Chapter 116 Epiretinal Membranes
Prevalence
Evidence regarding the epidemiology of ERMs predominantly comes from two large population studies, the Beaver Dam Eye Study and the Blue Mountains Eye Study.1–3 The overall prevalence of ERM in these populations was 7–11.8%, with a 5-year incidence of 5.3%.1–3 Idiopathic ERMs were bilateral in 19.5–31%, with a 13.5% 5-year incidence of second eye involvement.1–3
The age distribution shows a peak between the ages of 70 and 79 (11.6%), with ERMs being uncommon before the age of 60 (1.9%).3 The increased odds of ERM for persons over the age of 70 compared with those younger than 60 was 7.4.3 ERMs were more commonly diagnosed in women in the Beaver Dam cohort but not in the Blue Mountains Study and this difference may merely reflect the greater survival rate of women in this age group.
The prevalence of ERM appears to vary with ethnicity.4,5 Higher prevalence was noted in Chinese participants in a multiethnic epidemiological study (39% in Chinese versus 27.5% in Caucasians),5 whereas lower rates have been observed in the Japanese (4%).4 In the Blue Mountains Study, the prevalence of ERM was significantly increased following cataract surgery (16.8%) and retinal vein occlusion (12.5%);3 9.1% of patients with no retinal abnormality at baseline developed an ERM following cataract surgery.2
Classification
The majority of ERMs have no associated ocular abnormality and are termed idiopathic. ERMs may be classed as secondary when a pre-existing or coexisting condition has had a significant impact on development, and iatrogenic if they occur following medical or surgical intervention (Table 116.1).6
| Idiopathic
Secondary Retinal vascular disease Vascular occlusion, e.g. BRVO, CRVO Diabetic retinopathy Telangiectasias Macroaneurysm Sickle cell retinopathy Intraocular inflammation Trauma Retinal detachment and retinal tears Intraocular tumors Retinal angiomas Hamartomas Retinal dystrophies Retinitis pigmentosa Iatrogenic Postoperative Cataract Retinal detachment Silicone oil Retinopexy Laser or cryotherapy |
Clinical features
ERM is a spectrum of disease where mild forms are characterized by an abnormal retinal light reflex on fundoscopy with mild retinal thickening and no distortion of the retinal surface. In a proportion of patients, there may be progressive contraction of the ERM resulting in distortion of the retinal surface and, at times, intraretinal fluid accumulation while the membrane may become thicker and more opaque.7
A clinical grading system was proposed by Gass to describe the different stages of the disease.8
In Grade 0 (also termed cellophane maculopathy), a translucent membrane with no underlying retinal distortion is observed. These membranes are asymptomatic and the diagnosis is often an incidental finding during routine ophthalmic or optometric examination (Fig. 116.1).
An epiretinal membrane associated with irregular wrinkling of the inner retina is classed as Grade 1 (Fig. 116.2). When this involves the fovea, patients often complain of distorted or blurred vision. These symptoms may only be perceptible when the unaffected eye is covered, particularly if the ERM occurs in the nondominant eye. Other symptoms that patients may report include loss of binocularity, central photopsia, and macropsia. Anecdotally, monocular diplopia may also be a presenting symptom of ERM, however this does not appear to have been described by patients in cohorts published to date.7 Eccentric grade 1 ERMs that do not involve the fovea may be asymptomatic (Fig. 116.3).
A Grade 2 ERM is characterized by an opaque membrane causing obscuration of underlying vessels and marked full-thickness retinal distortion (Fig. 116.4). Increasing vascular tortuosity and size of vessel involved tend to be a sign of more advanced disease. ERMs with full-thickness retinal distortion may also be associated with cotton-wool spots, exudates, blot hemorrhages and microaneurysms (Fig. 116.5). Cystoid macular edema is present in approximately 20–40% of patients (Fig. 116.6).9–11 Vascularization of the ERM and underlying RPE disturbance are rare but indicate more severe disease. Although symptoms are more commonly associated with increasing severity of ERM, patients may have significant ERMs and remain asymptomatic.6 Approximately 80% of patients with Grade 2 ERM will have symptoms of blurred vision or metamorphopsia.12
A posterior vitreous detachment (PVD) is present in approximately 60–90% of patients at the time of diagnosis.9–11 Those with partial PVD and persistent vitreomacular adhesion are more likely to develop cystoid macular edema and present with a lower visual acuity.9 In cases where a PVD does not exist, the clinical findings may be very similar to those commonly seen in vitreomacular traction syndrome (VMT) (see Chapter 118, Cystoid macular edema and vitreomacular traction). The subsequent evolution of a PVD can result in avulsion of the ERM and this may be observed as a ‘scroll’ of tissue at the membrane edge or within the vitreous gel (Fig. 116.7). Avulsion of the ERM is usually accompanied by a reduction in or resolution of symptoms.
