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Intravitreale Fibrinolyse und retinaler Venenverschluss

Intravitreal fibrinolysis and retinal vein occlusion

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Zusammenfassung

Hintergrund

Ziel der vorliegenden Studie war es, verschiedene intravitreale Fibrinolyseparameter zu analysieren und zwischen Augen mit retinalem Zentralvenenverschluss (ZVV), retinalem Venenastverschluss (VAV) und einer Kontrollgruppe zu vergleichen. Die gefundenen Aktivitäten und Konzentrationen wurden mit der intravitrealen VEGF („vascular endothelial growth factor“)-Konzentration als Zeichen der Schwere der vorliegenden Blut-Retina-Schranken (BRS)-Störung korreliert.

Material und Methoden

Aus 14 Augen mit ZVV, 22 Augen mit VAV sowie 11 Kontrollaugen wurden Proben aus dem zentralen Glaskörper entnommen und auf die Aktivitäten bzw. Konzentrationen an Plasminogen, Plasmin-α2-Antiplasmin (PAP) und VEGF untersucht.

Ergebnisse

Die intravitrealen Aktivitäten/Konzentrationen lagen in der ZVV-/VAV-/Kontrollgruppe bei 2,07 ± 1,87 %/1,24 ± 1,12 %/0,38 ± 0,63 % für funktionelles Plasminogen, bei 8,14 ± 7,07 ng/ml/6,96 ± 4,8 ng/ml/9,74 ± 10,98 ng/ml für PAP und bei 1269 ± 1318 pg/ml/528 ± 543 pg/ml/105 ± 116 pg/ml für VEGF. Es zeigten sich signifikante Unterschiede in Bezug auf die intravitreale Plasminogenaktivität und VEGF-Konzentration zwischen den 3 Gruppen (jeweils p < 0,001). Die intravitreale Plasminogenaktivität korreliert mit der intravitrealen VEGF-Konzentration (r = 0,478, p = 0,001). Unerwünschte Nebenwirkungen oder schwerwiegende Komplikationen traten nicht auf.

Schlussfolgerung

Es bestehen signifikante Unterschiede zwischen der intravitrealen Plasminogenaktivität sowie der intravitrealen VEGF-Konzentration zwischen Augen mit ZVV, VAV und einer Kontrollgruppe. Die intravitreale Plasminogenaktivität ist direkt mit der Schwere der bestehenden BRS-Störung korreliert. Die genaue Kenntnis der intravitrealen Fibrinolyse kann neue therapeutische Ansätze in Augen mit einem retinalen Venenverschluss (RVO) eröffnen.

Abstract

Background

The aim of this study was to analyze and compare intravitreal activity and concentrations of different components of the fibrinolytic cascade in eyes with central retinal vein occlusion (CRVO) as well as branch RVO (BRVO) and healthy controls. These results were correlated with corresponding intravitreal vascular endothelial growth factor (VEGF) concentrations as a biomarker for the severity of blood-retina barrier (BRB) breakdown.

Material and methods

Vitreous samples were obtained from 14 eyes with CRVO, 22 eyes with BRVO and 11 controls and the activities and concentrations of plasminogen, plasmin-alpha2-antiplasmin (PAP) and VEGF were analyzed.

Results

Intravitreal activities and concentrations in the CRVO, BRVO and control groups were 2.07 ± 1.87 %, 1.24 ± 1.12 % and 0.38 ± 0.63 % for functional plasminogen, 8.14 ± 7.07 ng/ml, 6.96 ± 4.8 ng/ml and 9.74 ± 10.98 ng/ml for PAP while respective results for VEG levels were 1269 ± 1318 pg/ml, 528 ± 543 pg/ml and 105 ± 116 pg/ml, respectively. There were significant differences in intravitreal functional plasminogen and VEGF between the groups analyzed (in each case p < 0.001). Intravitreal functional plasminogen correlated with intravitreal VEGF concentrations (r = 0.478, p = 0.001). No adverse events or serious side effects occurred.

Conclusion

There were significant differences in intravitreal functional plasminogen and VEGF between eyes with CRVO, BRVO and controls. Intravitreal activity of plasminogen was significantly correlated with the severity of BRB breakdown in RVO affected eyes. The knowledge of intravitreal activities and concentrations of different components of the fibrinolytic cascade could offer new therapeutic strategies in RVO-affected eyes in the future.

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Finanzierung

Diese Studie wurde finanziell durch die Novartis Pharma AG, Nürnberg, unterstützt. Es bestand kein Einfluss auf die Konzeption, Durchführung und Auswertung der Studie.

Einhaltung ethischer Richtlinien

Interessenkonflikt. T. Bertelmann, T. Stief, W. Sekundo, M. Witteborn, S. Strodthoff, S. Mennel, N. Nguyen und M. Koss geben an, dass kein Interessenkonflikt besteht. Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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Authors and Affiliations

  1. Augenklinik, UKGM GmbH, Standort Marburg und der Philipps Universität Marburg, Baldingerstr., 35041, Marburg, Deutschland

    T. Bertelmann FEBO, W. Sekundo & S. Strodthoff

  2. Abteilung für Labormedizin und Pathobiochemie, molekulare Diagnostik, Philipps-Universität Marburg, Marburg, Deutschland

    T. Stief

  3. Zentrum Gesundheit, Leer, Deutschland

    M. Witteborn

  4. Abteilung für Augenheilkunde, Landeskrankenhaus Feldkirch, Feldkirch, Österreich

    S. Mennel

  5. Abteilung für Netzhaut- und Glaskörperchirurgie, Augenklinik, Goethe-Universität Frankfurt a. M., Frankfurt a. M., Deutschland

    N. Nguyen & M. Koss

Authors
  1. T. Bertelmann FEBO
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  2. T. Stief
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  3. W. Sekundo
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  4. M. Witteborn
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  5. S. Strodthoff
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  6. S. Mennel
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  7. N. Nguyen
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  8. M. Koss
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Corresponding author

Correspondence to T. Bertelmann FEBO.

Additional information

___ ___

Die Ergebnisse der vorliegenden Arbeit wurden auf dem 112. DOG-Kongress in Leipzig im September 2014 präsentiert.

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Bertelmann, T., Stief, T., Sekundo, W. et al. Intravitreale Fibrinolyse und retinaler Venenverschluss. Ophthalmologe 112, 155–161 (2015). https://doi.org/10.1007/s00347-014-3107-z

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