Epiretinal Membrane


Background

An epiretinal membrane (ERM) is a collection of collagenous cells that occurs on the inner surface of the central retina. These membranes have contractile properties and can lead to visual changes and metamorphopsia because of their effect on the underlying retina. See the image below.

Very dense epiretinal membrane with associated macVery dense epiretinal membrane with associated macular distortion.

This ocular pathology was first described by Iwanoff in 1865, and it has been shown to be a relatively common entity, occurring in about 7% of the population. Epiretinal membranes have been called various names, including epimacular membranes, cellophane maculopathy, preretinal macular gliosis, preretinal macular fibrosis, macular pucker, preretinal vitreous membranes, epiretinal astrocytic membranes, surface wrinkling maculopathy, internoretinal fibrosis, and silk-screen retinopathy; all of which pertain to clinico-anatomic descriptions of pathologic findings produced by epiretinal membranes of varying severity and differing morphologic characteristics.

Epiretinal membranes can be associated with various ocular conditions, such as posterior vitreous detachments (PVD), retinal tears, retinal detachments, retinal vascular occlusive diseases, ocular inflammatory diseases, and vitreous hemorrhage. However, a large proportion of cases do not occur in the context of any associated disease or known history and therefore are classified as idiopathic epimacular membranes (IEMM). Idiopathic and postdetachment membranes are the most common epiretinal membranes and, as such, are the focus of this article.

Pathophysiology

Epiretinal membranes are avascular, fibrocellular membranes that proliferate on the surface of the retina and can lead to varying degrees of visual impairment. These cells, once in contact and attached to the retina, may proliferate and form sheets of membranes over the surface of the retina. Through their contractile properties, the underlying retina is, in turn, distorted. The effect on vision is variable and determined by the severity of the distortion, the location, and other secondary effects on the retina.

The source of the cells producing these membranes has been the source of great debate. Earlier reports proposed that glial cells (primarily fibrous astrocytes) from the inner layers of the neurosensory retina proliferated through breaks in the internal limiting membrane (ILM) produced after a retinal tear or a posterior vitreous detachment. Modern vitrectomy specimens have shown that epiretinal membranes comprise glial cells, retinal pigment epithelial cells, macrophages, fibrocytes, and collagen cells. These cells are found in varying proportions in accordance with the etiology of the membrane. Membranes associated with retinal breaks, previous retinal detachments, or cryopexy are composed mainly of dispersed RPE cells, while cells of glial origin predominate in the IEMM. Furthermore, these cells also possess the ability to change into cells with similar appearance and function.

The incidence of associated PVD in cases of IEMM range from 75-93%, and PVD is present in virtually all eyes with retinal breaks or retinal detachments and subsequent epiretinal membrane formation. It has been suggested that PVD may contribute to epiretinal membrane formation in many ways. PVD can lead to retinal breaks that may liberate RPE cells that initiate membrane formation. Small breaks in the ILM after PVD also may provide retinal astrocytes access to the vitreous cavity, where they may subsequently proliferate. Finally, vitreous hemorrhage, inflammation, or both associated with a PVD also may stimulate epiretinal membrane formation.

Epiretinal membrane formation without PVD may predispose patients to vitreomacular traction syndrome (VMT). Chang et al evaluated patients with VMT using a spectral-domain ocular coherence tomography (SD-OCT) and ultrastructural correlation using samples obtained during surgery. [1They were able to document fibrocellular proliferation between the inner surface of the retinal and posterior surface of the vitreous, resulting in increased vitreoretinal adhesion. [1]

Bovey and Uffer observed a phenomenon of ILM tearing associated with epiretinal membrane. [2They hypothesize that the presence of ILM tears and folds are more likely when the epiretinal membrane forms prior to a posterior vitreous detachment, resulting in the subsequent cleavage plane being between the ILM and the inner retina rather than at the ILM surface. [2]

Epidemiology

Frequency

United States

The frequency at which epiretinal membranes occur varies according to the underlying disease. The idiopathic variety of epiretinal membranes has been shown to be present in up to 7% of the population. Bilateral cases have been seen in as much as 30% of the population. A 2016 examination of the Beaver Dam Eye Study cohort using OCT suggested a higher prevalence of epiretinal membrane in the population (34.1%). [3]

Clinically significant epiretinal membranes occur in 3-8.5% of eyes after successful primary retinal detachment surgery. Patients noted to be at the greatest risk for epiretinal membranes are those with preoperative signs of proliferative vitreoretinopathy, including rolled retinal edges, star folds, and equatorial ridges.

