Using Topical Difluprednate to Treat Noninfectious Uveitic Cystoid Macular Edema

By Daniel L. Feiler, MD, Sunil K. Srivastava, MD, Francesco Pichi, MD, James Bena, MS, Careen Y. Lowder MD, PhD

Cystoid macular edema (CME) is a common cause of visual loss in patients with uveitis, accounting for 42 to 44 percent of visual impairment or legal blindness.[i] Yet evidence-based treatment strategies for CME are lacking, with most uveitis experts relying on personal experience for treatment decisions.

Common treatments include systemic, periocular or intraocular steroids with innovations in delivery routes and steroid sparing agents showing reduced side effects, improved durability and, in some cases, increased efficacy. Also, local delivery in the forms of intravitreal injection or slow-release corticosteroid implants can be effective, though there are significant side effects including cataract formation, elevated risk of glaucoma, endophthamitis and retinal detachment.

Topical corticosteroid eye drops are a better-tolerated treatment. Historically, though, they have only been effective for anterior manifestations of uveitis. However, studies have shown that difluprednate (difluoroprednisolone butyrate acetate), which is a difluorinated prednisolone derivative with potent anti-inflammatory activity and limited systemic absorption, does penetrate into posterior retina and choroid.

We recently completed one of the first studies of uveitis CME patients who were treated with topical difluprednate to determine the treatment’s short-term safety and efficacy.

Study Design

We reviewed the records of 27 patients (35 eyes) diagnosed with CME associated with noninfectious uveitis via optical coherence tomography (OCT) between June 2014 and October 2015. Each patient received 0.05 percent difluprednate four times daily for three weeks.

We noted patients’ ocular history, medications for uveitis, visual acuity, intraocular pressure (IOP), ophthalmic examination, OCT and fluorescent angiography (FA) data.

For our analysis, we used a mixed model with each measure as the outcome, visit as the primary predictor and patient and eye as random effects.

Significant Results

Overall, we found significant decreases in central foveal thickness (CF), mild improvement in visual acuity and, in a few patients, elevation of intraocular pressure (IOP):

• At 30 ± 15 days, we found mean CFT decreased significantly to 117 um (P < 0.001) while visual acuity improved by a mean of five letters (P = 0.001) and mean increase in IOP was 1.48 mm Hg (P = 0.080).
• At 60 ±15 days, we found mean CFT decreased significantly to 124 um (P < 0.001) while visual acuity improved by a mean of five and a half letters (P = 0.007) and mean increase in IOP was 1.92 mm Hg (P = 0.110).
• At 180 ± 30 days, we found mean CFT decreased significantly to 152 um (P < 0.001) while visual acuity increased by a mean of seven letters (P = 0.032) and mean increase in IOP was 6.18 mm Hg (P = 0.001).

Frequent IOP monitoring recommended

We found a clinically significant increase in IOP after 75 days in a small number of patients: an IOP response defined as > 25mm Hg and > 10 mm Hg above baseline was observed in three patients. Two were successfully treated with glaucoma medication; one required glaucoma surgery after missing several appointments.

We believe our elevated IOP finding along with differing results in the literature concerning clinically significant elevations in IOP warrant frequent IOP monitoring in patients receiving topical difluprednate. On the plus side, the topical nature of difluprednate affords clinicians the option to make dosing adjustments if such an increase is found.

Another potential disadvantage of using topical difluprednate appears to be its relatively limited anti-inflammatory action when compared with intravitreal corticosteroid injection. This was demonstrated in three of the 35 eyes, which were unresponsive to topical difluprednate; however, CME resolved after introverteal corticosteroid injection. Additional complications such as cataract formation were not rigorously measured and therefore not evaluated in this study.

Overall our data illustrate that topical difluprednate is a well-tolerated and effective treatment for CME secondary to noninfectious uveitis. It also has several advantages when compared with alternative therapies such as intravitreal corticosteroids or corticosteroid implants, including avoiding the risks, costs and discomfort of intraocular injection or intraocular steroid implant.

Drs. Feiler and Pichi are fellows at Cole Eye Institute. Drs. Lowder and Srivastava are staff physicians in the Cole Eye Institute. Mr. Bena is a biostatistician for Lerner Research Institute.