## 4 Treatment and Management
### Proton Beam and Plaque Radiotherapy  
In cases of non-resectable iris melanoma, proton-beam radiotherapy offers excellent local tumor control [6; 32; 33], particularly in the diffuse form, and because of the scant alternatives, it offers an acceptable rate of complications, preserving visual function in most patients during follow-up [33] (Figure 1).  
Proton-beam therapy is a form of highly collimated external-beam radiotherapy that uses protons rather than X-rays. Proton beam therapy is characterized by precise dose delivery to the tumor through the cornea [33]. In plaque radiotherapy, a radioactive disc is sutured for a certain amount of time on the surface of the globe for the radiation of the iris melanoma through the cornea [4; 31]; it can be delivered without prior resection or after the resection of a high degree of a malignant iris melanoma, or when tumor cells reach the margin of the resection specimen [17]. In a review of 17 studies comprising a total of 761 eyes, [PERSON] et al. compared outcomes following the radiotherapeutic and surgical management of iris melanoma, with a particular focus on common complications, local tumor recurrence and metastases [1]. They reported that more tumors are treated with radiotherapy (with proton-beam therapy at 49.4% and plaque radiotherapy at 31.4% of the total) compared to surgical excision (19.2%). Rates of local recurrence (with a range of 0-8%) and metastatic development (0-5%) are favorable after proton-beam therapy and plaque radiotherapy. They also showed that the most common complications were cataract (36-73%) and glaucoma (3-92%) [1]. The exact etiology of elevated IOP after treatment appears to be a combination of both tumor seeding into the angle and radiation effects on the angle structures (increased pigmentation with open configuration, angle closure and neovascularization in a minority of cases) [1]. Glaucoma filtration procedures should not be performed in this setting in the case of a possible iris melanoma, as they might lead to the seeding of the tumor cells and metastasis [4].  
As opposed to choroidal melanoma [34; 35], no radiation maculopathy, papillopathy, vitreous hemorrhage or corneoscleral necrosis or chronic degeneration are observed. According to [PERSON] et al., no eyes require enucleation from complications of radiotherapy [4]. Proton-beam therapy and plaque radiotherapy are both able to treat all iris melanomas, even diffuse forms or those presenting angle seeding, and do not show side effects related to surgery [1]. Some centers prefer proton-beam  
Figure 1: Iris melanoma before proton-beam therapy (**A,C**), Ultrasound Bio Microscopy (UBM) of iris melanoma before proton-beam therapy, with a size of \(5.9\times 4.4\) mm. (**B,D**). Iris melanoma 6 months after proton-beam therapy (**E,G**), UBM of iris melanoma 6 months after proton-beam therapy with a size of \(5.3\times 4.1\) mm (**F,H**).  
radiotherapy as a first-line treatment, even for small and circumscribed tumors that might be treated with surgical excision [1].  
To summarize (as shown in Table 1), plaque radiotherapy and proton-beam radiotherapy show similar rates of recurrence and metastasis, but plaques are more widely diffuse and costs are considerably reduced [1]. Limbal stem cells or corneal epithelial/endothelial cell damage may occur after radiant or surgical treatments [1]. Proton-beam and plaque radiotherapy show rates of cataract and glaucoma development that are generally higher after treatment compared to surgical excision [1]. Finally, if radiotherapy is not possible because of diffusely growing or overly large tumors, enucleation may be required.