An epiretinal membrane (ERM) can be a common finding, particularly in the older population, however the clinical course is often variable with some being progressive and some remaining stable over time.
Additionally, patients can be symptomatic with bothersome metamorphopsia whereas others may remain asymptomatic despite progression. For these reasons, clinicians are often faced with the challenge of deciding whether to observe the patient or refer for the consideration of surgical intervention.
Although ERM exhibit a variable clinical course between individuals, clinical management is largely dependent on patient vision and symptoms
This article answers common questions that arise around ERM and provides an evidence-based approach to the clinical assessment and management of patients.
Epiretinal membranes are fibrocellular growths at the vitreomacular interface. They lead to the formation of a contractile membrane that can result in distortion of the underlying retinal structures.1 In the literature, ERM can also be referred to as a macular pucker, cellophane maculopathy, pre-retinal macular fibrosis, or epiretinal fibrosis or gliosis.
Despite having similar clinical presentations, ERM can be classified as idiopathic or secondary. The majority of ERM cases are idiopathic and occur without any associated ocular abnormalities apart from a posterior vitreous detachment.1 A secondary ERM occurs as a response to other ocular pathologies that promote fibro cellular proliferation (Figure 1).2
Figure 1. Example of a secondary ERM. (A-B) Colour fundus photography and red-free imaging show a reflective, semi-translucent membrane at the macula. (C) OCT shows a hyperreflective layer on the inner retinal surface. (D) Widefield imaging shows two peripheral retinal tears in the superonasal and superotemporal retina treated with barrier laser.
A recent study by Fung et al. provides a comprehensive list including conditions such as retinal tears and/or detachments, retinal vascular disease, ocular inflammatory disorders, intraocular surgery, and trauma.3
Epiretinal Membrane Progression
In early large population studies, the prevalence of idiopathic ERMs was about 7–12% based on colour fundus photography.4,5 However, with the advent of optical coherence tomography (OCT) imaging, the prevalence in older populations has been found to be as high as 34%.6
Natural history studies show that 39% of cases are stable; 26% of cases can regress; and 29% of cases can progress,7 with 10–21% ultimately requiring surgical intervention.8-10 From these studies, we can see that most ERMs are stable. This should be taken into consideration when managing patients.
Clinical Testing
All patients with ERM require a comprehensive clinical work up with integration of the following considerations.
History and Symptoms
Although most ERMs are asymptomatic, typical symptoms include reduced vision, blurry vision, metamorphopsia and, less commonly, monocular diplopia and reduced stereopsis.
Symptomatic patients should be further assessed on whether there is interference with quality of life such as driving, reading, and other tasks of daily living.
History-taking should also elicit for any secondary causes including floaters or photopsia, history of uveitis, retinal breaks and/or detachment, intraocular surgery, trauma, and systemic vascular disease including diabetes, hypertension, and hyperlipidaemia.3
Where other non-macular ocular pathologies exist, such as cataract or ocular surface disease, a history of metamorphopsia as the primary symptom suggests that the ERM is a major cause of the patient’s complaint.
Entrance Tests
Entrance tests should include visual acuity and monocular Amsler grid to assess and document any reduction in vision or metamorphopsia. Although less commonly used in clinical practice, contrast sensitivity can also be measured. This has been shown to progressively deteriorate with increasing degrees of retinal structural abnormality.11
Slit Lamp Examination
A slit lamp examination should carefully assess for signs of secondary ERM, including current or past uveitis, ocular trauma, intraocular surgery, or pigment in the anterior vitreous.
Fundus Examination
An ERM will appear as a greyish, semi-translucent sheet with a glistening reflex at the macula. It can be associated with loss of the normal foveal contour, fine wrinkling, and retinal folds.12 In severe cases, retinal haemorrhages, hard exudates, cystoid macular oedema, and macular holes can occur.12
Gass et al.13 initially proposed a classification system of ERM based on translucency, retinal distortions, and folds, however with the advent of OCT, this classification system is less widely used. A dilated fundus examination should be performed to exclude any secondary causes including retinal tears and/or detachments.
Integrating Imaging Modalities
Although the diagnosis of ERM can often be made on fundus examination, early presentations can be subtle and easily overlooked.
OCT is the most important imaging modality for diagnosis and structural assessment of an ERM, which appears as a hyperreflective membrane on the inner retinal surface.14 An ERM can be associated with macular thickening, loss of the foveal depression, macular holes, and foveoschisis. Examples are shown in Figure 2.
