ENZYMATIC ASSISTED VITRECTOMY
Mahmoud Abdalla Mostafa Hasan;
Abstract
Some vitreoretinal diseases like vitreous hemorrhage, macular hole, diabetic vitreoretinopaies, proliferative vitreoretinopathies 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. 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 the corpus vitreum (syneresis), thus facilitating the surgery or even replacing it to decrease the incidence of complications. These methods are simply by injection of some agents (enzymes) like Plasmin, Hyaluronidase, 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 or by urokinase.
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 breakdown of the vitreous gel. Concerning the efficacy, intravitreal plasmin injection in animal eyes was shown to induce liquefaction of the vitreous gel, and separation of the posterior hyaloid face.
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 electro physiologic and histologic examination techniques as compared to control eyes that received intravitreal injection of 0.1 ml of BSS instead.
Most recently, Ocriplasmin (Jetrea®) which is a recombinant plasmin enzyme has received FDA approval for intravitreal injection for the treatment of VMA.
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.
Nattokinase is a strong fibrinolytic agent, was originally derived from natto which is a popular soybean cheese in Japan. It produces PVD through a combination of direct liquefaction and plasmin-mediated vitreoretinal dehiscence
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 will be replaced by pharmacological vitreolysis hasn't yet come to know, multiple agents used to produce vitreolysis have been tried over years to reach that day.
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 the corpus vitreum (syneresis), thus facilitating the surgery or even replacing it to decrease the incidence of complications. These methods are simply by injection of some agents (enzymes) like Plasmin, Hyaluronidase, 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 or by urokinase.
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 breakdown of the vitreous gel. Concerning the efficacy, intravitreal plasmin injection in animal eyes was shown to induce liquefaction of the vitreous gel, and separation of the posterior hyaloid face.
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 electro physiologic and histologic examination techniques as compared to control eyes that received intravitreal injection of 0.1 ml of BSS instead.
Most recently, Ocriplasmin (Jetrea®) which is a recombinant plasmin enzyme has received FDA approval for intravitreal injection for the treatment of VMA.
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.
Nattokinase is a strong fibrinolytic agent, was originally derived from natto which is a popular soybean cheese in Japan. It produces PVD through a combination of direct liquefaction and plasmin-mediated vitreoretinal dehiscence
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 will be replaced by pharmacological vitreolysis hasn't yet come to know, multiple agents used to produce vitreolysis have been tried over years to reach that day.
Other data
| Title | ENZYMATIC ASSISTED VITRECTOMY | Other Titles | استئصال الجسم الزجاجي للعين بمساعدة الإنزيمات | Authors | Mahmoud Abdalla Mostafa Hasan | Issue Date | 2014 |
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