The past few years have witnessed the introduction of new medications and devices for managing dry eye. A quick perusal of the literature and the web-based education reveals an elevated awareness of, and interest in, dry eye. The same can be said for the “pipeline” of products in development or going through the U.S. Food and Drug Administration (FDA) approval process; there are currently eight dry eye products in phase 3 trials (www.fda.gov ). In this column, we will look at two agents that show promise.
Human tears contain more than 500 proteins; they play an important role in maintaining the ocular surface, influencing the health and turnover of ocular surface epithelial cells (Tsai et al, 2006). Proteins are found in both the aqueous and lipid phases of the tear film. Lacritin has gained significant interest as a potential treatment for dry eye. This human tear glycoprotein promotes basal tear secretion.
After exogenous lacritin was instilled in eyes of rabbits, their tear film increased by 210% over a period of 240 minutes. Basal tearing became progressively elevated over a period of 14 days and was 50% over baseline one week after cessation of treatment (Samudre et al, 2011).
Reduced lacritin has been associated with corneal neuropathy in individuals who have Sjögren’s Syndrome. McNamara et al (2016) reported more than a fourfold reduction in active lacritin in Sjögren’s patients compared to controls. They also found a strong correlation between reduced tear lacritin levels and clinical signs and symptoms of dry eye disease.
A commercial form of lacritin is currently in an FDA trial, which is projected to be completed in 2018 (https://clinicaltrials.gov/ct2/show/study/NCT03226444 ).
Brimonidine is a well-known α2 adrenergic agonist that reduces intraocular pressure (IOP) by decreasing aqueous production. It is also found in a topical gel formulation (brimonidine 0.33%) for the treatment of persistent erythema of rosacea (www.drugbank.ca/drugs/DB00484 ).
One company is conducting a 12-week, three-arm study evaluating brimonidine (0.2%) for dry eye. In all arms of the study, the dosing is twice daily. The first arm uses brimonidine followed by a corticosteroid drop, the second arm consists of brimonidine followed by a placebo drop, and the third arm is a placebo carboxymethylcellulose (https://clinicaltrials.gov/ct2/show/NCT03418727 ).
It would be logical to question how a molecule used for lowering IOP could be of benefit for dry eye patients. Zhang et al (2017) reported that timolol and pilocarpine actually impair cell morphology, proliferative capacity, and survival of human meibomian gland epithelial cells.
The Tear Film and Ocular Surface Society’s Dry Eye Workshop II reported that evaporative dry eye (EDE) is the most common cause of dry eye, and meibomian gland dysfunction (MGD) is the primary underlying cause. Han et al (2018) evaluated brimonidine as a potential therapy for MGD. They found that adrenergic agonists, especially at physiological levels, are beneficial for human meibomian gland epithelial cell function; however, at higher concentrations, this effect is lost. CLS
For references, please visit www.clspectrum.com/references and click on document #272.