Epiretinal Membrane and Proliferative Vitreoretinal Retinopathy: Risk Factors and Management

Educational Objectives

The goal of this program is to improve management of epiretinal membrane and proliferative vitreoretinopathy. After hearing and assimilating this program, the clinician will be better able to:

1. Recognize possible mechanisms of development and stages of epiretinal membrane.
2. Analyze the risk of developing proliferative vitreoretinopathy in the second eye.

Summary

Epiretinal membrane (ERM): ≈33% of elderly patients develop an ERM, almost always after a posterior vitreous detachment (PVD); ERM in the other eye is a risk factor; possible mechanisms of development — include glial cell proliferation after dehiscence of internal limiting membrane (ILM), residual ILM remnant after PVD (ILM peel is protective against recurrence of ERM after surgery), and proliferation or transdifferentiation of cortical hyalocytes or migration of blood-derived cells (eg, macrophage); ERM composed of glial cells are hard to peel and tend to fragment; retinal pigment epithelium (RPE)-like ERM consists of a monolayer and commonly occurs after a retinal break; RPE cells are released into the vitreous after retinal detachment (RD) and ERM develops as a mild form of proliferative vitreoretinopathy (PVR); RPE-like ERM tend to peel off as a sheet, and recurrence is less likely; fluorescein angiography reveals diffuse leakage, with disruption of the vasculature; ERM appears corrugated and may lead to retinal striae in the macula (macular pucker); retina may show macular thickening (with minimal leakage)

Ectopic inner foveal layers (EIFL): associated with visual outcomes; inner layers are dragged into the fovea; EIFL is the best marker for vision; ellipsoid zone disruption is another predictor of visual outcomes

Stages of ERM: stage 1 — preserved foveal pit; well-defined retinal layers (WDRL); surgery is not typically required; stage 2 — absence of foveal pit; WDRL; stage 3 — traction on the retina; disruption of the retinal inner layers; visual outcomes are better with stage 2 compared with stage 3; better predictors of outcome after vitrectomy for symptomatic ERM are an unmet need

ERM progression: for mild ERM that does not disrupt the macula, observation may suffice (may not progress); however, quick progression is observed in some cases

ERM contraction: in ERM with a pseudohole with vertical edges, fovea is not involved, and surgery is not required; ERM contraction often occurs toward the fovea with a dome-like contour and often improves with ERM peeling (ERMP); ERM contraction away from the fovea may result in fovea maculoschisis, and the lips of the retina are drawn up; vision is often disrupted, and vitrectomy with ERMP can be considered

Aniseikonia: distortion in the macula caused by the ERM can cause diplopia; patients can read individual letters, but the eyes may not be functional; if the macula is compressed, images appear larger (macropsia); if the macula is stretched, images appear smaller (micropsia)

Vitrectomy: ERM is the second most common indication for vitrectomy; although surgery was deferred until visual acuity (VA) declined >20/40, vitrectomy is currently being performed earlier

Ongoing randomized trial (NCT05145491): is comparing immediate vs deferred surgery for symptomatic ERMs; background — although vitrectomy with ERMP has high success rates, some patients experience less than optimal visual outcomes; better predictors of outcomes after surgery are needed; complications (eg, cataract) may arise after surgery and further surgical procedures may be necessary; however, deferred surgery may result in worse visual outcomes; the optimal time for surgical intervention is unclear; better predictors of progression are needed; trial design — patients with symptomatic ERM and VA ≥20/40 are randomized to surgery ≤2 mo or deferred surgery over 3 yr (surgery is performed for progression with worsening vision); visual outcome is compared at 36 mo; criteria for vitrectomy in the deferred group — decrease in VA ≥10 letters at a single visit or ≥5 letters at 2 consecutive visits, and worsening symptoms, eg, ERM contraction; visual outcomes — VA is measured using Early Treatment Diabetic Retinopathy Study charts; M-charts have a straight line and 19 kinds of dotted lines at intervals ranging from 0.2 to 2.0 degrees of visual angle both vertically and horizontally and are used to quantitate distortion; functional outcome is measured using MNREAD acuity charts; vitrectomy procedure — the surgeon can choose the staining agent; the procedure can be combined with cataract surgery

