Video monitoring of neovessel occlusion induced by photodynamic therapy with verteporfin (Visudyne®), in the CAM model

The aim of the present study was to monitor photodynamic angioocclusion with verteporfin in capillaries. Details of this process were recorded under a microscope in real-time using a high-sensitivity video camera. A procedure was developed based on intravenous (i.v.) injection of a light-activated drug, Visudyne®, into the chorioallantoic membrane (CAM) of a 12-day-old chicken embryo. The effect of light activation was probed after 24 h by i.v. injection of a fluorescent dye (FITC dextran), and analysis of its fluorescence distribution. The angioocclusive effect was graded based on the size of the occluded vessels, and these results were compared with clinical observations. The time-resolved thrombus formation taking place in a fraction of the field of view was video recorded using a Peltier-cooled CCD camera. This vessel occlusion in the CAM model was reproducible and, in many ways, similar to that observed in the clinical use of verteporfin. The real-time video recording permitted the monitoring of platelet aggregation and revealed size-selective vascular closure as well as some degree of vasoconstriction. Platelets accumulated at intravascular junctions within seconds after verteporfin light activation, and capillaries were found to be closed 15 min later at the applied conditions. Larger-diameter vessels remained patent. Repetition of these data with a much more sensitive camera revealed occlusion of the treated area after 5 min with doses of verteporfin and light similar to those used clinically. Consequently, newly developed light-activated drugs can now be studied under clinically relevant conditions

Submacular predominantly hemorrhagic choroidal neovascularization: resolution of bleedings under anti-VEGF therapy

Spyridon Dimopoulos, Martin Alexander Leitritz, Focke Ziemssen, Bogomil Voykov, Karl Ulrich Bartz-Schmidt, Faik Gelisken Centre for Ophthalmology, Eberhard-Karls University, Tuebingen, Germany Purpose: To report the visual and morphological outcomes following intravitreal bevacizumab in neovascular age-related macular degeneration (nAMD) with submacular, predominantly hemorrhagic, lesions.Methods: Retrospective study of patients with a follow-up after 1 year. All eyes with submacular hemorrhages larger than 50% of the total lesion size and received only anti-VEGF (vascular endothelial growth factor) monotherapy (intravitreous administration of 1.25 mg bevacizumab, PRN). The primary endpoint was the change in hemorrhage size and time to resolution, in association with the mean best-corrected visual acuity (BCVA). The eyes were grouped based on the size of the hemorrhage: group A (≥1 to <4 disc area [DA]), group B (≥4 to <9 DA), and group C (≥9 DA).Results: Forty-six consecutive eyes were included. The mean area of the hemorrhage was 6 DA at baseline. Eyes with smaller bleeding (group A) had better chances of stabilized or improved vision. Complete resolution of the hemorrhage was seen in 96% of the eyes within 1 year. The mean BCVA increased from 0.81 logarithm of the minimum angle of resolution (logMAR) (95% confidence interval [CI]: 0.70–0.92) (Snellen 20/125) at baseline to 0.75 logMAR (95% CI: 0.62–0.88) (20/125) after 1 year (P=0.11). BCVA improved (one or more ETDRS [Early Treatment of Diabetic Retinopathy Study] lines) in 57% of the eyes (13/23) in group A; 53% (8/15) in group B; and 38% (3/8) in group C.Conclusion: Many of the eyes with hemorrhagic lesions showed stabilization or improvement of the mean BCVA after treatment within 1 year. Anti-VEGF treatment can be considered as a useful treatment option in eyes with hemorrhages secondary to nAMD. Keywords: age-related macular degeneration, bevacizumab, submacular hemorrhag