Histopathological changes following photodynamic therapy in human eyes
Schlötzer-Schrehardt U., Viestenz A., Naumann G. O. H., Laqua H., Michels
S.,
Schmidt-Erfurth U.
Departments of Ophthalmology, University Erlangen-Nürnberg and University
of Lübeck
Objective: To determine the effects of photodynamic therapy (PDT)
on choroidal and retinal structures of human eyes.
Methods: Three eyes of three patients with large malignant melanomas
of the uvea planned for enucleation received PDT using verteporfin (Visudyne)
in unaffected chorioretinal areas. Two laser spots and two light doses
(50J/cm2 and 100 J/cm2) were applied according to the approved treatment
recommendations in patients with age-related macular degeneration. Characteristic
hypofluorescent areas were seen by fluorescein as well as indocyanine
green angiography. Enucleation was performed one week later. The globes
were fixed in buffered paraformaldehyde/glutaraldehyde solution, bisected
along the laser spots, and processed for light and electron microscopy.
Results: PDT-treated areas showed occlusion and degenerative alterations
of the choriocapillaris as compared to untreated areas. Vascular alterations
comprised swelling, shrinkage and fragmentation of endothelial cells,
detachment from their basement membrane up to complete degeneration of
the endothelial lining, and complete occlusion of capillary lumina by
fibrin, thrombocytes, and cellular debris. Granulocytes and macrophages
were found to accumulate in the periphery of degenerated vessels. Remaining
intact endothelial cells appeared to reorganize into novel smaller vascular
channels. Degenerative changes of deeper choroidal vessels and focal vacuolar
degeneration of the retinal pigment epithelium could be observed in the
100 J/cm2, but not in the 50 J/cm2 treated areas. The overlying photoreceptor
layer appeared intact in all PDT areas.
Conclusion: PDT at a dosage used clinically induces selective alterations
of vascular endothelial cells of the choriocapillary layer leading to
vasoocclusion and thrombosis of normal choriocapillaris, but repair mechanisms
and recanalization of physiological choroid are observed as early as one
week following PDT. Significant alterations of the retinal pigment epithelium
and neural retina do apparently not occur.
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