Proliferative Vitreoretinopathy

PVR: the major complication causing failure after rhegmatogenous RD (RRD) repair (5%-10%); primarily managed by vitrectomy, membrane peeling, scleral buckle, and gas or silicone tamponade; medical interventions include steroids, methotrexate (intravitreal or oral), neoplastic agents, biologics, and curcumin (anti-inflammatory effects)

Retrospective study: Shepherd et al (2024) analyzed data of patients in the Vestrum Health Database who underwent unilateral RRD repair ≤1 mo of diagnosis (to avoid misdiagnosis); in addition to being listed, PVR was also identified with the presence of texts including subretinal membrane, subretinal fibrosis, and retinal “starfold” in the electronic medical records; the study evaluated the risk of developing PVR in the second eye; in the first eye, 11% of patients developed PVR after the initial RRD repair; risk factors for PVR — include age (maximum risk, 2-9 yr of age; also high in the elderly), eyes with worse baseline vision, and involvement of the macula (chronic or severe detachment); by multivariate analysis, risk factors include age, smoking, hypertension, and female sex; although PVR appears to be common in men, PVR after trauma is common and trauma commonly occurs in men; ocular risk factors include vitreous hemorrhage, history of ocular trauma, giant retinal tear (release of RPE cells), choroidal detachment, history of uveitis, and endophthalmitis

Results: unilateral RRD without PVR in the first eye — 9% of patients developed RRD in the second eye, of which 3% developed PVR (second eye); unilateral RRD with PVR in the first eye — 6% of patients developed RRD in the second eye, of which 10% developed PVR (odds ratio, ≈3.5)

Implications: if the second eye develops RRD, methotrexate is advisable to avoid development of PVR in the second eye

Visual outcomes at 1 yr: first eye with no PVR — better vision for first RD with no PVR and for second RD with no PVR; visual outcome is worse with RD in the second eye with PVR; first eye with PVR — vision remains the same in the first eye; visual outcome is better with RD in the second eye with no PVR; interestingly, outcome is slightly better with RD in the second eye with PVR (maybe because of early intervention)

Limitations: retrospective dataset; limited access to operative notes; risk for PVR in second eye may be confounded by surgical techniques

Readings

Benegas NM, Egbert J, Engel WK, et al. Diplopia secondary to aniseikonia associated with macular disease. Arch Ophthalmol. 1999;117(7):896-899. doi:10.1001/archopht.117.7.896; 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):710-717. doi:10.1097/IAE.0000000000002486; Idrees S, Sridhar J, Kuriyan AE. Proliferative vitreoretinopathy: a review. Int Ophthalmol Clin. 2019;59(1):221-240. doi:10.1097/IIO.0000000000000258; Schumann RG, Schaumberger MM, Rohleder M, et al. Ultrastructure of the vitreomacular interface in full-thickness idiopathic macular holes: a consecutive analysis of 100 cases. Am J Ophthalmol. 2006;141(6):1112-1119. doi:10.1016/j.ajo.2006.01.074; Shepherd EA, Minaker SA, Bomdica PR, et al. Risk of proliferative vitreoretinopathy in the second eye in adult patients with bilateral retinal detachment. Ophthalmol Retina. 2024;8(12):1174-1180. doi:10.1016/j.oret.2024.06.007.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. MacCumber was recorded at the 23rd Annual Downeast Ophthalmology Symposium, held September 27-29, 2024, in Bar Harbor, ME, and presented by The Maine Society of Eye Physicians and Surgeons. For more information about upcoming CME activities from this presenter, please visit https://maineeyemds.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

OP630501

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.