Ocriplasmin shows promise for assortment of retinal diseases

While MIVI-TRUST outcomes suggest ocriplasmin’s efficacy, spectral-domain OCT supports the drug’s applicability to numerous other diseases.

Pravin U. Dugel

In light of mounting concerns over the treatment burden of anti-VEGF monotherapy, ocriplasmin may offer another option for managing retinal diseases via combination therapy.

In a presentation at the American Society of Retina Specialists meeting, Pravin U. Dugel, MD, said that ocriplasmin (ThromboGenics), a form of microplasmin specifically designed for the phase 3 MIVI-TRUST (Microplasmin for intravitreous injection-traction release without surgical treatment) program, shows potential for indications beyond those evaluated in its first 800 patients.

“This drug has a very broad spectrum of application in many of the clinical diseases that we treat today, and as such … has the potential to change the way that we practice,” he said.

The MIVI-TRUST program included two randomized, placebo-controlled, double-masked, multicenter studies assessing effects of a single dose of 125-µg intravitreal ocriplasmin over a 6-month period. Analyses focused on the drug’s use for vitreomacular adhesion and macular holes, but as Dr. Dugel noted in a telephone interview with Ocular Surgery News, spectral-domain optical coherence tomography images are suggesting that vitreous adhesion plays a role in the pathogenesis of many diseases.

“Formerly, vitreomacular traction syndrome was the only syndrome we knew of where the vitreous got stuck in the back of the eye. Now we are recognizing that this idea of the vitreous getting stuck is actually significantly more common. … It is in the pathogenesis of a lot of diseases, such as macular holes, epiretinal membrane and perhaps, according to accumulating evidence, neovascular macular degeneration, diabetic macular edema and retinal vein occlusion,” Dr. Dugel said.

Revolutionizing treatment

Before ocriplasmin, most patients with vitreomacular adhesion or its offshoot, vitreomacular traction syndrome, simply underwent observation, because surgical intervention has a less-than-optimal risk-benefit ratio, Dr. Dugel said. However, ocriplasmin may mimic the effects of surgery without causing as many adverse effects.

“Ocriplasmin does two things. It causes the vitreous to liquefy and it causes the vitreous to separate from the retina. There are earlier products that have not been as effective, which only do one or the other,” he said.

At the 6-month mark, there was an upward trend in the number of patients who gained two or three lines of vision, much like what happens with surgery. According to Dr. Dugel, a patient’s best vision may not present for up to a year.

“It is unfortunate that the study only went for 6 months. I wish it went for a year or longer. I think we would have continued to see visual improvement,” he said, highlighting plans to evaluate a broad spectrum of potential indications with longer follow-up.

Additionally, there was a ceiling for anticipated visual acuity improvement in the MIVI-TRUST trials because participants with exceptionally good baseline vision were enrolled, Dr. Dugel noted.

MIVI-TRUST outcomes

At 28 days, vitreomacular adhesion resolved in 29.8% of the 464 eyes treated with ocriplasmin and 7.7% of the 188 eyes given placebo. In terms of visual acuity, 25.5% of treated eyes gained two or more lines at 6 months, and 10.1% gained three or more lines.

Total posterior detachment occurred in 17% of treated eyes and 2.6% of placebo eyes, but according to Dr. Dugel, almost all adverse events spontaneously resolved within 1 week.

“If we look at the most serious complications, retinal breaks, tears and detachments, these actually occurred more in the placebo group than in the ocriplasmin group, likely due to the vitrectomy procedure,” he added.

In a subanalysis presentation at the ASRS meeting, Peter K. Kaiser, MD, OSN Retina/Vitreous Board Member and colleague of Dr. Dugel, said that 40.6% of treated eyes also achieved full-thickness macular hole closure, compared with 17% of non-treated eyes.

“There is good evidence to suggest that sequential injections, maybe two or three, might improve ocriplasmin’s efficacy significantly,” Dr. Dugel said.

In short, the timing may be optimal for ocriplasmin to join the treatment paradigm because spectral-domain OCT is now highlighting the significant role of vitreomacular adhesion in retinal diseases, and the ophthalmic community is seeking to decrease treatment burden. – by Michelle Pagnani

• Pravin U. Dugel, MD, can be reached at Retinal Consultants of Arizona, 1101 E. Missouri Ave., Phoenix, AZ 85014; 602-222-2221; fax: 602-266-2044; email: pdugel@gmail.com.
• Disclosure: Dr. Dugel has no relevant financial disclosures.