Corticosteroid provides potent, safe ocular allergy control


Experience from clinical trials and daily clinical practice indicate that loteprednol etabonate 0.2% (Alrex, Bausch & Lomb) is a valuable therapeutic option for both short- and longer-term management of allergic conjunctivitis, according to ophthalmologists who have studied and used this novel anti-inflammatory corticosteroid agent.

The efficacy of loteprednol etabonate for providing rapid and sustained control of allergic signs and symptoms in patients with seasonal allergic conjunctivitis has been well-demonstrated in randomized, double-masked studies in which patients were randomly assigned to four times daily use of the corticosteroid or placebo for 6 weeks.

"While steroids are widely considered the first drug of choice for managing intraocular inflammatory conditions, such as postoperative inflammation and uveitis, ophthalmologists have tended to shy away from prescribing these effective agents to manage external inflammatory surface diseases due to concerns about adverse events. That mindset is in stark contrast to the prescribing patterns of our allergy colleagues who do not hesitate in the least to use topical steroids, as illustrated by the popularity of nasal steroids for controlling allergic rhinitis," observed Charles B. Slonim, MD, affiliate professor of ophthalmology, University of South Florida College of Medicine, Tampa.

"Structurally designed to be a safer steroid, loteprednol etabonate provides an ideal way to jumpstart control of allergic conjunctivitis when a patient's allergic condition warrants the use of a more potent intervention," Dr. Slonim said.

Multimodal approach

The therapeutic benefits attainable with topical loteprednol etabonate are derived from its inhibition of the ocular allergic response through multimodal mechanisms.

"Compared with agents that work as antihistamines and/or mast cell stabilizers, steroids block the inflammatory response more completely through a variety of pathways and so provide relief much faster and to a greater degree," said Dr. Devgan.

Dr. Slonim explained that the corticosteroid loteprednol etabonate blocks or reduces the production or activity of a variety of chemical and cellular mediators that play a role in the inflammatory cascade. By inhibiting DNA transcription, steroids reduce the generation of inflammatory precursor proteins at the nuclear level. They also stabilize intracellular and extracellular membranes and interrupt the activation of phospholipase A to prevent synthesis of arachidonic acid, which is a precursor for the generation of prostaglandins, leukotrienes, and other pro-inflammatory compounds. In addition, steroids suppress mast cell proliferation and inhibit cell-mediated immune responses.

"The end result is that because loteprednol blocks so many arms of the allergic response, it provides greater efficacy than can be achieved using a topical nonsteroidal anti-allergy product," Dr. Slonim said.

The excellent safety profile of loteprednol etabonate is accounted for by its unique structural design. In contrast to conventional corticosteroids, loteprednol features an ester moiety at the 20-carbon position instead of a ketone. The ester is rapidly hydrolyzed by esterases in the cornea into an inactive metabolite soon after loteprednol has bound to surface receptors and exerted its therapeutic effect. Therefore, there is minimal active steroid available to exert an adverse effect (e.g., increase IOPs) while circulating in the anterior chamber.

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