ERM, macular holes and PVR

Epiretinal Membrane (ERM / Macular Pucker)

An epiretinal membrane (macular pucker, cellophane maculopathy) represents an avascular fibrocellular proliferation proliferating along the inner surface of the internal limiting membrane (ILM) across the macular region.

Etiology and Histopathology

• Idiopathic ERM (Primary, $>80\%$): Occurs in older adults (peak incidence $>65$ years) following posterior vitreous detachment. Partial or anomalous PVD causes microscopic dehiscences in the ILM, through which retinal glial cells (Müller cells, fibrous astrocytes) migrate onto the inner retinal surface. They undergo transdifferentiation into contractile myofibroblasts, laying down extracellular collagen and fibronectin.
• Secondary ERM: Develops secondary to predisposing ocular conditions: retinal breaks, cryopexy or laser retinopexy, previous retinal detachment surgery, retinal vascular occlusions, diabetic retinopathy, or posterior uveitis.

The Govetto OCT Staging Classification

Govetto and colleagues established the modern spectral-domain OCT classification of idiopathic ERMs, based on the presence of Ectopic Inner Foveal Layers (EIFL):

1. Stage 1: Mild, thin epiretinal membrane with normal foveal architecture; foveal depression is fully preserved.
2. Stage 2: Progressive tangential traction produces widening and complete loss of the foveal depression (flattened fovea); all retinal layers remain anatomically demarcated and organized.
3. Stage 3: Characterized by the presence of a continuous hyporeflective or isoreflective band of Ectopic Inner Foveal Layers (EIFL) traversing horizontally across the central foveal area, connecting the inner plexiform and inner nuclear layers. Retinal layers remain organized.
4. Stage 4: Continuous ectopic inner foveal layers with disrupted retinal layers. This is not a requirement for complete destruction of every layer and does not alone determine whether surgery will improve symptoms.

Surgical Management: Vitrectomy & Chromovitrectomy

• Indications: Symptomatic reduction in best-corrected visual acuity ($20/50$ or worse), disabling metamorphopsia (distorted lines interfering with binocular reading or driving), or monocular diplopia.
• Chromovitrectomy Dye Staining: Vital dyes are utilized to distinguish transparent membranes:
  • Trypan Blue ($0.15\%$): Selectively stains the pathological epiretinal membrane dark blue, facilitating initial edge grasp with endgripping vitreoretinal micro-forceps.
  • Brilliant Blue G (BBG, $0.025\%$): Selectively and brilliantly stains the Internal Limiting Membrane (ILM) without significant neuroretinal toxicity.
  • Triamcinolone Acetonide: Suspended corticosteroid crystals that coat and highlight vitreous cortical strands to ensure a complete posterior vitreous detachment.
• The Value of ILM Peeling: Peeling the ILM concurrently during ERM removal eliminates residual myofibroblast scaffolds, reducing the historical long-term ERM recurrence rate from $12-15\%$ down to $<2\%$.

Full-Thickness Macular Hole (FTMH)

A full-thickness macular hole is an anatomic defect involving all neurosensory retinal layers from the internal limiting membrane to the outer photoreceptor segments at the foveal center.

The Classic Gass Biomicroscopic Classification

Donald Gass established the historical classification based on slit-lamp biomicroscopy and dynamic tangential traction:

• Stage 1 (Impending Macular Hole): Localized foveolar detachment caused by anterior and tangential vitreofoveal traction. Visual acuity $20/30$ to $20/60$:
  • Stage 1A: Small central yellow spot ($100-200\,\mu\text{m}$) with flattening of the foveal pit.
  • Stage 1B: Yellow halo or yellow ring ($200-300\,\mu\text{m}$); centrifugal displacement of photoreceptors.
  • Spontaneous resolution occurs in up to $50\%$ of Stage 1 cases upon spontaneous release of vitreofoveal traction.
• Stage 2 (Small Full-Thickness Hole): True full-thickness dehiscence measuring $<400\,\mu\text{m}$, typically starting as a crescentic or eccentric tear with a partially attached pre-foveolar operculum.
• Stage 3 (Large Full-Thickness Hole without PVD): Fully developed round foveal defect measuring $\ge 400\,\mu\text{m}$, surrounded by a ring of thickened, edematous retina and a prominent cuff of subretinal fluid, with yellow drusen-like deposits at the base. The posterior hyaloid face is detached from the fovea but remains adherent to the optic disc.
• Gass stage 4: A full-thickness hole with complete PVD, regardless of hole diameter. Modern OCT describes minimum linear diameter and vitreomacular attachment separately.

