Proliferative Vitreoretinopathy

Definition & Pathophysiology

Proliferative vitreoretinopathy (PVR) is the growth and contraction of cellular membranes on the retinal surfaces, both epiretinal and subretinal, and within the vitreous cavity itself. It is not really a separate disease. It is the eye's own wound-healing response to a retinal break or detachment, overshooting: scar-like membranes form, contract, and pull the retina back off the wall it was just reattached to. PVR is the leading cause of surgical failure after rhegmatogenous retinal detachment (RRD) repair, and the reason a seemingly straightforward primary detachment can turn into a recurrent, multi-operation problem.

The membranes form from a mixture of cell types, chiefly retinal pigment epithelial (RPE) cells, glial cells, and inflammatory cells, that migrate, proliferate, and lay down contractile extracellular matrix on both sides of the retina. As the membranes mature and contract, that traction can reopen the original break, create new breaks, or simply drag the retina into fixed folds with no break involved at all.

Cellular & Molecular Pathogenesis

The RPE cell is the predominant driver of both epiretinal and subretinal membrane formation. Once a retinal break or surgical manipulation disperses these cells from their normal monolayer into the vitreous cavity and subretinal space, they dedifferentiate, proliferate, and begin depositing extracellular matrix. The result behaves less like a quiet pigmented epithelium and more like an activated fibroblast.

That transformation has a name: epithelial-mesenchymal transition (EMT). RPE cells undergoing EMT lose their epithelial polarity and intercellular junctions and acquire a migratory, contractile, fibroblast-like phenotype. This is what lets them contribute directly to fibrous membrane formation instead of sitting inert on the retinal surface. Transforming growth factor-beta2 (TGF-β2) is the most strongly implicated molecular driver of the process: it promotes the fibroblast-like transformation of RPE cells and stimulates the extracellular matrix production that gives PVR membranes their contractile strength.

Risk Factors

Several preoperative and intraoperative findings are established risk factors for developing PVR after retinal detachment repair:

• Choroidal detachment accompanying a retinal detachment signals significant blood-retinal barrier breakdown and inflammation, both of which promote PVR development.
• Vitreous hemorrhage introduces blood breakdown products and macrophages that stimulate RPE cell proliferation and inflammation, two of the central drivers of PVR formation.
• Giant retinal tears (breaks spanning more than 90° of the retinal circumference) expose unusually large areas of RPE and release abundant cellular material into the vitreous. The resulting PVR risk is substantially higher than with a small, localized break.

Clinical Signs & Grading

The characteristic clinical finding in advanced PVR is the star fold: full-thickness, circumferential retinal folds radiating around a fixed point, where contracted epiretinal membrane has pulled the retina into that pattern.

Severity is graded using the Retina Society classification, introduced in 1983 (Grades A–D) and revised in 1991. In the revised system:

• Grade A: vitreous haze and pigment clumping.
• Grade B: wrinkling of the inner retinal surface.
• Grade C: full-thickness, fixed retinal folds in one or more quadrants, more advanced than A or B. The 1991 revision split Grade C into posterior (CP) and anterior (CA) subtypes, based on whether the contraction sits posterior or anterior to the equator, with further subclassification by pattern and clock hours involved.
• Grade D: the most severe form, with circumferential involvement of all four quadrants and a closed or funnel-shaped retina.

Anterior PVR involves contraction of the vitreous base and residual cortical vitreous, pulling the peripheral retina and ciliary body anteriorly and centrally. It often creates a circumferential trough, a distinct surgical challenge from posterior membrane peeling.

Surgical Management

The primary surgical approach to a PVR-complicated detachment is pars plana vitrectomy with membrane peeling. PVR membranes are fibrocellular and contractile, so scleral buckling alone, pneumatic retinopexy, or laser without surgery cannot relieve the traction they generate. Vitrectomy lets the surgeon directly identify and peel epiretinal and subretinal membranes before the retina can be safely reattached.

Several intraoperative techniques and adjuncts are specific to PVR surgery:

• Perfluorocarbon liquid (PFCL), heavier than water, is instilled over the posterior pole to unfold and stabilize the retina, pushing subretinal fluid toward the periphery while membranes are dissected.
• Relaxing retinectomy is reserved for fixed folds that persist despite thorough membrane peeling: a full-thickness cut through the retina itself releases the residual traction that peeling alone could not.
• Silicone oil tamponade is usually preferred over intraocular gas in eyes with severe PVR needing prolonged internal support. Unlike gas, it does not resorb over weeks, and it allows more flexible patient positioning and ambulation during healing.
• 5-fluorouracil (5-FU), combined with low-molecular-weight heparin in the infusion fluid, has been studied as an intraoperative adjunct that inhibits fibroblast and glial proliferation, aiming to reduce recurrent membrane formation after surgery.

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