With a plethora of nonpharmacologic and pharmacologic treatments for dry eye disease (DED), clinicians must choose therapeutic strategies for the common condition carefully, experts told MedPage Today.

“DED is multifactorial, with a vicious circle of cofactors that vary in proportion from Patient to patient,” said John Sheppard, MD, a professor of ophthalmology at Eastern Virginia Medical School in Norfolk. “The clinician must intelligently select those factors most likely to respond to a therapeutic or environmental intervention.”

The first clinical challenge is recognizing DED. About 7% of U.S. adults have been diagnosed with the condition, another 2.5% have symptoms of it, and DED can range widely in its severity.

The obvious symptoms are eye burning and redness, and a common patient complaint is blurred vision.

“If vision fluctuates from clear to blurry to clear, this indicates there may be an unstable Tear film,” said Walter Whitley, OD, director of professional relations and education at Virginia Eye Consultants.

Typically, DED patients have started using over-the-counter artificial tears several times a day, with little to no effect. Once a clinician suspects DED, patient questionnaires such as the Standard Patient Evaluation of Eye Dryness Questionnaire (SPEED) and Ocular Surface Disease Index (OSDI) surveys can help establish the diagnosis.

“We make sure to consistently ask four simple questions: Are you bothered by dry eyes? Do you feel the need to use eye drops? Does your vision change or fluctuate during the day? Are you bothered by red eyes?” said Whitley.

If patients exhibit symptoms or signs of eye dryness, then clinicians will test for corneal surface damage and quick tear film breakup time, look at the eyelids to address any bacteria or mite infection, and examine the quality of the meibomian glands, as well as conduct tests for matrix metalloproteinase-9 (MMP-9) for possible inflammation. In addition, they will study tear film stability or the osmolarity of tears.

The Tear Film & Ocular Surface Society notes that 80% of patients have mixed mechanism DED, said Whitley. DED can be divided into two major categories: aqueous tear deficiency and evaporative dry eye, which is mostly due to meibomian gland dysfunction (MGD).

Many factors can contribute to the development of DED, including ocular and systemic diseases, topical and systemic medications, and environmental conditions. Because DED is a chronic disorder, treatment is most often long-term and may utilize both nonpharmacologic and pharmacologic interventions to address all etiologic components.

Conservative Nonpharmacologic Treatments

Typical initial conservative therapies for DED include environmental and lifestyle modifications, said Sheppard, including artificial tears, reduced wind and other desiccation factors, reduced cigarettes, improved diet, reduced glaucoma drops, and reduced preservatives in drops.

At-home therapies can also include warm compresses with a washcloth or eye mask, a lid hygiene cleanser, nutraceuticals such as omega-3 supplements to reduce inflammation, a humidifier to moisten room air, taking computer breaks to restore tear film to the eyes, and better hydration to insure adequate function of the secretory apparatus.

“The most important part of treatment is to explain basic eye anatomy in easy terms to educate patients so they invest themselves in the treatment,” said Chantal Cousineau-Krieger, MD, of the National Eye Institute. “Understanding of the treatment leads to better patient engagement and compliance.”

Systemic conditions also need to be identified. More than 50% of diabetes patients have DED. Multiple medications, including antidiuretics, sedatives, allergy treatments, systemic antihistamines, and autoimmune therapies can lead to more eye dryness. In the eye itself, chronic glaucoma therapy with preserved drops and contact lenses can lead to dryness.

Pharmacologic Treatments

With multiple treatment options, clinicians must choose among the available drugs and decide when to use off-label therapies.

The commonly prescribed topical and systemic agents used to treat DED, said Sheppard, include five currently approved agents: cyclosporine 0.05% (Restasis), lifitegrast (Xiidra), cyclosporine 0.09% (Cequa), loteprednol (Eysuvis), and varenicline solution (Tyrvaya) nasal spray. Other oral medications include doxycycline, azithromycin, and prescription polyunsaturated fatty acids, none of which are specifically FDA-approved for DED.

“Based on clinical findings, I may choose a corticosteroid, which may work the fastest,” said Whitley. Clinicians generally prefer on-label therapy for their proven efficacy and safety.

Corticosteroid eye drops can result in significant improvement of DED signs and symptoms, but the duration of therapy should be kept short to avoid steroid-related adverse events. Topical cyclosporine A is commonly used for DED, however, a long duration of use is required to achieve optimal response.

“Restasis has been a tried-and-true treatment for more than 20 years. There is strong data that Xiidra provides relief in as little as 2 weeks, and Cequa treats corneal staining in as little as 1 month,” said Whitley. Some patients prefer nasal sprays or have comorbidities that obviate the use of oral medications.

However, insurance companies often dictate what’s covered, said Cousineau-Krieger, and cost can be a big challenge.

“Lubricating drops are not covered by most insurance companies, and can be quite expensive if patients need them frequently,” she said. Prior authorization can also be a challenge, she said.

Clinical findings dictate choice of therapy. “Once we have a diagnosis, we tell patients this is their condition, why they have it, and our strong recommendation on what to do about it,” said Whitley. “There’s no one-size-fits-all therapy. That’s why we need so many options.”

Three new drug applications have been submitted to the FDA as well for DED: perfluorohexyloctane (NOV03), cyclosporine ophthalmic solution (CyclASol), and lotilaner.

Procedural Therapies and Devices for DED

Due to comorbidities and the severity of the disease, clinicians often have to utilize other treatments, including point-of-service cash-pay procedural therapies and devices. Common procedural therapies, said Sheppard, include punctal plugs, thermal pulsation, and lid margin microdermabrasion. Device-based therapies in common use are LipiFlow, BlephEx, and TearCare.

Again, a good diagnosis is imperative. “If we find a patient has MGD, then treatment may include topical therapy or procedures such as thermal pulsation, intense pulsed light, or meibomian gland probing,” said Whitley.

An underutilized DED treatment option is punctal occlusion to reduce tear outflow. Cases that don’t respond to lubrication alone can be successfully relieved by occlusion of the lacrimal puncta with absorbable or nonabsorbable plugs.

In cases of significant DED with no response to other therapies, autologous serum drops may be useful. These drops, made from the patient’s own blood, contain highly concentrated growth factors essential for ocular surface health. They are used to treat ocular surface diseases, such as persistent epithelial defects, superior limbic keratoconjunctivitis, and neurotrophic keratopathy.

A viable option for severe refractory DED is scleral contact lenses. They prevent evaporation and avoid corneal desiccation, and the large lens diameter protects the entire ocular surface. Another higher cost choice is prosthetic replacement of the ocular ecosystem, or PROSE, a precisely custom fit and manufactured gas-permeable rigid scleral lens that maintains an oxygenated fluid reservoir over the corneal epithelium.

“DED affects up to half of the eye-care population. It’s a quality-of-life issue, and therefore important to optimize the ocular surface to provide clear, comfortable vision,” said Whitley.