الفهرس 
Historical background of intravitreal injectionOnly 14 pages are availabe for public view
 |  | from | 172 |  |  |
| | | from | 172 | | |
Abstract
Some vitreoretinal diseases like vitreous hemorrhage, macular hole, Diabetic vitreoretinopaies, proliferative vitreoretinopaies and retinal detachment lead to fibrotic changes of the vitreous gel that may induce tractional retinal detachment or retinal tears; that may end by loss of vision. Vitreous surgeons are usually invited to mechanical vitrectomy to such complicated cases.
Despite of improvement of surgical techniques of mechanical vitrectomy, the complete removal of the vitreous remains difficult with increased incidence of complications mostly iatrogenic retinal tears and vitreous hemorrhage.
Difficulty of surgery depends on adhesions between the vitreous cortex and the retina, and presence or absence of PVD. Recent methods have been developed to produce liquefaction of the vitreous body (synchisis) and to relieve adhesion at the vitreoretinal interface leading to separation and collapse of corpus vitreum (syneresis), thus facilitates the surgery or even replaces it to decrease the incidence of complications. These methods are simply by injection of some agents (enzymes) like Plasmin, Hyalase, Dispase, and Chondroitinase. Plasmin is best known by its role in the fibrinolytic cascade, where it is converted from plasminogen either by tissue plasminogen activator (TPA) or by urokinase (UK).
Plasmin degrades a variety of substances in the extracellular matrix including laminin and fibronectin, which have been implicated in normal vitreoretinal adhesions. In addition to its action on fibrin, plasmin activates latent matrix metalloproteinases (collagenases), with the break down of the vitreous gel. With regards to the efficacy, intravitreal plasmin injection in animal eyes was shown to induce liquefaction of the vitreous gel, and separation of the posterior hyaloid face.
Although the former observation was merely based on clinical subjective evaluation since there was no available technique to objectively evaluate its degree, yet the latter was confirmed by studying the histopathologic slides through various techniques to occur in a relatively consistent dose dependant response.
Plasmin toxicity and efficacy was studied on rabbit eyes at varying doses starting from 0.1 IU reaching up to 3.0 IU. No evidences of toxicity were demonstrated by the electrophysiologic and histologic examination techniques as compared to control eyes that received intravitreal injection of 0.1 ml of BSS instead.
Dispase, a neutral protease from bacillus polymyxa, which cleaves the basal lamina in various tissues including retina, thus separating vitreoretinal interface, acts on type IV collagen and fibronectin.
Urokinase is a plasminogen activator of human origin which breaks up fibrin base of blood clots. It was used in vitreous hemorrhage, but increased doses lead to glaucoma and retinal fibrosis.
Hyaluronidase is a specific enzyme that cleaves hyaluronan into its disaccharide components by splitting the bond between glucosamine and C4 of glucuronic acid, leading to separation of vitreoretinal interface and vitreous gel liquefaction especially with SF6 injection.
Chondroitinase is a specific enzyme that lyses chondroitin sulfate proteoglycan associated with vitreoretinal interface. It induces disinsertion of vitreous body to separate vitreoretinal interface.
Collagenase is a substrate specific enzyme which is a clostridiopeptidase (A) in nature. It facilitates removal of epiretinal membranes by partial digestion of epiretinal collagenous fibrous tissues before mechanical surgery.
This review strongly suggests that, the benefits from using enzymes especially plasmin, either on animal or human eyes, plays an important role in vitreous gel liquefaction or facilitates separation of the posterior hyaloid face in a relatively consistent time and dose dependent response. However, although the day when vitreous surgery wills be replaced by pharmacological vitreolysis hasn’t yet come to know, multiple agents used to produce vitreolysis have been tried over years, but none has been met with sufficient success to stimulate wide spread use, yet it holds great promise.
Additionally it has been proved that enzymes can be used successfully as an adjuvant to mechanical vitrectomy, or in a non surgical technique, in the appropriate dose, to create a spontaneous PVD.