Some patients treated with a bimatoprost slow-release implant over 1 year can maintain the IOP-lowering effect without relapse for 2 years or even 4 years after the last administration, according to a study.

“We believe that upregulation of the metalloproteinases and other extracellular matrix proteins produced by high bimatoprost concentrations in target tissues may lead to sustained tissue remodeling and long-term IOP reduction in the absence of drug,” Felipe A. Medeiros, MD, PhD, said at the virtual Association for Research in Vision and Ophthalmology meeting.

Durysta (bimatoprost implant, Allergan) is administered intracamerally using a preloaded applicator with a 28-gauge needle. Preclinical studies have shown that the drug concentration achieved in the target tissues is significantly higher than with topical administration and that the effect lasts for about 4 months. In the ARTEMIS 1 phase 3 study, patients received three consecutive implant administrations at 4-month intervals and were monitored for a further year thereafter. In 83% of the eyes, the IOP decrease was maintained to the end of the follow-up without further treatment after the third implant. In an ongoing extension of the ARTEMIS study, the duration of IOP control provided by the implant was evaluated in 181 patients over 2 years of additional follow-up.

“In 32 patients, no further treatment was needed for over 2 years after the third implant administration. The baseline IOP at the beginning of the ARTEMIS study was 23.4 mm Hg, was down to 17 mm Hg during the study and remained at 18 mm Hg at the last recoded visit in the extension study, which on average happened 2.6 years after the third implant administration. So, substantial reduction was maintained without repeating the treatment. Seven patients remained untreated for 3 to 4 years,” Medeiros said.

This long-term pressure control may be due to enhanced expression of metalloproteinases that induce long-term changes in the target tissue, enhancing aqueous outflow. Evidence of this hypothesis has been shown in a study by W. Daniel Stamer, PhD, and co-authors. Cultured human trabecular meshwork scleral fibroblast and ciliary muscle cells from donor eyes were exposed to the concentrations of bimatoprost observed with bimatoprost implant vs. eye drops.

“With the higher concentrations, higher expression of genes related to the extracellular matrix and levels of selected secreted matrix metalloproteinases were found in all the target tissues,” Medeiros said.

Clinical studies are in progress to further understand the duration of effect of the bimatoprost implant and the factors that may predict long-term response.

References:

https://www.healio.com/news/ophthalmology/20210517/bimatoprost-implant-shows-extended-ioplowering-effect-after-1-year-of-treatment