title: Wavelength and fluence effect on vascular damage with photodynamic therapy on skin.
abstract: Normal skin phototoxicity is clinically predictable during photodynamic therapy with light at 690 and 458 nm wavelengths, in the first 5 h after intravenous bolus infusion of benzoporphyrin derivative mono-acid ring A. This study goal was to determine histologic milestones that lead to tissue necrosis with exposure to red (690 nm) and blue (458 nm) light. The threshold doses for skin necrosis on rabbits were equal at both wavelengths. Lower, equal to, and higher than threshold fluences were delivered in duplicates at hourly intervals, with 40% increments, at constant irradiance. Pathology specimens from irradiated and control sites, were collected at 0, 2, 7, 24, 48 h, and 2 wk after treatment and were paired to equivalent treated sites for clinical evaluation. Immediately after irradiation, at 690 and 458 nm thresholds, light microscopy showed stasis and inflammatory infiltrate in the papillary dermis, respectively; electron microscopy demonstrated pericyte and endothelial cell damage - greater at 690 than 458 nm. At day 1, vascular stasis in the dermis showed a steeper dose-response with red than blue light, and led to necrosis of skin appendages (day 1) and epidermis (days 1-2) at both wavelengths. Sub-threshold fluences induced similar, but significantly milder (p < 0.05) changes and epidermis recovered. Skin necrosis, at threshold fluences in photodynamic therapy with benzoporphyrin derivative mono-acid ring A, was primarily due to vascular compromise to a depth potentially reaching the subcutaneous muscle at 690 nm, whereas at 458 nm vascular damage was confined to upper dermis. This system facilitates selective destruction of skin vasculature, sparing normal epidermis.
authors.affiliation: Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Tsoukas
authors.forename: S
authors.initials: S
authors.lastname: González
authors.forename: T J
authors.initials: TJ
authors.lastname: Flotte
authors.forename: R R
authors.initials: RR
authors.lastname: Anderson
authors.forename: M E
authors.initials: ME
authors.lastname: Sherwood
authors.forename: N
authors.initials: N
authors.lastname: Kollias
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D009336:Necrosis; D010778:Photochemotherapy; D011693:Purpura / Q000188:drug therapy*; D011817:Rabbits; D012867:Skin / Q000098:blood supply*; D012871:Skin Diseases / Q000473:pathology; D014652:Vascular Diseases / Q000188:drug therapy*