Difluprednate: A Novel Steroid for the Eye

Ocular inflammation has multiple causes, but one of the most common is ocular surgery. Approximately 5 million ophthalmic surgeries performed annually in the US today (most common cataract surgery), and as our "I want 20/20" baby boomer generation requires these surgeries, controlling intraocular inflammation will not only be important to continue to achieve excellent results, but also to deliver to the patient that premium service they demand. The most common method of controlling intraocular inflammation is with corticosteroids.

Corticosteroids can be delivered in multiple formats, whether intravenous, oral, subconjunctival, intracameral injection, or by topical drops. With any of these deliveries, risks and benefits must be weighed. While systemic corticosteroid preparations will affect the eyes, they can also affect other endocrine systems, sometimes negatively. Thus the majority of treatment of ophthalmic inflammation today is by topical drops or local injections. Local injections can profoundly decrease ocular inflammation, and are particularly useful in cases of patient noncompliance. In a study by Karalezi et al¹, subjects faired equally well after cataract surgery if they used topical prednisolone drops or had 1 mg intracameral triamcinolone. Unfortunately, controlling elevated intraocular pressure in this population may be challenging as the depot cannot be easily removed, and in today’s era of TASS there is much concern over intracameral injections (particularly when layered corticosteroid may be difficult at times to distinguish from hypopyon).

Thus, following ophthalmic surgery most ophthalmologists elect first to use topical corticosteroids, the most common being prednisolone acetate 1% (Pred Forte, Allergan). The gold standard competitor in clinical trials of corticosteroids, it possesses 4-5x potency of cortisol. By comparison, dexamethasone has 25x the potency of glucocorticoids. As expected, it also carries a higher risk of adverse events such as elevated intraocular pressure. This led to the development of "softer steroids" such as loteprednol (Lotemax, Bausch & Lomb). While they do have a lower incidence of elevated intraocular pressure, in the same vein they also may have lower efficacy for clearing severe inflammation².

More recently, difluprednate (Durezol, Alcon) was introduced by Sirion, then acquired by Alcon. A pro-drug, it rapidly penetrates the corneal epithelium where it quickly deacetylates to difluoroprednisolone butyrate (DFPB), the active metabolite. This DFPB has strong corticosteroid receptor agonist activity, and in clinical trials has been demonstrated to be more powerful than betamethasone, which is considered to have 6x the potency of prednisolone³. Another factor which may contribute to its potency is that it is an emulsion; it does not require any shaking any each drop possesses 100% of the label claim of product.

With all these ophthalmic preparations available, it can be difficult to choose one. In my experience, eradicating ocular inflammation as quickly as possible not only leads to quicker visual recovery but also better patient experience. In addition, I believe that with no precipitation of medication and no BAK, this is an overall more comfortable drop. Because of its strength, I dose it at half of whatever I would dose prednisolone acetate, and have not seen any less efficacy. In summary, this medication has allowed me to increase compliance by reducing frequency of drops with a more potent, more comfortable effect.

REFERENCES:

1. Karalezli A, Borazan M, Akova YA. Acta Ophthalmologica 2008; 86:183-87
2. Rowen S. Curr Opin Ophthalmol 1999; 10:29-35; Pavesio CE, Decory HH. Br J Ophthalmol 2008;92:455-59
3. Mochizuki M, et al. A Phase III, Open-Label, Clinical Study of Difluprednate Ophthalmic Emulsion (DFBA), 0.05%, in the Treatment of Severe Refractory Anterior Uveitis. ARVO Annual Meeting, May 6–10, 2007, Ft Lauderdale, FL, poster B809, program 3905. Schimmer BP, Parker KL.. In: Hardman JG, Limbird LE, Gilman, AG, eds. Goodman & Gilman’s the Pharmacological Basis of Therapeutics. 10th ed. McGraw-Hill, New York, NY; 2001