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My understanding is pts are frustrated with how long it takes to get relief with Restasis(cyclosporine) and Xiidra. Both have significant side effects upon initiation and can take weeks if not months before the patient gets relief and that translates to a high discontinuation rate (60-70% within 2-3 mos)). Both Restasis and Xiidra must be taken continuously which becomes expensive. According to surveys 82% of Restasis and Xiidra pts suffer from flares. The DED population is severely underserved...90% of DED pts are not on either Rx and 80-90% of DED pts suffer from flares.

For dry eye flares Eysuvis works much faster than Restasis or Xiidra...within 2 days the patient feels less discomfort. Lotemax (Bausch & Lomb) is the same drug (loteprednol etabonate) as Eysuvis except Eysuvis uses a proprietary nanoparticle delivery technology (AMPPLIFY) which increases LE penetration to corneal and aqueous humor by more than 3x. Lotemax is not approved for DED flares but some optometrists have been prescribing Lotemax off-label. Currently about 3% of the 17.2M DED pts are prescribed off-label steroids. The KALA investment thesis is that optometrists will switch from off label steroids i.e. Lotemax to Eysuvis for flares, will also prescribe Eysuvis when starting pts on Restasis or Xiidra and will switch those who discontinue to Eysuvis with the aim of prescribing 4-5 cycles over a yr. The average patient experiences 2 to 7 dry eye flares on a yearly basis.

some perspectives on flares from a few eye docs...

https://www.eyeworld.org/download/file/fid/453#:~:text=The%20average%20patient%20experiences%202,eye%20flares%20throughout%20the%20year.

Rapid relief
Richard Lindstrom, MD, noted that he understands the expectations and demands of these patients for several reasons including that he has firsthand experience with dry eye symptoms. “I have mild dry eye and I experience flares that are primarily a result of environmental influences.

When these flares occur, I want a solution that produces a rapid response. I want something that is powerful and potent and works fast,” he said. Although artificial tears may provide some palliative relief, they do not address the underlying inflammation that is the primary driver of a flare and thus are typically insufficient to provide adequate relief. Likewise, currently approved anti-inflammatory therapies may be appropriate for chronic management but not for episodic symptom flares, as the onset of relief is not rapid enough for acute symptom relief from a dry eye flare.

Dr. Donnenfeld said that addressing this need is paramount. “Dry eye flares are an extraordinarily common part of dry eye management. Although there are excellent dry eye therapies available, we haven’t had therapeutics specifically for managing dry eye flares. This opens up a new avenue for managing dry eye because patients who are on maintenance therapy but still have flares are not happy with their treatment,” he said. “The majority of dry eye patients are not on therapy and they may just have episodic dry eye that occasionally flares up, and a periodic short course of therapy might be adequate for them,” he continued. “However, most patients who are on maintenance therapy, whether it be artificial tears, immunomodulators, or oral medications, still experience flares throughout the year as well.”

https://docs.google.com/viewer?url=https%3A%2F%2Fwww.reviewofoptometry.com%2FCMSDocuments%2F2020%2F10%2FSunPharma.pdf

Dr. Kabat: Until the late 1990s, drug therapy for dry eye was
unheard of. We had artificial tears, which accounted for as
much as 80% of our therapeutic management, and the re-
mainder of patients became candidates for punctal occlusion.

Dr. Steven Pflugfelder and other pioneers showed us that
anti-inflammatory medications could provide significant relief
for those suffering from dry eye,19 but many of us hesitated
because the approach involved off-label use of a corticoste-
roid—a drug class that we had been taught was to only be
used in extreme cases and with the utmost caution. When
topical cyclosporine was introduced in 2003, we were initially
elated to finally have a medication that was specifically indicat-
ed for treating keratoconjunctivitis sicca. However, we quickly
found that a good percentage of patients failed to respond
to this new formulation in the manner that we had hoped.
Moreover, it was very difficult to predict which patients would
succeed and which would ultimately fail or discontinue therapy
because of intolerability, cost issues, or simply frustration.
My biggest challenge in developing an effective treatment
regimen for dry eye is two-fold. First, it has taken many years
to realize that not all dry eye is alike in its composition or man-
ifestations, and, hence, there is no single therapy that works
for every patient. A good dry eye doctor understands that, to
be successful, one must first identify the most significant con-
tributory element of the ocular surface disease and manage it
aggressively through whatever means are most appropriate.

Second, when inflammation is present, we can no longer af-
ford to use agents that take up to six months to begin yielding
improvement. If my experience has taught me anything, it’s that
patients are not very patient! The symptomatic individuals who
I see today want and expect relief, or at least some indication
of recovery, in a matter of days or perhaps weeks. If I’m lucky,
they may give me one or two months.