title: Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes.
abstract: OBJECTIVE
  To determine the effects of photodynamic therapy (PDT) on choroidal and retinal structures of human eyes.
  
  
  METHODS
  One eye from each of three patients with large malignant melanomas of the uvea destined for enucleation received PDT using verteporfin according to the approved treatment recommendations for patients with age-related macular degeneration. Two laser spots and two light doses (50 J/cm(2) and 100 J/cm(2)) were applied in unaffected chorioretinal areas. The effects of PDT were assessed by fluorescein and indocyanine-green angiography. The eyes were enucleated 1 week later, fixed in buffered paraformaldehyde/glutaraldehyde solution, bisected along the laser spots, and processed for light and electron microscopy.
  
  
  RESULTS
  In agreement with the clinical angiographic findings of hypofluorescence, a rather selective occlusion of the choriocapillary layer was observed in the 50-J/cm(2) PDT areas, whereas the 100-J/cm(2) PDT areas additionally revealed closure of deeper choroidal vessels and focal alterations of the retinal pigment epithelium. The overlying neurosensory retina, including photoreceptors and retinal capillaries, was well preserved in all PDT areas. Electron microscopy showed that alterations of the choriocapillary endothelium comprised swelling, shrinkage and fragmentation of endothelial cells, detachment from their basement membrane up to complete degeneration of the endothelial lining, leading to platelet aggregation, degranulation, and thrombus formation. Complete occlusion of capillary lumina by fibrin, thrombocytes, and cellular debris was observed. Remaining intact endothelial cells appeared to be reorganized into novel smaller vascular channels within occluded lumina.
  
  
  CONCLUSIONS
  PDT with verteporfin at a dosage used clinically induces selective occlusion of the physiological choriocapillaris without affecting deeper choroidal, retinal, and optic nerve vessels or the overlying retinal pigment epithelium and neurosensory retina. The main mechanism of action appears to be vascular thrombosis induced by cytotoxic damage of endothelial cells and platelet activation. An increase in light dose enhances the occlusive effect with thrombosis within deeper choroidal layers and damage to the retinal pigment epithelium. However, photoreceptors remained intact at all light doses used.
authors.affiliation: Department of Ophthalmology, University Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany. ursula.schloetzer@augen.imed.uni-erlangen.de
authors.forename: Ursula
authors.initials: U
authors.lastname: Schlötzer-Schrehardt
authors.forename: Arne
authors.initials: A
authors.lastname: Viestenz
authors.forename: Gottfried O H
authors.initials: GO
authors.lastname: Naumann
authors.forename: Horst
authors.initials: H
authors.lastname: Laqua
authors.forename: S
authors.initials: S
authors.lastname: Michels
authors.forename: Ursula
authors.initials: U
authors.lastname: Schmidt-Erfurth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000473:pathology; D002196:Capillaries / Q000187:drug effects / Q000648:ultrastructure; D002829:Choroid / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D007208:Indocyanine Green; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D011446:Prospective Studies; D012160:Retina / Q000187:drug effects* / Q000648:ultrastructure; D012171:Retinal Vessels / Q000187:drug effects / Q000648:ultrastructure; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077362:Verteporfin
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D007208:Indocyanine Green