Study into pathology, treatment of epimacular membrane continues

Research into macular pucker seeks to define pathogenesis and histological characteristics, among other issues.

Issue: January 2012

ByDaniele Veritti, MD

BySara Macor, MD

Daniele Veritti

Macular pucker is just one of the many terms used to describe the presence of an epimacular membrane in the inner surface of the retina. Many terms are clinically used to describe both morphologic characteristics and severity of pathologic changes induced by epimacular membranes on the retinal surface. This condition is also known as cellophane maculopathy, epiretinal membrane, preretinal macular gliosis, preretinal macular fibrosis and preretinal vitreous membrane.

To better understand this concept, it is useful to mention the Gass classification proposed in 1987, in which he outlined three stages of epimacular membrane (EMM), depending on severity of clinical manifestations and morphological characteristics: grade 0 cellophane maculopathy, grade 1 crinkled cellophane maculopathy and grade 2 macular pucker.

The main problem related to the presence of an EMM is that, due to its contractile proprieties, it leads to traction on the retinal surface, causing changes in neuroretinal morphology and consequently visual function impairment. Symptoms are directly correlated either with the thickness of the membrane or with the severity of distortion. Affected patients may be asymptomatic or present with variable degrees of visual loss, metamorphopsia, micropsia or macropsia, and, in rare cases, diplopia caused by foveal ectopia secondary to a tangential traction on the macula.

Thanks to epidemiological studies, we know that this condition affects up to 7% of the population. EMMs are idiopathic in 68% of cases. This includes EMMs associated with posterior vitreous detachment, which can be found in 75% to 93% of idiopathic EMMs. In the other 32% of cases, EMMs are associated with a variety of ocular conditions, including retinal vascular diseases, retinal detachments or retinal breaks, surgical procedures, posterior segment inflammatory diseases and post-traumatic conditions.

Diagnosis

Diagnosis can be easily made with complete ophthalmologic assessment and optical coherence tomography evaluation. Ophthalmologists can note great differences on fundus examination depending on the degree of contraction, as first-stage membranes can be seen as a subtle “sheen” in the macular region with a frequent association with posterior vitreous detachment (PVD).

In advanced stages, the membrane appears with identifiable striae in the inner retina associated with an important distortion of retinal vessels. Additional findings may include small intraretinal hemorrhages, areas of inner retinal whitening due to ischemia, central macular edema with pseudocystic configuration, foveal ectopia secondary to contraction and macular pseudoholes, which have been reported in about 8% to 20% of eyes with EMMs.

OCT plays an important role in the diagnosis of EMM, in preoperative planning and in postoperative follow-up.

All about EMM

But what really is an epiretinal membrane? First described by Iwanoff in 1865, today we define it as an avascular, fibrocellular membrane with contractile proprieties that proliferates on the surface of the retina. Numerous studies were conducted to better understand both the pathogenesis and histological characteristics. Early histological studies from Foos and colleagues showed that EMMs are composed by glial cells, more recently called laminocytes, located on the surface of the inner limiting membrane (ILM) and originated from accessory glial cells migrating from the nerve fiber layers to the surface of the ILM.

Modern studies also found RPE cells, endothelial cells, macrophages and fibrocytes composing EMM. In more recent research by Snead and colleagues, using surgical membranes peel specimens and normal cadaver globes, various types of EMMs were characterized by distinctive cells. This allows us to classify EMMs into different clinical groups that reflect different etiologies. Simple idiopathic EMMs are characterized by laminocytes and ILM; in tissue repair EMMs secondary to retinal tear, trauma or infections, RPE cells, fibroblasts and macrophages can be found; and neovascular EMMs secondary to proliferative diabetic retinopathy or vasoproliferative tumors are composed of capillaries and acellular stromal tissue.

In idiopathic EMM, the most common type, histological characteristics are useful to better understand its pathophysiology. Several theories have been proposed, and a lot of authors agree with the central role of PVD, present in 75% to 93% of idiopathic EMMs.

Some authors believe that subtle retinal breaks secondary to PVD liberate RPE cells that initiate membrane formation; others give a central role to laminocytes (astroglia cells), which migrate after PVD and proliferate on the ILM surface. This second theory might explain the success of ILM peeling in repairing macular pucker, and it is supported by the study from Snead and colleagues, in which it was demonstrated that normal cadaver globes with PVD had a higher laminocyte concentration than those with a normal vitreomacular interface.

Nevertheless, occasional laminocytes lying between ILM and vitreous can be found in eyes with an attached vitreous, giving them an active role in PVD development.

A third theory, proposed by Sebag and colleagues, gives a primary role to hyalocytes (phagocytes that are embedded within the posterior vitreous and the ILM) that can stimulate cell proliferation as well as induce vitreoretinal contraction. Finally, in cases of EMM without PVD, many studies documented the presence of a fibrocellular membrane on the inner surface of the retina.

Pars plana vitrectomy with ILM peeling is the standard treatment for surgical removal of the EMM. Although the need for ILM peeling has been doubted for some time, today the majority of authors believe that it is beneficial in terms of visual outcomes and recurrence rates. This technique removes glial cells, hyalocytes and fibroblasts lying on ILM, a well-known source of cell proliferation and EMM recurrence.

References:

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Daniele Veritti, MD, can be reached at Department of Ophthalmology, University of Udine, p.le S. Maria della Misericordia, 33100 Udine, Italy 33100; +39-0432-559907; email: verittidaniele@gmail.com.

Disclosure: Dr. Veritti and Dr. Macor have no relevant financial disclosures.