December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
Clearance and Safety of Intravitreal Human Plasmin in Rabbits
Author Affiliations & Notes
  • MK Hartzer
    NuVue Technologies Keene NH
  • M Mahgoub
    Ophthalmology Ain Shams University Cairo Egypt
  • T Youssef
    Ophthalmology Ain Shams University Cairo Egypt
  • MI Azrak
    NuVue Technologies Keene NH
  • H Raza
    NuVue Technologies Keene NH
  • C Alldredge
    Associated Retinal Consultants Royal Oak MI
  • M Trese
    Associated Retinal Consultants Royal Oak MI
  • GA Williams
    Associated Retinal Consultants Royal Oak MI
  • Footnotes
    Commercial Relationships    M.K. Hartzer, NuVue Technologies E, P; M. Mahgoub, None; T. Youssef, None; M.I. Azrak, None; H. Raza, None; C. Alldredge, None; M. Trese, NuVue Technologies I, P; G.A. Williams, NuVue Technologies I, P.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 3532. doi:
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      MK Hartzer, M Mahgoub, T Youssef, MI Azrak, H Raza, C Alldredge, M Trese, GA Williams; Clearance and Safety of Intravitreal Human Plasmin in Rabbits . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3532.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose:To determine the rate of clearance from the vitreous and safety of intravitreal human plasmin in rabbits Methods:Plasmin was prepared from human donor plasma by affinity chromatography followed by streptokinase activation. For clearance studies, doses of 0.4 U and 1.0 U (0.1 cc)were injected into the mid vitreous. Animals were sacrificed from 5 minutes to 24 hours after injection, the vitreous removed and plasmin activity analyzed spectrophotometrically. Four eyes were used per time point. For safety studies, plasmin doses from 0.1-3.0 U (0.1 cc) were injected into the mid vitreous. Control eyes were injected with BSS (0.1 cc). Thirty minutes after injection, a two port vitrectomy was performed. Fundus and slit lamp examinations were performed on days one and seven. On days two and seven, bright flash electroretinography was performed and compared with preoperative recordings. Some animals receiving high doses of plasmin (1.0-3.0 U) were followed for six months with ERGs recorded monthly. Most animals were sacrificed on day seven and eyes prepared for LM or TEM. Micrographs were graded by individuals masked to the plasmin dose. Results:Following plasmin injection, the highest plasmin vitreous levels were measured 30 minutes after injection. At two hours after injection, the plasmin levels had decreased to 15.8% (1.0 U) and 17.6% ( 0.4 U) of the maximum values. By four hours, plasmin activity had decreased to less than 5% of the maximum level and was not detectable at 24 hours. In the safety studies, intravitreal fibrin was seen in both control and plasmin-treated eyes on one day, but disappeared by day seven from the plasmin eyes. ERGs of vitrectomized control eyes showed the following changes from preoperative values (48 hrs: a wave (-9.6%) b wave (-24.9 %); 7 days: a wave (+6.1%), b wave (-14.6%). For the plasmin-treated group: 48 hours: a wave (-22%), b wave (-17%); 7 days : a wave(-11%), b-wave (+1 %). These differences between control and plasmin-treated groups were not statistically significant and there was no evidence of dose-dependent ERG changes in plasmin-treated eyes. No differences were seen in the light and transmission electron micrographs from control eyes and eyes receiving high doses (1.0-3.0 U) of plasmin. Conclusion:: Following intravitreal injection of human plasmin in rabbit eyes, the highest activity was measured at 30 minutes and rapidly decreased with only 5% of the maximum activity present after 4 hours. Plasmin doses up to 3.0 U were found to be safe when injected into rabbit eyes followed by vitrectomy.

Keywords: 630 vitreous substitutes • 399 enzymes/enzyme inhibitors 

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