Prior to the development of good operating microscopes and sutures fibrin was explored as an adjunct to anterior segment surgery( 180-2). More recently fibrin has been used to seal leaking glaucoma blebs(183) and in repairing scleral
defects(184). Fibrin has also been used to secure lamellar corneal grafts and epikeratophakia corneal lenticules, both experimentally and clinically(185). In the first study fibrin from two sources was used 1) autologous plasma was mixed with bovine thrombin, and 2) a commercial preparation was used, which contains bovine thrombin, human fibrinogen, calcium chloride and aprotonin (a broad-spectrum protease inhibitor that delays fibrinolysis). The major problem encountered was the temporary nature of the fibrin adhesive. This could be partially rectified by using aprotonin, an antifibrinolytic agent.
Fibrin has also been investigated as a means of sealing retinal breaks. In 1949 Brown treated 30 patients with surface diathermy, drainage of SRF and transcleral injection of thrombin and a small volume of autologous plasma into the subretinal space. Retinal reattachment occurred in 60% of cases but it was noticed that the subretinal fibrin gradually disappeared(180). In 1986 Nasaduke undertook experiments using rabbits to investigate possible toxic or inflammatory reactions and to assess fibrin retinopexy. He used either pooled rabbit plasma as a source of fibrinogen or commercially prepared freeze-dried rabbit fibrinogen. The adhesive was delivered using simultaneous injection of thrombin/calcium chloride in one syringe and fibrinogen/aprotonin in a second syringe joined by a Y shaped connector, via a 22g needle. In one group of animals 0.1 cc of fibrin was injected into the mid-vitreous cavity. The fibrin gradually lysed, leaving small vitreous opacities. Histological examination of the retinae showed no abnormality and ERGs were normal. In a second group of animals a localised RD was created in non- vitrectomised eyes and fibrin injected into the subretinal space, although this could not be achieved in all animals. Clinically and histologically there was no difference between treated eyes and control eyes; all had attached retinas with essentially normal histology. In a third group retinal breaks and RDs were created in vitrectomised eyes, and fibrin injected into the subretinal space. Both treated eyes and controls showed the same rate of retinal reattachment, RD and formation of vitreous membranes. Nasaduke concluded that fibrin was not retinotoxic, but eval uation in the rabbit is unsatisfactory as the retina reattaches spontaneously(186).
Further experimental and clinical work has been undertaken by Coleman who used either freeze-dried human or rabbit fibrinogen, or autologous plasma, mixed with bovine thrombin, calcium chloride and aprotonin. Experiments were performed on non-vitrectomised rabbit and pig eyes, with injection of fibrin either into the subretinal space after creating a localised RD, or into the mid-vitreous cavity. In the rabbit experiments little inflammatory reaction was seen and retinal reattachment occurred at the same rate in treated and control eyes (who had had a RD created but no subretinal injection of fibrin). No histological evidence of tissue
toxicity was found with any of the fibrin preparations, and clinically none of the eyes developed traction RD secondary to proliferative processes. Two of the four eyes with subretinal injection followed for one year showed histological evidence of chorioretinal adhesion, but this was not found in the other eyes. In the pig model, both treated eyes showed histological evidence of chorioretinal adhesions as the breaks were sealed to the underlying RPE by fibrous scar tissue. Coleman also treated seven patients with fibrin retinopexy, five of whom had macular holes and two who had post traumatic giant retinal tears. In each instance vitrectomy and fluid/air exchange was followed by application of fibrin (made from autologous plasma) to the flattened retinal break. Internal tamponade with gas was used in three eyes. The postoperative inflammatory reaction was mild and in those with retinal reattachment visual recovery was good, suggesting no local toxicity. Four of the eyes with macular holes reattached after this procedure (three had also had intravitreal gas injection) but neither eye with a giant retinal tear reattached. This clinical study shows that fibrin retinopexy has no deleterious effects, but little conclusion can be drawn from such a small study about the effectiveness of fibrin in break sealing, particularly as a high percentage of macular holes respond to vitrectomy and internal tamponade alone. The author concludes that fibrin may have some part to play in peroperative retinal fixation as fibrin does not provide permanent adhesion(187).
Emmerich performed similar experiments to those of Nasaduke, injecting fibrin into the subretinal space of rabbits after vitrectomy. He observed that the degree of postoperative inflammation and ERM formation was dose dependent. ERG changes were not noted. When small volumes of fibrin were injected complete lysis took 7-14 days, but when larger volumes were injected lysis took up to 28 days. From these observations Emmerich concluded that fibrin may have some part to play in temporary break sealing(188).
Further toxicity studies were performed on rabbits by Gerding. Retinal breaks and localised RDs were created in vitrectomised eyes and the breaks plugged with fibrin. Electrodiagnostic testing showed no evidence of toxicity, but ERM formation with or without extensive RD developed (no data is given in the abstract)(189).