Plasmin enzyme shows promise in vitreous

Kimberly Drenser, MD, of Associated Retinal Consultants, Novi, MI, United States, discussed plasmin enzyme and some of its derivatives, as well as studies and ways in which it may be able to be used soon.

She mentioned that two of her colleagues, Michael T. Trese, MD, and George A. Williams, MD, created plasmin enzyme, and they have a financial interest in it.

Plasmin enzyme is found in the blood, Dr. Drenser said.

"It's activated when plasminogen is converted into plasmin," Dr. Drenser said. "When this is concentrated, it's helpful in the eye, in the vitreous. It has two forms of action. In high concentrations, it liquefies the vitreous, but more importantly, it also creates a posterior vitreous detachment or dissociation of the hyaloid from the posterior retina. This can be very helpful in a number of cases."

Forms of plasmin include pooled human plasmin; autologous human plasmin (also known as APE), which has been the most vigorously studied and is created from patient or maternal blood, and the more recent recombinant plasmin-including microplasmin and delta plasmin-which does not require preparation from a patient's blood and can be ready at any time in the operating room. Delta plasmin has not been used as much as microplasmin, she said.

Pooled human plasmin has many viral contaminants as well as mutagenicity and therefore is not considered safe, Dr. Drenser added.

APE has been studied in relation to traumatic macular holes, idiopathic macular holes, and use in diabetic eyes.

"We also use this quite a bit in the pediatric population," she said.

To determine whether creating a posterior vitreous detachment and liquefying the vitreous alters biochemistry within the eye, Dr. Drenser and colleagues analyzed oxygen concentrations in injected eyes compared with control (uninjected) eyes.

"We used two different concentrations of plasmin or hyaluronidase," she said, adding, "The difference between plasmin enzyme and hyaluronidase is that the plasmin enzyme liquefies the vitreous at high concentrations but also creates a loosening of the vitreoretinal junction. The hyaluronidase only creates liquefaction but does not create a posterior vitreous detachment or alter the vitreoretinal junction."

Studies of the avascular retina in animal eyes demonstrated a "very big difference in the rate of oxygenation in the vitreous cavity, not only in its total concentrations but also in its response to adding additional oxygen or turning the oxygen off," Dr. Drenser said. In plasmin-treated eyes, there was a rapid change in oxygen levels within the eye, which can lead to cataract formation.

Examination of vascular retinas demonstrated a similar response: the plasmin-injected eyes had the most rapid change in oxygen concentration.

The researchers also looked at vascular endothelial growth factor (VEGF) to see whether it could be altered. In rabbit eyes, the VEGF level seemed to be "rapidly turned over" in the eyes with liquefied vitreous, she said. In cat vitreous, however, which is fully vascularized and more like that seen in humans, the microplasmin-treated eyes had rapid elimination of VEGF levels to close to non-detectable.

"We think this may have important implications in biochemical treatments for manipulations within the vitreous without resulting in surgery or other pharmacotherapies," Dr. Drenser said.

Plasmin also may be beneficial for retinopathy of prematurity and diabetes, she said.