Release of experimental retinal vein occlusions by direct intraluminal injection of ocriplasmin.
OBJECTIVE
Retinal vein occlusions (RVO) are a major cause of vision loss in people aged 50 years and older. Current therapeutic options limit the consequences of RVO but do not eliminate the cause. Cannulation of the involved vessel and removal of the clot may provide a more permanent solution with a less demanding follow-up. However, cannulation of smaller retinal veins remains challenging. This paper explores the use of ocriplasmin (recombinant plasmin without its kringles) to clear RVO, using a robotic micromanipulator.


METHODS
Branch RVO were induced in a porcine model with rose bengal followed by 532 nm endolaser to the superior venous branch of the optic nerve. The vein was cannulated proximal to the occlusion or beyond the first branching vessel from the obstruction. The vein was infused with a physiologic citric acid buffer solution (CAM) or CAM/ocriplasmin. The time of cannulation, number of attempts, and the ability to release the thrombus were recorded.


RESULTS
Cannulation and infusion was possible in all the cases. The use of a micromanipulator allowed for a consistent cannulation of the retinal vein and positional stability allowed the vein to remain cannulated for up to 20 min. In none of the attempts (5/5) with CAM did the thrombus dissolve, despite repeat infusion/relaxation cycles. In 7/7 injections of CAM/ocriplasmin near to the point of obstruction, the clot started to dissolve within a few minutes of injection. An infusion, attempted beyond the first venous branch point proximal to the clot, was unsuccessful in 2/3 attempts.


CONCLUSIONS
Ocriplasmin is effective in resolving RVO if injected close to the site of occlusion with the use of a micromanipulator.
MicroInvasive Ocular Surgery Center (MIOS sa), Lausanne, Switzerland.|Preceyes nv, Eindhoven, The Netherlands.
Marc D
http://orcid.org/0000-0002-9217-5603
MD
de Smet
Crystapharm bvba, Lubbeek, Belgium.
Jean Marie
JM
Stassen
Preceyes nv, Eindhoven, The Netherlands.
Thijs C M
TC
Meenink
Thrombogenics nv, Leuven, Belgium.
Tom
T
Janssens
Thrombogenics nv, Leuven, Belgium.
Valérie
V
Vanheukelom
Preceyes nv, Eindhoven, The Netherlands.
Gerrit J L
GJ
Naus
Preceyes nv, Eindhoven, The Netherlands.
Maarten J
MJ
Beelen
Thrombogenics nv, Leuven, Belgium.
Bart
B
Jonckx
D000818:Animals; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000008:administration & dosage*; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D007275:Injections, Intravenous; D010446:Peptide Fragments / Q000008:administration & dosage*; D012169:Retinal Vein; D012170:Retinal Vein Occlusion / Q000175:diagnosis / Q000188:drug therapy*; D012371:Robotics / Q000379:methods; D013552:Swine
D010446:Peptide Fragments; C054561:microplasmin; D005341:Fibrinolysin
Drugs; Experimental &#8211 animal models; Pharmacology; Retina; Treatment Surgery
Curr Eye Res. 2010 Oct;35(10 ):909-15
20858112
Acta Ophthalmol. 2008 May;86(3):245-52
18494725
Retina. 2009 Sep;29(8):1167-74
19734765
Invest Ophthalmol Vis Sci. 2009 Feb;50(2):814-9
18806295
Curr Eye Res. 2008 Apr;33(4):365-76
18398711
Graefes Arch Clin Exp Ophthalmol. 2008 Oct;246(10):1429-39
18642023
Retina. 2004 Aug;24(4):530-40
15300073
J Geriatr Oncol. 2014 Apr;5(2):204-18
24495695
Baillieres Clin Haematol. 1995 Jun;8(2):277-90
7549063
PLoS One. 2016 Sep 27;11(9):e0162037
27676261
Arch Ophthalmol. 1982 Jul;100(7):1132-40
6178389
J Thromb Haemost. 2010 Sep;8(9):1886-94
20492457
Science. 1980 May 30;208(4447):1036-7
6990488
J Thromb Haemost. 2003 Feb;1(2):307-13
12871505
Curr Eye Res. 2008 Feb;33(2):111-31
18293182
Graefes Arch Clin Exp Ophthalmol. 2014 Feb;252(2):257-65
24292703
Trans Am Ophthalmol Soc. 1981;79:371-422
7342407
Ophthalmology. 2007 Apr;114(4):716-23
17141322
Graefes Arch Clin Exp Ophthalmol. 2004 Mar;242(3):223-8
14685873
Retina. 2005 Jul-Aug;25(5):625-32
16077361
J Thromb Haemost. 2004 Sep;2(9):1617-21
15333039
Ophthalmology. 2010 Feb;117(2):313-9.e1
20022117
Retina. 1987;7(4):252-9
2448855
Cell Mol Life Sci. 2011 Mar;68(5):785-801
21136135
J Am Coll Cardiol. 2015 Apr 28;65(16):1683-99
25908074