RESUMEN
BACKGROUND: The generation of an atraumatic posterior vitreous detachment (PVD), a common goal in vitreoretinal surgery, is a challenge particularly in children and young trauma patients. Plasmin has been proposed as a surgical adjunct to enzymatically generate a PVD. This study assesses the performance and safety of a new system for rapid purification of plasmin as an adjunct to vitrectomy. METHODS: Plasminogen was isolated from human plasma by affinity chromatography using a disposable rapid purification kit, and activated to plasmin with streptokinase. Activities were assessed spectrophotometrically. For safety studies, 38 rabbits received intravitreal injections of one of the following compounds in 0.1 ml respectively: 4.7, 12.7 and 24 IU plasmin, 15 mg dextran, 4,100 U streptokinase, 500 µg ε-aminocaproic acid, 0.1 M potassium phosphate or balanced salt solution (BSS). Thirty min after injection, a two-port vitrectomy was performed. Rabbits were followed clinically and with bright flash electroretinography (ERG) for up to 9 months. The eyes were investigated by light and transmission electron microscopy. RESULTS: The specific plasmin activity obtained from blood of healthy volunteers averaged 42.3 ± 6.6 IU/ml (range 21.6 IU/ml to 54.5 IU/ml). The identity and purity of the enzyme was confirmed by several methods. Clinically, a mild to moderate inflammatory response was seen in most eyes on day 1, but had disappeared by day 7. ERG showed moderate depressions of a- and b-wave amplitudes on day 2, particularly in the potassium phosphate (a: -29.16 ± 4.56, b: -21.23 ± 6.31), 4.7 (a: -34.38 ± 6.64, b: -26.66 ± 6.06) and 24 IU (a: -38.25 ± 4.05, b: -23.38 ± 4.29) plasmin groups, but also in the BSS- (a: -11.19 ± 21.78, b: -11.41 ± 15.47) and dextran- (a: -17.86 ± 14.18, b: -6.67 ± 18.14) treated eyes. ERG changes recovered during follow-up. One rabbit each from the 12.7 and the 24 IU plasmin groups showed a minimal discoloration of one medullary ray after 9 months. Histology did not reveal morphologic signs of toxicity. CONCLUSION: The isolation system generated plasmin with a high degree of purity. A failure-mode analysis did not reveal significant risks of toxicity. A single preparation can provide a maximum dose of 10.9 IU/200 µl, the likely target clinical dose being 1.88 IU. Plasmin doses of at least 12.7 IU appear be safe when injected into rabbit eyes, followed by vitrectomy.
Asunto(s)
Fibrinolisina/aislamiento & purificación , Fibrinolisina/toxicidad , Fibrinolíticos/aislamiento & purificación , Fibrinolíticos/toxicidad , Vitrectomía , Desprendimiento del Vítreo/cirugía , Animales , Cromatografía de Afinidad , Terapia Combinada , Equipos Desechables , Electroforesis en Gel de Poliacrilamida , Electrorretinografía , Fibrinolisina/química , Fibrinolíticos/química , Humanos , Conejos , Juego de Reactivos para Diagnóstico , Cirugía Vitreorretiniana , Cuerpo Vítreo/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate the effects of scleral buckling surgery on the developing eye in an animal model. METHODS: Eleven young rabbits underwent scleral buckling surgery in one eye. In 6 rabbits, a 2.5 x 0.6-mm solid silicone encircling band (240 style) with a Watzke sleeve was used, and in 5 rabbits, a 2.0-mm silicone encircling sponge (502 style) with its ends abutting, but not connected, was used. After 3 months, both eyes of each animal were enucleated. Six eyes of an additional 3 rabbits served as baseline controls for determining initial globe volumes. RESULTS: Of the eyes buckled with a 240 band, 4 of 6 developed glaucoma compared with 0 of 5 eyes buckled with a 502 sponge (P =.06). Migration of the element occurred in all eyes with a 240 band (3 anterior, 3 posterior), while none of the 502 sponges migrated. There was no significant difference in the mean final corneal diameter between eyes with a 240 band (P =.94) and untreated fellow eyes or between eyes with a 502 sponge and untreated fellow eyes (P =.25). The mean axial length of eyes with a 240 band and untreated fellow eyes was 19.57 mm and 16.83 mm, respectively (P =.009). The mean axial length of eyes with a 502 sponge and untreated fellow eyes was 16.67 mm and 16.50 mm, respectively (P =.67). When comparing eyes with a 240 band with eyes with a 502 sponge, a significant difference was observed in the mean axial length (P =.006) and mean volume (P =.006) between the 2 scleral buckle groups. CONCLUSIONS: The use of a noninterrupted solid silicone encircling band appeared to have significant effects on the growth of young rabbit eyes. The use of an interrupted silicone sponge produced a buckling effect similar to the solid silicone band and did not migrate, adversely affect eye growth, or result in glaucoma. CLINICAL RELEVANCE: Noncontinuous encircling elements may prove to be as beneficial as continuous encircling elements in the treatment of tractional and rhegmatogenous retinal detachment in infant eyes without the potentially deleterious effects associated with a nondivided encircling band or the need for a second surgery to divide the encircling element.