Safety profile of the intravitreal streptokinase-plasmin complex as an adjunct to vitrectomy in the rabbit
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Insights
Intravitreal streptokinase-plasmin up to 3 activity units (AU) demonstrated safety in rabbit eyes undergoing vitrectomy. This enzymatic approach shows promise for generating posterior vitreous detachment (PVD) in challenging surgical cases.
Area of Science:
- Ophthalmology
- Biochemistry
- Surgical Innovation
Background:
- Generating atraumatic posterior vitreous detachment (PVD) is crucial in vitreoretinal surgery, especially for pediatric and trauma patients.
- Plasmin has been investigated as an adjunct to vitrectomy to enzymatically facilitate PVD creation.
- Previous human pilot studies used low doses of streptokinase-activated plasmin.
Purpose of the Study:
- To assess the safety range of intravitreal human streptokinase-plasmin in a rabbit model.
- To determine the maximum safe dosage of streptokinase-plasmin for intravitreal injection prior to vitrectomy.
Main Methods:
- Human plasminogen was isolated and activated with streptokinase to form the enzyme complex.
- Doses ranging from 0.1 to 7 activity units (AU) of streptokinase-plasmin were injected into rabbit vitreous cavities.
- Following injection, vitrectomy was performed, and eyes were evaluated through clinical examinations, funduscopy, slit-lamp microscopy, and electroretinography (ERG).
Main Results:
- Mild-to-moderate inflammation was observed initially but resolved by day 7 in most eyes, except for the highest dose group (7 AU).
- Electroretinography showed significant changes in both control and enzyme-treated eyes, with no dose-dependent ERG alterations observed up to 5 AU.
- Histopathological examination of eyes treated with up to 3 AU revealed no signs of toxicity.
Conclusions:
- Streptokinase-plasmin doses up to 3 AU were found to be safe in rabbit eyes when administered before vitrectomy.
- The findings support the potential of streptokinase-plasmin as a safe adjunct for inducing PVD in vitreoretinal surgery.
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.