One study noted no significant difference in the frequency of epiretinal membranes in eyes that underwent subretinal fluid drainage compared to those that had nondrainage procedures. The possible risk of epimacular development in eyes that have undergone cryotherapy or laser photocoagulation for retinal tears is difficult to quantify because it is almost impossible to determine whether the cellular dispersion was caused by the retinal tear itself or the subsequent therapy for it.

The incidence of epiretinal membrane formation associated with other ocular pathologies, such as retinal vascular occlusive disease, ocular inflammation, or vitreous hemorrhage, is unknown.

Mortality/Morbidity

The visual loss depends on the severity of the distortion of the retina, the location of the wrinkling of the retina, and any other secondary effects of the membrane on the retina (eg, edema, hemorrhage).

Sex

Both sexes appear to be affected in relatively equal percentages.

Age

Epiretinal membranes occur more frequently in the older population, with postmortem studies showing 2% prevalence in individuals aged 50 years and as much as 20% prevalence in individuals aged 75 years.

Prognosis

Numerous studies have addressed the potential benefit of surgery to remove the epiretinal membranes. These studies have looked at the quantification of the postoperative visual acuity improvement as well as the subjective improvements through postoperative quality of life questionnaires. They have also looked at other prognostic factors that may influence visual outcomes.

Surgical removal of clinically significant epiretinal membranes usually results in improvement in both visual acuity and biomicroscopic appearance of the retina. Studies have shown that, postoperatively, 78-87% of patients with IEMM and 63-100% of patients with postdetachment membranes improved at least 2 Snellen lines. Patients with poorer preoperative vision tended to improve the most, but those patients with better preoperative vision obtained the best final results. Dawson et al reviewed 10 years of visual outcomes following epiretinal membrane surgery. They validated that the greatest improvement in visual acuity was seen in patients with the poorest initial visual acuity and that patients with the best preoperative visual acuity had the best visual results in this series. They also showed that surgical results improved over time. [4]

Visual acuity has also been evaluated through the use of postoperative questionnaires. A large-scale study showed that surgery improved the symptom of distortion the most, with moderate-to-severe symptoms most improved. Improvement was also seen in other daily tasks, such as reading small print.

Sometimes, however, the metamorphopsia may persist despite improvement in visual acuity. This is seen mostly in cases where there is incomplete peeling of the membrane. On the other hand, there are cases wherein the distortion is improved but the Snellen acuity remains unchanged. This mainly is encountered in cases where there is long-standing macular edema.

The presence of new or accelerated cataract formation has been shown to occur in the surgical treatment of epiretinal membranes.



History

The type and degree of symptoms experienced by an individual with epiretinal membrane (ERM) depends largely on the thickness of the membrane, the degree of retinal distortion it causes, the location of the wrinkling, and the presence or the absence of retinal detachment or edema. [5]

The usual symptoms caused by epiretinal membranes run the spectrum from no symptoms at all to severe visual dysfunction.

Early on, epiretinal membranes cause little or no visual disturbance.

As the membrane progresses, the visual disturbance is often vague and difficult for the patient to describe.

Mild distortion or blurring is the most common symptom.

Vision better than 20/50 is present in 78-85% of cases, while 56-67% have vision better than 20/30. Only 2-5% have vision poorer than 20/200.

In more advanced cases, metamorphopsia, micropsia, or Amsler Grid abnormalities may be present.

In contrast, vision is markedly reduced in patients with epiretinal membranes associated with retinal detachment. Vision is 20/60 or better in only 7% of cases and 56% have vision poorer than 20/200 after successful retinal reattachment surgery.

In a 2016 preferred practice guideline for epiretinal membranes, the authors reported that, over a 5-year period, 29% of epiretinal membranes progressed, 26% regressed, and 39% remained stable. [3]

Use of spectral domain ocular coherence tomography (SD-OCT) has correlated inner nuclear layer thickness with the symptom of metamorphopsia. Ichikawa et al suspect that tangential retinal displacement distorting Muller cells results in metamorphopsia. [6]

Physical

The clinical findings in epiretinal membranes vary according to the degree of severity of the membrane. Gass formulated a classification system based on the appearance of the membrane and the underlying retinal tissue and vessels. This grading system is not typically used in clinical practice, but it is interesting from a historical perspective.

Grade 0 membranes

Grade 0 epiretinal membranes are translucent membranes not associated with any retinal distortion.

These epiretinal membranes also are known as cellophane maculopathy owing to the cellophanelike sheen coming from the inner retinal surface as it is seen ophthalmoscopically.

