Another Option for Patients with Vitreomacular Adhesion

Another Option for Patients with Vitreomacular Adhesion


By Pravin U. Dugel, MD

We have come to realize that it is not as simple for posterior vitreous detachment (PVD) to occur as we had originally thought. There are two fairly complicated steps that must occur — and these two steps must happen in synchrony. One step is the liquification of the vitreous and the other is the separation of the vitreous from the retina. If you have one without the other, you get something called anomalous vitreous detachment. So, you may get liquification of the vitreous, but it may not separate fully and may get “stuck” — that is it may cause vitreomacular adhesion. This will cause a mechanical action to pull on the retina, which, in turn, will cause different kinds of pathology.

Ocriplasmin (microplasmin, ThromboGenics) is the first drug capable of both liquefying the vitreous and cleaving the vitreoretinal interface simultaneously and successfully.1


Currently, there is an unmet need among patients who have vitreomacular adhesions at the macula. When they come into our office, they may have good vision (measuring 20/30 or 20/40), but they are very bothered by distortion and blurry vision. Surgery is the only option to treat this problem, but because their visual acuity is still fairly good, we usually hesitate to offer surgery. Although the patient may have legitimate and bothersome symptoms, the risk-benefit ratio of surgery is not warranted. If a drug could offer a better risk-benefit ratio than surgery, then this population of patients, who currently go untreated, would have a treatment option.

Additionally, we know that anomalous vitreomacular adhesion is important in the pathogenesis of other common eye diseases. For instance, there may be a direct impact of having vitreomacular adhesion on neovascular AMD, DME and vein occlusion. So, a treatment for vitreomacular adhesions may have wide applications, not just in patients who have vitreomacular traction, but also in those with other common eye diseases. As such, it seems to be a very opportune time for this drug to be introduced.


I think the timing is ideal because of a collision of three different forces:

1. The drug itself. This is a well-studied drug. Nearly a thousand patients have been injected with this drug in a number of studies.2 We have information on this drug spanning nearly a decade and the safety profile is excellent.

2. Imaging. Not long ago, it was difficult to see vitreomacular adhesion, using conventional methods. With OCT, we can see the influence and impact of vitreomacular adhesions on a number of diseases.

3. Wide applicability. The appearance of vitreomacular adhesions in a variety of diseases increases the importance of finding a better treatment option.

These three forces are colliding at this point; it seems an opportune time to have this drug in our armamentarium.


All studies with this drug, except for a single-phase study, the MIVI 2T trial, have been done with a single injection. Too few patients have received multiple injections to understand the safety and efficacy of multiple injections and at this time, only single injections should be considered.

For example, in the past, if you have a patient with a macular hole, that is 250 microns or smaller in diameter, and he complains of poor vision, we could say, “We can take you into surgery, where you will have a gas bubble placed inside your eye. You will have to remain facedown for a few days. If you are phakic, this procedure will increase the risk of a cataract, but the surgical success rate is about 90%.”

When Ocriplasmin is approved, we can say, “We can give you a single injection of ocriplasmin and there’s a 60% chance that your macular hole will be fixed without any need for surgery or facedown positioning. If the single injection is not successful, you can still have the surgery without any decrease in the rate of surgical success.”

Why wouldn’t someone take the nonsurgical option? It has a 60% success rate with a single injection in a small- to medium-sized macular hole. It’s a safe pharmacologic option.


There are three types of patients who should be considered for this drug. The first group, discussed earlier, who have good vision, maybe 20/30, but experience distortion due to vitreomacular traction. We now have a non-invasive option for these patients. In the past, when we had to take an “watchful waiting” approach, these patients didn’t always fare well in the long term. Over a period of 5-6 years, many experienced cystic changes and/or pigmentary changes. With Ocriplasmin, we can satisfy a previously unmet need.

The next group of patients has a macular hole. These patients usually go to surgery with a much shorter watchful waiting period than vitreomacular adhesion. However, in some patients, gas bubble or facedown positioning is not be possible, or in most patients not desirable. All of these would be candidates for the treatment.


Studies have shown that injecting a higher dose of Ocriplasmin does not necessarily improve efficacy. This is because the drug is non-specific and a larger bolus will simply cause the drug to inactivate itself. Thus, the recommended dosage of 125-μg should be used.

Where you inject the drug also has a significant impact. Right now, we inject the drug in the mid-vitreous. If we can inject this drug exactly where we need it, for instance right at the vitreomacular interface, or close to it, the efficacy theoretically would improve.

As our understanding of this drug matures, I believe drug-delivery devices will be evaluated so we can inject this drug exactly where it belongs since location is key and the drug itself is nonspecific.

People often ask how this drug will be used and what its applications will be in the future. I believe this drug will be the first of its kind in a field where there is nothing else available. Once approved, there are many ways to potentially use this drug. It has the potential of having broad and game-changing applications, but that’s all based on safety. The safety profile for the potential uses discussed here appears to be excellent. Remember that the drug has a history of almost a decade, and I think we will be using it for a variety of diseases moving forward.

Dr. Dugel is Managing Partner of Retinal Consultants of Arizona in Phoenix; Clinical Associate Professor of Ophthalmology, Doheny Eye Institute, Keck School of Medicine at the University of Southern California, Los Angeles; and Founding Member of the Spectra Eye Institute in Sun City, Ariz.


1. ThromboGenics Announces New Phase III Ocriplasmin Data Presented at the 2011 Annual Meeting of the American Society of Retina Specialists (ASRS). Accessed July 16, 2012.
2. Thrombogenics, Inc. Data on file, 2012.