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Dry eye disease is a heterogeneous condition associated with a wide range of conditions and approaches to treatment. Two of the more prevalent causes of dry eye symptoms are immune-mediated conditions such as keratoconjunctivitis, and blepharitis due to demodex.

"Different 'dry eye' subtypes need different approaches," Anat Galor, MD, MSPH, a professor of ophthalmology at the University of Miami and a spokesperson for the American Academy of Ophthalmology, told 乌鸦传媒. "For a long time, our focus was on anti-inflammatory medications, which makes sense because many (but not all) subtypes have inflammation as a key component."

"Allergic keratoconjunctivitis is often managed with cromolyn sodium eye drops, mast cell stabilizers that work by preventing mast cells from triggering the immune response," explained Chantal Cousineau-Krieger, MD, staff ophthalmologist at the National Eye Institute in Bethesda, Maryland.

"Another option is olopatadine hydrochloride (Pataday), which works two ways -- as an antihistamine and a mast cell stabilizer," she noted. "It's available over-the-counter [OTC] in a lower strength. I was very happy when that came on the market."

You have to be careful what you're using with the OTC products, Cousineau-Krieger noted. "Patients should be counselled against a common practice of using redness-reducing eye drops for longer than 2 or 3 days, since chronic use can lead to permanent dilation of the blood vessels."

In general, Cousineau-Krieger advises dry eye disease patients to avoid smoking, use a humidifier, and limit screen time or use a timer to schedule more frequent breaks: "Use the 20-20-20 rule – for every 20 minutes of screen time, look at something at least 20 feet away for a minimum of 20 seconds."

Cyclosporine: Evolution of a Treatment Mainstay

has been established for years to treat chronic dry eye where inflammation leads to reduced tear production and ocular surface disruption, Galor noted. "Over time, companies have changed the medication's formulation and concentration to try to improve efficacy and decrease side effects, such as burning and a pain sensation often reported by patients: First, we had 0.05% cyclosporine emulsion (Restasis), followed by Cequa, which is a higher 0.09% concentration in an aqueous solution."

A 0.1% cyclosporine ophthalmic emulsion (Verkazia) was recently for the treatment of vernal keratoconjunctivitis and , both subtypes of allergic disorders in which inflammation plays a prominent role, said Galor. New formulations of cyclosporine are currently being investigated in clinical trials, with promising results as well.

The LFA-1 antagonist lifitegrast (Xiidra) also aims at decreasing T-cell inflammation, noted Cousineau-Krieger: "What's hard is that it takes several weeks of continued application to work, and there may be stinging or redness or burning, so a lot of people abandon these treatments quite early, after a few days of trying them. People need to be counseled that it's going to take weeks before there's any improvement, and up to 3 months to relieve symptoms."

Lifitegrast can also cause a bit of an abnormal taste, added Nandini Venkateswaran, MD, a cornea specialist at Massachusetts Eye and Ear in Boston. "Often when I start patients with topical immunomodulators, I prescribe 2 weeks of steroids so that the side effects such as irritation and burning are less pronounced. They are able to acclimate to the treatment quicker and these side effects are usually short-lived."

"Loteprednol 0.25% (Eysuvis) is manufactured with a special mucus-penetrating particle technology, called MPP technology, so even though it's a lower concentration of steroid, the molecule can more effectively penetrate the ocular surface and deliver steroid to the ocular surface tissue," Venkateswaran noted.

Cousineau-Krieger also uses steroids "for less than 2 weeks to break the cycle of inflammation, while you're waiting for long-acting treatments to come into play. However, long-term use can cause increased pressure, glaucoma or cataracts, or change the texture of the skin around the eye."

Galor said that "not everyone who fits under the umbrella of dry eye needs an anti-inflammatory, or that's not all they need, which raises the question of what else needs to be treated."

In cases of meibomian gland dysfunction, "we sometimes prescribe topical azithromycin (AzaSite)," noted Venkateswaran. "It's harder to get now due to supply shortages, but patients who have used it love it."

In the Pipeline

Topical ivermectin 1% cream (TP-03) is under investigation for demodex blepharitis, which is fairly prevalent in the older population, although it may not always cause symptoms, noted Galor. An early suggests that applying the cream for 15 minutes once weekly in addition to eyelid hygiene improved symptoms compared with eyelid hygiene alone.

"Up to now, we've been using topical OTC products that contain tea tree oil or oral ivermectin to treat demodex blepharitis," said Galor. "We still need more information to understand which cases of demodex need to be treated, but the idea that we're going to have a specific product to treat a specific ocular surface condition is exciting," she noted.

Researchers are also examining which other aspects of the immune system can be modulated in patients with ocular surface inflammation, Galor told 乌鸦传媒. Reproxalap, an investigational small-molecule modulator of reactive aldehyde species (RASP) currently in phase III clinical development as a 0.25% ophthalmic solution, is being investigated as a novel therapy for dry eye disease and allergic conjunctivitis.

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