## 4 Discussion
Early detection and treatment of intraocular inflammation after radiotherapy is crucial since, if misdiagnosed, such a complication may result in secondary enucleation, even in the absence of tumor recurrence [34]. Uveitis may affect the anterior segment (iritis), the ciliary body (cyclitis), the posterior segment (choroiditis), or the whole uveal layer (panuveitis). In this last case, MRI may reveal a thickening of the anterior segment and the posterior aspect of the globe, associated with conspicuous enhancement on fat-suppressed T1-weighted images acquired after contrast agent administration [35]. In endophthalmitis the inflammatory process causes an increase in the protein content of the vitreous body and anterior chamber, due to leakage from retinal and choroidal vessels [35]. These vitreous changes are easily detectable in the form of increased signal intensity on unenhanced T1-weighted sequences, and also on T2-weighted FLAIR sequences commonly used in the brain MR protocol. On the other hand, vitreous alterations are less visible on contrast-enhanced T1-weighted sequences (because of modifications of the MR dynamic range induced by gadolinium) and hardly detectable on T2-weighted images. Uveitis and endophthalmitis can coexist, and may also be associated with choroidal and retinal detachment [35]. It has been hypothesized that in the pathogenesis of radiation-related inflammation, tumor necrosis plays a relevant role through the release of proinflammatory cytokines [34]. This assumption is consistent with our series; in the patient showing the most severe inflammatory complications, with concomitant panuveitis and endophthalmitis, the choroidal melanoma was wholly replaced by necrosis without appreciable neoplastic tissue. This patient underwent secondary enucleation four years after proton beam radiotherapy. In this case, at gross examination, the eyeball was surrounded by pus, and the posterior chamber showed necrotic-hemorrhagic content. Under MRI the edematous thickening of the periocular tissues displayed high signal intensity on fat-suppressed T2-weighted (STIR) images, restricted diffusion on DW images, and marked enhancement on contrast-enhanced fat-suppressed T1-weighted images. Moreover, the last sequence excellently demonstrated the diffuse thickening and enhancement of the detached choroid. The alterations to the anterior chamber and vitreous body, typically seen in endophthalmitis, were better demonstrated on unenhanced T1-weighted sequences. Chronic conjunctivitis is a rather common complication following proton beam radiotherapy, and is related both to the direct action of radiation on the conjunctival epithelium, and to changes in the tear film caused by the treatment [36]. In one enucleated eye of our series, at the histologic examination, we observed an evident (sub)-conjunctival inflammatory infiltrate consistent with chronic conjunctivitis. Following MR this alteration was clearly detectable only on fat-suppressed T1-weighted sequences acquired after contrast medium administration, which showed a conspicuous enhancement and thickening of the conjunctiva of the treated eye. On the other hand, these findings were hardly or not at all perceptible on T2-weighted and plain T1-weighted sequences. Vitreous hemorrhage is observable in about 8% of patients treated with proton beam radiotherapy. It is less common after proton beam radiotherapy than after brachytherapy. In cases of recurrent vitreous hemorrhage, enucleation can be indicated because of the impossibility of performing a correct fundoscopic evaluation during follow-up [37]. The composition of the vitreous body (acellular fluid with 99% water content) explains its physiological water-like appearance under MRI [38]. In our series, vitreous hemorrhage occurred in 2/9 patients; in identifying this alteration, T1-weighted sequences performed better than T2-weighted ones, due to T1 shortening provided by subacute blood products (methemoglobin).