Figure 2: ERM with (A) macular thickening but a preserved foveal pit, (B) macular thickening and loss of the foveal pit, (C) foveoschisis, and (D) lamellar macular hole and disruption of the ellipsoid zone.
In recent years, several important advances in OCT have also enhanced our ability to detect prognostic markers or structural signs that can be used to predict visual outcomes.3,15
These OCT signs include:
• Disruption of the ellipsoid zone or interdigitation zone. The ellipsoid zone and interdigitation zones are often used to evaluate the integrity of photoreceptors. In ERM, disruption of these layers is not only associated with reduced visual acuity but is a significant factor in predicting postoperative outcomes.19,20
A greater central foveal thickness and ganglion cell layer thickness,21,22 presence of cystoid macula oedema19 and acquired vitelliform lesions,23 have also been associated with poorer visual prognosis.
There has also been a focus on specific inner retinal changes that can occur, including the formation of ectopic inner foveal layers (EIFL) and disorganisation of the retinal layers. Studies suggest that Surgical intervention may be beneficial prior to the development of these signs:
• EIFL are defined as a continuous hyper or hyporeflective band that extends from the inner nuclear and inner plexiform layer across the fovea (Figure 3C).15 The presence of this sign is associated with lower visual acuity and poorer visual outcomes after surgery.16,17 Gonzalez et al. showed that less than 50% of eyes with EIFL were able to achieve a post-operative visual acuity of 6/12 or better compared to over 90% of eyes without EIFL.17
• Disorganisation of the retinal layers can also occur (Figure 3D). It is similarly associated with worse preoperative and postoperative visual outcomes.15,18 Severe presentations may show limited improvement of visual function following surgery.18
In 2017, Govetto et al. proposed a four-stage classification system based on the presence or absence of a foveal pit, EIFL, and disorganisation of the retinal layers (Figure 3).15 Although there is currently no widely accepted ERM classification system, it has been shown that the successive ERM stages in Govetto et al.’s system are associated with progressively worse visual acuity. The higher the ERM stage, such as stage three or four, the greater the decline in visual acuity.15
Figure 3. Examples of ERM staging according to Govetto et al.,15 using cases from Centre for Eye Health. (A) Stage 1 ERM with a preserved foveal pit and distinguishable retinal layers, VA 6/7.5+2. (B) Stage 2 ERM with loss of the foveal depression but retinal layers are still distinct, VA 6/7.5-2. (C) Stage 3 ectopic inner foveal layers with a continuous layer across the fovea (white arrow), VA 6/12-2. (D) Stage 4 ectopic inner foveal layers with disorganisation of the inner retinal layers (white asterisks), VA 6/15.
Other Imaging Techniques
Interoperative OCT, where available, can be used to evaluate the effectiveness of surgical manoeuvres in real time.24,25
OCT-angiography (OCT-A) can help exclude retinal pathologies, such as diabetic retinopathy or retinal vein occlusions as the cause of a secondary ERM. In recent research, OCT-A has been applied to assess contraction, which could lead to deformation of the retinal vasculature and foveal avascular zone.26
When Should I Refer?
There is currently no universal consensus on when to refer for surgical intervention but the majority of ERMs remain stable and do not require treatment. The decision to refer should be made on a Case-by-case basis.
In most instances, asymptomatic patients with normal visual acuity can be monitored every six to 12 months and provided with an Amsler grid.
Consider referral in patients with a reduction in visual acuity, metamorphopsia, difficulty in binocularity, or experiencing limitations in tasks of daily living. Patients presenting with structural markers on an OCT associated with a poor visual prognosis, as described above, may also prompt referral. In all cases, referral should be directed to an ophthalmologist with subspecialty training in vitreoretinal surgery.
When uncertain about whether to refer, it is important to bear in mind that delayed surgical intervention can result in suboptimal post-operative outcomes.
The presence of an ERM can also impact visual outcomes and recovery from cataract surgery, with a higher risk of cystoid macular oedema seen in these patients.27,28 As a result, if both ERM and cataracts are present, earlier referral should be considered in consultation with the relevant surgeon regarding their preferences on treatment timing and methods.
Surgical Interventions
When a decision is made to refer, the treatment for an ERM is surgical. The goal of surgical intervention is to improve or preserve vision, reduce metamorphopsia or other symptoms, and ultimately improve quality of life.
The current recommended surgical intervention is a pars-plana vitrectomy (PPV) with ERM peeling. In brief, this technique is performed under the operating microscope via sclerotomy incisions through which illumination and micro-instruments are introduced.
