Epiretinal Proliferation

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Disease Entity

Over the years, some terms have been used to describe this entity including “thick membrane”, “dense epiretinal membrane” and “lamellar hole-associated epiretinal proliferation”.


Epiretinal proliferation (ERP) is a fibro cellular tissue found on the inner surface of the retina. ERP has been primarily described associated with lamellar macular holes (LMH) cases and then associated with full-thickness macular holes (FTMH) and epiretinal membranes (ERM).(1–3) More recently, in 2020, it was identified in eyes with various retinal conditions, including age-related macular degeneration, vein occlusion, diabetic retinopathy, high myopia, and refractory chronic macular edema. (4)


The origin of ERP has been a subject of debate. One theory suggests its origin to be the vitreous because they found that ERP cells had hyalocytes, fibroblasts, and glial cells without contractive properties, whereas myofibroblasts with contractive properties are predominant in conventional ERM cells. Also, they observed vitreous collagen strands in ERP tissue through an electron microscope.(5,6) On the other hand, Pang et al. claim that ERP pathogenesis may involve a Müller-cell-driven process that originates from the inner retinal layers during LMH development. (7) Furthermore, there is a theory that suggested that retinal pigment epithelial (RPE) can proliferate through IS/OS junction defects and contribute to the formation of ERP. (8)


The diagnosis is done by spectral-domain optical coherence tomography (SD-OCT) and it is defined as an isoreflective space-filling material over the retinal surface, often delimited by a thin highly reflective line, and without tractional properties.

Differential diagnosis

Its clinical appearance on OCT is distinctive. However, the main distinction must be made with ERM. First, ERM on the SD-OCT appears as a hyperreflective layer often irregularly over the inner surface of the retina. Second, EPR drapes over the epiretinal surface, tightly following the underlying retinal contour. In contrast, in some cases of ERM, there is space between it and the underlying RNFL. Third, EPR does not have strong contractile properties, unlike ERM, which can cause traction and underlying striae of the inner retinal surface as well as tortuosity of the surrounding vasculature. Intraoperatively, they also differ. EPR is visible as a sticky, yellowish substance that is more integrated with the intrinsic retinal surface. Son et al. termed it a “perifoveal crown phenomenon” because, after peeling the ILM, it persisted as a floating crown-like yellowish tissue with its base attached to the edge of the hole margin. (2,8)


It was first described by Witkin et al. in 2006 as a thick membrane seen on OCT and they thought it could be either trapped vitreous between the ERM and the retina or a thickened posterior hyaloid attached to the retina.(9) Parolini et al. reported an unusual ERP in eyes with lamellar macular holes in a case series and named it “dense” epiretinal membranes that differ from “tractional” epiretinal membranes according to their morphologic components. (10) This finding was later re-defined by Pang et al. in 2014 as a “lamellar hole-associated epiretinal proliferation”. (1)

Signs and symptoms

Individually, it is thought to be asymptomatic. Signs and symptoms are related to the associated pathologies.

Medical treatment

Currently, there is no medical treatment.

Surgical treatment

Based on current evidence, it has no surgical indication per se. However, it can be removed in surgeries for other pathologies (FTMH, LMH, or ERM).


Some studies have attempted to assess the consequence of the presence of ERP.

Marques et al. concluded that ERP associated with LMH correlated with the anatomical conformation of the LMH, yielding thinner floors and larger external diameters. However, it did not correlate with the anatomical or functional results, both in the patients who underwent surgery and in those managed conservatively.(11)

Lee Kim E. et al. studied FTMH who were submitted to surgery - patients with FTMH and ERP were older, more often male, had more advanced macular hole stages, had significantly less improvement in visual acuity 12 months post-operatively, had higher rates of ellipsoid and external limiting membrane defects and had a higher rate of failure to close with one surgery compared to FTMH without ERP. (2)


1. Pang CE, Spaide RF, Freund † K Bailey. EPIRETINAL PROLIFERATION SEEN IN ASSOCIATION WITH LAMELLAR MACULAR HOLES A Distinct Clinical Entity [Internet]. Available from: http://links.lww.com/IAE/A232 2. Lee Kim E, Weiner AJ, Ung C, Roh M, Wang J, Lee IJ, et al. Characterization of Epiretinal Proliferation in Full-Thickness Macular Holes and Effects on Surgical Outcomes. Ophthalmol Retina. 2019 Aug 1;3(8):694–702. 3. Itoh Y, Levison AL, Kaiser PK, Srivastava SK, Singh RP, Ehlers JP. Prevalence and characteristics of hyporeflective preretinal tissue in vitreomacular interface disorders. British Journal of Ophthalmology. 2016 Mar 1;100(3):399–404. 4. Chehaibou I, Pettenkofer M, Govetto A, Rabina G, Sadda SVR, Hubschman JP. Identification of epiretinal proliferation in various retinal diseases and vitreoretinal interface disorders. Int J Retina Vitreous. 2020 Jul 10;6(1). 5. Compera D, Entchev E, Haritoglou C, Scheler R, Mayer WJ, Wolf A, et al. Lamellar Hole-Associated Epiretinal Proliferation in Comparison to Epiretinal Membranes of Macular Pseudoholes. Am J Ophthalmol. 2015 Aug 1;160(2):373-384.e1. 6. Compera D, Entchev E, Haritoglou C, Mayer WJ, Hagenau F, Ziada J, et al. Correlative microscopy of lamellar hole-associated epiretinal proliferation. J Ophthalmol. 2015;2015. 7. Pang CE, Maberley DA, Bailey Freund K, White VA, Rasmussen S, Matsubara JA. Clinicopathologic Correlation LAMELLAR HOLE-ASSOCIATED EPIRETINAL PROLIFERATION A Clinicopathologic Correlation. Vol. 36, RETINA. 2016. 8. Son G, Lee JS, Lee S, Sohn J. Epiretinal Proliferation Associated with Macular Hole and Intraoperative Perifoveal Crown Phenomenon. Korean J Ophthalmol. 2016 Dec 1;30(6):399–409. 9. Witkin AJ, Ko TH, Fujimoto JG, Schuman JS, Baumal CR, Rogers AH, et al. Redefining lamellar holes and the vitreomacular interface: An ultrahigh-resolution optical coherence tomography study. Ophthalmology. 2006;113(3):388–97. 10. Parolini B, Schumann RG, Cereda MG, Haritoglou C, Pertile G. Lamellar macular hole: A clinicopathologic correlation of surgically excised epiretinal membranes. Vol. 52, Investigative Ophthalmology and Visual Science. 2011. p. 9074–83. 11. Marques MF, Rodrigues S, Raimundo M, Costa J, Marques JP, Alfaiate M, et al. Epiretinal Proliferations Associated with Lamellar Macular Holes: Clinical and Surgical Implications. Ophthalmologica. 2018 Jun 1;240(1):8–13.

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