Safety Profile of the Intravitreal Streptokinase-plasmin Complex As an Adjunct to Vitrectomy in the Rabbit

Overview

Journal Graefes Arch Clin Exp Ophthalmol

Specialty Ophthalmology

Date 2005 Dec 21

PMID 16365737

Citations 5

Authors

M Hermel

M Mahgoub

T Youssef

M I Azrak

H Raza

C Alldredge

M Trese

G A Williams

M Hartzer

Affiliations

Soon will be listed here.

Abstract

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 an adjunct to vitrectomy to enzymatically generate a PVD. Low doses of streptokinase-activated plasmin were tested in human pilot studies. This dose-escalation study assesses the safety range of intravitreal human streptokinase-plasmin in rabbits.

Methods: Plasminogen was isolated from human plasma by affinity chromatography, followed by activation with streptokinase (1:1), to generate the streptokinase-plasmin complex. Enzyme doses from 0.1-7 activity units (AU, in 0.1 ml) were injected into the mid-vitreous of 35 eyes; six control eyes were injected with balanced salt solution (BSS, 0.1 ml). Thirty minutes after injection, a two-port vitrectomy was performed. Fundus and slit lamp examinations were performed on days 1 and 7. On days 2 and 7, bright flash electroretinography was performed and compared with preoperative recordings. Some animals receiving higher doses of streptokinase-plasmin (1-7 AU) were followed clinically and with electroretinography for up to 9 months.

Results: A mild-to-moderate inflammatory response was seen in both control and plasmin-treated eyes on day 1, but had disappeared completely by day 7 in most eyes. In the 7 AU group, inflammation was stronger and more protracted. Two of three eyes from this group developed wrinkling of the medullary rays; one of them showed discoloration and traction at the medullary rays in the late follow-up. Electroretinograms (ERGs) of vitrectomized control eyes showed the following changes from preoperative values: 48 h, a-wave -11.10% [no significant (n.s.)], b-wave -14.62% (P=0.046); 7 days, a-wave +9.18% (n.s.), b wave +11.69% (n.s.). For the enzyme-treated eyes: 48 h: a-wave -20.43% (P<0.001), b-wave -9.57% (p<0.001); 7 days: a wave -14.21% (P<0.001), b-wave +2.48% (P<0.001). There was no evidence of dose-dependent ERG changes in enzyme-treated eyes at doses up to 5 AU. Groups of up to 3 AU were investigated by light and transmission electron microscopy, without evidence of toxicity.

Conclusion: Streptokinase-plasmin doses up to 3 AU were found to be safe when injected into rabbit eyes followed by vitrectomy.

Citing Articles

Lens subluxation after plasmin and SF6 injections in rabbit eyes.

Wu W, Liu C, Wang N, Chen K, Chen T, Hwang Y PLoS One. 2014; 9(11):e112957.

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Efficient vitreolysis by combining plasmin and sulfur hexafluoride injection in a preclinical study in rabbit eyes.

Wu W, Liu C, Chen C, Wang N, Chen K, Chen T Mol Vis. 2012; 18:2361-70.

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A disposable system for rapid purification of autologous plasmin as an adjunct to vitrectomy - performance and safety profile.

Hermel M, Dailey W, Trese M, Hartzer M Graefes Arch Clin Exp Ophthalmol. 2010; 249(1):37-46.

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Effect of intravitreal plasmin on vitreous removal through a 25-gauge cutting system in the rabbit in vivo.

Hermel M, Prenner J, Alabdulrazzak M, Dailey W, Hartzer M Graefes Arch Clin Exp Ophthalmol. 2008; 247(3):331-4.

PMID: 19034484 DOI: 10.1007/s00417-008-1000-7.

Efficacy of plasmin enzymes and chondroitinase ABC in creating posterior vitreous separation in the pig: a masked, placebo-controlled in vivo study.

Hermel M, Schrage N Graefes Arch Clin Exp Ophthalmol. 2006; 245(3):399-406.

PMID: 16900357 DOI: 10.1007/s00417-006-0388-1.

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