Original Paper Ophthalmic Res 2014;52:74–80 DOI: 10.1159/000362340
Received: November 27, 2013 Accepted after revision: March 17, 2014 Published online: July 23, 2014
Intravitreal Functional Plasminogen in Eyes with Branch Retinal Vein Occlusion Thomas Bertelmann a Walter Sekundo a Stefan Strodthoff a Michael C.P. Witteborn d Thomas Stief b Sebastian Irle c Nauke Nguyen e Michael J. Koss f Stefan Mennel g Departments of a Ophthalmology and b Laboratory Medicine, and c Institute of Medical Biometry and Epidemiology, Philipps University Marburg, Marburg, d Ambulatory Healthcare Center and Day Hospital GbR, Leer, and e Section of Vitreo-Retinal Surgery, Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany; f Doheny Eye Institute, University of California, Los Angeles, Calif., USA; g Department of Ophthalmology, Feldkirch Regional Hospital, Feldkirch, Austria
Abstract Purpose: To evaluate whether intravitreal functional plasminogen is elevated in eyes with branch retinal vein occlusion (BRVO) and to discover whether intravitreal plasminogen activities are correlated with the extent of blood-retina barrier (BRB) breakdown. Methods: Our study is a prospective case series of 20 consecutive patients with BRVO and 10 consecutive patients serving as controls. Vitreous taps were extracted from the central vitreous body and plasminogen was functionally determined in an innovative, ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). Intravitreal VEGF levels were assayed to estimate BRB breakdown. Results: Intravitreal functional plasminogen was detected in all analyzed samples (n = 30) and mean (±SD) plasminogen activities were found to be 0.97 ± 1.06%N (range: 0.03–3.9%N). Patients suffering
© 2014 S. Karger AG, Basel 0030–3747/14/0522–0074$39.50/0 E-Mail [email protected] www.karger.com/ore
from BRVO exhibited significantly higher intravitreal plasminogen (1.35 ± 1.11%N) in comparison with controls (0.20 ± 0.21%N, p < 0.001). Intravitreal VEGF concentrations in the BRVO group (576 ± 547 pg/ml) were significantly higher than these in controls (111 ± 120 pg/ml, p = 0.003). There was a significant correlation between intravitreal functional plasminogen and intravitreal VEGF levels (r = 0.519, p = 0.003). Conclusions: Intravitreal functional plasminogen is significantly elevated in eyes suffering from BRVO and correlates with the extent of BRB breakdown. The induction of posterior vitreous detachment by using intravitreally administered recombinant tissue plasminogen activator (enzymatic vitreolysis) should be explored in further investigations. © 2014 S. Karger AG, Basel
Introduction
Branch retinal vein occlusion (BRVO) is the second most common vascular disorder of the eye [1]. It can provoke a sustainable decrease in visual acuity due to cystoid macular edema (CME) or neovascularizations in different compartments of the eye [2]. Intravitreally applied Thomas Bertelmann, MD Department of Ophthalmology Philipps University Marburg, Baldingerstrasse DE–35043 Marburg (Germany) E-Mail thomas.bertelmann @ staff.uni-marburg.de
Downloaded by: Selçuk Universitesi 193.255.248.150 - 2/7/2015 6:45:06 PM
Key Words Branch retinal vein occlusion · Enzymatic vitreolysis · Fibrinolysis · Plasminogen · Tissue plasminogen activator · Vitreomacular adhesion · Vitreomacular traction
ular pathologies (macular hole, n = 2; macular pucker, n = 3, or vitreal floaters, n = 5) serving as controls were included in our series after written consent was obtained from each subject, following an explicit explanation of the purpose and potential adverse side effects of the procedure. Patients with recent onset of BRVO no more than 6 weeks previously were included in the study group if typical clinical signs of BRVO were present and BRVO was confirmed by fundus photography and fluorescein angiography. BRVO was classified as ischemic if nonperfused retinal areas of 5 or more disk diameters were detected in 50-degree fluorescein angiography [14] using the OIS WinStation (11KTM, CCS Pawlowski GmbH, Jena, Germany). Furthermore, a CME involving the fovea and a central macular thickness (CMT) of
