Thomas Morrow, MD

For many affected by vitreous degradation, surgery was the only treatment until the development of ocriplasmin

Thomas Morrow, MD

Thomas Morrow, MDUnless you have been involved in ophthalmology specifically, you have probably never heard of a sight-threatening condition called vitreomacular adhesion (VMA). There is limited epidemiologic data about this progressive, commonly asymptomatic disease, and the precise incidence has not been established.

Once it becomes symptomatic, it can cause diminished visual acuity, distorted vision, and a central visual blind spot that can affect overall visual function and result in a decrease in the ability to perform activities of daily living such as driving, reading, or enjoying some entertainment activities.

Diagnosis includes the use of optical coherence tomography (OCT), a study that produces an image that would remind readers of an ultrasound but uses infrared light instead of sound to create the image.

The cause of VMA remains unknown, but it is primarily an aging phenomenon. To understand this condition, you must recall your anatomy studies.

Vitreous degrades

Normally the eye contains a gel-like material called the vitreous that occupies the space between the lens and the retina and allows for unfettered transmission of light. The vitreous actually adheres to the retina (think of sticky gelatin). The structure of the gel and its adhesion are the result of a complex matrix of proteins that include collagen, laminin, and fibronectin.

The vitreous protein matrix slowly degrades and undergoes liquefaction, resulting in loss of adhesion to the retina as the gel becomes more liquid. The vitreous separates from the retina, a process termed posterior vitreous detachment (PVD), and is replaced with a more fluid substance. PVD proceeds without incident or symptoms.

Occasionally, the adhesion between the retina and the vitreous does not completely separate and remains strong near the macula, the most critical anatomic section of the retina for acute vision. The adhesion eventually produces traction on the macula, termed vitreomacular traction (VMT), which can cause a macular hole, seriously damaging vision resulting in the symptoms listed above. Only about 10 percent of cases of symptomatic VMA resolve spontaneously, so once symptoms develop, patients face an uncertain future with probable progressive vision loss.

Eye surgery

The only therapy available until recently has been surgical removal of the vitreous, a major surgical procedure reserved for severe cases where lack of intervention would lead to serious visual loss. This involves removal of the vitreous gel and may include peeling of the retinal membranes. Among the adverse effects of this surgery are hemorrhage, intraocular infection, cataract formation, and retinal detachment. Cataract formation is almost predictable, resulting in a second intraocular procedure in most patients within two years to remove the opacified lens.

Recovery after surgery requires the patient to be immobilized in a “head down” position for 7–14 days and near complete dependence on others. Considering the adverse events and surgical risks, most patients are monitored with clinical examinations and OCT scans until the disease progresses. But many experts feel that vitrectomy is most effective for those whose symptoms have been present for the shortest period, suggesting that earlier treatment might achieve better overall outcome.


All this may change with the FDA approval of ocriplasmin (Jetrea) intravitreal injection.

This injection could displace a rather risky surgical procedure — and is certainly a development that elderly people suffering from VMA will relish. The procedure will prevent the need for surgery in many who are already suffering from enormous health burdens. But it is likely that it will be used much earlier in the disease process because surgery is basically withheld until the condition has deteriorated to a point that it offers no real downside. Thus, many will be saved symptoms and disability that heretofore would have been just a part of aging.

Ocriplasmin was designed specifically to accelerate the liquefaction of the vitreous and cleave the components of VMA that cause the vitreous to remain adherent to the retina.

Ocriplasmin is a recombinant, shortened version of human serine protease plasmin that retains the enzymatic activity that causes proteolytic effects on collagen, fibronectin, and laminin, basically producing what normally occurs — liquefaction.

Ocriplasmin does not remain in the eye long. It is undetectable within seven days of a single intravitreal injection.

Clinical trials

ThromboGenics, in collaboration with retina specialists, designed clinical trials that consisted of four phase 2 dose-ranging trials and two phase 3 trials: MIVI-TRUST (Microplasmin for IntraVitreous Injection–Traction Release without Surgical Treatment).

The trials were termed TG-MV-006 and TG-MV-007 and collectively studied 652 patients. Although there were slight differences in the randomization allocation (2:1 in TG-MV-006 and 3:1 in TG-MV-007) and they had different locations, they had identical study designs.

Overall, 464 eyes received a single 100 uL intravitreal injection containing 125ug of ocriplasmin and 188 patients received a placebo injection.

Eligibility was defined as VMA confirmed by OCT scan of the macula and elevation of the posterior vitreous — symptoms considered by the investigator as being due to VMA — and best corrected visual acuity (BCVA) of 20/25 or worse. Patients with large macular holes (>400um in diameter) were excluded, as this size is difficult to close even with surgical intervention. Patients were followed for six months after receiving the single injection of either ocriplasmin or placebo. The primary endpoint was OCT-confirmed resolution of VMA at day 28 , as measured by an independent central reading center. Resolution of the VMA is universally used to guide treatment decisions and hence is the best-known endpoint for any trial.

Ocriplasmin was, in general, well tolerated. Safety was demonstrated for the ocriplasmin groups, with the differences in adverse events reflecting the mechanism of action, such as vitreous floaters, or with the injection procedure itself. No serious adverse events were noted.

For each trial, VMA resolved in just over 10 percent for the placebo groups (both individually and combined). About a quarter of patients in the ocriplasmin-treated group had resolution of VMA at day 28.

Of interest is that the majority of patients in the treatment group resolved by day 7. Likewise, secondary endpoints of “avoiding vitrectomy” by six months and visual acuity improvement at six months favored the ocriplasmin treated groups.

The proportion of patients with macular hole closure at day 28 was 40 percent in the ocriplasmin group and just 10 percent in the placebo treated group.

Of note is that if injection with ocriplasmin does not resolve the VMA, surgery is still an option and ocriplasmin treatment does not compromise the results of surgery.

Thomas Morrow, MD, is the immediate past president of the National Association of Managed Care Physicians. He has 24 years of managed care experience at the payer or health plan level. Contact him at

The author is a director in the value-based health department at Genentech. He has had no other industry affiliations in the past three years. The views expressed in Tomorrow’s Medicine are the author’s alone.

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