EPIRETINAL MEMBRANE
Dr Pravin Jain,Dr P.N.Nagpal
Retina Foundation and Eye Research Center,Ahmedabad
Epiretinal membranes(ERM) are acquired formation of semi-transparent cellular sheets on the macular surface, which are formed due to varied etiologies. These membranes have contractile properties, often leading to mechanical distortion of macula.
The proliferation of ERM on the inner retinal surface along the internal limiting membrane was first described by Iwanoff in 1865 1. In 1971, Roth and Foos reported that in a series of autopsied eyes, ERM were present in 2 percent of patients aged 50 yr and in more than 20 percent of patients by age 75 yr2. Pearlstone reported an incidence of 6.4 percent in 1000 consecutive routine eye examinations in patients older than 50 yr, with 20 percent being bilateral 3,4. Other authors report bilateral involvement in 10 to 20% of cases5,6,7.The Los Angeles Latino Eye Study (LALES) found that of the participants with ERM, 19.9% had bilateral ERMs. The prevalence of ERM increased from 10.1% in persons 40 to 49 years of age to 35.7% in those aged 70 to 79 years and was 22.5% in persons aged 80 years or more. The prevalence was similar in men and women. ERMs were present in 71% of eyes with macular holes and were more common in individuals who had undergone cataract surgery (39.9%), those with proliferative diabetic retinopathy (25.7%), and those with any retinal disease (27.5%). 8
The wrinkling of the retinal surface caused by ERMs in the macular region has been termed surface wrinkling retinopathy,2 macular pucker, 9–10 cellophane maculopathy,11, 12 wrinkling of the internal limiting membrane,13 preretinal macular fibrosis,13,14 epiretinal macular membrane, primary retinal folds,15 internoretinal fibrosis,16 idiopathic preretinal macular gliosis,6,17,18 undetected central retinal vein occlusion,19 and silkscreen retinopathy. The term macular pucker has most frequently been applied to the condition when retinal surface wrinkling occurs following reattachment of a rhegmatogenous retinal detachment. This condition complicates 4 to 8 percent of otherwise successful primary retinal reattachments.20,21
ETIOLOGICAL CLASSIFICATION:
Primary ERMs are idiopathic in nature and are seen in patients over 50 years of age. Anomalous posterior vitreous detachment (PVD), has been described to be important in the pathogenesis of idiopathic epiretinal membrane, reported to have been present in 75% of cases.2-6,11,22,23 It constitutes of (1) vitreous liquefaction with an accumulation of fluids in the premacular portion of the vitreous cavity; (2) varying degrees of persistent adhesion between the posterior cortical vitreous and the internal limiting membrane (ILM); (3) splitting, or “vitreoschisis,” of the posterior cortical vitreous at the time of PVD; and (4) residual islands of cortical vitreous attached to the ILM following separation of the majority of the gel from the surface of the retina 24.
Secondary ERMs have been found in association with retinal vascular deseases, retinal breaks and detachments 25, ocular trauma, intraocular inflammation (Pars planitis/uveitis/Vitritis, CME) 26, uveitis, and following retinal cryopexy, laser photocoagulation 27, and intraocular surgery. Both types of epiretinal membranes have similar clinical appearance and may be differentiated on the basis of history or other associated features. Clarkson and coworkers, in a review of 1612 postmorterm eyes, noted epiretinal membranes in 1.7 percent of eyes that had not undergone previous ocular surgery 3. In one study it was found that 46.2% of patients with epiretinal memebranes were idiopathic while 53.8% had epiretinal membranes following previous vitreoretinal surgery. Main reasons for vitreoretinal surgery in this group was – 60% complications of diabetic retinopathy, 2.8% endophthalmitis after cataract surgery, 5.7% uveitis, 14.2% retinal detachment, 8.6% trauma and 8.6% vitreous hemorrhage because of retinal vein occlusion 28. The prevalence of ERMS formation has been shown to increase by 71.4% during the first 6 months after uneventful ECCE with PC IOL implantation. Authors concluded that ERMs were probably induced by the uneventful surgery29. Following pars plana vitrectomy (PPV) for repair of primary rhegmatogenous retinal detachment 12.8% eyes were noted to have a postoperative epiretinal membrane, clinically 30. ERM is also rarely reported with retinal tumors (neurofibromatosis 31, vasoproliferative tumors 32, macro aneurysms), drugs (NSAID’s. Tamoxifen, PFCL, S.O.).
