Article

More treatments, more refined targets

New dry eye disease treatments take aim at tear quality, not just quantity.

Since the early 2000s our knowledge of dry eye disease — its various pathologies, the different diagnoses and multiple modes of treatment – has increased considerably.

So what have we done with all this knowledge?

Along with the importance of treating lid margin disease, researchers have furthered our understanding of the role that inflammation and tear quality, not just tear volume, play in DED. These advances led to the development of the first anti-inflammatory treatments to increase tear production, including Restasis (cyclosporine emulsion 0.05%, Allergan), which received FDA clearance in October 2003.

Cyclosporine’s approval is indicated to increase tear production in patients when it is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.

Last year, Shire introduced a new DED treatment that targets the inflammatory cycle: lifitegrast ophthalmic 5% solution (Xiidra, Shire), the first prescription drug to receive FDA clearance to treat the signs and symptoms of DED in adults. Lifitegrast is the first in a new class of drugs known as lymphocyte function-associated antigen 1 (LFA-1) antagonists

And now, with both medications to work with, physicians have been figuring out which treatment works best for which disease type.

au naturel Restasis

TrueTear’s (see sidebar p. 34) approval follows that of Restasis Multidose (cyclosporine ophthalmic emulsion 0.05%, Allergan). Introduced in October 2016, Restasis MultiDose is a preservative-free, multidose formulation of Allergan’s 2003 FDA-cleared treatment. The earlier version comes in single-dose vials, which older patients sometimes have had difficulty squeezing, says Marjan Farid, MD. “Many of my older patients often ask me, ‘Does Restasis come in a bottle?’ And the original doesn’t. [But now] the multidose bottle offers ophthalmic professionals a new delivery solution for these patients.”

–– Joseph F. Jalkiewicz

TARGETED PATIENTS

I have found cyclosporine and lifitegrast to be effective first-line treatments for two types of DED patients. The first are those who complain of chronic dryness due to heavy computer use, reading and other activities that require close-up eye work, despite their use of artificial tears and eye drops.

New product brings tears to your eyes

By Joseph F. Jalkiewicz

In April, Allergan received marketing approval from the FDA for TrueTear Intranasal Tear Neurostimulator, the first cleared device to temporarily increase tear production during neurostimulation in adult patients.1

According to a company statement, TrueTear is a handheld stimulator with daily disposable tips inserted into the nasal cavity to induce tear production.

“It’s a neurostimulator device that patients actually place into their nose and it gives a small electrical stimulation to the nerve endings of the nose that create a little stimulation and cause a release of tears, sort of a welling up of tears in the eye,” says Marjan Farid, MD, director of Cornea, Cataract, and Refractive Surgery and vice-chair of Ophthalmic Faculty, Gavin Herbert Eye Institute, University of California-Irvine.

Dr. Farid says the tears generated by the device aren’t just reflex tears, but complete tears, comprising the oily, aqueous and mucous layers.

Two clinical studies that enrolled 145 aqueous-deficient adult dry eye patients showed positive safety and the device’s effectiveness in the increase of tear production. During these clinical trials, researchers did not assess the direct clinical benefit of temporarily increasing tear production as a therapy for DED patients, the company says.1

The most commonly reported side effects in the trials included:

  • nasal pain, discomfort or burning (10.3%)
  • transient electrical discomfort (5.2%)
  • nosebleed (5.2%)
  • nasal congestion (3.1%)
  • headaches (2.1%)
  • trace blood, dot heme in nostril (2.1%)
  • facial pain (2.1%)
  • sore eye (1.0%)
  • sinus pain (1.0%)
  • periorbital pain (1.0%)
  • runny nose (1.0%)
  • nasal ulcers (1.0%)
  • light-headedness (1.0%).1

REFERENCE

  1. Allergan granted marketing authorization by the FDA for TrueTear, the first intranasal neurostimulating device proven to temporarily increase tear production [Allergan, Plc Press Release]. Dublin, Ireland. April 25, 2017.

Older, cataract-surgery patients comprise the second group. A large percentage of patients come in for cataract surgery and don’t necessarily feel dry, but they show signs of DED. Dry eyes can adversely impact testing outcomes, which in turn can impact postsurgical outcomes, so it’s a good idea to treat DED before performing biometry measurements for cataract surgery. In our practice, lifitegrast has proven a quick and effective DED treatment for these patients.

AN ALTERNATIVE, PLEASE

Ophthalmologists need an alternative anti-inflammatory for patients who do not respond well to cyclosporine. Cyclosporine and lifitegrast are two different drugs that work by different mechanisms of action.

No two dry eye patients are the same, and some may respond to one drug and not the other.

Outside of corticosteroids, we have no other long-term anti-inflammatory treatment options for DED patients. Corticosteroids are great; they have a quick onset of action, but because of their potential to raise intraocular pressure and their cataractogenic properties, their use is limited to the short term. The good thing about cyclosporine and lifitegrast is that we can use them over the long term as they have good tolerability and safety profiles.

QUALITY, NOT QUANTITY

Anti-inflammatory medications are effective, but they cannot do the job if we don’t educate those professionals who manage DED patients. The 2016 ASCRS survey showed that most general and anterior segment optometrists and ophthalmologists still treat DED with artificial tears alone or by addressing tear volume with artificial tears or punctal plugs.

And while these treatments have their place, we need to amplify the message that DED treatment is about tear quality, not simply tear volume. We need to learn to use these advances and remain open to new treatments that can improve the causes of DED.

So many different factors play a role, from hormonal changes in women to occupational, environmental and autoimmune factors, and this makes every dry eye patient so different. Our goal should be to find the right treatment regimen for our patients so they think about their dry eyes less and have more good days than bad. OM

About the Author

Marjan Farid, MD is the director of Cornea, Cataract, and Refractive Surgery, and the vice-chair of ophthalmic faculty at the Gavin Herbert Eye Institute, University of California-Irvine.
Disclosure: Dr. Farid is a consultant to Allergan, Shire and Johnson & Johnson Vision.