What is Proliferative Vitreoretinopathy (PVR)?
Proliferative vitreoretinopathy (PVR) is an abnormal wound healing response following retinal injury or detachment, characterized by the formation of contractile scar tissue membranes on and beneath the retina that cause tractional retinal detachment and represent the most common cause of surgical failure after retinal detachment repair. 1, 2
Pathophysiology and Cellular Mechanisms
PVR develops through a maladaptive healing process where retinal pigment epithelial (RPE) cells migrate into the vitreous cavity and undergo epithelial-to-mesenchymal transition, forming contractile membranes within the vitreous and along the retinal surface. 2, 3
The cellular components driving PVR formation include:
- Retinal pigment epithelial cells that proliferate and migrate from their normal location 2, 4
- Glial cells (primarily Müller cells) that become activated and contribute to membrane formation 2
- Fibroblasts that produce extracellular matrix and contractile elements 2
- Inflammatory cells (macrophages and lymphocytes) that perpetuate the proliferative response 2, 3
These cells proliferate abnormally and produce scar tissue that contracts, creating tractional forces that pull on the retina, leading to new retinal breaks, retinal shortening, and ultimately recurrent retinal detachment. 2, 4
Clinical Incidence and Risk Factors
PVR complicates up to 10% of spontaneous rhegmatogenous retinal detachment repairs in the general population. 1
In high-risk scenarios, PVR rates are dramatically higher:
- Up to 50% of open globe injury-related retinal detachments develop PVR 1
- Eyes with penetrating ocular trauma that alter vitreous or retinal structure face increased risk 5
Clinical Presentation and Diagnosis
PVR manifests as:
- Pre-retinal and sub-retinal membrane formation visible on fundoscopic examination 2
- Retinal gliosis and retinal shortening due to membrane contraction 2
- Tractional retinal holes and breaks caused by membrane traction 2
- Recurrent retinal detachment following initial surgical repair 1, 2
Examination findings include visible epiretinal membranes, retinal folds, and fixed retinal detachment that does not flatten with positioning, distinguishing it from rhegmatogenous detachment alone. 2, 4
Current Treatment Landscape
Surgical intervention is currently the only effective treatment for established PVR, with vitrectomy and scleral buckling as the main approaches. 2, 4
Surgical management by PVR stage:
- PVR stage B or C1/C2: Scleral buckling provides good anatomic results 4
- PVR stage C3 and beyond: Vitrectomy offers superior outcomes 4
A critical pitfall: Patients with PVR require multiple operations to remove scar tissue, but visual outcomes remain suboptimal and often fail to meet patient expectations despite anatomic success. 2
Pharmacologic Prevention—Current State
Despite 40 years of research and multiple large clinical trials testing various candidate drugs, no proven adjunctive pharmacologic treatment currently exists to prevent, reduce, or treat PVR formation. 1, 2
Recent systematic review findings (2025) demonstrate:
- Multiple studies have investigated non-surgical interventions including antiproliferative agents and anti-inflammatory therapies 1
- While several individual studies showed some improvements, concerns with risk of bias were identified 1
- Results were not replicated in larger included studies, and none have demonstrated clinically significant, repeatable benefits 1
The therapeutic targets that remain under investigation include:
- Cellular proliferation pathways targeting RPE, glial, inflammatory, and fibroblastic cell proliferation 2
- Intraocular inflammatory response as a realistic target for adjunctive treatments 2
- Growth factor pathways, particularly PDGF receptor α and VEGF signaling that enable cell survival in vitreous 6
Clinical Implications for Practice
Early surgical intervention for retinal detachment is currently the only intervention proven to reduce PVR incidence. 1
When evaluating patients at risk for PVR:
- Obtain detailed history of ocular trauma, prior retinal detachment, and previous vitreoretinal surgery 5, 2
- Perform thorough peripheral retinal examination with scleral depression to identify early membrane formation 5
- Use B-scan ultrasonography when media opacity prevents direct visualization 5
A common pitfall: Delaying surgical intervention in eyes with retinal detachment increases PVR risk, as prolonged retinal detachment allows more time for cellular proliferation and membrane formation. 1, 2