Eleni Kottaridou

Introduction

Epiretinal membrane (ERM) may be defined as the pre-retinal proliferation of myofibroblastic cells associated with the extracellular matrix (ECM) (1). Although various aetiologies have been documented, these cannot be distinguished through histological variations. This review elucidates the most recent evidence concerning the epidemiology, aetiology, clinical findings, and investigation of ERMs.

Epidemiology

Epidemiology of ERMs has been substantiated through the execution of extensive studies that incorporate examination via Optical Coherence Tomography (OCT). A meta-analysis encompassing 13 population-based studies, conducted by Xiao et al. in 2017, revealed an overall prevalence of ERMs at 9.1% (2). Age has been correlated with an increasing incidence of ERMs, peaking in the seventh decade of life. Additionally, it is imperative to consider the disparities among racial groups and countries as a risk factor. The Multi-Ethnic Study of Atherosclerosis, which involved 5,960 United States citizens, demonstrated that the prevalence of ERMs was significantly higher among individuals of Chinese descent (39%) compared to Hispanics (29%), Caucasians (27.5%), or African Americans (26.2%). Gender and refractive associations have yielded inconsistent results (3).

Aetiology

The aetiology of ERMs has been classified as either primary or secondary. Idiopathic ERMs (iERMs) occur in absence of associated ocular abnormalities or solitary posterior vitreous detachment (PVD).  However, a PVD is present in 78% to 95% of iERMs, indicating its significance in the pathogenic process (4). On the contrary, secondary ERMs refer to the coexistence of ocular disease. Among all ERMs, 32.3% may be classified as secondary with most frequent causes being previous cataract surgery, diabetic retinopathy and retinal vein occlusion (5).

Pathophysiology

ERMs typically consist of two layers situated above the internal limiting membrane (ILM). The outermost layer is composed of non-cellular ECM proteins, which include bundles of extracellular fibrils arranged in a random orientation. Above this lies an inner cellular layer, formed by a single or multiple layers of epiretinal cells. It is hypothesized that residual cortical vitreous, resulting from posterior vitreous detachment or partial separation of the posterior hyaloid, may lead to dehiscence of the ILM (6). This dehiscence facilitates the migration of microglial cells to the retinal surface within the vitreo-retinal space, where they differentiate into fibroblast-like cells. Additionally, hyalocytes in the vitreous, upon interaction with microglial cells, differentiate into myofibroblasts. The differentiation of various cell types into myofibroblasts is regarded as the central pathogenic mechanism in ERM formation.

Inflammatory mediators further contribute to fibrocellular proliferation, particularly in cases of secondary ERM formation. Secondary ERMs commonly include retinal pigment epithelial (RPE) cells, macrophages, and T- and B-lymphocytes. As the ERM progresses, it leads to a progressive loss of the foveal dip, ectopic inner foveal layers, disruption of retinal layers, cystoid macular oedema and foveal pathology (6).

Symptoms

Although most patients are asymptomatic, the literature reports symptoms such as metamorphopsia, blurred vision, monocular diplopia, and micropsia (6).

Diagnosis

OCT is the most valuable diagnostic tool for ERM. OCT enables both precise qualitative assessment and quantitative analysis, facilitating correlation with visual prognosis. ERM is characterized by a hyperreflective linear band on the inner retina. In some cases, ERM may be associated with foveoschisis, a separation between the outer nuclear layer (ONL) and the outer plexiform layer (OPL) (7). Fundus autofluorescence can reveal retinal vessel tortuosity and the presence of acquired vitelliform lesions (1). Fluorescein angiography is particularly useful in secondary cases of ERM, such as those associated with retinal vascular occlusions, intraocular tumours, or macular oedema. Additionally, OCT angiography (OCTA) may be required preoperatively to identify underlying secondary causes of ERM. Studies analysing ERMs using OCTA have demonstrated a reduction or loss of the foveal avascular zone (FAZ), attributed to the stretching and displacement of vessels within both the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) (8).

