Università degli Studi del Molise Dipartimento di Medicina e di Scienze per la Salute Clinica di Oftalmologia Direttore: Prof. Ciro Costagliola

Roberto dell’Omo

Differences between idiopathic, secondary and diabetic epiretinal membrane

ERM

• TYPE I vitreoschisis collagen between ILM and epiretinal membrane • TYPE II PVD Cleft of the ILM (rare) ILM and ERM are attached

seen in microscopy specimens

ILM collagen

proliferating cells

ERM PATHOLOGY

1) cells of retinal and extraretinal origin 2) extracellular matrix (collagen)

blood vessels, inflammatory cells

Glial cells Hyalocytes Macrophages RPE cells Fibroblasts Myofibroblast

IDIOPATHIC and SECONDARY ERM LIGHT MICROSCOPY

• Glial • Fibrous • Cortical vitreous • Pigment epithelial • Fibroinflammatory • Combinations

• Glial preretinal membrane

ORIGIN discontinuity in the ILM continuity with the optic nerve head

Supportive structures around the nerve Müller cells Retinal astrocytes

ERM

ILM

• Glial preretinal membrane

PATHOGENESIS

Trauma or prior ocular surgery 39 DM or arteriosclerosis 15 Intraocular tumor 3 Retinal detachment 6 Repaired retinal detachment 3

75% of cases with partial or complete PVD

• Fibrous preretinal membranes

Largely hypocellular, multilaminated connective tissue Collagen and rare cells ( quiescent fibroblasts)

PATHOGENESIS Trauma or prior ocular surgery (mostly PVR) 11 DM or hypertensive retinopathy 10

20 MEMBRANES WERE VASCULARIZED

• Cortical vitreous preretinal membranes

Monolayered hypocellular membranes with collagen and infrequent cells

PATHOGENESIS Trauma or prior ocular surgery 8 DM or hypertension 4 No trauma/surgery/ocular disease 10

• Retinal pigment epithelial preretinal membranes

Fibrous tissue (predominant component) with melanin-containg cells arranged in lamellar configuration

PATHOGENESIS Retinal detachment 16 Retinal surgery 5 Chronic uveitis 2 Ocular trauma 7

• Müller cells • hyalocytes • RPE cells

myofibroblast

mechanical tension AGEs PVD

transdifferentiation

• Exclusion criteria • retinal tears or holes (including lattice with atrophic holes) • history of previous photocoagulation or cryo • history of previous eye surgery including cataracts • history of previous intraocular hemorrhage • history of inflammation • presence of developmental abnormalities

101 cases, ERM removed at the time of vitrectomy

Age: 1-83 years median, 66 55 years or older 82% PVD: all cases

multilaminated basement membrane

RPE cells

1 cell type: 63% of cases Presence of myofibroblast: 63% Blood vessels: 12% Macrophages: 20%

multilaminated basement membrane

RPE cells

1 cell type: 63% of cases Presence of myofibroblast: 63% Blood vessels: 12% Macrophages: 20%

High incidence of RPE cells in idiopathic ERMs

No other cell type in 25% of the cases

multilaminated basement membrane

RPE cells

1 cell type: 63% of cases Presence of myofibroblast: 63% Blood vessels: 12% Macrophages: 20%

High incidence of RPE cells in idiopathic ERMs

No other cell type in 25% of the cases

Data NOT confirmed by subsequent studies

Glial cells and hyalocytes seem to be predominant in ERMs

Hyalocytes

Müller cells

endothelial cells macrophages

a proportion of cells was not labeled with any marker

Fraser-Bell S, et al. Ophthalmology 2003;110:34–40. Ng CH, et al. Ophthalmology 2011;118:694–9.

Studied for years with color fundus images…..

ERM IMAGING

Gass JDM. Macular dysfunction caused by epiretinal membrane contraction. In: Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. Vol 2. 4th ed. St Louis, MO: Mosby; 1997:938–950.

Grade 0: Cellophane Maculopathy Grade 1: Crinkled Cellophane Maculopathy Grade 2: Preretinal Macular Fibrosis or Pucker

Nowadays OCT is the gold standard but

multimodal imaging is better

EPIRETINAL MEMBRANES

pre-op post-op

Blue-Fundus AutoFluorescence

cotton-ball sign

abnormalities of the outer retinal bands

disrupted outer retinal bands ???

mfERG P1 amplitude

BCVA

AJO 2017

OCT ANGIOGRAPHY

FAZ AREA

AJO 2017

ERM PVR

Müller cells Astrocytes RPE cells

ERM PVR

fingerlike projections

Retina 2014

PVR

Idiopathic

ERM and UVEITIS

2010

2013

2016

B-FAF

Quantiferon test positive for tubercolosis

3 weeks after treatment

B-FAF

ERM and DIABETES Complete PVD is rare and vitreoschisis is common The vitreous cortex is firmly adherent to the ILM Native vitreous collagen forms the scaffold for fibrovascular and fibrocellular proliferation