Topical mycophenolate shows efficacy in rabbit model of anterior uveitis

Researchers have developed and tested topical formulations of mycophenolate as a potential nonsteroidal treatment for anterior uveitis, reporting efficacy comparable to prednisone in a rabbit model.¹

The study was led by Jyoti Chauhan, PhD, of the Center for Engineered Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, in Cambridge, Massachusetts.¹

Uveitis, an inflammatory condition affecting the uveal tract, is a leading cause of blindness and accounts for an estimated 30,000 new cases of legal blindness annually in the US. Anterior uveitis is the most common form. Corticosteroids remain the mainstay of treatment but are associated with adverse effects including elevated intraocular pressure, glaucoma, and cataract formation, particularly with long-term or frequent use. Systemic immunomodulatory therapies are available for steroid-refractory cases, though they carry systemic risks and are not administered topically.¹

“Similarly, methotrexate and mycophenolate are used off-label to treat steroid-refractory cases,” the study authors stated. “However, these therapeutics are administered systemically, and there is an unmet need for testing a topically administered immunomodulatory agent to treat anterior uveitis.

“To address this need, we developed and tested two topical formulations of mycophenolate, which is currently approved by the FDA for prophylaxis of organ rejection.”

Investigators formulated mycophenolate as both a 1% and 2% ointment (mycophenolate mofetil) and a 1% and 2% suspension eye drop (mycophenolate sodium). Mycophenolate inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme critical for T- and B-cell proliferation.¹

Molecular modeling using AlphaFold 3 characterized binding of mycophenolic acid to human IMPDH2, identifying conserved residues involved in inhibitor binding. Ex vivo corneal permeability testing using goat corneas showed concentration-dependent drug penetration for both formulations, with the suspension eye drop demonstrating greater corneal flux than the ointment. In whole-eye pharmacokinetic studies, the 2% suspension achieved higher and earlier peak concentrations in the anterior chamber compared with the 2% ointment, though both reached levels exceeding those needed to inhibit IMPDH2.¹

Ocular irritation testing in rabbits found no clinical signs of toxicity with any formulation. In a bovine serum albumin–induced rabbit model of uveitis, both the 2% mycophenolate ointment and 2% suspension significantly reduced uveitic scores, inflammatory flare, and leukocyte infiltration in the anterior chamber compared with vehicle. No statistical difference was observed between mycophenolate-treated groups and prednisone-treated controls.¹

The authors concluded that topical mycophenolate demonstrated acute ocular safety and efficacy in treating anterior uveitis in vivo, supported by pharmacokinetic data showing therapeutic intraocular concentrations. They noted that further chronic safety studies and additional work to enhance corneal penetration are needed before clinical application.¹

“In conclusion, we have demonstrated the acute ocular safety and efficacy, underpinned by ocular pharmacokinetics, of topical mycophenolate formulations as a non-steroidal option for the treatment of anterior uveitis. Steroids are used widely at present to treat inflammation in the eye, but we have shown that topical application of mycophenolate is as effective and devoid of the complications associated with the use of steroids,” the study authors stated.

Reference:

1. Chauhan J, Gherardi E, Jang HL, Sengupta S. Topical mycophenolate for the treatment of uveitis-associated inflammation. J Ophthal Inflamm Infect. 2026;16(8). https://doi.org/10.1186/s12348-026-00569-y