Proliferative vitreoretinopathy (PVR) can be thought of as a reparative or scarring mechanism. Contact inhibition is lost because of mechanical disruption of a tissue such as the retinal pigment epithelium (RPE), and the response is migration, contraction, and moderate proliferation of cells. A defect in the internal limiting membrane (ILM) can be created by vitreous traction, a retinal break, or membrane dissection. Glial cells then migrate, proliferate to some extent, and contract the retinal surface as if to repair the retina-ILM defect. Retinal breaks “heal” as a result of this mechanism as has been shown in macular hole surgery and retinotomies for submacular surgery. Similarly, if the retina is separated from the RPE, the RPE cells migrate to the retinal surface and the posterior surface of the posterior vitreous cortex (PVC). Monocytes can gain access to the retinal surface from the iris and ciliary body capillaries as a result of ocular inflammation. It is known that these cells can migrate, proliferate, and contract on the retinal surface (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13). Glial, RPE, and monocytic cells share in common the migration along an existing substrate or to a new tissue surface. As cellular migration occurs, intracellular contraction of the cells occurs, creating tangential traction on the retina. All healing mechanisms studied have demonstrated a microtubule, smooth muscle-like contraction process occurring with many cells acting in concert. The myofibroblasts have coated pits, which have specific receptor sites for collagen, fibrin, and elastin. These pits contain fibronectin, which allows the cells to attach to collagen fibers (14,15). Growth factors (TGF-β, etc.), metalloproteinases, fibronectin, and receptors for collagen, elastin, and fibrin are components of the migration and contraction phenomenon. Proliferation (mitotic activity) is of much lesser importance. This process can be thought of as hypocellular periretinal scarring, analogous to hypocellular vitreous contraction. PVR is somewhat of a misnomer; there is minimal mitotic activity in PVR, and antimetabolites have been shown to be ineffective; in fact, the disease is more like a keloid. To emphasize the hypocellular nature of this process, the authors suggest taking the “P” out of PVR. Like a keloid, PVR is excessive healing or scarring. Scarring is biologically identical to healing; scarring is basically a functional description. PVR should be thought of as a hypocellular interaction between various cell types and the extracellular matrix (ECM). RPE cells, glial cells, and inflammatory cells have been shown to be involved in PVR. Better understanding of the disease process leads to better treatment strategies; excessive retinopexy leads to PVR, and repeated surgical interventions with brief intervals between procedures are common causes of PVR. Lengthy procedures, extensive retinopexy, iris trauma (retractors), combined phaco and intraocular lens (IOL) implantation, and excessive peripheral “membrane peeling” instead of retinectomy are all factors in iatrogenic PVR. Unlike cancer surgery or draining an abscess, the goal is minimal tissue destruction, not removal of all pathologic tissue. The PVR surgeon should think like a plastic surgeon, not a cancer surgeon.

Tangential shortening of the cells occurs prior to collagen production, which may be thought of as a late stabilization phase. The generation of basement membrane and collagen can be thought of as a recreation of Bruch’s membrane or the ILM, as if to duplicate the process that occurs in embryonic development.

PVR can be localized and create isolated star folds, fixed folds, subretinal changes, or epimacular membranes (16, 17, 18). It can be more widespread, which gave rise to the no longer used term, “massive periretinal proliferation.” If the proliferation of glial or RPE cells extended onto the contiguous posterior surface of the PVC, the older term “massive vitreous retraction” would have been used. At this time, there is no proof of the role of hyalocytes in the pathogenesis.

Understanding surgical anatomy is a crucial component of surgical intervention. Core vitrectomy is actually removal of confluent PVC and anterior vitreous cortex (AVC) in the frontal plane (FP); there is no spherical core vitreous in these cases. It is important to recall that the vitreous base has no volume and cannot be “shaved” as surgeons often state; it is a zone of adherence between the peripheral vitreous and the
retina. Often surgeons state that they perform vitreous base dissection; this is simply not the case, although so-called shaving of the peripheral vitreous close to the retina surface is essential. Circumferential vitreous collagen fibers shortened by hypocellular contraction pull the equator inward; these fibers are contiguous with the vitreous base and rarely removable by peeling. Anterior-posterior-oriented vitreous collagen formerly contiguous with the vitreous base shortened by hypocellular contraction causes what the principal author initially identified as anterior loop traction; resection of this component of anterior PVR is essential to reduce the anterior pull on equatorial retina. Epiretinal membranes (ERMs) are always behind to the posterior margin of the vitreous base; peeling peripheral PVR membranes is a misnomer as well.

Scarring in the subretinal space can occur in many physical configurations, as discussed later (see “Subretinal Proliferation”). A placoid configuration can create an inverted star fold configuration. Subretinal bands (strands) occur presumably as tubes of RPE cells proliferate along a fibrin strand; these then contract, causing an extended dendritic configuration. If the band is circumferential at the midretinal level, it can create an annular configuration with a resultant closed cone retinal detachment.