Take-home: New drugs and new delivery methods, many in clinical trials, may offer clinicians additional therapeutic options for the treatment of uveitis.
Local therapy plays a significant role in the treatment of uveitis, either as monotherapy or in combination therapy. Alongside a number of pharmacotherapeutic agents, new products and technologies are in development that could expand clinicians’ options and improve outcomes.
“Properly delivered, both by route and dose, local therapy can provide steady control of inflammation to achieve zero tolerance of inflammatory activities,” said Quan Dong Nguyen, MD, FAAO, professor of ophthalmology, Stanford University, Stanford, CA.
Local nonsteroidal, anti-inflammatory agents are among the most common local therapies, and one of the products in the pipeline is the investigational aldehyde trap (ADX-2, formerly known as NS2, Aldeyra Therapeutics). ADX-2 is an amine that binds and traps pro-inflammatory and cytotoxic aldehydes. A topical formulation is undergoing clinical trials for the treatment of anterior uveitis as well as allergic conjunctivitis.
Results of a phase II clinical trial in May 2016 demonstrated activity comparable to corticosteroids in reducing anterior chamber cell count in patients with noninfectious anterior uveitis, said Dr. Nguyen. A phase III trial is planned.
While therapies such as ADX-2 are promising, local corticosteroids remain the first-line treatment for noninfectious anterior uveitis. Steroids can be administered by intravitreal or intraocular routes, and there are two approved delivery systems, a dexamethasone implant (Ozurdex, Allergan) and a fluocinolone implant (Retisert, Bausch + Lomb).
A second phase III trial of a fluocinolone insert (Medidur, pSivida) has met its target enrollment and is now underway, and results are expected soon, Dr. Nguyen said. A previous phase III study of this sustained-release technology met the primary endpoint of prevention of recurrence of posterior segment uveitis at 6 months.
Novel injection technique
Regional or suprachoroidal administration of triamcinolone is also being evaluated, according to Dr. Nguyen, who was one of the investigators in the Dogwood clinical trial of one device. In this randomized, masked, controlled, multicenter phase II study in patients with macular edema secondary to uveitis, individuals were treated with a novel suprachoroidal-injection technique developed by Clearside Biomedical using a proprietary formulation of triamcinolone.
Results reported in August 2016 showed a significant reduction in macular edema at 2 months in patients who had received a 4 mg dose of triamcinolone (n = 16, p = 0.0017), Dr. Nguyen said. Vitreous haze also improved. No corticosteroid-related increases in intraocular pressure (IOP) were reported in either the phase I or phase II study.
“Suprachoroidal delivery of corticosteroid may be a potential approach to consider in the future,” Dr. Nguyen said, adding that enrollment in a phase III trial of this technology is ongoing.
Local steroidal agents used to treat noninfectious uveitis include the familiar topical drugs prednisolone and difluprednate. Iontophoresis–the delivery of dexamethasone through a low-level electrical current–is an alternative approach.