Long-term blood vessel removal with combined laser and topical rapamycin antiangiogenic therapy: implications for effective port wine stain treatment

Abstract

Background and objectives: Complete blanching of port wine stain (PWS) birthmarks after laser therapy is rarely achieved for most patients. We postulate that the low therapeutic efficacy or treatment failure is caused by regeneration and revascularization of photocoagulated blood vessels due to angiogenesis associated with the skin's normal wound healing response. Rapamycin (RPM), an antiangiogenic agent, has been demonstrated to inhibit growth of pathological blood vessels. Our objectives were to (1) investigate whether topical RPM can inhibit reperfusion of photocoagulated blood vessels in an animal model and (2) determine the effective RPM concentration required to achieve this objective.

Study design/materials and methods: For both laser-only and combined laser and RPM treated animals, blood vessels in the dorsal window chambers implanted on golden Syrian hamsters were photocoagulated with laser pulses. Structural and flow dynamics of blood vessels were documented with color digital photography and laser speckle imaging to evaluate photocoagulation and reperfusion. For the combined treatment group, topical RPM was applied to the epidermal side of the window daily for 14 days after laser exposure.

Results: In the laser-only group, 23 out of 24 photocoagulated blood vessels reperfused within 5-14 days. In the combined treatment group with different RPM formulae and concentrations, the overall reperfusion rate of 36% was much lower as compared to the laser-only group. We also found that the reperfusion rate was not linearly proportional to the RPM concentration.

Conclusions: With topical RPM application, the frequency of vessel reperfusion was considerably reduced, which implies that combined light and topical antiangiogenic therapy might be a promising approach to improve the treatment efficacy of PWS birthmarks.

Figures

Fig. 1

A window preparation without any intervention. Although development of granulation tissue hindered the field of view in the reflectance images, there was no significant change in vessel structure and flow dynamics as shown in the transilluminated images and LSI flow maps. [Figure can be viewed in color online via www.interscience.wiley.com.]

Fig. 2

The reflectance image (a) and LSI flow map (b) of a DWC were shown. Blood vessel photocoagulation was induced by laser pulses (5 pulses, 26 Hz, 3 J/cm2 per pulse) (b,f). However, vascular regeneration and reperfusion around the irradiated were seen on Day 7 (c,g) and the irradiated blood vessels reperfused on Day 14 (d,h). Black arrow: arteriole; white arrow: venule. [Figure can be viewed in color online via www.interscience.wiley.com.]

Fig. 3

A DWC treated with combined laser irradiation and 1% topical RPM cream (first formula). Reflectance image and LSI flow map before laser irradiation (a,e). Intense photocoagulation was induced by laser pulses (5 pulses, 26 Hz, spot 1–3:3 J/cm2 per pulse; spot 4–5: 4 J/cm2 per pulse) (b,f). The window was erythematous and small blood vessels were seen on Day 7 (c,g). Reperfusion of most coagulated blood vessel was not observed on Day 14 (d,h). [Figure can be viewed in color online via www.interscience.wiley.com.]

Fig. 4

Reperfusion rates of the coagulated blood vessels on Day 14 for laser only, laser+vehicle and combined treatment groups. F1: first formula; F2: second formula; error bar: median absolute deviation.