Eyeworld

I JUNE 2019 | EYEWORLD | 51 a steroid as my second medication than a drug with a similar mechanism." New formulations Existing anti-inflammatory agents are evolving through new formulations. "I'm excited about a new clinical trial on loteprednol 0.25%, which is under the study name of KPI-121 [Kala Pharmaceuticals]," Dr. Holland said. "This technology is a nanoparti- cle suspension that has a mucous-penetrating property, so it penetrates the ocular surface well, and therefore, you can lower the concentration and get a better effect." Inveltys, a 1% formulation using the pro- prietary AMPPLIFY mucus-penetrating particle drug delivery technology (Kala Pharmaceuti- cals) described by Dr. Holland, has already been approved by the FDA as the only twice-daily ocular corticosteroid for the treatment of in- flammation and pain after ocular surgery. A solution form of cyclosporine 0.09% is FDA-approved and available as Cequa (Sun Pharma). Another cyclosporine solution formu- lation, CyclASol 0.1% (Novaliq), is in Phase 3 clinical trials. The FDA-approved Cequa is 0.09% cyclo- sporine encapsulated in nanomicelles and stored in solution, delivered via classic dropperette. It's a more potent concentration, and the micelle encapsulation allows greater tissue penetra- tion—"so we need to get comfortable with its tolerability in the eye," Dr. Hovanesian said. "Theoretically, the increased concentra- tion and the formulation in solution of Cequa, which is a solution of the historically highly insoluble molecule cyclosporine, should create increased bioavailability and thus an increased patient response," Dr. de Luise said. Meanwhile, "CyclASol is interesting be- cause it is not a water-based drop," Dr. Hova- nesian said. Rather, the 0.1% concentration is delivered in a perfluorocarbon liquid, so "it is probably better tolerated than any other formu- lation of this drug on the eye," he said. have flares," he said. "I like to use pulse therapy with steroids to cover these flares." Meanwhile, Dr. Pflugfelder will use a ste- roid pulse with cyclosporine, tapering to a stop after 1 month. Patients going on short-course therapies of about 2 weeks don't typically need a follow-up visit unless symptoms persist or flare; patients on maintenance therapy will typically be seen for follow up in a month to 6 weeks by Dr. Ho- vanesian, in 6 weeks by Dr. Holland. Treatment failure is rarely an issue—"Typically, steroids don't fail," Dr. Hovanesian said—but additional therapies or adjuncts such as punctal occlusion are considered depending on patient response. Lifitegrast, cyclosporine combo? Some patients report using both lifitegrast and cyclosporine together. Dr. Pflugfelder said that while there is no evidence to support this con- cept, he has patients who use both and think the combination is better than monotherapy. "I don't think there's any real science behind whether that works," Dr. Hovanesian said. "Both are T-cell inhibitors, so it's hard to construct a logical argument that they would be highly additive to each other. Yet they are two drugs that work on the same disease, so it makes sense to try them together." Dr. de Luise said that the two drugs do work in different places and at different points in the inflammatory cascade: lifitegrast on the ICAM-LFA interaction, cyclosporine on calci- neurin inhibition on newly hatched T-cells. "To the extent that the dry eye in a given patient is predominantly or totally related to inflammation (which is not always the case), there may be a synergistic benefit to using both medications," he said. "However, in the real-world scenario, there may be insurance limitations, and using both may have to be paid out of pocket by that particular patient." Despite anecdotal reports, Dr. Holland doesn't see a role for the combination. "If I were to add a second medication, I would rather not put them on two drugs that work on a similar pathway," he said. "I would rather add About the doctors Vincent de Luise, MD Assistant clinical professor of ophthalmology Yale University School of Medicine New Haven, Connecticut Edward Holland, MD Director of Cornea Services Cincinnati Eye Institute Cincinnati John Hovanesian, MD Harvard Eye Associates Laguna Hills, California Stephen Pflugfelder, MD James and Margaret Elkins Chair in Ophthalmology Baylor College of Medicine Houston Financial interests de Luise: None Holland: Kala Pharmaceuticals, Novartis, Takeda, Senju Hovanesian: Alcon, Allergan, BlephEx, Johnson & Johnson Vision, Sun Pharmaceutical, Novaliq, Shire, Eyevance Pflugfelder: Shire, Allergan, Senju Aqueous deficient dry eye disease, showing decreased tear film meniscus and positive lissamine staining of cornea and conjunctiva Source: Vincent de Luise, MD continued on page 52

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