Intraocular pressure is maintained by a fluid infusion through another sclerotomy site. The vitreous core is removed, and a posterior vitreous detachment is induced or completed, if not already present. The ERM is stained using a non-toxic dye and peeled with the aid of microforceps and other instruments. The retina is examined for breaks to the level of the ora serrata and if present, treated with cryotherapy or laser retinopexy. Sutureless closure is increasingly common, with an intraocular gas bubble used to seal the wounds.
An internal limiting membrane (ILM) peel may also be performed at the discretion of the treating surgeon to reduce the risk of recurrence, as the ILM is thought to be a scaffold for glial cell proliferation.29-31 However, the role of ILM peeling remains controversial as it can cause loss of inner retinal tissue leading to inner retinal dimpling,29 paracentral macular holes,32 and micro-scotomas.33
Although not commonly employed in Australia, in cases where there is concurrent vitreomacular traction (VMT), there is published evidence regarding the possible advantage of vitreopharmacolysis with ocriplasmin to address the VMT, however it has no impact on the ERM itself.34
Conclusion
Although ERM exhibit a variable clinical course between individuals, clinical management is largely dependent on patient vision and symptoms. As the majority of cases are stable, observation is the mainstay management, particularly in asymptomatic patients who are functionally well and lacking objective visual acuity deficits that can be attributed to the ERM. Imaging modalities, such as OCT imaging, can be used to detect structural signs that carry a negative prognosis, which may trigger an earlier referral to a vitreoretinal surgeon.
The authors acknowledge Michael Yapp and Judy Nam who reviewed and contributed to this article.
Sophia Zhang is a senior staff optometrist at the Centre for Eye Health, University of New South Wales. Her interest lies in the early detection of ocular disease and she is currently involved in the glaucoma/ neuro-ophthalmology and macula unit. In addition to the provision of clinical services, Ms Zhang is focussed on clinical education, co-ordinating the undergraduate optometry placement program and professional development resources at the Centre for Eye Health.
Dr Mitchell Lee MBBS FRANZCO completed his ophthalmology training at Prince of Wales Hospital (Sydney). He is the incoming vitreoretinal fellow at Westmead Hospital, Sydney, Australia.
References
1. Bu S.C., Kuijer .R, Li X.R., et al., Idiopathic epiretinal membrane. Retina. 2014;34(12):2317-35.
2. Appiah A.P., Hirose T., Secondary causes of premacular fibrosis. Ophthalmology. 1989;96(3):389-92.
3. Fung A.T., Galvin J., Tran T., Epiretinal membrane: A review. Clinical & Experimental Ophthalmology. 2021;49(3):289-308.
4. Mitchell P., Smith W., Chey T., et al., Prevalence and associations of epiretinal membranes: the Blue Mountains Eye Study, Australia. Ophthalmology. 1997;104(6):1033-40.
5. Klein R., Klein B., Wang Q., Moss S.E., The epidemiology of epiretinal membranes. Transactions of the American Ophthalmological Society. 1994;92:403.
6. Meuer S.M., Myers C.E., Klein B.E., et al., The epidemiology of vitreoretinal interface abnormalities as detected by spectral-domain optical coherence tomography: the beaver dam eye study. Ophthalmology.2015;122(4):787-95.
7. Fraser-Bell S., Guzowski M., Rochtchina E., et al., Five-year cumulative incidence and progression of epiretinal membranes: the Blue Mountains Eye Study. Ophthalmology. 2003;110(1):34-40.
8. Chen X., Klein K.A., Shah C.P., Heier J.S., Progression to surgery for patients with idiopathic epiretinal membranes and good vision. Ophthalmic Surgery, Lasers and Imaging Retina. 2018;49(10):S18-S22.
9. Kim J.H., Kim J.W., Kim C.G., Lee D.W., Long-term natural history of the idiopathic epiretinal membrane in children and young adults. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2020;258:2141-50.
10. Luu K.Y., Koenigsaecker T., Yazdanyar A., et al., Longterm natural history of idiopathic epiretinal membranes with good visual acuity. Eye. 2019;33(5):714-23.
11. Liu L., Wang Y., Liu J., Liu W., Retinal-image quality and contrast sensitivity function in eyes with epiretinal membrane: a cross-sectional observational clinical study. BMC ophthalmology. 2018;18(1):1-6.
12. Kanukollu V.M., Agarwal P.. Epiretinal Membrane. StatPearls [Internet]: StatPearls Publishing; 2022.
13. Gass J., Macular dysfunction caused by epiretinal membrane contraction. Stereoscopic atlas of macular diseases. 1997:938-51.
