protecting corneal epi- vision. and desiccation.6 As a result, trehalose thelial cells from apoptosis after des- has the unique ability to stabilize pro- iccation. It also supports homeostasis Dr. McDonald practices at Ophthal- teins and the lipid bilayer.6 of the tear fi lm by restoring osmotic mic Consultants of Long Island, a Dry Remarkably, trehalose can also act balance to the ocular surface. Eye Center of Excellence in Lynbrook, as a water substitute. Classified as a The increased bioprotectant fea- New York. kosmotrope or water-structure maker, tures and enhancement of tear fi lm this molecule is involved in various bio- thickness contribute to greater pa- 1. Baudouin C, Aragona P, Messmer EM, et al. Role of hyperosmolarity in the pathogenesis and management of dry 6 protective actions. tient comfort and less fl uctuating vi- eye disease: proceedings of the OCEAN group meeting. Ocul sion—the end goal of any ocular sur- Surf. 2013 Oct;11(4):246-58. Future of Treatment face therapy. 2. The 2017 Gallup Study of Dry Eye Sufferers (conducted by Multi-sponsor Surveys, Inc.). New trehalose-containing solutions Clinicians should absolutely consider 3. Nelson JD, Craig, JP, Esen A, et al. TFOS DEWS II Report. Ocul are becoming available to help eye using these drops as a fi rst-line treat- Surf 2017; 2017 July;15(3):269-650. care professionals offer patients an al- ment against OSD and DED. Artifi cial 4. Jones L, Downie LE, Korb D, et al.