Non-Cancer Effects following Ionizing Irradiation Involving the Eye and Orbit

Abstract

The eye is an exemplarily challenging organ to treat when considering ocular tumors. It is at the crossroads of several major aims in oncology: tumor control, organ preservation, and functional outcomes including vision and quality of life. The proximity between the tumor and organs that are susceptible to radiation damage explain these challenges. Given a high enough dose of radiation, virtually any cancer will be destroyed with radiotherapy. Yet, the doses inevitably absorbed by normal tissues may lead to complications, the likelihood of which increases with the radiation dose and volume of normal tissues irradiated. Precision radiotherapy allows personalized decision-making algorithms based on patient and tumor characteristics by exploiting the full knowledge of the physics, radiobiology, and the modifications made to the radiotherapy equipment to adapt to the various ocular tumors. Anticipation of the spectrum and severity of radiation-induced complications is crucial to the decision of which technique to use for a given tumor. Radiation can damage the lacrimal gland, eyelashes/eyelids, cornea, lens, macula/retina, optic nerves and chiasma, each having specific dose-response characteristics. The present review is a report of non-cancer effects that may occur following ionizing irradiation involving the eye and orbit and their specific patterns of toxicity for a given radiotherapy modality.

Keywords: brachytherapy; ocular tumor; orbit; proton beam therapy; radiation-induced adverse events; radiotherapy; toxicities.

Figure 1

Radiotherapy techniques of and corresponding radar charts. (A) Brachytherapy is a conformal technique that does not deliver radiation dose outside the eye. The principle is to apply a radioactive isotope to the sclera that will deliver radiation over a short distance to the tissue. The plaque delivers a heterogeneous dose from the sclera to the apex of the tumor. (B) Conventional 3D radiotherapy delivers a uniform dose to the eye using 1 to 3 fields. Intensity-modulated radiotherapy (IMRT) uses 5 to 9 fields and a multileaf collimator, allowing complex concave radiation dose distribution. (C) Stereotactic beam radiotherapy (SBRT) delivers radiotherapy from many different positions around the organ so that the beams meet at the tumor. The tumor receives a high dose of radiation and the healthy tissues around it only a low dose. (D) Proton beam therapy (PBT) allows a very focused and high-dose volume of energy deposition due to the physical properties of protons. The energy is delivered with a sharp Bragg peak allowing preservation of surrounding tissues. Adapted from Mathis et al., 2019 [14].

Figure 2

Treatment of radiation-induced dry-eye syndrome.

Figure 3

Radiation retinopathy in a patient treated with plaque brachytherapy for choroidal melanoma; (A) Fluorescein angiography (FA) at baseline showing the localization of the melanoma close to the macular area; (B) FA at 2 years showing 2 retinal ischemic areas (white arrows); (C) FA at 3 years showing the enlargement of the foveal avascular zone and the increased surface of ischemic areas. Laser photocoagulation was partially performed.

Figure 4

Radiation-induced optic neuritis following proton beam irradiation of a juxtapapillary choroidal melanoma. (A) Treatment planning system (TPS) at baseline showing isodoses on fundus autofluorescence and color widefield retinography. Approximately 50% of the optic nerve was planned to receive the full radiation dose. (B) At 32 months after irradiation. Observation of optic disc swelling, hemorrhages and cotton wool spots; the tumor site is atrophic. Inset: enlarged view and fluorescein angiography confirming optic nerve edema.

Figure 5

Intraocular hemorrhage following proton beam therapy for choroidal melanoma; (A) Retinography at baseline before irradiation. (B) Retinography at 6 months after irradiation showing intratumoral bleeding and toxic tumor syndrome (inferior exudative retinal detachment). The patient refused any medical or surgical intervention. (C) Retinography at 9 months after irradiation showing subretinal bleeding and exudative retinal detachment. (D) Retinography at 12 months after irradiation showing total intravitreal bleeding.

Figure 6

Neovascular glaucoma in a patient treated with proton beam therapy for a large choroidal melanoma (12 mm in height and 20 mm in diameter).