Intravitreal liposome-encapsulated bromfenac offers promise as treatment for refractory DME

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Intravitreal liposome-encapsulated bromfenac may prove to be a promising alternative treatment for patients with diabetic macular edema (DME) who do not respond to anti-vascular endothelial growth factor or steroidal drugs.

However, in a pilot study of the intravitreal implant, inflammation developed that must be addressed before the product moves forward, according to Rodrigo Garcia-Santisteban, who reported the results of a pilot study on behalf of Hugo Quiroz-Mercado, MD.

Results of the pilot study were released at the American Society of Retina Specialists virtual annual meeting.

According to Garcia-Santisteban, the current therapies for DME include steroids, photocoagulation, and anti-VEGF injections, but these are not effective in up to 40% of patients.

“It is necessary to find alternative therapies for patients who do not have an adequate response in order to fill this unmet need,” Garcia-Santisteban said, noting the importance of developing new treatment strategies because of the long-term side effects of anti-VEGF therapy and steroids, such as macular atrophy and steroid-induced glaucoma and cataracts.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have the potential to fill this void, and bromfenac inhibits COX-2 up to 18 times more than other NSAIDs, he noted.

When placed inside liposomes, small amounts of medication are continuously released inside the eye.

“This approach, designed by our team, provides prolonged intravitreal release and protects the drug from enzymatic breakdown,” he explained.

The investigators’ previous work demonstrated the non-toxicity of these liposomes and no retinal inflammation in a rabbit model.¹

Human study
The investigators conducted a prospective, non-randomized pilot study in 10 patients with refractory DME to evaluate the safety and efficacy of liposome-encapsulated bromfenac.

All patients had received more than 3 anti-VEGF injections without a good response.

The patients periodically underwent measurements of the the central macular thickness and visual acuity (VA), and ophthalmologic evaluations were performed weekly. The primary endpoints were the best-corrected VA and the central macular thickness.

The investigators tested two doses: 7 patients had a 2-month follow-up and received 2 0.5-ml doses (1 at baseline and 1 after 1 month), and 3 patients were followed for 1 month and were treated with 1 0.5-ml dose.

Garcia-Santisteban reported that 70% of patients showed improvement in the final optical coherence tomography (OCT) images, with a mean 118.4-µ decrease in the central macular thickness. The central macular thickness did not change significantly in 30% of patients.

The VA improved in 50% of patients by a mean of 2 lines (mean change of +11 letters). In some patients the VA improved from 0 to 20 letters, while 30% of patients had no significant change in the VA.

In 20% of eyes, the mean VA worsened by 15 letters because of the development of inflammation.

Following treatment, the VA was restored. Topical prednisolone resolved the inflammation in 10% of patients for 5 days, while 30% required intraseptal betamethasone administration (2 eyes required two intraseptal betamethasone applications and 1 eye topical administration.) Overall, 40% of eyes developed mild-to-moderate inflammation in response to treatment.

“To our knowledge, this is the first use of such a suspension for patients with DME refractory to standard treatment,” according to Garcia-Santisteban. “We hypothesized that the side effects may be due to hypersensitivity to some components of the liposome layer and that the side effects can be overcome by purifying the phospholipids in the bilipid membrane.”

Based on their results, the investigators concluded that the suspension is effective, and that the inflammation must be address before another study is undertaken. In a subsequent study, they will determine the number of injections needed to control DME and the therapeutic effects on different causes of macular edema separate from DME.

See more by Lynda Charters

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Hugo Quiroz-Mercado, MD
E: hugoquiroz-mercado@ucdenver.edu
Dr. Quiroz-Mercado is professor of ophthalmology, Rocky Mountain Lions Eye Institute, University of Colorado, Denver, Colorado. Garcia-Santisteban is a medical student and has no financial interest in this subject matter. Dr Mercado owns intellectual property rights to the liposome suspension.

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Reference
1. Sanchez-Santos I, Garcia-Sanchez G, Gonzalez-Salinas R, et al. Intravitreal bromfenac liposomal suspension (100 μg/0.1 ml). A safety study in rabbit eyes. Exp Eye Res 2020;published online March 2020.