ERMs may also be associated with macular pseudoholes, lamellar holes, and much less commonly, with full-thickness macular holes, presumably as a result of tangential traction. It is possible that lamellar holes form when retinal cysts associated with the ERM rupture forming inner neural defects. When contraction of the ERM distorts the underlying retina to form a steepened foveal contour that clinically resembles a macular hole, the term pseudohole is used (Fig. 116.8). This has been described in up to 20% of patients.13
Although rapid progression of the disease has been described,14 the usual course is one of stability or slow progression over years with the visual acuity rarely deteriorating below 20/200. In a study by Appiah et al., of 324 idiopathic ERMs with a mean follow-up of 33.6 months, 49.5% maintained a visual acuity within 1 line of the initial acuity; 37.4% showed a reduction in vision, and 13.1% stayed the same.9 In the Blue Mountains Study, the area of retina occupied by the ERM remained stable in 39%, regressed in 25.7% and progressed 28.6% in a 5-year period, where change was defined as a change in area of >25%.
Pathogenesis
In general terms, ERMs have two main components: an extracellular matrix (consisting of collagen, laminin, tenascin, fibronectin, vitronectin, etc.) and cells of retinal and extra retinal origin (such as glial cells, neurites, retinal pigment epithelium, immune cells and fibrocytes).15,16 The relative abundance of these components within the ERM reflects the underlying etiology, severity of disease or its duration. For example, ERMs secondary to proliferative vitreoretinopathy (PVR) are more heavily pigmented due to a high RPE content when compared with idiopathic ERMs which are composed predominantly of glial elements (Fig. 116.9).17–19 Similarly, ERMs that develop in response to retinal ischemia and neovascular proliferation may have a larger vascular component. Growth factors play an important role in the formation, progression and transformation of membranes with differential expression being observed in membranes according to their etiology.20 A summary of some of the growth factors involved in the development of idiopathic and secondary ERMs is given in Table 116.2.
Membranes appear to develop predominantly where Müller cells have proliferated and migrated onto the inner surface of the retina and where hypertrophied cell processes extend towards the vitreous cavity. In idiopathic ERMs, it is possible that vitreous separation at the time of PVD exerts traction on the retina and induces Müller cell gliosis, a process of cellular hypertrophy, upregulation of cellular proteins such as vimentin and GFAP and transient cellular proliferation. Müller cells are thought to migrate to the epiretinal surface via small defects in the internal limiting membrane (ILM),15 which may occur naturally, such as those commonly seen near retinal vessels, or as a result of larger paravascular breaks observed following PVD.21,22 Activation of Müller cells may continue even once the original stimulus has been withdrawn. In retinal detachment activated Müller cells, that have penetrated the ILM and migrated on to the epiretinal surface, continue to proliferate even once retinal reattachment is achieved.23
Where ERMs form in the absence of PVD, a period of vitreomacular traction may cause chronic irritation of Müller cells inducing gliosis and vascular leakage. Foos noted the presence of vitreous between ERM and ILM in some specimens suggesting that an ERM may form prior to PVD and is a distinct entity from vitreomacular traction.21 In the absence of a PVD, glial cells appear to grow through the posterior hyaloid which then in turn becomes incorporated into the membrane. This may explain the mechanism behind spontaneous avulsion of ERMs following PVD.
More advanced ERMs have contractile components that exert traction on the underlying retina and distort the retinal vasculature with or without a breakdown of blood–retina barrier and fluid accumulation in the macula. In these membranes a higher content of contractile actin or myofibroblasts is observed. This is also described in some secondary ERMs such as those found in PVR and PDR, and in these cases ERMs may lead to detachment of the underlying retina. As the ERM matures the contractile nature of the membrane may change. This is characterized by an alteration in the expression of surface proteins, for example a reduction in GFAP and increase in α-smooth-muscle actin are associated with increasing contractility.24
