October 2018


Pharmaceutical focus
Xiidra out of the comfort zone

by Maxine Lipner EyeWorld Senior Contributing Writer

Relatively severe dry eye patient with aqueous deficiency had almost complete resolution in 1 month of treatment with Xiidra
Source: Henry Perry, MD

“I think we should start diagnosing dry eye earlier in the disease process, be aggressive with dealing with the pathophysiology, and try to stop the progression.”
—Edward Holland, MD

Managing lifitegrast pseudo-failures

Many practitioners are now reaching for Xiidra (lifitegrast, Shire, Lexington, Massachusetts) 5% for dry eye cases, but sometimes a patient may not initially be considered a success. Here’s what leading practitioners are doing to help more patients find respite with Xiidra.
Edward Holland, MD, professor of ophthalmology, University of Cincinnati, pointed out that Xiidra is one of the fastest growing pharmaceuticals in ophthalmology. “Already, many dry eye patients have benefited from it, including a significant number of patients who were Restasis [cyclosporine, Allergan, Dublin, Ireland] failures,” he said.
The patients he typically looks to put on Xiidra are young to middle-aged women with aqueous tear deficiency as their primary cause of inflammatory dry eye. However, when the dry eye is very early, some patients may be overlooked for Xiidra. “Patients may present with significant symptoms because they’re early on in the disease course, but they don’t have a lot of clinical signs of dry eye,” he said. “If you control inflammation, you could turn that patient around.” In these early symptomatic patients, Dr. Holland recommends listening carefully to the patient’s history and using lissamine green to pick up interpalpebral staining instead of using fluorescein to detect dry eye.
There are some patients who have complaints of redness, burning, and pain when starting on Xiidra, Dr. Holland noted. When burning does occur, he finds that use of loteprednol first can be helpful. He cited a study he took part in that considered the question of loteprednol pretreatment prior to initiation of Restasis.1 The trial showed improved patient acceptance of Restasis as well as efficacy of the drug.
While such burning is less frequent with Xiidra, Dr. Holland will use steroid induction therapy with loteprednol in two types of cases. This includes patients who voice early complaints of burning and stinging when first placed on Xiidra, as well as those who may have significant inflammation from severe dry eye such as Sjögren’s syndrome, Stevens-Johnson syndrome, and graft-versus-host disease. With the first kind of patient, Dr. Holland will stop the Xiidra and initiate loteprednol for 2–4 weeks. In the case of extreme dry eye, he will initiate loteprednol first for this same period depending on their clinical response before introducing Xiidra.
Henry Perry, MD, chief of the cornea service, Nassau University Medical Center, East Meadow, New York, and professor, Hofstra University Medical Center, Hempstead, New York, tends to try Xiidra first without any pre-steroids, especially in mild patients.
“If they complain of burning, I usually use a mild synthetic steroid like loteprednol four times a day for 1–2 weeks, to quiet things down, then use this concurrently.” He eventually stops the steroid within 1 month. “This is similar to what we did with Restasis, but a lot of patients tolerate Xiidra the first time,” Dr. Perry said.
Dr. Perry warns against putting patients on a corticosteroid before the practitioner is sure it’s a dry eye case. “If the patient is very symptomatic, it is better to try Xiidra than a corticosteroid because a corticosteroid can mask too many things going on,” he said. He starts with lid hygiene, then moves to Xiidra, neither of which interfere with dry eye testing.
When Xiidra was initially approved, Dr. Perry often first used it on his Restasis failures. In some cases, the patients with extremely dry eyes continued to take this in conjunction with Xiidra to do whatever they could to prevent progression. “A group of patients stayed on both of those drugs,” he said. “Unfortunately, as time passed, their pharmacies required that they choose one or the other.” For patients the decision was fairly even.
Dr. Holland does not put patients on Xiidra and Restasis since they both target inflammation along a similar pathway. “If I’m going to add a second medication, I’m going to add a steroid,” he said.
