Effects of radiotherapy on uveal melanomas and adjacent tissues

Abstract

Most uveal melanomas are treated with radiotherapy. An adequate understanding of the effects of radiation on the tumour and the healthy ocular tissues is necessary. Ionizing radiation damages cell membranes, organelles, and DNA. Irradiated cells are lysed or undergo apoptosis, necrosis, and senescence. These effects occur in tumour cells and vascular endothelial cells, resulting in tumour shrinkage, ischaemia, infarction, exudation, and fibrosis, which can cause exudative maculopathy, serous retinal detachment, rubeosis, and neovascular glaucoma (ie, 'toxic tumour syndrome'). Such abnormalities must be distinguished from collateral damage to healthy ocular tissues that receive high doses of radiation, and these include radiation-induced retinopathy, optic neuropathy, choroidopathy, cataract, and scleral necrosis. Radiation retinopathy can be treated effectively with photodynamic therapy, anti-angiogenic agents, and intravitreal steroid injections. In some patients, optic neuropathy may improve with intravitreal steroids or anti-angiogenic agents. Neovascular glaucoma resolves with intra-cameral bevacizumab. Exudative retinal detachment can regress with intra-vitreal steroid injections. Cataract is treated in the usual manner. Scleral necrosis, if severe, may require grafting, possibly using a lamellar flap from the same eye. Depending on the bulk of the residual toxic tumour, treatment can consist of intra-vitreal steroids and/or anti-angiogenic agents, transpupillary thermotherapy or photodynamic therapy to the tumour, or surgical removal of the tumour by endo- or exo-resection. Measures aimed at preventing collateral damage include eccentric placement of ruthenium plaques or iodine seeds and delivery of a notched proton beam. The decision to treat a uveal melanoma with radiotherapy requires the ability to manage iatrogenic side effects and complications.

Figure 1

Colour photograph showing radiation-induced maculopathy 1.5 years after ruthenium-106 plaque brachytherapy of a choroidal melanoma (a). Fluorescein angiogram showing an abnormal perifoveolar capillary network with early views defining leaking microaneurysms (b) and late views demonstrating leakage causing the characteristic petaloid pattern of cystoid macular oedema (c).

Figure 2

Colour photographs showing radiation retinopathy with cotton-wool spots and retinal haemorrhages (a) and optic neuropathy, with optic nerve oedema and peripapillary exudates (b). Both photographs were taken 2 years after proton beam radiotherapy for choroidal melanoma.

Figure 3

Fundus photograph showing macular exudates after plaque radiotherapy of a choroidal melanoma in the left eye (a). OCT scan showed marked cystoid macular oedema, which reduced the visual acuity to 6/60 (b). OCT scan 1 month after an intravitreal injection of bevacizumab, showing significant anatomic improvement (c). The visual acuity improved to 6/36.

Figure 4

Preventative strategies of radiation-induced complications. Colour photograph of the right fundus 2 years after brachytherapy of a choroidal melanoma with eccentric ruthenium-106 plaque placement (ai). The visual acuity was 6/6 with no signs of macular oedema on the OCT (aii) Proton beam treatment plan showing a notch to reduce irradiation of the optic nerve (b).

Figure 5

Severe exudation after proton beam radiotherapy of a choroidal melanoma in the left eye (a). The visual acuity was counting fingers. Resolution of the exudation after endoresection of the toxic tumour (b).