Clinical features
Patients with epiretinal membranes peripheral to the macula are generally asymptomatic. When the membranes involve the macula or are perimacular, however, the type and degree of symptoms experienced will depend on the membrane thickness, the degree of retinal distortion caused by the overlying membrane, the presence or lack of significant traction that can cause a micro detachment of the posterior pole, and the presence or lack of edema in the macular and perimacular regions.
Thin epiretinal membranes usually cause few symptoms. The condition appears to be relatively stable or slowly progressive with only a small number of patients, approximately 5 percent, having a vision of 20/200 or worse.5, 33,34 In more advanced cases, there is a reduction in vision, micropsia, metamorphopsia, Amsler grid distortion, and occasionally monocular diplopia. Spontaneous separation of an epiretinal macular membrane, although uncommon(1%), can occur; when this happens, there is a general decrease in symptoms and a concomitant improvement in visual acuity. 12, 15, 35–38
Gass in 1987 classified ERM in three grades(Fig 1).
Grade 0: cellophane maculopathy, characterized by translucent membranes with no retinal distortion or obscuration of underlying vessels. There may be a irregular reflex, mild sheen or glint, without a distinct edge,
Grade 1: crinkled cellophane maculopathy, causing irregular wrinkling of inner retina but underlying vessels are still visible. They cause increased vascular tortuosity, with perimacular vessels seen to be pulled toward an epicenter and
Grade 2: macular pucker with opaque membranes obscuring underlying vessels, prominent retinal distortion and arcuate vessels are closer togather, often leading to foveal ectopia , heterotopia or shallow tabletop retinal detachment.
Other findings that may be present include small intraretinal hemorrhages, cystic changes in the macula, cotton wool spots39 and macular edema. Pseudoholes or macular cysts have been noted in up to 8 percent of idiopathic cases.6,40 The thicker and occasionally pigmented membranes are often seen following retinal detachment surgery, severe inflammatory conditions, and trauma.
Figure 1a,b,c: Cellophane, Crinkled cellophane maculopathy and Macular pucker
Pathology
The source of the cells producing these membranes has been controversial. Early reports suggested endothelial cells1, extension of muller cells process 41, fibroblasts in the vascular connective tissue 42, pigmented or nonpigmented cells of the pars ciliaris, inflammatory cells within the vitreous, or retinal glial cells 43, etc as source of ERMs. Later, vitrectomy specimens have shown that epiretinal membranes comprise of 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. Foos suggested that the glial cells found in the thin idiopathic membranes were derived from the glial cells of the superficial retina and had migrated through breaks in the internal limiting lamina to proliferate on retinal surface 44. Smiddy and associates suggest that the retinal pigment epithelial cells gain access to the retinal surface by various methods, including migration through occult breaks, inactivation of developmental rests of retinal pigment epithelial cells already on the surface of the retina, transformation from other cell types, or via transretinal migration.45 Stern and coworkers46 suggested that the contractile forces of the membranes were related to their constituent cell types and were not dependent on intercellular collagen as suggested by previous investigators. The general consensus is that 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 idiopathic ERM. 45, 47
Fluorescein Angiography (fig 2) in cases of ERMs does not contribute anything significant in its diagnosis since the clinical picture is often specific enough. FA can help in assessing the degree of vascular tortuosity and tethering, extent of wrinkling, vascular leakage and macular edema. Vascular leakage when present is irregular, asymmetric and corresponds to the area of the ERM. It can also be done to differentiate pseudohole (absence of window defect) from true macular hole or rule out other lesions that may mimic ERM such as SRNVM, etc.
Figure 2: Angiographic features of ERM
OCT demonstrate ERM as thin hypereflective band over the surface of retina (fig 3). Majority (70%) are globally adherent to the retina while rest are focally adherent. OCT image of secondary ERM typically demonstrates diffuse thickening with loss of foveal pit. In idiopathic ERM mean central macular thickness correlates with visual acuity48. OCT helps in quantitative measurement of retinal thickness, membrane thickness, presence of CME, extent and adhesion points of membranes to the retinal surface, differentiates pseudohole from true macular holes (fig 4), lamellar holes, and macular cysts. It also provides beneficial information in monitoring surgical removal of ERM (fig 5) and decrease of intraretinal oedema after the surgery.49 Tsuchihashi Takashi 50 has classified ERM on findings based on OCT as
1.Total adhesion with patent foveal pit ,
2.Total adhesion with absent foveal pit,
3.Pseudohole,
4.Partial adhesion
