Description, Causes and Risk Factors:
The retina is located at the back of the eye and is made up of a network of nerves and receptors which convert light into signals that are transmitted to the brain to produce vision. The retina normally lies on a layer of epithelial cells that, in turn, rest on a bed of blood vessels. Sometimes the retina becomes partially or completely detached from its support tissues which impairs or completely prevents vision. Successful retinal reattachment can be achieved surgically in about 90% of cases. However, in the remaining 10%, the surgery results in contractile scarring on the surfaces of the retina, preventing reattachment. This condition is known as proliferative vitreoretinopathy (PVR) and blindness or extremely limited vision is an inevitable consequence. Current therapies are limited to the use of drugs that act to reduce scar formation by inhibiting proliferation of the cells that form the scars. However, these drugs are quickly metabolised within the eye minimising their long term effectiveness. High doses of these drugs may also be toxic to the retina.
Proliferative vitreoretinopathy is the most common complication of a retinal detachment (RD), and occurs in approximately 8-10% of patients who develop an RD. Proliferative vitreoretinopathy, despite the long name, is simply scar tissue formation within the eye. This condition has been called by many names, including massive periretinal proliferation (MPP) and massive vitreous retraction (MVR), and was finally dubbed proliferative vitreoretinopathy (PVR) by the Retina Society Terminology Committee. "Proliferative" because cells proliferate and "Vitreoretinopathy" because the problems involve the vitreous and retina. Proliferative vitreoretinopathy can be divided into multiple categories based on the configuration of the retina and the location of the scar tissue, and this categorization is used by eye care specialists to describe to one another the severity and configuration of the retina in PVR.
During rhegmatogenous retinal detachment (RRD), 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.
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.
Field loss - Shadows, loss of portions of the visual field.
Combination of star folds, fixed folds, subretinal proliferation, and vitreous contraction - In some patients, the vitreous contraction component predominates, whereas in other patients, the periretinal proliferation is more apparent. Subretinal proliferation can be annular (napkin ring), placoid, or dendritic (bands, strands). Hypocellular vitreous contraction can involve circumferential fibers, radial pre-equatorial fibers, and contracted anterior and posterior vitreous cortex.
Visual loss in the part of the visual field corresponding to the initial area of retinal detachment (chief complaint).
In eyes with clear media, the diagnosis of PVR is straightforward. A history of retinal detachment surgery and the clinical features just described do not generally present a diagnostic problem. In eyes with opaque media, B-scan ultrasonography is necessary to reveal the stiffened, detached retina and associated membranes.
The surgery to repair an eye detached from PVR includes pars plana vitrectomy, membrane peeling where we use small instruments to peel the membranes from the surface of the retina, and scleral buckling.
These techniques are combined with fluids placed in the eye to flatten the retina and reattach it to the outer wall of the retina followed by laser photocoagulation to connect the retina to the outer layers permanently. In recent years Perfluoron (PFO), perfluoro-n-octane, has revolutionized our surgery by allowing us to push the retina into its normal position with this heavier-than-water fluid. Perfluoron, when injected, settles to the back of the eye and pushes the subretinal fluid to the front, simplifying removal.
A gas bubble may be placed in the eye to hold the retina in place while it is healing, or as an alternative silicone oil may be used to hold the retina in position. The advantage to the gas bubble is that is goes away on its own, and the patient does not require another operation. The advantage to the silicone oil bubble is that the patient does not have to have any head positioning for two to three weeks following surgery like they do with gas and can go back to normal activities in a few days. The disadvantage is that silicone oil requires removal in several months following the procedure. These were compared in the Silicone Oil Study and were found to be equivalent in outcome (long-acting gas vs. silicone oil).
Research: A new study carried out by scientists from The Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, and published in the December issue of The American Journal of Pathology suggests that an effective treatment could be a cocktail that contains reagents to neutralize a relatively small subset of vitreal growth factors and cytokines.
Platelet-derived growth factor receptor ? (PDGFR?) is linked to PVR and strongly promotes experimental PVR in animal models, whilst vitreal growth factors outside of the PDGF family promote an indirect route to activate PDGFR?. Significantly, PDGFR? that is activated indirectly engages a characteristic set of signaling events and cellular responses that are tightly linked to PVR. The researchers aimed to identify which factors would induce those events and develop therapeutic strategies to prevent patients from developing PVR.
The researchers obtained vitreous from normal rabbits or those in which PVR was either developing or stabilized. They found that normal vitreous contains substantial levels of growth factors and cytokines. These change in quantity or quality as PVR develops.
They discovered that a set of nine growth agents was most abundant and therefore most likely contributed to PVR. By neutralizing a subset of these factors in rabbit vitreous the scientists eliminated their ability to induce PVR-relevant signaling and cellular responses, and they discovered that a single dose of neutralizing reagents effectively protected rabbits from developing retinal detachment.
The researchers quantified the level of growth factors and cytokines from human donors that had either PVR or a non-PVR retinal condition in order to establish the possible growth factors that drive PVR in humans. They discovered large concentrations in PVR vitreous in 14 of the 24 quantified agents and neutralizing just 7 of these prevented vitreous-induced activation of PDGFR?. In addition, the cocktail also suppressed the contraction of these cells in collagen and therefore demonstrated the same neutralization strategy that prevented PVR in rabbits also prevented human PVR vitreous from inducing PVR-relevant responses. This is a strong indication that a dose of neutralizing reagents may also protect humans from PVR.
NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.
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