This article was originally published in a sponsored newsletter.

For more than a decade, the topical ophthalmic steroid landscape has included betamethasone, dexamethasone, difluprednate, fluorometholone, loteprednol, medrysone, prednisolone acetate, prednisolone phosphate and rimexolone.¹ In the first quarter of 2024, however, U.S. practitioners saw the entry of the first new steroid eyedrop in 15 years when the FDA approved clobetasol propionate 0.05% for the treatment of inflammation and pain after ocular surgery.²

Steroids, though vital for postoperative care due to their ability to control postoperative inflammation and pain, are also well known for their side effects. They can cause cataract formation and increased intraocular pressure (IOP); suppress the local immune response, which affects the ability to combat ocular infections (fungal and viral, in particular); and lead to delayed epithelial healing of the cornea, especially after injury.

Though all corticosteroids share most of these side effects, subtle differences can guide prescribers to a specific compound or agent for a particular class of patients. When treating patients with moderate and severe glaucoma, for example, one of the greatest concerns with the use of topical steroids is elevated IOP, which can lead to progression in glaucomatous visual loss. The most likely cause of this rise in IOP appears to be increased outflow resistance at the trabecular meshwork.³ While earlier-generation steroids such as prednisolone and dexamethasone have traditionally been associated with elevated IOP, the later corticosteroids have less of an effect on IOP while offering similar anti-inflammatory efficacy.⁴ Difluprednate is an exception; it seems to have a higher propensity for IOP elevation associated with greater potency.⁵

Agents such as rimexolone, fluoromethalone and the retro-metabolically-designed loteprednol are often chosen to maintain similar efficacy as their older counterparts, but with fewer side effects. Generic active ingredient equivalents to these topical agents offer less expensive treatment options for patients. Access to these options has been particularly helpful for patients with glaucoma who undergo eye surgery and are at greater risk for even a mild increase in IOP from their topical steroid regimen. Though there is a paucity of comparative studies evaluating the side effect profile from one steroid agent directly to another, data from the clinical trials required for approval of each of these agents can be evaluated to determine their relative risk of IOP elevation.

The active ingredient is not the only important factor in determining the risk profile of a topical steroid. We also need to consider the concentration of that ingredient. It stands to reason that a lower concentration of an agent would have fewer side effects. If efficacy were shown to be equal, then the lowest concentration available would be preferable for routine use to minimize the side effect potential. In recent years, the class of steroids with a post-surgical FDA approval indication has included loteprednol etabonate formulated at a lower concentration of 0.35% (Lotemax SM, Bausch + Lomb) vs. its original concentration of 0.5%. This lower concentration demonstrates similar efficacy in controlling postoperative inflammation and pain. The dosage interval approved for this formulation was also decreased from q.i.d. (for both prior versions of loteprednol 0.5%, suspension and gel) to t.i.d., thus achieving another step in decreasing the overall burden of steroid exposure. Coupled with the loteprednol molecule’s lower propensity for causing IOP elevation as compared to older agents,⁶ the lower-concentration option has been a welcome addition in corticosteroid treatment options for the postoperative care of glaucoma patients.

References:

1. Fung AT, Tran T, Lim LL, et al. Local delivery of corticosteroids in clinical ophthalmology: a review. Clin Exp Ophthalmol. 2020 Apr;48(3):366-401. doi:10.1111/ceo.13702.
2. U.S. Food and Drug Administration. Clobetasol propionate ophthalmic suspension 0.05%prescribing information. Updated March 2024. Accessed August 19, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218158s000lbl.pdf
3. Feroze KB, Zeppieri M, Khazaeni L. Steroid-induced glaucoma. StatPearls. January 2024. Updated July 16, 2023. Accessed August 19, 2024. https://www.ncbi.nlm.nih.gov/books/NBK430903/
4. Pleyer U, Ursell PG, Rama P. Intraocular pressure effects of common topical steroids for post-cataract inflammation: are they all the same? Ophthalmol Ther. 2013 Dec;2(2):55-72. doi:10.1007/s40123-013-0020-5
5. American Academy of Ophthalmology. Steroid-induced glaucoma. AAO EyeWiki. March 29, 2022. Accessed August 19, 2024. https://eyewiki.aao.org/Steroid-Induced_Glaucoma#:~:text=Intraocular%20pressure%20rise%20may%20occur,risk%20of%20elevating%20the%20IOP
6. Sheppard JD, Comstock TL, Cavet ME. Impact of the topical ophthalmic corticosteroid loteprednol etabonate on intraocular pressure. Adv Ther. 2016 Apr;33(4):532-552. doi:10.1007/s12325-016-0315-8