Epiretinal Membranes Looking Beyond the Macula

This article steps through several cases  of secondary ERMs reviewed at the  Centre for Eye Health. It provides an  evidence-based approach to the clinical  assessment of ERMs, with particular  emphasis on the role of multimodal  imaging as a diagnostic tool.

IDIOPATHIC VS SECONDARY ERM

An ERM (also commonly known as macular  pucker or cellophane maculopathy) is  a growth of fibrocellular tissue at the  vitreomacular interface.³  ERMs can be  classified as either idiopathic or secondary to  ocular diseases, trauma, or retinal surgery.

A number of theories are currently proposed  with regards to the cause of idiopathic  ERMs. They include the proliferation of glial  cells migrating through focal defects in the  internal limiting membrane⁴  or, alternatively,  the transformation of hyalocytes on the  retinal surface following posterior vitreous  detachment. Retinal pigment epithelium  (RPE) migration has also been suggested.^5,6

On the other hand, secondary ERMs are the  result of a coexisting or preceding ocular  pathology and make up 32.3% of cases.⁷ The most frequent causes include previous  cataract surgery, and vascular diseases such  as diabetic retinopathy and retinal vein  occlusions. In particular, proliferative diabetic  retinopathy has been shown to be a strong  risk factor for secondary ERMs.⁸  Secondary  ERMs are also associated with intraocular  inflammation. Approximately 40–50% of  cases of intermediate and posterior uveitis  develop an ERM.⁹  Additionally, retinal  detachments and tears, ocular trauma, and  other retinal surgical procedures can lead to  ERM formation.^2,10,11 A comprehensive list of  secondary causes is outlined in Table 1.

The underlying mechanism involves  inflammatory mediators and growth factors,  which are responsible for stimulating  fibrocellular growth. In addition, retinal  pigment epithelial cells migrating through  retinal breaks can proliferate on the inner  retinal surface, contributing to ERM  development.^10,12 Compared with idiopathic  ERMs, the secondary form has more focal  points of adhesion to the retina.13 Secondary  ERMs tend to have thicker central macular  thickness, poorer presenting visual acuity,  worse metamorphopsia, and more optic disc  and extramacular involvement.^12,13,14 They  occur more frequently in younger populations  compared with idiopathic ERM patients.^12,14

CLINICAL WORKUP OF  SECONDARY ERMS

It is not usually clinically possible to detect  whether an ERM is idiopathic or secondary  from the appearance of the ERM itself. As a  result, as well as investigating and documenting  the ERM, clinical assessment needs to be  targeted to exclude secondary causes.

History and Symptoms

While many patients with ERMs may be  asymptomatic,15 those with secondary ERMs  are more likely to experience blurred vision,  metamorphopsia, micropsia or macropsia,  photopsia, diplopia, loss of stereopsis or  aniseikonia.2  For this reason, it is important  to ask whether the patient is experiencing  any difficulties with reading, working,  driving or other day-to-day activities. History  taking should also elicit for any secondary  causes, including flashes or floaters, previous  intraocular surgery, uveitis, retinal breaks  or trauma.2  Vascular diseases (diabetes,  hypertension, hyperlipidaemia) can be  associated with ERMs secondary to central  or branch vein occlusions, so including these  in history taking is also prudent.

Entrance Tests

Visual acuity and monocular Amsler grid  testing should be performed to evaluate  for vision reduction and metamorphopsia.  Amsler grid testing results should be  interpreted with caution however, as the  Amsler grid relies heavily on subjective  interpretation and has poor sensitivity in the  early detection of metamorphopsia.¹⁶ Less  commonly, other functional tests such as  contrast sensitivity charts, microperimetry,  M-charts for metamorphopsia, and  aniseikonia test charts, may also be used to  document subjective vision changes.¹⁷

Slit Lamp Examination

A thorough examination of the anterior eye  is necessary to identify secondary causes of  an ERM. Signs of current uveitis may include  anterior chamber cells and/or flare, hypopyon,  keratic precipitates or inflammatory cells  within the vitreous. Posterior synechiae,  pigmented keratic precipitates or rubeosis  iridis may suggest a chronic or prior event.¹⁸ Previous ocular trauma may manifest as  corneal scars, traumatic mydriasis or miosis,  corectopia, iris stromal tears, angle recession  on gonioscopy, cataracts or lens subluxation.¹⁹

Posterior Eye Examination

A dilated fundus examination should be  performed on all patients with ERMs,^2,3 particularly if they are a new patient or if the  ERM is a new finding. As well as assessing  and documenting the characteristics of the  ERM itself, it is important to screen for any  peripheral retinal breaks, signs of posterior  uveitis or previous intraocular surgery, such as  laser retinopexy or panretinal photocoagulation  therapy. Retinal haemorrhages or evidence  of ischemia may be indicative of diabetic  retinopathy or vascular occlusions. Advanced  ERMs can be associated with small retinal  haemorrhages, cystoid macular oedema and  lamellar or full thickness macular holes.^2,3

Multimodal Imaging

Multimodal imaging is a key component in  both the analysis of ERMs themselves as well  as enhancing the detection of secondary causes.