Received: November 27, 2013 Accepted after revision: March 17, 2014 Published online: July 23, 2014
Intravitreal Functional Plasminogen in Eyes with Branch Retinal Vein Occlusion Thomas Bertelmann a Walter Sekundo a Stefan Strodthoff a Michael C.P. Witteborn d Thomas Stief b Sebastian Irle c Nauke Nguyen e Michael J. Koss f Stefan Mennel g Departments of a Ophthalmology and b Laboratory Medicine, and c Institute of Medical Biometry and Epidemiology, Philipps University Marburg, Marburg, d Ambulatory Healthcare Center and Day Hospital GbR, Leer, and e Section of Vitreo-Retinal Surgery, Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany; f Doheny Eye Institute, University of California, Los Angeles, Calif., USA; g Department of Ophthalmology, Feldkirch Regional Hospital, Feldkirch, Austria
Abstract Purpose: To evaluate whether intravitreal functional plasminogen is elevated in eyes with branch retinal vein occlusion (BRVO) and to discover whether intravitreal plasminogen activities are correlated with the extent of blood-retina barrier (BRB) breakdown. Methods: Our study is a prospective case series of 20 consecutive patients with BRVO and 10 consecutive patients serving as controls. Vitreous taps were extracted from the central vitreous body and plasminogen was functionally determined in an innovative, ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). Intravitreal VEGF levels were assayed to estimate BRB breakdown. Results: Intravitreal functional plasminogen was detected in all analyzed samples (n = 30) and mean (±SD) plasminogen activities were found to be 0.97 ± 1.06%N (range: 0.03–3.9%N). Patients suffering
© 2014 S. Karger AG, Basel 0030–3747/14/0522–0074$39.50/0 E-Mail [email protected] www.karger.com/ore
from BRVO exhibited significantly higher intravitreal plasminogen (1.35 ± 1.11%N) in comparison with controls (0.20 ± 0.21%N, p < 0.001). Intravitreal VEGF concentrations in the BRVO group (576 ± 547 pg/ml) were significantly higher than these in controls (111 ± 120 pg/ml, p = 0.003). There was a significant correlation between intravitreal functional plasminogen and intravitreal VEGF levels (r = 0.519, p = 0.003). Conclusions: Intravitreal functional plasminogen is significantly elevated in eyes suffering from BRVO and correlates with the extent of BRB breakdown. The induction of posterior vitreous detachment by using intravitreally administered recombinant tissue plasminogen activator (enzymatic vitreolysis) should be explored in further investigations. © 2014 S. Karger AG, Basel
Introduction
Branch retinal vein occlusion (BRVO) is the second most common vascular disorder of the eye [1]. It can provoke a sustainable decrease in visual acuity due to cystoid macular edema (CME) or neovascularizations in different compartments of the eye [2]. Intravitreally applied Thomas Bertelmann, MD Department of Ophthalmology Philipps University Marburg, Baldingerstrasse DE–35043 Marburg (Germany) E-Mail thomas.bertelmann @ staff.uni-marburg.de
Downloaded by: Selçuk Universitesi 193.255.248.150 - 2/7/2015 6:45:06 PM
Key Words Branch retinal vein occlusion · Enzymatic vitreolysis · Fibrinolysis · Plasminogen · Tissue plasminogen activator · Vitreomacular adhesion · Vitreomacular traction
ular pathologies (macular hole, n = 2; macular pucker, n = 3, or vitreal floaters, n = 5) serving as controls were included in our series after written consent was obtained from each subject, following an explicit explanation of the purpose and potential adverse side effects of the procedure. Patients with recent onset of BRVO no more than 6 weeks previously were included in the study group if typical clinical signs of BRVO were present and BRVO was confirmed by fundus photography and fluorescein angiography. BRVO was classified as ischemic if nonperfused retinal areas of 5 or more disk diameters were detected in 50-degree fluorescein angiography [14] using the OIS WinStation (11KTM, CCS Pawlowski GmbH, Jena, Germany). Furthermore, a CME involving the fovea and a central macular thickness (CMT) of