14. Do D.V., Cho M., Nguyen Q.D., et al., The impact of optical coherence tomography on surgical decision making in epiretinal membrane and vitreomacular traction. Transactions of the American Ophthalmological Society. 2006;104:161.
15. Govetto A., Lalane III R.A., Sarraf D., et al., Insights into epiretinal membranes: presence of ectopic inner foveal layers and a new optical coherence tomography staging scheme. American Journal of Ophthalmology. 2017;175:99-113.
16. Govetto A., Virgili G., Rodriguez F.J., et al., Functional and anatomical significance of the ectopic inner foveal layers in eyes with idiopathic epiretinal membranes: surgical results at 12 months. Retina. 2019;39(2):347-57.
17. González-Saldivar G., Berger A., Wong D., et al., Ectopic inner foveal layer classification scheme predicts visual outcomes after epiretinal membrane surgery. Retina. 2020;40(4):710-7.
18. Zur D., Iglicki M., Feldinger L., et al., Disorganization of retinal inner layers as a biomarker for idiopathic epiretinal membrane after macular surgery—the DREAM study. American journal of ophthalmology. 2018;196:129-35.
19. Fang I.M., Hsu C.C., Chen L.L., Correlation between visual acuity changes and optical coherence tomography morphological findings in idiopathic epiretinal membranes. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2016;254:437-44.
20. Shimozono M., Oishi A., Hata M., et al., The significance of cone outer segment tips as a prognostic factor in epiretinal membrane surgery. American Journal of Ophthalmology. 2012;153(4):698-704. e1.
21. Iuliano L., Fogliato G., Gorgoni F., et al., Idiopathic epiretinal membrane surgery: safety, efficacy and patient related outcomes. Clinical Ophthalmology. 2019:1253-65.
22. Pierro L., Iuliano L., Gagliardi M., et al., Role of ganglion cell complex in visual recovery following surgical internal limiting membrane peeling. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2015;253:37-45.
23. Govetto A., Bhavsar K.V., Virgili G., et al., Tractional abnormalities of the central foveal bouquet in epiretinal membranes: clinical spectrum and pathophysiological perspectives. American Journal of Ophthalmology. 2017;184:167-80.
24. Ehlers J.P., Khan M., Petkovsek D., et al., Outcomes of intraoperative OCT–Assisted epiretinal membrane surgery from the pioneer study. Ophthalmology Retina. 2018;2(4):263-7.
25. Tuifua T.S., Sood A.B., Abraham J.R., et al., Epiretinal membrane surgery using Intraoperative OCT-guided membrane removal in the DISCOVER study versus conventional membrane removal. Ophthalmology Retina. 2021;5(12):1254-62.
26. Chen H., Chi W., Cai X., et al., Macular microvasculature features before and after vitrectomy in idiopathic macular epiretinal membrane: an OCT angiography analysis. Eye. 2019;33(4):619-28.
27. Schaub F., Adler W., Enders P., et al., Preexisting epiretinal membrane is associated with pseudophakic cystoid macular edema. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2018;256:909-17.
28. Chu C.J., Johnston R.L., Buscombe C., et al., Risk factors and incidence of macular edema after cataract surgery: a database study of 81984 eyes. Ophthalmology. 2016;123(2):316-23.
29. Jung J.J., Hoang Q.V., Ridley-Lane M.L., et al., Longterm retrospective analysis of visual acuity and optical coherence topographic changes after single versus double peeling during vitrectomy for macular epiretinal membranes. Retina (Philadelphia, Pa). 2016;36(11):2101.
30. Schechet S.A., DeVience E., Thompson J.T., The effect of internal limiting membrane peeling on idiopathic epiretinal membrane surgery, with a review of the literature. Retina. 2017;37(5):873-80.
31. Fang X.L., Tong Y., Zhou Y.L., et al., Internal limiting membrane peeling or not: a systematic review and metaanalysis of idiopathic macular pucker surgery. British Journal of Ophthalmology. 2017;101(11):1535-41.
32. Sandali O., El Sanharawi M., Basli .E, et al., Paracentral retinal holes occurring after macular surgery: incidence, clinical features, and evolution. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2012;250:1137-42.
33. Deltour J.B., Grimbert P., Masse H., et al., Detrimental effects of active internal limiting membrane peeling during epiretinal membrane surgery: microperimetric analysis. Retina. 2017;37(3):544-52.
34. Folk J.C., Adelman R.A., Flaxel C.J., et al., Idiopathic epiretinal membrane and vitreomacular traction Preferred Practice Pattern Guidelines. Ophthalmology. 2016;123(1):P152-P81.