Grade 1 membranes

Membranes causing an irregular wrinkling of the inner retinal surface are classified as grade 1 epiretinal membranes.

The crinkled cellophane appearance is caused by the gathering of the inner retinal layers into folds following the contraction of the overlying membrane.

Fine, superficial, radiating folds extend outward from the margins of the contracted membrane.

Wrinkling may be sufficient to produce tortuosity of the paramacular vessels pulling them toward the fovea.

Cystoid macular edema, retinal hemorrhage, exudates, and RPE disturbances are typically absent.

Grade 2 membranes

Membranes, especially those that develop after retinal detachment surgery, have an opaque, thick appearance.

Gross, full-thickness puckering of the macula may be present along with retinal edema, small hemorrhages, cotton-wool spots, and, infrequently, a localized detachment of the retina.

These membranes are labeled macular puckers or grade 2 membranes.

Pseudoholes

A pseudohole is depicted in the image below.

Grade 2 epiretinal membrane causing striations in Grade 2 epiretinal membrane causing striations in the retinal surface. Note the presence of a pseudohole.

Causes

See Pathophysiology.


Differential Diagnoses



Imaging Studies

Fluorescein angiography

Performing an angiogram in cases of epiretinal membranes (ERMs) does not contribute anything significant in its diagnosis since the clinical picture is often specific enough. In less advanced cases, the angiographic picture is basically unremarkable. More significant findings, such as vessel tortuosity and macular edema, may be seen in more advanced cases.

Perform fluorescein angiography to rule out other lesions that may mimic epiretinal membranes.

Macular holes typically show early background fluorescence through the hole that disappears in the later phases.

Epiretinal membranes with pseudoholes typically do not exhibit this fluorescence since normal retinal tissue exists in the area.

An exudative macular degeneration also may mimic the appearance of an epiretinal membrane, but its angiographic picture of early fluorescence and leakage is easily distinguishable from epiretinal membranes.

Fluorescein angiograms of epiretinal membranes can reveal subtle leakage of the perifoveal capillaries or evidence of ischemia due to capillary dropout, which can assist with counseling for postoperative expectations. See the image below.

Fluorescein angiogram demonstrating retinal vasculFluorescein angiogram demonstrating retinal vascular distortion. Note the leakage of the dye in the macular area, which represents secondary macular edema.

Ocular coherence tomography

Ocular coherence tomography (OCT) can elucidate the presence or absence of an epiretinal membrane.

OCT can objectively measure other effects of the epiretinal membrane on the retina, such as macular thickening, presence or absence of macular edema (eg, cystoid macular edema), and any associated vitreous traction on the retina.

Rouvas et al monitored patients with nontractional epiretinal membrane over time and demonstrated stability of visual acuity. They defined nontractional epiretinal membranes as membranes noted to have a tear or discontinuity on at least one line of the OCT scan. The mean follow-up period was 38.2 months, and 84.4% of patients were noted to have improvement or stabilization of visual acuity at the end of follow-up. The authors suggest that patients with nontractional epiretinal membranes may safely be monitored over follow–up, deferring surgery. [7]

OCT allows the monitoring of the postoperative return of the normal retinal architecture as well as the presence of persistent traction or folds of the retina.

Evaluation of the inner-segment/outer-segment (IS/OS) junction on OCT appears to be correlated with postoperative visual acuity. [3Hosoda et al also identified that the degree of photoreceptor deformation was predictive of postoperative visual acuity. They described a "photoreceptor deformation index" based on characteristics on the OCT. [8]

Gupta et al used combined OCT/scanning laser ophthalmoscopy (SLO) to evaluate 44 consecutive eyes with epiretinal membrane. [9Of the patients evaluated, 20 out of 44 demonstrated multiple foci of contracture within the epiretinal membrane. They subdivided epiretinal membrane into “simple puckers" and “complex puckers.” Complex puckers had a higher rate of intraretinal cysts and macular thickening than simple puckers. However, no difference in visual dysfunction existed between the two groups; the authors hypothesize that architectural differences in the retina may precede visual acuity loss.

Kromer et al correlated high preoperative retinal volumes on OCT with more benefit from surgical interval. They suggested that increased volumes were related to increased tractional components on the retina.


Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Vitreolytics

Class Summary

Vitreolytic agents are used in the treatment of symptoms resulting from epiretinal membrane.

Ocriplasmin (Jetrea)

Ocriplasmin exerts proteolytic effects on the components of vitreomacular adhesion, including fibrinogen, fibronectin, and, to a lesser extent, laminin and collagen.