Proton beam therapy and iris neovascularisation in uveal melanoma.
OBJECTIVE
Local treatment of uveal melanoma by radiotherapy involves the use of brachytherapy with radioactive plaques attached to the sclera, or proton irradiation. Both treatments induce growth arrest within the tumour and its slow involution over several years. Although ocular retention rates are excellent, regrowth of tumours due to resistance and neovascular glaucoma leads to enucleation of up to 10% of affected eyes. Proton irradiation involves part of the iris in most cases and we noticed that neovascularisation only occurred in the part of the iris that was not irradiated. We therefore conducted this study to determine the relationship between the development of iris neovascularisation and iris irradiation.


METHODS
A total of 21 enucleation specimens from patients who had previously had proton irradiation were collected from the files of the Department of Pathology, Moorfields Eye Hospital during the 5-year period from 1994 to 1999. Sections of these eyes were assessed for VEGF-A, bFGF, and von Willebrand Factor (vWF) by immunohistochemistry. Ophthalmic notes and radiotherapy records were reviewed to assess the extent of iris irradiation.


RESULTS
In all, 11 cases showed clinical evidence of iris neovascularisation and were selected for further study. Three of these eyes also showed clinical evidence of regrowth of the tumour. Histological evidence of iris neovascularization was noted in all 11 of the eyes examined, and was only present in the nonirradiated side of the iris in 8/11 eyes. NVI was present on both sides of the iris in three cases, but was less severe in the irradiated part. Expression of VEGF-A was at most weak within the tumour, but was present in the detached retina and in the epithelium of both ciliary body and iris. Some bFGF staining was noted around vessels in the iris stroma.


CONCLUSIONS
Our results suggest that irradiation leads to iris atrophy, and that atrophic, irradiated iris is resistant to the development of neovascularisation.
Boyd
S R
SR
Department of Pathology, Institute of Ophthalmology, University College London, London, UK.
Gittos
A
A
Richter
M
M
Hungerford
J L
JL
Errington
R D
RD
Cree
I A
IA
D000328:Adult; D000368:Aged; D001284:Atrophy; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007498:Iris / Q000098:blood supply* / Q000473:pathology / Q000528:radiation effects; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000532:radiotherapy*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000473:pathology; D061766:Proton Therapy; D011882:Radiotherapy, High-Energy; D012189:Retrospective Studies; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D016222:Fibroblast Growth Factor 2