Huge strides for VMA

March 1, 2013

San Francisco

San Francisco-The baseline features that are positive predictors of pharmacologic resolution of vitreomacular adhesion (VMA) following ocriplasmin treatment (Jetrea, ThromboGenics) are smaller adhesion base size, absence of an epiretinal membrane (ERM), presence of a full-thickness macular hole, patient age below 65 years, and phakic status.

Subhransu K. Ray, MD, PhD, presented the results of the phase III Ocriplasmin Program on behalf of the MIVI-Trust Study Group.

“Two treatment options are available for symptomatic VMA: observation or vitrectomy,” said Dr. Ray, a partner at Bay Area Retina Associates in northern California, and an associate clinical professor of Ophthalmology, University of California, San Francisco.

However, in October 2012, the FDA approved the use of ocriplasmin to treat symptomatic VMA. The drug targets fibronectin and laminin and induces liquefaction and subsequent release of the VMA, Dr. Ray explained.

MIVI-Trust studies

Ocriplasmin was tested clinically in two phase III trials (MIVI-006 and MIVI-007) in a total of 652 patients. The patients received either one intravitreal injection of ocriplasmin or a placebo injection of saline. The primary endpoint was the effectiveness at 28 days after the injection.

The MIVI-Trust Study group then conducted additional analyses to determine which baseline features were predictive of the most successful VMA release rates, Dr. Ray explained.

“The positive predictors of VMA resolution are adhesion size <1,500 µm, the absence of an ERM, presence of a full-thickness macular hole, patient age below 65 years, and phakic status,” he said.

The combined data from both MIVI-Trust studies showed that across all populations, ocriplasmin treatment induced a higher rate (26.5%) of VMA resolution compared with placebo (10.1%).

“This corresponded to a significant improvement in the number of patients who gained two or more lines of best-corrected visual acuity [BCVA] 6 months after treatment,” Dr. Ray said. “The number of patients who gained three or more lines of BCVA vision was also sustained at the 6-month time point in those who achieved VMA resolution compared with patients who did not achieve VMA resolution.”

Predictive factors

Non-anatomic predictive baseline factors were treatment group and age. Analysis showed, not surprisingly, that treatment with ocriplasmin resulted in a higher rate of VMA release. Similarly, age <65 years was a positive predictor of higher rates of VMA resolution. However, even among the patients who were over 65 years of age, the rate of VMA release was also significantly (p < 0.001) higher among the patients treated with ocriplasmin compared with placebo (22.1% versus 6.2%, respectively).

Detailed analysis of the anatomic features also revealed the impact of ocriplasmin on VMA release. Ocriplasmin treatment resulted in a rate of VMA release of 50% among patients with a full-thickness macular hole. However, even in patients who did not have a full-thickness macular hole, the VMA release rate was higher in patients treated with ocriplasmin as compared with placebo (19.6% versus 5.0%, respectively).

“This overall resulted in a four-fold higher rate of macular hole closure rate in those patients treated with ocriplasmin (40.6% versus 10.6%, respectively),” Dr. Ray said. At 6 months, 76.7% of patients with macular hole closure had a sustained and significant improvement in visual acuity of at least two lines and 51.2% had at least a three-line gain in visual acuity.

Adhesion size <1,500 µm resulted in VMA release in 34.7% of treated patients compared with 14.6% of those randomly assigned to placebo. Nevertheless, even in patients with adhesions exceeding 1,500 µm, 5.9% achieved VMA release when treated with ocriplasmin as compared with 0% among the placebo-treated patients.

The absence of an ERM was an overwhelming positive predictor for successful VMA release following ocriplasmin treatment; 34.7% of patients without ERM had VMA release with ocriplamin versus 14.3% with placebo. Once again, though, even in those with an ERM, ocriplasmin resulted in a higher VMA release compared with placebo (8.7% versus 1.5%), though at an overall lower rate.

The adverse events associated with ocriplasmin treatment include significant rates of vitreous floaters, photopsia, blurred vision, transient visual acuity decrease, transient visual impairment, retinal edema, and macular edema. Many of these might be attributed to the process of VMA release itself and not specifically to an unrelated adverse effect of the drug, Dr. Ray noted.

“When determining whether to incorporate this treatment into your clinical practice, it is important to note that ocriplasmin had a positive effect across all VMA subgroups,” he said. “Specific baseline features were predictive of a higher success rate.

“Each patient must be evaluated and educated about the relative benefits of the three treatment options available for symptomatic VMA, namely, observation, ocriplasmin, and vitrectomy,” Dr. Ray concluded.OT

 

FYI

Subhransu K. Ray, MD, PhD

E-mail: retina01@gmail.com

Dr. Ray has no financial interest in the subject matter. This article was adapted from Dr. Ray’s presentation during Retina 2012 at the annual meeting of the American Academy of Ophthalmology.