Proliferative vitreoretinopathy
Encyclopedia
Proliferative Vitreo Retinopathy (PVR) is a disease that develops as a complication, secondary to 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.
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 cell
s) and vitreo retinopathy to include the tissues which are affected, namely the vitreous humor (or simply vitreous) and the retina
.
(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.
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.
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, macrophage
s and fibrocyte
s, 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.
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.
, high levels of vitreous proteins, 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:
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.
Retinal detachment
Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...
. 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
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
but the visual outcome of the surgery is very poor.
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 cell
Glial cell
Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
s) and vitreo retinopathy to include the tissues which are affected, namely the vitreous humor (or simply vitreous) and the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
.
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 transitionEpithelial-mesenchymal transition
Epithelial-mesenchymal transition or transformation is a hypothesized program of development of biological cells characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell mobility...
(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
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
) 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.
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.
- Grade A is characterized by the appearance of vitreous haze and RPE cells in the vitreous.
- Grade B is characterized by wrinkling of the edges of the retinal tear or the inner retinal surface.
- Grade C is characterized by the presence of retinal membranes.
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 epiretinalEpiretinal membrane
Epiretinal membrane is a disease of the eye in response to changes in the vitreous humor or more rarely, diabetes. It is also called macular pucker. Sometimes, as a result of immune system response to protect the retina, cells converge in the macular area as the vitreous ages and pulls away in...
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, macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s and fibrocyte
Fibrocyte
A fibrocyte is an inactive mesenchymal cell, that is, a cell showing minimal cytoplasm, limited amounts of rough endoplasmic reticulum and lacks biochemical evidence of protein synthesis.The term fibrocyte contrasts with the term fibroblast...
s, 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.
Cytokines involved in PVR
A number of cytokines such as tumor necrosis factor alpha (TNFα), transforming growth factorTransforming growth factor
Transforming growth factor is used to describe two classes of polypeptide growth factors, TGFα and TGFβ....
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
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
into the vitreous by epithelial cells of the ciliary body
Ciliary body
The ciliary body is the circumferential tissue inside the eye composed of the ciliary muscle and ciliary processes. It is triangular in horizontal section and is coated by a double layer, the ciliary epithelium. This epithelium produces the aqueous humor. The inner layer is transparent and covers...
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
Hepatocyte growth factor
Hepatocyte growth factor/scatter factor is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on haemopoietic progenitor cells...
(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.
Predisposing factors
Predisposing factors for Postoperative PVR are preoperative PVR, aphakiaAphakia
Aphakia is the absence of the lens of the eye, due to surgical removal, a perforating wound or ulcer, or congenital anomaly. It causes a loss of accommodation, hyperopia, and a deep anterior chamber. Complications include detachment of the vitreous or retina, and glaucoma.Aphakic people are...
, high levels of vitreous proteins, 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 uveitisUveitisUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
) + 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.