Symptomatic Vitreomacular Adhesion Overview

The Retina

The retina, a light-sensitive tissue that lines the back of the eye, absorbs light and sends visual signals to the brain, where they are processed into images. At the back of the eye, directly in line with the pupil, is an area of the retina called the macula. The area located in the center of the macula is the fovea. The macula (and in particular the fovea) is the most sensitive part of the retina, filled predominantly with cones, allowing for central vision that is crisp, clear, and detailed. Any condition that impairs this area of the retina will adversely affect central vision and ultimately impair the ability to perform many activities that are important to daily life.

The Vitreous

The vitreous is a clear jellylike substance within the eye that takes up the space behind the lens and in front of the retina. Water makes up 99% of the vitreous, with macromolecules such as hyaluronic acid, proteins, and collagens comprising the remainder. The outer part of the vitreous (the vitreous cortex) contains the highest concentration of collagen. The vitreous is attached to the retina by a matrix of fibers, including fibronectin, laminin, and type IV collagen. The attachment is stronger in places such as the equator of the eye and over the macula. Additional areas of adhesion occur along the inner limiting membrane of the retina, the optic nerve, and blood vessels of the retina.

The Aging Vitreous and Posterior Vitreous Detachment (PVD)

With age, the vitreous begins to liquefy, creating fluid-filled areas that can coalesce or combine to form pockets of vitreous that are mostly liquid with very small concentrations of collagen. If these areas are close to the interface between the vitreous and the retina, they can cause complete separation of the vitreous from the retina in a normally occurring process (with age) called posterior vitreous detachment (PVD). If the separation of the vitreous from the retina is not complete, areas of focal attachment or vitreomacular adhesion (VMA) can occur. The incomplete separation of the vitreous from the retina is called pathologic or anomalous PVD.

Vitreomacular Adhesion (VMA)

VMA can also lead to the development of traction-related complications such as macular puckers and macular holes, each of which can lead to distorted vision (called metamorphopsia), visual impairment, and/or blindness.

Symptomatic VMA

Traction caused by VMA is the underlying pathology of an eye disease called symptomatic VMA. There is evidence that symptomatic VMA can contribute to the development of several well-known eye disorders, such as macular hole and macular pucker, that can cause visual impairment, including blindness. It may also be associated with wet age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion, and diabetic retinopathy (DR).

Diagnosis and Treatment of Symptomatic VMA

Careful eye examination by an ophthalmologist is critical for diagnosing symptomatic VMA. Imaging technologies such as optical coherence tomography (OCT) have significantly improved the accuracy of diagnosing symptomatic VMA.

Today, there is no recommended treatment available for the patient with mild symptomatic VMA. The standard of care in the treatment of symptomatic VMA in these patients is “watchful waiting.” In symptomatic VMA patients with more significant vision loss, the standard of care is vitrectomy, which involves surgically removing the vitreous from the eye, thereby surgically releasing the symptomatic VMA. An estimated 850,000 vitrectomy procedures are performed globally on an annual basis—250,000 in the United States alone.

ThromboGenics is developing a new biologic agent called ocriplasmin (microplasmin), and this drug was being studied in the MIVI-TRUST (MIcroplasmin for VItreous Injection) Phase III clinical trial program. The primary end point of these trials was looking at pharmacologic resolution of symptomatic VMA, and the results of these trials have now been reported at eye meetings and in the literature.

Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME)

According to the World Health Organization, the population of diabetes patients is likely to double over the next 25 years. Over time, diabetes can lead to diabetic retinopathy, which is damage to the blood vessels within the retina caused by many pathologic changes including fluctuating blood glucose levels. Diabetic retinopathy is the most common cause of blindness among working-aged people in the developed world. As this damage continues, blood vessels in the retina begin to leak fluid, leading to a condition known as diabetic macular edema (DME), where fluid accumulates in and around the macula. Patients with DME typically experience blurred vision and metamorphopsia, which may progress to blindness. Upwards of 75,000 new cases occur every year.²

In many patients with diabetic retinopathy it has been noted that there is VMA, with associated VMT, that contributes to the underlying cause of the DME.³

Vitrectomy can be performed for severe cases of DME and VMT, and after successful surgery, retinal thickening is reduced in most eyes.

Neovascular Age-Related Macular Degeneration (nAMD)

Neovascular age-related macular degeneration (nAMD) is a degenerative condition of the macula. It is the most common cause of vision loss in the age group 50 years or older, in the westernized world, with the disease affecting approximately 1.2 million Americans.

It has been estimated that as many as approximately one-third of subjects with nAMD have VMA.^{4, 5} Additionally, it has been hypothesized that PVD can prevent subjects from progressing to the neovascular form of AMD.⁶ Data has shown that subjects that have the dry form of AMD also have higher incidence of PVD.⁶

1. Sebag and Wang. In: Holz and Spaide. 2009:157–167; 2. Koerner and Garweg. DocumentaOphthalmologica. 1999:97:449–458

2. Gandorfer et al. Invest Ophthalmol Vis Sci. 2004;45:641–647.  2.  In vitro experiments.  ThromboGenics, Data on File.

3. Doi N, Uemura A, Nakao K, Sakamoto T.  Retina. 2005 Sep;25(6):742-5.

 

4. Krebs et al. Am J Ophthalmol. 2007;144:741–746;

5. Robison CD et al. Am J Ophthalmol. 2009;148:79-82.e2.

6. Gawecki M, Doroszkiewicz M, Rydzewski J. Age related macular degeneration and presence of posterior vitreous detachment. KlinOczna. 2010; 112 (7-9): 210-2.