Evaluation of ultrasound-assisted thrombolysis using custom liposomes in a model of retinal vein occlusion

Abstract

Purpose: To study the potential efficacy of ultrasound (US) assisted by custom liposome (CLP) destruction as an innovative thrombolytic tool for the treatment of retinal vein occlusion (RVO).

Methods: Experimental RVO was induced in the right eyes of 40 rabbits using laser photothrombosis; the US experiment took place 48 hours later. Rabbits were randomly divided into four equal groups: US+CLP group, US+saline group, CLP+sham US group, and no treatment group. The latter three groups acted as controls. Fundus fluorescein angiography and Doppler US were used to evaluate retinal blood flow.

Results: CLP-assisted US thrombolysis resulted in restoration of flow in seven rabbits (70%). None of the control groups showed significant restoration of retinal venous blood flow.

Conclusions: US-assisted thrombolysis using liposomes resulted in a statistically significant reperfusion of retinal vessels in the rabbit experimental model of RVO. This approach might be promising in the treatment of RVO in humans. Further studies are needed to evaluate this approach in patients with RVO. Ultrasound assisted thrombolysis can be an innovative tool in management of retinal vein occlusion.

Figure 1.

Fundus fluorescein angiographic images of a rabbit in the US+CLP group. Baseline imaging (A) shows normal retinal venous filling. Post laser imaging (B) shows no flow in a segment of the temporal retinal vein but retrograde filling from venous tributaries (indicates partial venous occlusion). Final imaging after CLP-enhanced US thrombolysis (C) shows return of flow in the occluded retinal vein and complete retinal venous filling.

Figure 2.

Fundus photography and fundus fluorescein angiogram of a rabbit in the US+CLP group with partial venous occlusion pattern. Baseline imaging shows normal retinal vessels in color photograph (A), early arterial flow shows up at 8 seconds (B), and when retinal venous filling is complete (C). Post laser imaging shows no flow in the nasal and temporal retinal veins in a small segment at the edge of the optic disc (D, E), while the remaining retinal veins fill late by collaterals (F). Black arrows point to the site of laser application. Final imaging after US experiment shows modest return of flow in the partially occluded retinal veins with complete filling by 22 seconds (G, H, I). White arrows point to filling of the previously occluded venous segment.

Figure 3.

Fundus photographs and fundus fluorescein angiogram of a rabbit in the US+saline group. Images (A, B, C) represent those taken before laser photothrombosis, while (D, E, F) represent the images taken 48 hours after retinal vein occlusion, and (G, H, I) represent images taken at the end of therapeutic US application. Arrows in (D) and (F) point to site of laser application. Note the non filling of the proximal segment of the laser-treated retinal veins and the absence of filling after US application. The distal segments of these veins fill from collaterals.

Figure 4.

Graph shows the mean retinal venous blood velocity as measured before LPT (baseline), post laser, and after the US experiment (after treatment). Only the US+CLP group showed statistically significant improvement of blood flow at the end of the US experiment. *Refers to P < 0.05 with statistical significance

Figure 5.

Spectral Doppler imaging of a rabbit in the US+CLP group shows no recordable retinal venous blood flow as measured from the retinal surface (A), while after CLP-enhanced US thrombolysis, retinal venous blood flow in the treated vein is restored, and the calculated average blood velocity is 1.0 cm/s (B).