1. Optical coherence tomography (OCT) is the most useful imaging modality for assessing the structural features of ERMs as  well as for assessing whether vitreomacular  traction is implicated as the underlying  cause.²⁰ ERMs appear as a hyper-reflective  layer on the internal limiting membrane and  can be associated with underlying retinal  wrinkling and loss of the foveal pit.

ERMs may also result in cystoid spaces,  foveoschisis, macular holes, disorganisation  of the retinal layers, and disruption to the  ellipsoid zone or interdigitation zone.²  When  vitreomacular disease or any of these features  are present, a combination of horizontal  raster scans and radial scans is likely to  be beneficial to maximise detection and  monitoring of these associated signs.

2. Ultra-widefield retinal imaging can be used to supplement a dilated fundus examination to document any vascular or peripheral  retinal lesions likely to be linked to secondary  causes of ERMs. Posterior pole, and in  particular widefield autofluorescence, can also  be used to help exclude retinal dystrophies  that may be associated with ERMs.
3. OCT-angiography (OCT-A) can assist with further information on the extent of vascular diseases associated with ERMs. Furthermore,  OCT-A may reveal alterations in the foveal  avascular zone21 and changes to the tortuosity of  retinal vessels,²² especially in advanced stages.

CONCLUSION

A thorough clinical examination and dilated fundus examination is integral for differentiating  between idiopathic and secondary ERMs. Multimodal imaging is particularly useful in  the detection of secondary causes of ERMs and  should be included as appropriate to assist the  comprehensive work up.

For further reading, we recommend referring  to Fung et al., in Clinical and Experimental  Ophthalmology for a comprehensive review  of ERMs.²

CASE EXAMPLES

Case 1: ERM Secondary To Posterior Uveitis  

A 38-year-old Caucasian female (Mrs Apple*)  was referred to the Centre for Eye Health for  further investigation and documentation of a  toxoplasmosis scar in the left eye. Mrs Apple  had been diagnosed as having toxoplasmosis  in her left eye in 2005 and had an injection  in the eye at the time of diagnosis. She noted  difficulties with night driving and fluctuating  reading vision. She denied any flashes or  floaters, or past history of uveitis, retinal breaks  or trauma. Medical history was unremarkable.

Best-corrected visual acuities were RE 6/4.8 and  LE 6/24+2 (which did not improve on pinhole).  Amsler grid results were clear in the right eye,  with metamorphopsia centrally in the left eye.

Anterior ocular examination was unremarkable.  Posterior pole examination was unremarkable  in the right eye, however, there were multiple  areas of chorioretinal atrophy and associated  RPE hyperplasia at the left macula, consistent  with scarring from toxoplasmosis (Figure 1). Cirrus OCT through the area revealed  outer retinal atrophy inferior to the lesion,  vitreoretinal adhesion, and an overlying  ERM (Figure 2). The peripheral retina was  unremarkable in both eyes (Figure 3).

Case 2: ERM Secondary to  Treated Retinal Detachment

A 60-year-old Asian male (Mr Barry*) was  referred to the Centre for Eye Health for  further investigation and documentation  of an ERM in the right eye. Mr Barry  noted occasional floaters in each eye, but  no significant visual concerns. He had  experienced a previous retinal tear and  detachment in the right eye, which had been  lasered two years ago. He denied any flashes,  or history of uveitis or trauma. His medical  history was unremarkable.

Mr Barry’s best-corrected visual acuities were  RE 6/4.8 and LE 6/6+2. Amsler grid results  revealed metamorphopsia centrally in the  right eye, but clear in the left eye.

Anterior ocular examination was  unremarkable apart from age-appropriate  cataracts in each eye. Posterior ocular  examination showed a semitranslucent,  grey-white membrane with superficial  retinal folds over the foveal and parafoveal  area of the right eye (Figure 4). Dilated  fundus examination revealed extensive laser  retinopexy surrounding lattice degeneration  in the superior periphery of the right eye.  There was also an area of laser retinopexy  surrounding a horseshoe tear and associated  retinal detachment in the temporal periphery  (Figure 5). The left fundus was unremarkable.

Cirrus OCT scans showed an ERM with associated foveoschisis at the right macula  (Figure 6). The right eye peripheral  findings were confirmed via OCT line  scans (Figure 7).

*Patient names changed for anonymity.

The author acknowledges Michael Yapp and  Michele Clewett who reviewed and contributed  to this article.

Tania Lu BSc MClinOptom completed her Bachelor  of Vision Science and Master of Clinical Optometry  from The University of New South Wales. She works  in both corporate optometric practice and as a staff  optometrist at the Centre for Eye Health. She has  an interest in treating posterior ocular diseases and  reducing preventable blindness in the community.

*Patient names changed for anonymity.

The author acknowledges Michael Yapp and Michele Clewett who reviewed and contributed to this article.

Tania Lu BSc MClinOptom completed her Bachelor of Vision Science and Master of Clinical Optometry from The University of New South Wales. She works in both corporate optometric practice and as a staff optometrist at the Centre for Eye Health. She has an interest in treating posterior ocular diseases and reducing preventable blindness in the community.

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