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.
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Very 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.
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.[1] They 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.[2] They 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]
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.
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.
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]
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.
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Grade 2 epiretinal membrane causing striations in the retinal surface. Note the presence of a pseudohole.
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.
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Fluorescein angiogram demonstrating retinal vascular distortion. Note the leakage of the dye in the macular area, which represents secondary macular e....
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.[3] Hosoda 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.[9] Of 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.[10]
Isolate epiretinal membrane (ERM) as the main cause of a patient's visual impairment prior to planning a corrective procedure. Evaluate the patient carefully to rule out other pathologic conditions, such as macular holes, subfoveal choroidal neovascular membranes, cystoid macular edema, or retinal vascular occlusive disease, that may mimic the appearance of a true membrane.
Surgical treatment of epiretinal membrane is usually not an emergent procedure. Only when there is macular edema does it become a more urgent procedure.
Frequently, patients are referred for evaluation of an asymptomatic epiretinal membrane identified via OCT in primary care optometric and ophthalmologic practices. Thus, preoperative patient evaluation and counselling are important to identify surgical candidates and to set appropriate postoperative expectations. For such asymptomatic patients, the decision to intervene with surgery is not straightforward. Rahman and Stephenson demonstrated in a retrospective review that earlier intervention resulted in more rapid recovery and better final visual acuity.[11] However, Kofod et al evaluated early versus deferred surgery in epiretinal membrane and found that, while early surgery resulted in excellent vision, patients in the deferred surgery group did not lose 5 letters of ETDRS vision. Thus, they deemed surgery deferral a safe clinical decision.[12] Rouvas et al also recommended that nontractional epiretinal membranes may be monitored safely over time if the patient is not a good surgical candidate.[7]
Several surgical techniques exist for the treatment of epiretinal membrane. However, 3 basic stages of treatment exist.
Vitrectomy
Pars plana vitrectomy is performed to excise the posterior and central vitreous in phakic patients and the remainder of the anterior vitreous in aphakic and pseudophakic patients. This step is especially important in cases where marked adherence of the vitreous to the macula is present.
Lately, questions have been raised regarding the need for vitrectomy in epiretinal membrane peeling, especially in those cases where no significant PVR exists.
The main advantages of doing a vitrectomy are the prevention of vitreous contraction and elimination of vitreous traction on the macula. In addition, removal of the vitreous is believed by many to increase the safety of the mechanical aspects of the membrane removal.
The main disadvantages of vitrectomy include cataractogenesis and increased possibility of creating iatrogenic retinal breaks. Vitrectomy has been shown to increase the rate of cataract formation through unclear mechanisms.
Studies have shown that a 3-fold increase in the rate of significant cataract formation exists in patients that have undergone vitrectomy after a follow-up period of only 6 months.
Some surgeons feel that the effectiveness of membrane peeling is negated significantly by the cataract formation such that they have foregone vitrectomy in selected cases, opting to perform no-infusion/no-vitrectomy membrane peelings. The main disadvantage of this technique is the persistence of floaters postoperatively, which may be very bothersome to some patients. Furthermore, some surgeons have seen no significant difference in either cataractogenesis or development of retinal breaks/detachments in their series comparing vitrectomizing and nonvitrectomizing techniques.
Management of epiretinal membrane with vitrectomy is predisposed to smaller-gauge vitrectomies (25-gauge, 27-gauge).[13, 14, 15] These systems are transconjunctival with the potential to create self-sealing wounds. Complications appear low while affording the potential for more rapid surgical and visual recovery.
Use of intravitreal steroids such as triamcinolone or dexamethasone has been associated with a more rapid visual recovery and better final surgical outcomes.[16]
Epiretinal membrane peeling
From the time Machamer developed the concept of membrane peeling in the mid-1970s, several variations and refinements in both technique and instrumentation have been developed.
This procedure basically involves identifying the outer edge of the membrane and creating a dissection plane with the use of a blunt-tipped pick or a bent needle.
Once the edge of the membrane is seen, it may be gently lifted off the retinal surface with the use of a pick or fine forceps.
The membrane should be lifted in a tangential rather than an anteroposterior fashion so as not to pull on the underlying retina and create tears. This maneuver is relatively straightforward if the edge of the membrane is visible.