Management

Conservative

ERM is a chronic, slowly progressive condition in which the majority of patients do not require intervention. Currently, there is no specific medical treatment available for ERM. However, macular oedema associated with certain secondary causes of ERM, such as diabetic retinopathy, retinal vein occlusion, or uveitis, may respond to intravitreal therapies, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, or non-steroidal agents (1).

Surgery

Vitreoretinal surgery for epiretinal membrane (ERM) is typically indicated in cases of vision loss or symptoms that interfere with activities of daily living (1). The optimal timing of surgery to prevent irreversible damage remains uncertain. The primary objective of surgery is to remove the membrane and relieve retinal traction. The internal limiting membrane (ILM) is believed to serve as a scaffold for cellular proliferation, and it has become standard practice to perform an ERM/ILM double peel during surgery. Removing the ILM ensures a more complete elimination of the ERM. The recurrence rate of ERM is significantly lower with double peeling compared to ERM peeling alone, thereby reducing the likelihood of repeat surgery.

The surgical approach for secondary ERM is similar to that for idiopathic ERM (iERM), although addressing the underlying aetiology is essential to prevent recurrence (1). Management of the underlying cause may involve retinal laser or cryotherapy for retinal tears, retinopexy and intravitreal tamponade for retinal detachment, panretinal photocoagulation for proliferative diabetic retinopathy (PDR), sector laser photocoagulation for neovascularization secondary to retinal vein occlusion, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for choroidal neovascularization, or periocular/intravitreal corticosteroids for uveitis.

Complications

Generic complications of vitrectomy surgery include cataract, endophthalmitis, haemorrhage, hypotony and retinal detachment (9).

References

1.Fung AT, Galvin J, Tran T. Epiretinal membrane: A review. Clinical & Experimental Ophthalmology [Internet]. 2021 Apr 1;49(3):289–308. Available from: https://pubmed.ncbi.nlm.nih.gov/33656784/

2.Xiao W, Chen X, Yan W, Zhu Z, He M. Prevalence and risk factors of epiretinal membranes: a systematic review and meta-analysis of population-based studies. BMJ Open [Internet]. 2017 Sep 25 [cited 2021 Jan 3];7(9). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623383/

3.Ng CH, Cheung N, Wang JJ, Islam AFM, Kawasaki R, Meuer SM, et al. Prevalence and Risk Factors for Epiretinal Membranes in a Multi-Ethnic United States Population. Ophthalmology. 2011 Apr;118(4):694–9.

4.Wiznia RA. Posterior vitreous detachment and idiopathic preretinal macular gliosis. American Journal of Ophthalmology [Internet]. 1986 Aug 15 [cited 2024 Mar 30];102(2):196–8. Available from: https://pubmed.ncbi.nlm.nih.gov/3740180/

5.Kawasaki R, Jie Jin Wang, Mitchell P, Aung T, Saw SM, Tien Yin Wong. Racial difference in the prevalence of epiretinal membrane between Caucasians and Asians. British Journal of Ophthalmology. 2008 Oct 1;92(10):1320–4.

6.Omesh P. Gupta, MD, MBA. Epiretinal Membrane – EyeWiki [Internet]. eyewiki.org. 2024. Available from: https://eyewiki.org/Epiretinal_Membrane

7.Hubschman JP, Govetto A, Spaide RF, Schumann R, Steel D, Figueroa MS, et al. Optical coherence tomography-based consensus definition for lamellar macular hole. British Journal of Ophthalmology. 2020 Feb 27;104(12):1741–7.

8.Mastropasqua R, D’Aloisio R, Viggiano P, Borrelli E, Iafigliola C, Di Nicola M, et al. Early Retinal Flow Changes after Vitreoretinal Surgery in Idiopathic Epiretinal Membrane Using Swept Source Optical Coherence Tomography Angiography. Journal of Clinical Medicine. 2019 Nov 24;8(12):2067.

9.Fabian ID, Moisseiev J. Sutureless vitrectomy: evolution and current practices. British Journal of Ophthalmology. 2010 Aug 23;95(3):318–24.