May 15, 2017Ophthalmology
Uveitis is an inflammatory disease of the eye and the fifth leading cause of vision loss in the United States. Concerns about potential adverse effects of systemic corticosteroid and immunosuppressive therapy drove the development of an intraocular implant to treat uveitis locally. The fluocinolone intraocular implant, developed by Bausch & Lomb, was approved by the FDA in 2005. Early data suggested the implant was effective at controlling inflammation but had local ocular side effects. The Multicenter Uveitis Steroid Treatment Trial (MUST) was undertaken to evaluate whether the implant treatment was an improvement over systemic therapy for management of uveitis.
According to an article published online in JAMA (6 May 2017), after seven years, an NIH-funded clinical trial found that systemic therapy consisting of corticosteroids and immunosuppressants preserved vision of uveitis patients better -- and had fewer adverse outcomes -- than a long-lasting corticosteroid intraocular implant. Visual acuity, on average, remained stable among participants on systemic therapy but declined by an average of six letters (about one line on an eye chart) among participants who had the implant.
The study recruited 255 uveitis patients at 23 sites (21 in the U.S., one in the U.K., and one in Australia) and randomly assigned them to receive the fluocinolone implant or systemic treatment with corticosteroids (prednisone) and immunosuppressants (such as methotrexate or mycophenolate mofetil). While systemic corticosteroids, which are FDA-approved for treatment of uveitis, reduce acute inflammation effectively, they have potential systemic adverse effects when used at a high dose for a long time. The immunosuppressants, which are not FDA-approved for uveitis, inhibit pathological immune responses, thus reducing the amount of corticosteroids needed over the long-term, mitigating such side effects.
Through the first two years, the visual acuity remained about the same in the two groups (results published in 2011). However, at the end of the study, visual acuity on average remained stable in the systemic group but declined about six letters in the implant group. The authors found that implant-treated eyes also had reactivations of uveitis after about five years, which coincided with a decline in visual acuity. The loss of vision in the implant group appears to have been due to increased damage in the retina and choroid (a tissue rich in blood vessels lying underneath the retina).
With respect to side effects, patients in the implant group were more likely to develop ocular side effects like cataracts, intraocular pressure elevation that required treatment with medicine and often surgery, and glaucoma. Patients receiving systemic therapy had increased risk of needing treatment with antibiotics, possibly due to immunosuppression, but otherwise did not have large increases in the risk of adverse effects typically associated with systemic corticosteroids such as high blood pressure or diabetes.