Charles developed a maneuver that approaches the membrane from inside out in cases where the edge is difficult to identify.[17] It involves creating a slit on the thickest part of the membrane with a straight microvitreoretinal blade and using this opening as the edge with which to start the peeling. The peeling is performed moving the forceps in a circular fashion similar to capsulorrhexis. The freed membrane should be removed either by pulling it out with the forceps through the sclerotomy or by using the vitreous cutter.
Internal limiting membrane (ILM) peeling
Removal of the ILM at the time of epiretinal membrane peeling is a current controversy, both for use of vital dyes and the necessity to peel the ILM in addition to the epiretinal membrane.
Vital stains, such as indocyanine green (ICG) dye and Trypan blue dye, have been used to assist ILM and epiretinal membrane peeling. Another ophthalmic stain, brilliant blue G (TissueBlue), was approved by the FDA in December 2019. It is a disclosing agent administered intravitreally that selectively stains the ILM. Dyes that stain the ILM highlight foci of epiretinal membrane and potentially reduce the risk of recurrence or the persistence of symptoms.
Similar to its use in macular hole surgery, the use of ICG has proponents and detractors on the basis of its potential toxic effects. Haritoglou et al suggested that ICG-assisted ILM peeling may adversely affect the functional outcome of surgery for epiretinal membrane.[18, 19]
Hillenkamp et al prospectively evaluated the effect of ICG dye in the setting of epiretinal membrane surgery.[20] No difference or evidence of ICG toxicity was observed. Both visual function and macular morphology improved in patients with and without ICG dye use.
However, Garweg et al suggested that ILM peeling with ICG dye, but not with trypan blue dye, may result in loss of the central visual field over time.[21] No difference in visual acuity was noted. This study suggests that the ICG dye, not necessarily the ILM peeling, may have an adverse effect following epiretinal membrane surgery.
Liu et al performed a meta-analysis of epiretinal membrane surgery with and without ILM peeling and found that patients who underwent ILM peeling had better visual acuity at 12 months postsurgery. However, by 18 months postoperatively, the meta-analysis of two papers suggested that patients who had not undergone ILM peeling had marginally better visual acuity.[22]
Microperimetric analysis of patients undergoing ILM peeling versus no ILM peeling during epiretinal membrane surgery suggested a benefit to not peeling ILM. The sensitivity of the central 4° showed faster recovery and fewer absolute microscotomas in patients who did not undergo ILM peeling.[23]
Management of retinal breaks
Once the membrane is removed, it is imperative for the surgeon to look for any breaks in the retina, both in the posterior pole and in the periphery.
Any maneuvers completed to remove the membranes, no matter how elegant, become irrelevant if the retina detaches because of missed breaks.
Careful scleral depression of the anterior retina combined with indirect ophthalmoscopy should be performed to detect breaks in the periphery.
Breaks without subretinal fluid accumulation can be treated by laser retinopexy or cryoretinopexy.
The presence of significant amounts of subretinal fluid necessitates internal drainage under air, retinopexy, and gas tamponade.
The most frequently encountered intraoperative complications with vitrectomy and membrane peeling include intraocular bleeding and the development of retinal breaks.
Petechial hemorrhage along the internal retinal surface may be seen as the membrane is peeled off the retina but usually resolves within days of the operation.
More significant bleeding is encountered when an underlying vessel is damaged as a strongly adherent membrane is being peeled. This bleeding usually can be controlled by raising the intraocular pressure temporarily and waiting for the vessel to stop bleeding spontaneously or by applying cautery on the offending vessel.
The development of retinal breaks is the most important intraoperative complication that may be encountered. The incidence of intraoperative posterior pole breaks ranges anywhere from 0-15%, while that of peripheral breaks ranges from 5-6%.
Chung et al reviewed 174 eyes undergoing a vitrectomy for epiretinal membranes. The incidence of iatrogenic retinal breaks was 6.9%. They identified that the induction of a posterior vitreous detachment was a key risk factor for the development of iatrogenic retinal breaks. Only 28 (16%) of 174 eyes required the induction of a posterior vitreous detachment during surgery. However, this group accounted for 9 of 12 retinal breaks in this series. When a posterior vitreous detachment was already present, the incidence of iatrogenic retinal breaks was only 2.1%.[24]
Meticulous peeling of the membrane and careful examination of the peripheral retina are the most effective means to minimize postoperative problems associated with these retinal breaks.
