Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure

Abstract

Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term use. Though highly effective at suppressing inflammatory and allergic responses, topical ophthalmic corticosteroids carry an inherent risk of side effects, including elevated intraocular pressure (IOP), a risk factor for the development of glaucoma. The corticosteroid loteprednol etabonate (LE) contains an ester rather than a ketone at the C-20 position, minimizing the potential for side effects, including IOP elevation. In early pivotal clinical trials of LE ophthalmic suspension for conjunctivitis (allergic, giant papillary), anterior uveitis, and post-operative inflammation, LE had minimal impact on IOP over short-term (<28 days) and long-term (≥28 days) use. Since then, new LE formulations—including a gel, an ointment, and a suspension of LE in combination with tobramycin—have become commercially available. Multiple studies evaluating the safety and efficacy of LE for inflammatory conditions have been reported, including those requiring longer-term treatment such as photorefractive keratectomy, corneal transplantation, and dry eye disease. We review the available published data on the effect of LE on IOP and report on the cumulative incidence of clinically significant IOP elevations (≥10 mm Hg from baseline) with short-term and long-term LE use. In all studies, LE consistently demonstrated a low propensity to elevate IOP, regardless of formulation, dosage regimen, or treatment duration, including in known steroid responders. The cumulative proportion of patients exhibiting clinically significant IOP increases was 0.8% (14/1725 subjects) in studies evaluating short-term LE treatment and 1.5% (21/1386 subjects) in long-term studies. Furthermore, use of LE was associated with significantly lower rates of IOP elevation ≥10 mm Hg as compared to prednisolone acetate or dexamethasone (when used in combination with tobramycin). The cumulative data to date substantiates a favorable IOP-safety profile for LE with both short-term and long-term use.

Management of ocular allergy

“…A second review demonstrated significantly lower rates of IOP elevation (≥10 mm Hg) when compared to topical prednisolone 1% or dexamethasone 0.1%, suggesting a favorable IOP safety profile for loteprednol with both short‐term and long‐term use. However, this review received a critically low AMSTAR score …”

“…Prolonged treatment with topical steroids should be avoided since glaucoma can occur in all age‐groups . Withdrawal of steroids and addition of antiglaucoma medications is effective in controlling IOP in the majority of patients .…”

Comparison of the Safety and Efficacy of Loteprednol Etabonate 0.5%/Tobramycin 0.3% with Dexamethasone 0.1%/Tobramycin 0.3% Following Strabismus Surgery

“…Earlygeneration topical corticosteroids, such as DM, have been used for a long time for relieving ocular inflammation after strabismus surgery [1][2][3]16]. Although they are effective in suppressing postoperative inflammation, they also have the potential to induce adverse effects, such as an increase in IOP, delay in wound healing, and decrease in resistance to infections [3,14,17].…”

“…After exerting its effects, LE is rapidly metabolized by tissue esterases, limiting any potential adverse effects associated with its use. LE is reported to be highly lipophilic and has strong binding affinity to glucocorticoid receptors [4,17,18]. Compared with DM, its lipophilicity was 10 times higher and its binding affinity to a glucocorticoid receptor was 4.3 times higher [4].…”

“…LE is indicated for the treatment of various ocular surface and anterior segment inflammatory conditions such as seasonal allergic conjunctivitis, blepharokeratoconjunctivitis, and uveitis [17,4]. It offers a safe and proven management of postoperative pain and inflammation after cataract surgery [6,14,17].…”