November 2017


Dry eye disease update
Taking stock of dry eye treatment’s present and future

by Vanessa Caceres EyeWorld Contributing Writer

Kazuo Tsubota, MD, gives
step-by-step instructions on how to properly wash eyes with Eye Shampoo Long

Aqueous deficient dry eye disease; lissamine staining of cornea and conjunctiva
Source: Vincent de Luise, MD

Patient with cornea punctate epithelial erosions (left) and corresponding fluorescein staining indicative of dry eye disease and unstable tear film (right)
Source: Preeya Gupta, MD


Restasis and Xiidra remain big players; other therapies will join the mix

For many years, dry eye patients and their ophthalmologists struggled with a lack of treatment options.
Now, as dry eye therapy comes into its own, the available treatments continue to expand.
Dry eye experts perform the requisite assessments to determine if a patient has aqueous deficient or evaporative dry eye so they can tailor treatment accordingly. Experts interviewed for this article will also assess for meibomian gland disease (MGD), a common and sometimes overlooked condition, said Preeya K. Gupta, MD, associate professor of ophthalmology, cornea and refractive surgery, Duke University Eye Center, Durham, North Carolina.
The subsequent treatments will often depend on the type of dry eye present and will follow recommendations from evidence-based guidelines by the Delphi Panel or the recently updated Dry Eye WorkShop (DEWS II) information. In Japan,
another set of recommendations that can guide treatment is Tear
Film Oriented Therapy from the Dry Eye Society, according to Kazuo Tsubota, MD, professor and chairperson, Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
To treat aqueous deficient dry eye patients, Vincent de Luise, MD, assistant clinical professor of ophthalmology, Yale University School of Medicine, New Haven, Connecticut, recommends increased humidification, foods rich in omega-3, and non-preserved tears. Dr. de Luise recommends a short course of loteprednol (Lotemax, Bausch + Lomb, Bridgewater, New Jersey) and initiation of cyclosporine (Restasis, Allergan, Dublin, Ireland) or Xiidra (lifitegrast, Shire, Lexington, Massachusetts).
In evaporative dry eye patients, his recommendations include a diet rich in omega-3, topical azithromycin, warm compresses, expression of the meibomian glands, use of LipiFlow (TearScience, Morrisville, North Carolina), and oral minocycline.
As newer options become part of dry eye treatment, ophthalmologists must consider what is appropriate to add or substitute.

Restasis and Xiidra

One major new player for dry eye therapy is Xiidra, which was approved by the U.S. Food and Drug Administration (FDA) in July 2016. Dry eye practitioners now must consider whether patients are better suited for Restasis or Xiidra.
“I think both are excellent molecules, and I use both in my treatment of dry eye disease,” Dr. Gupta said. Because clinical trials show that Xiidra is effective in as early as 2 weeks in some studies, she’ll use the latter when patients need to optimize their ocular surface before surgery. Some patients have trouble with Xiidra because of side effects such as burning or blurred vision.
Dr. Gupta has many years of clinical experience with Restasis and finds it helpful. “I have used Restasis off-label in many patients to help with certain corneal conditions associated with chronic inflammation,” she said.
Dr. de Luise also recommends Restasis and advises short-term use of an ester steroid like loteprednol to “kick start” the anti-inflammatory process as Restasis takes effect.
In some patients, Xiidra does indeed work faster, he added. It also may be a good option for patients when Restasis does not work. However, insurance issues are often a deciding factor. “Restasis has been approved since 2003 and is on most formularies. Xiidra is now on many formularies, but there are still some issues with coverage,” Dr. de Luise said.
As Xiidra and Restasis are not available in Japan, Dr. Tsubota could not comment on their effectiveness. However, he noted that with the Tear Film Oriented Therapy he targets aspects of dry eye disease beyond just inflammation. “There are many targeted therapies for the tear and mucin layers, or MGD treatment for the lipid layer,” he said.
Dry eye experts are adding other new treatments to their armamentarium.
“The newest treatment that I have been using for my moderate to severe patients is amniotic cytokine extract drops,” Dr. Gupta said. “These drops are made by Ocular Science [Manhattan Beach, California] via a compounding pharmacy and are shipped to the patient. They store them in the freezer and then open one vial per day.” Dosing is one drop twice a day. “I have had patients significantly improve with respect to corneal staining and symptoms,” she said.
Dr. Gupta has also begun to use the TrueTear Intranasal Tear Neurostimulator (Allergan) to stimulate tear production, meibum secretion, and goblet cell degranulation. “Patients can use this ‘on demand’ at home to help with symptoms of dry eye disease,” she said.
A newer product developed in Japan called Eye Shampoo Long (MediProduct, Tokyo, Japan) could potentially be helpful to patients with MGD, Dr. Tsubota said. In a study with 10 patients who used Eye Shampoo Long, there was a significant improvement in symptoms.1

Dry eye pipeline

Ophthalmologists say they are enjoying this time of a larger number of options available or under development for dry eye.
One upcoming product that Dr. Gupta is watching is P-321 (Parion Sciences, Durham, North Carolina), an ENaC inhibitor that blocks tear loss through the absorptive pathway. So far, a Phase 1/2a study has been done in 53 patients, according to the Parion Sciences website.
Another agent she is optimistic about is recombinant human lubricin (PRG4, Lubris BioPharma, Framingham, Massachusetts), which is found on knee cartilage and other tissues throughout the body. Lubricin had a greater than 72% reduction in foreign body sensation, burning/stinging, pain, and other factors in a small clinical trial.2
Dr. de Luise cited various therapies under development, including lubricin and the KPI-121 nanoparticle (Kala Pharmaceuticals, Waltham, Massachusetts), currently in Phase 3 trials.
One other product of interest to Dr. de Luise is tavilermide (MIM-D3, Mimetogen, Gloucester, Massachusetts), a mucin agonist that may help patients with dry eye. “Currently, there is no FDA-approved medication that specifically targets evaporative dry eye. Tavilermide could be one of those agents,” he said.


1. Kobayashi A, et al. Effects of a new eyelid shampoo on lid hygiene and eyelash length in patients with meibomian gland dysfunction: A comparative open study. J Ophthalmol. 2016;2016:4292570.
2. Lambiase A, et al. A two-week, randomized, double-masked study to evaluate safety and efficacy of lubricin (150 μg/mL) eye drops versus sodium hyaluronate (HA) 0.18% eye drops (Vismed) in patients with moderate dry eye disease. Ocul Surf. 2017;15:77–87.

Editors’ note: Dr. Gupta has financial interests with Allergan, Novartis (Basel, Switzerland), Ocular Science, and Shire. Dr. Tsubota has financial interests with MediProduct. Dr. de Luise has no financial interests related to his comments.

Contact information

de Luise

Taking stock of dry eye treatment’s present and future Taking stock of dry eye treatment’s present and future
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