Proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is a disease that develops as a complication of rhegmatogenous retinal detachment. PVR occurs in about 8–10% of patients undergoing primary retinal detachment surgery and prevents the successful surgical repair of rhegmatogenous retinal detachment. PVR can be treated with surgery to reattach the detached retina but the visual outcome of the surgery is very poor.[1][2]

PVR was originally referred to as massive vitreous retraction and then as massive periretinal proliferation. The name Proliferative vitreo retinopathy was provided in 1989 by the Silicone Oil Study group. The name is derived from proliferation (by the retinal pigment epithelial and glial cells) and vitreo retinopathy to include the tissues which are affected, namely the vitreous humor (or simply vitreous) and the retina.[3]

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.[4] Phospholipase A2 and cyclooxygenase blocking reduced structural abnormalities of the rat retina in concanavalin model of PVR.[5]

PVR is graded as Grade A, B, or C by the Silicone Oil Study and as Grade A, B, C, or D by the Retina Society Terminology Committee.[6]

Retinal membranes

The RPE cells migrate out into the vitreous, proliferate excessively and lay down ECM on both side sides of the detached retina. The ECM laid on the vitreous side of the retina are referred to as epiretinal or preretinal membranes and those laid down between the RPE layer and the photoreceptors are referred to as subretinal or retroretinal membranes. The two membranes differ in composition in that the ERM is composed of RPE cells, glial cells, macrophages and fibrocytes, while the SRM is rich in RPE cells. The subretinal membranes are of two types. One forms as diffuse sheets, which are not contractile and either lack or contain very little ECM. The presence of this type of membrane does not usually affect retinal reattachment surgery. The retina can be reattached even with the membrane in place. 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.[7][8]

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.[9] Expression of PDGF in particular PDGF-AA is triggered during ocular injury and contributes to PVR pathology.[10] 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.[11]

Predisposing factors

Predisposing factors for Postoperative PVR are preoperative PVR, aphakia, high levels of vitreous proteins,[12] duration of retinal detachment before corrective surgery, the size of the retinal hole or tear, intra-ocular inflammation, vitreous hemorrhage, and trauma to the eye. An equation to calculate the patient's risk for acquiring PVR is:

PVR score = 2.88 × (Grade C PVR)+ 1.85 × (Grade B PVR) + 2.92 × (aphakia) + 1.77 × (anterior uveitis) + 1.23 × (quadrants of detachment) + 0.83 × (vitreous haemorrhage) + 23 × (previous cryotherapy)

1 is added if the risk factor is present and 0 if the risk factor is absent. A patient is at a high risk for developing PVR is the PVR score is >6.33.[13]

References

  1. ↑ Leaver PK (1995). "Proliferative vitreoretinopathy". British Journal of Ophthalmology 79 (10): 871–872. doi:10.1136/bjo.79.10.871. PMC 505283. PMID 7488570.
  2. ↑ "Proliferative Vitreoretinopathy". Retina and Vitreous of Texas. Retrieved 2009-05-28.
  3. ↑ Ceron OM and Arroyo JG (2009). "Better Outcomes May Be Ahead for PVR". Review of Ophthalmology 16: 1. Retrieved 2009-05-29.
  4. ↑ Kase S, Saito W, Ohno S, Ishida S. (May 2010). "Cyclo-oxygenase-2 expression in human idiopathic epiretinal membrane". Retina 30: 719–23. doi:10.1097/IAE.0b013e3181c59698. PMID 19996819.
  5. ↑ Erdiakov A, Gavrilova S (August 2014). "Influence of lornoxicam and triamcinolone on the dynamics of eye remodeling in concanavalin model of inflammation". Acta Ophthalmologica 92. doi:10.1111/j.1755-3768.2014.F077.x.
  6. ↑ Spirn MJ, Regillo C (January 2008). "Proliferative Vitreoretinopathy". Retinal Physician. Retrieved 2009-05-29.
  7. ↑ Hiscott P and Grierson I (1991). "Subretinal membranes of proliferative vitreoretinopathy". British Journal of Ophthalmology 75 (1): 53. doi:10.1136/bjo.75.1.53. PMC 504108. PMID 1991089.
  8. ↑ Casaroli-Marano RP, Pagan R, and Vilaró S (1999). "Epithelial–Mesenchymal Transition in Proliferative Vitreoretinopathy: Intermediate Filament Protein Expression in Retinal Pigment Epithelial Cells". Investigative Ophthalmology & Visual Science 40 (9): 2062–2072. PMID 10440262.
  9. ↑ Connor TB, Roberts AB, Spom MB, Danielpour D, Dart LL, Michels RG, Bustros SD, Enger C, Kato H, Lansing M, Hayashi H, and Glaser BM (1989). "Correlation of Fibrosis and Transforming Growth Factor-β Type 2 Levels in the Eye". The Journal of Clinical Investigation 83 (5): 1661–1666. doi:10.1172/JCI114065. PMC 303874. PMID 2708527.
  10. ↑ Andrews A, Balciunaite E, Leong FL, Tallquist M, Soriano P, Refojo M, Kazlauskas A (1999). "Platelet-derived growth factor plays a key role in proliferative vitreoretinopathy". Investigative Ophthalmology & Visual Science 40 (11): 2683–2689. PMID 10509666.
  11. ↑ Kauffmann DJH, van Meurs JC, Mertens DAE, Peperkamp E, Master XC and Gerritsen ME (1994). "Cytokines in Vitreous Humor: Interleukin-6 Is Elevated in Proliferative Vitreoretinopathy". Investigative Ophthalmology & Visual Science 35 (3): 900–906. PMID 8125753.
  12. ↑ Kon CH, Asaria RHY, Occleston NL, Khaw PT, Aylward GW (2000). "Risk factors for proliferative vitreoretinopathy after primary vitrectomy: a prospective study". British Journal of Ophthalmology 84 (5): 506–511. doi:10.1136/bjo.84.5.506. PMC 1723478. PMID 10781515.
  13. ↑ Kon CH, Tranos P and Aylward GW (2005). "Risk Factors in Proliferative Vitreoretinopathy". In Kirchoff B, Wong D. Vitreo-retinal Surgery. Springer Berlin Heidelberg. pp. 121–134. ISBN 978-3-540-20044-4.

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