Sequence of early vascular events after photodynamic therapy.
OBJECTIVE
To identify early vascular changes in choroidal neovascularization (CNV) and in adjacent normal choroid, after photodynamic therapy (PDT).


METHODS
In a prospective study, 40 patients with predominantly classic CNV due to age-related macular degeneration (AMD) were treated with PDT performed with verteporfin. Verteporfin was administered intravenously at a dose of 6 mg/m(2) body surface area. A near infrared laser light dose of 50 J/cm(2), an irradiance of 600 mW/cm(2) and a wavelength of 692 nm was applied. A scanning laser system was used to perform confocal fluorescein angiography (FA) and indocyanine green angiography (ICGA) before treatment and regularly at 5 hours, 1 day, 1 week, and 3 months after PDT. Images were analyzed for CNV size and leakage area as seen by FA and ICGA. Collateral damage within the surrounding choroid was documented based on the hypofluorescence in early- and late-phase ICGA.


RESULTS
No immediate occlusion of the CNV complex was found angiographically, but a dynamic change over time was observed in the early perfusion patterns and late-phase hyper- and hypofluorescence. At 5 hours after treatment, large portions of the CNV lesion were still perfused. One day after PDT, CNV size in early FA and early ICGA reached its minimum, at 0.49 mm(2) (15.7%) and 0.78 mm(2) (31.1%) of the initial area, respectively. In late-phase FA and ICGA, however, an immediate massive exudation with a continuous increase in hyperfluorescence originated from the CNV and surrounding choroid, with a maximum in leakage area at 1 day. At 1 week PDT-induced exudation slowly resolved. Eyes in 36 patients showed some choroidal hypofluorescence by ICGA before treatment. A progressive increase of the hypofluorescent area surrounding the CNV was observed, which correlated with the size of the laser spot. Maximum hypofluorescence was noted at 1 week with an average size of 11.1 mm(2) in early- and late-phase ICGA.


CONCLUSIONS
In contrast to findings in experimental animals, PDT in humans with classic CNV did not induce immediate thrombosis, but primarily caused a breakdown of vascular barriers. A characteristic sequence of vascular changes was observed with early, enhanced leakage from the CNV and normal choroid followed by nonperfusion later. Occlusion of the CNV lesions occurred 1 day after treatment, but closure of the adjacent choroidal vessels proceeded slowly over as long as 1 week.
Michels
Stephan
S
University Eye Hospital Lübeck, Lübeck, Germany. stmichels@web.de
Schmidt-Erfurth
Ursula
U
D002829:Choroid / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D004396:Coloring Agents; D005451:Fluorescein Angiography; D006801:Humans; D007208:Indocyanine Green; D008268:Macular Degeneration / Q000150:complications*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D011446:Prospective Studies; D000077362:Verteporfin
D004396:Coloring Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D007208:Indocyanine Green