A patient is at a high risk for developing PVR if their PVR score is >6.33. Pathology
During rhegmatogenous retinal detachment, fluid from the vitreous humor enters a retinal hole. The mechanisms by which retinal holes or tears form are not fully understood yet. The accumulation of fluid in the subretinal space and the tractional force of the vitreous on the retina result in rhegmatogenous retinal detachment. During this process the retinal cell layers come in contact with vitreous cytokines. These cytokines trigger the ability of the retinal pigmented epithelium (RPE) to proliferate and migrate. The process involved resembles fibrotic wound healing by the RPE cells. The RPE cells undergo epithelial-mesenchymal transition (EMT) and develop the ability to migrate out into the vitreous. During this process the RPE cell layer-neural retinal adhesion and RPE-ECM (extracellular matrix) adhesions are lost. The RPE cells lay down fibrotic membranes while they migrate and these membranes contract and pull at the retina. All these finally lead to secondary retinal detachment after primary retinal detachment surgery. A number of studies have also shown that arachidonic acid metabolic cascade (one of the major inflammatory cascades) is important in the development of PVR. COX-2 expression was found in human idiopathic epiretinal membranes. Phospholipase A2 and cyclooxygenase blocking reduced structural abnormalities of the rat retina in concanavalin model of PVR and reduced the frequency of membrane formation by 43% in the dispase model of PVR and by 31% in the concanavalin one.
The other type forms as very thick contractile membranes which pull at the retina. These are opaque and block the light falling on the retina so the retinal reattachment surgery needs to be performed after manually peeling the membrane off. Cytokines involved in PVR
A number of cytokines such as tumor necrosis factor alpha (TNFα), transforming growth factor beta 2 (TGFβ2), platelet derived growth factor (PDGF) and interleukins have been shown to play a role in PVR progression. TGFβ2 levels have been shown to be elevated up to three times normal during the progression of PVR. TGFβ2 is the most predominant isoform in the eye and is secreted as a latent inactive peptide into the vitreous by epithelial cells of the ciliary body and the lens epithelium and is also produced by the RPE cells and the Muller cells of the retina. TGFβ2 is known to induce EMT in RPE cells and fibrosis in the eye. Expression of PDGF in particular PDGF-AA is triggered during ocular injury and contributes to PVR pathology. RPE cells express the receptor for hepatocyte growth factor (HGF). HGF stimulates RPE cell migration and its presence is also strongly detected in retinal membranes. Interleukin 6 levels are elevated in the vitreous humor during PVR. References
External links
GeneReviews/NCBI/NIH/UW entry on VCAN-Related Vitreoretinopathy