In terms of contraindications, there aren’t many to offering Xiidra, Dr. Holland finds. “Unlike most things, this was not a systemic medication that was converted to a topical,” he said. “So we have no history of allergies systemically.” However, for those who have an active ophthalmic infection, it may be wise to avoid Xiidra because it’s going to suppress the immune reaction on the surface of the eyes. When it comes to patients with a history of previous viral conditions like herpes simplex virus, Dr. Holland has not had any issues with using Xiidra to this point. “I have used it in several cases of known herpes simplex virus (HSV) and have not seen it,” he said, adding that the experiences have not been long enough to know if there is cause for concern in such patients.
Based on his experience with Restasis, which did not seem to exacerbate HSV, Dr. Holland is confident that this will not be an issue with Xiidra. In fact, Xiidra could be a beneficial agent in HSV cases where steroid-sparing anti-inflammatory control is needed. Steroids are known to increase the risk of reactivation of herpes simplex virus and bring with them the need for oral prophylaxis, Dr. Holland explained, adding that it is too early to tell whether Xiidra will have a role in controlling inflammation in immune stromal keratitis.
Dr. Holland finds that one key to success with Xiidra is warning patients about potential side effects with the medication. “The patient who hears the potential side effects ahead of time will be less alarmed than the one experiencing them who has to call you back,” he said. Typically, he talks about dysgeusia with patients, warning them that there can be taste issues, although he has had minimal complaints about this. Also, in cases where there has been stinging and redness, he either will have patients dilute the Xiidra drop with an artificial tear or will add loteprednol to the regimen. In some cases, this may mean stopping Xiidra for a few weeks, then continuing after using the loteprednol.
Dr. Holland also warns patients that there are a few who experience a continued blur with the drop. “It can persist for a significant amount of time,” he said. “We can try again with a dilution of an artificial tear, but if it doesn’t bring the vision back, they won’t stay on the medication long term.” Patients won’t tolerate long-term blur but fortunately, this is uncommon, Dr. Holland noted. For patients who fail Xiidra, he recommends moving the patient to Restasis.
It’s also important to determine and classify why the patient has dry eye—whether they fit into the aqueous tear deficiency or the meibomian gland dysfunction (MGD) category, Dr. Holland said. “Try to figure out the primary pathophysiology and treat that entity first,” he said, adding that some practitioners treat all dry eye patients the same even though MGD has a different treatment paradigm. “About half of patients can have components of both, but you have to decide which treatment paradigm you want to treat first,” he said.
In cases where a patient looks like a primary aqueous tear deficiency case and they improve somewhat after taking Xiidra but still have dry eye complaints, Dr. Holland advised reassessing the meibomian glands to see if this may be the lingering issue. If someone looks as if they have primary aqueous tear deficiency and minimal MGD, Dr. Holland will usually get the patient comfortable with Xiidra alone and will add in one or two MGD therapies and see how they do.
Dr. Perry stressed that with recalcitrant dry eye cases, it’s important to cover all bases. “Nutrition is also important in terms of treating the meibomian gland disease, which may have a bacterial or a dermatologic component to it,” Dr. Perry said. “I think it’s good to check the meibum and see how that is.” Also, many patients who have dry eye also have significant blepharitis, which should be treated in conjunction with dry eye disease, Dr. Perry continued, adding that he typically checks meibography and does microblepharoexfoliation to clean the lid margins.
“Xiidra and Restasis are part of the solution, but if you’re not doing lid hygiene, if you’re not paying attention to nutrition, possible bacterial colonization, infestation, or are not aware of what’s going on in terms of dermatologic problems like acne rosacea, you’re not doing service to your patient,” Dr. Perry said.
In Dr. Holland’s view, practitioners are only diagnosing a small percentage of patients with dry eye, including those who if promptly diagnosed could be helped by Xiidra at the start instead of having to turn things around with the drug later. “I think we should start diagnosing dry eye earlier in the disease process, be aggressive with dealing with the pathophysiology, and try to stop the progression,” Dr. Holland said.


1. Sheppard JD, et al. Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%. Eye Contact Lens. 2014;40:289–96.

Editors’ note: Dr. Holland has financial interests with Shire. Dr. Perry has financial interests with Allergan and BlephEx (Franklin, Tennessee).

Contact information

: eholland@holprovision.com
Perry: hankcornea@gmail.com

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