The Modern International Vitreomacular Traction Study (IVTS) Classification

The IVTS classification updated macular hole staging using objective Spectral-Domain OCT measurements:

Surgical Technique for Macular Holes & The Inverted ILM Flap

Standard surgical intervention for full-thickness macular holes entails:

1. Three-port pars plana vitrectomy with induction of a complete posterior vitreous detachment;
2. Micro-peeling of the internal limiting membrane (ILM) in a $360^{\circ}$ radius of $1.5$ to $2$ disc diameters around the hole, facilitated by Brilliant Blue G staining;
3. Complete fluid-air exchange followed by non-expansile gas endotamponade ($20\%\ SF_6$ for small-to-medium holes, or $12\%\ C_3F_8$ for large holes);
4. Postoperative face-down (prone) positioning for $3$ to $7$ days to keep the buoyant gas bubble compressing the hole edges against the RPE.

The Inverted ILM Flap Technique (Michalewska Technique)

For large macular holes ($>400-500\,\mu\text{m}$), chronic holes ($>1\,\text{year}$ duration), or myopic macular holes, conventional ILM peeling yields disappointing anatomical closure rates ($<70-80\%$) and high rates of "flat-open" configurations. In 2010, Zofia Michalewska introduced the inverted ILM flap technique:

• The ILM is peeled circumferentially toward the hole margin, but is NOT completely avulsed or removed. A small remnant remains attached to the hole rim.
• The attached ILM flap is inverted upside-down over the hole, covering or plugging the open crater.
• The inverted ILM acts as a biological basement-membrane scaffold that stimulates glial cell proliferation (Müller cell migration) and neurotrophic factor secretion, driving physiological closure.
• The inverted ILM flap technique has elevated anatomical closure rates in large holes from $70\%$ to over $95\%$, significantly improving functional photoreceptor reconstitution.

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Proliferative Vitreoretinopathy (PVR)

PVR represents the leading cause of surgical failure following rhegmatogenous retinal detachment repair, occurring in $5\%$ to $10\%$ of all RRD cases. It is characterized by the migration, transdifferentiation, and contractile proliferation of cellular membranes across both surfaces of the detached neurosensory retina and the vitreous scaffolding.

The Pathophysiological Cellular Cascade

1. Cellular Dispersion: Retinal pigment epithelial (RPE) cells liberated through a retinal break into the vitreous encounter serum cytokines ($PDGF$, $TGF-\beta$, $FGF$, fibronectin) leaking through the disrupted blood-retinal barrier.
2. Epithelial-Mesenchymal Transition (EMT): Under the influence of $TGF-\beta$, polarized epithelial RPE cells lose their cell junctions, downregulate cytokeratins, and transform into motile, spindle-shaped fibroblast-like and myofibroblast cells expressing $\alpha$-smooth muscle actin ($\alpha\text{-SMA}$).
3. Contraction and Retinal Distortion: Myofibroblasts and retinal glial cells (Müller cells, fibrous astrocytes) synthesize dense collagenous extracellular matrix, forming rigid sheets that contract, producing full-thickness retinal starfolds, stiff fixed folds, and subretinal bands.

The Updated 1991 Retina Society PVR Classification

• Grade A (Minimal PVR): Presence of vitreous haze, pigment clumping in the vitreous body (Shafer's sign), and clusters of pigmented RPE cells on the inferior peripheral retina.
• Grade B (Moderate PVR): Superficial inner retinal wrinkling, stiffness of the detached retina, rolled or curled edges of the retinal break, and vascular tortuosity.
• Grade C (Marked PVR): Characterized by full-thickness fixed retinal folds, starfolds, and rigid subretinal bands. Subdivided by anatomical location and circumferential extent:
  • Posterior (Grade C-P): Fixed folds located posterior to the equator (clock hours $1$ to $12$);
  • Anterior (Grade C-A): Fixed folds, circumferential troughing, and anterior displacement located anterior to the equator.