Postoperative
The most frequent postoperative complication that may be seen is the accelerated progression of nuclear sclerosis of the lens, which may occur in as many as 75% of eyes over time.
Most patients have to undergo cataract extraction within 2 years to maximize the benefits afforded by membrane peeling.
Postoperative retinal detachment may be caused either by a missed break or by a new break that developed after further contraction of the remaining anterior vitreous. This detachment happens in 3-6% of patients and nearly always is treated successfully by another operation.
Recurrence of epiretinal membrane happens in less than 5% of idiopathic cases but may be higher for postdetachment and postinflammatory cases.
Postoperative macular holes following epiretinal membrane surgery are estimated to occur infrequently. In a review of 423 cases of epiretinal membrane surgery with internal limiting membrane peeling, 11 cases (2.6%) of postoperative macular holes were identified. The majority of holes (9 of 11) were eccentric primarily found along the margin of the internal limiting membrane peel. The incidence of central macular holes, requiring additional vitrectomy and gas tamponade, was 0.5% (2 of 423).[25]
Yannuzzi et al proposed that ILM peeling at the time of rhegmatogenous retinal detachment repair may decrease the likelihood of symptomatic ERM development and the need for subsequent surgery. A meta-analysis of six studies suggested that the rate of symptomatic ERM following retinal detachment repair without ILM peeling was 29% versus 3% with ILM peeling at the time of retinal detachment repair. The subsequent surgical rate was 16% for patients with retinal detachment repair without ILM peeling and 0% for patients with retinal detachment repair and ILM peeling. Yannuzzi et al suggest that the decreased rate of secondary pars plana vitrectomy (PPV) and ERM peeling may justify ILM peeling at the time of retinal detachment repair for prevention of symptomatic ERM.[26]
Clinical Context:
Ocriplasmin exerts proteolytic effects on the components of vitreomacular adhesion, including fibrinogen, fibronectin, and, to a lesser extent, laminin and collagen.
Kean Theng Oh, MD, Consulting Staff, Associated Retinal Consultants, PC
Disclosure: Nothing to disclose.
Coauthor(s)
John H Drouilhet, MD, FACS, Clinical Professor, Department of Surgery, Section of Ophthalmology, University of Hawaii, John A Burns School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Steve Charles, MD, Founder and CEO of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine
Disclosure: Received royalty and consulting fees for: Alcon Laboratories.
Chief Editor
Douglas R Lazzaro, MD, FAAO, FACS, Chairman, Professor of Ophthalmology, The Richard C Troutman, MD, Distinguished Chair in Ophthalmology and Ophthalmic Microsurgery, Department of Ophthalmology, State University of New York Downstate Medical Center; Chief of Ophthalmology, Director of Cornea, Director of Surgical Training, Kings County Hospital Center
Disclosure: Nothing to disclose.
Additional Contributors
V Al Pakalnis, MD, PhD, Professor of Ophthalmology, University of South Carolina School of Medicine; Chief of Ophthalmology, Dorn Veterans Affairs Medical Center
Disclosure: Nothing to disclose.
Acknowledgements
Bradley M Hughes, MD Assistant Professor, Department of Ophthalmology, Retina and Vitreous Service, University of Arkansas for Medical Sciences
Bradley M Hughes, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Ophthalmology
Disclosure: Nothing to disclose.
Sherman O Valero, MD Consulting Staff, Department of Ophthalmology, Makati Medical Center, Philippines
Very dense epiretinal membrane with associated macular distortion.
Grade 2 epiretinal membrane causing striations in the retinal surface. Note the presence of a pseudohole.
Fluorescein angiogram demonstrating retinal vascular distortion. Note the leakage of the dye in the macular area, which represents secondary macular edema.
Very dense epiretinal membrane with associated macular distortion.
Grade 2 epiretinal membrane causing striations in the retinal surface. Note the presence of a pseudohole.
Fluorescein angiogram demonstrating retinal vascular distortion. Note the leakage of the dye in the macular area, which represents secondary macular edema.
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