**2. Epiretinal membrane**

Idiopathic ERMs occur when there are no associated ocular pathologies. Secondary ERMs are considered those associated with an ocular pathology and account for about 30% of ERMs [8].

Regardless of its etiology, an epiretinal membrane is formed by an innermost single or multilayer of cells and an outermost noncellular layer, which is in contact with the ILM. The cellular layer constituents include retinal glial cells, hyalocytes, retinal pigment epithelial cells, and fibroblasts, and these cells originate myofibroblasts through transdifferentiation [9–11]. The main component of the outermost layer is different types of extracellular collagen divided into native vitreous collagen, reminiscent on the retinal surface after posterior vitreous detachment (PVD), and newly formed collagen, synthesized and secreted by the cellular layer [12, 13].

Since a PVD is present in the majority of cases [14, 15] it has been suggested its participation during idiopathic ERM formation. After PVD, it is theorized that reminiscent of hyalocytes on the retinal surface starts a process of metaplasia and ends up forming the ERM [16].

Another etiology proposed, although less accepted, is the migration of retinal glial cells to the retinal surface through defects on ILM after a PVD [17].

Classification based on clinical findings proposed by Gass [18] is still widely used. Along with developments in OCT (optical coherence tomography), several classifications based on this technology have been proposed based on the identification of associated retinal anatomic changes [19–23].

Based on new OCT findings, including ectopic inner foveal layers, a recent grading scheme had been proposed [24]. Stage 1 was defined as the presence of an ERM, seen as a hyperreflective line above the inner retina, with negligible retinal anatomic changes. Stage 2 was defined as the presence of ERM causing loss of foveal depression and stretching of the outer nuclear layer. Stage 3 was defined as the presence of an ERM with continuous ectopic inner foveal layers added to stage 2 findings. Stage 4 was defined as the presence of stage 3 findings added to the disorganization of retinal layers.

#### **3. Internal limiting membrane**

The ILM is composed of an innermost structure formed by a meshwork of collagen fibers, glycosaminoglycans, laminin, and fibronectin called cuticular layer, and an outmost structure, facing the retina surface, formed by the footplates of Müller cells [25, 26]. The internal limiting membrane has a smooth vitreal side and an irregular retinal side where folds are in apposition to Muller cells footplates [27].

Muller cells are the main glial cell of the retina. They give structural stability to the fovea and have an important role in metabolic functions, such as regulating the balance of relevant ions, removing metabolic waste, and providing trophic substances to neurons [28]. The inner processes of Muller cells, formed by its footplates (**Figure 1**), participate in the outmost structure of ILM [25]. The outer processes of Muller cells surround the somata of photoreceptor cells and together constitute the external limiting membrane (ELM) (**Figure 1**).

Muller cells are differentiated into two groups according to their fovea location: Müller cell cone and outer processes of the Müller cells of the foveal walls [29, 30]. The Muller cell cone acts as a plug binding together the receptor cells in the foveola, *Internal Limiting Membrane Peeling in Idiopathic Epiretinal Membrane DOI: http://dx.doi.org/10.5772/intechopen.108772*

#### **Figure 1.**

*Muller cells of foveal walls, Muller cells cone, external limiting membrane (ELM), and internal limiting membrane (ILM). Schematic drawing by Luciana S.Q. Makarczyk.*

increasing resistance against mechanical stress, since the radiating nerve fibers would be highly susceptible to disruption in this region [31]. It has been suggested that the Muller cells of the foveal wall give stability to the outer layers of the fovea and parafovea [32, 33].

Muller cells of the foveal walls display a z-shaped pattern as a result of the centrifugal displacement of the inner retina and the centripetal displacement of the outer retina and photoreceptors. Muller cells' vertical processes run from the ILM to the inner nuclear layer (INL), then diagonally within Henle's fiber layer (HFL) and, once more, vertically to the outer limiting membrane (OLM). The morphology of this type of Müller cell may absorb mechanical tension according to a physical model study [34]. This model considered those cells as the main determinants of force transmission and suggested their importance in the structural stability of the parafovea by increasing retinal compliance to mechanical stress.

The thickness of the ILM within 400 μm from the foveal center ranges from 0.050 to 0.2 μm. From 400 to 600 μm from the center of the fovea, its thickness varies from 0.08 to 1.0 μm. At a distance of 600 to 900 μm from the foveal center, ILM showed a thickness from 1.4 to 2.4 μm. Between 900 and 1050 μm from the foveal center, ILM reaches 4.0 μm of thickness. At the disc, its thickness ranges from 0.07 to 0.1 μm and it is thicker in the posterior pole than the equator [27, 35].

Analyses of ILM stiffness matched thickness findings according to geographical distribution, meaning that higher stiffness values were found in the posterior pole compared with the mid-peripheral quadrants [27].

Biomechanical analyses of the ILM showed that it provides a protective function to the retina. Removal of the ILM showed to reduce the mean strength of the central retina by 53.6% [36].

Several diseases affecting the vitreomacular interface could be attributed to foveal mechanical instability: vitreous adhesion, a higher thickness and stiffness of the ILM at the macular area added to a known absence of cellular connections between the cells of the Müller cell cone and the outer processes of the Müller cells of the foveal walls [30, 37].

#### **Figure 2.**

*Epiretinal membrane causing tractional lamellar hole. a. Before surgery. Ectopic inner foveal layer (asterisks). Stretched Muller cell cone processes (arrow). b. Two months after ERM and ILM peeling and absorption of C3F8 gas - Luciana S.Q. Makarczyk, MD, PhD.*

#### **3.1 Ectopic inner foveal layers**

Ectopic inner foveal layers have been defined by Govetto et al. [37, 38] as displacement of retina architecture with gliosis and proliferation of Muller cells, characterized on OCT as a continuous, homogenous, hypo or hyper-reflective band, extending from the inner nuclear layer and inner plexiform layer across the foveal region (**Figure 2**). This ectopic layer does not possess contractile characteristics.
