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Purpose: To analyze the risk factors for the development of neovascular glaucoma (NVG) of patients with choroidal melanoma after proton beam therapy (PBT)., Method: Clinical case series, retrospective study. We evaluated 629 consecutive patients receiving proton beam therapy for the treatment of a choroidal melanoma at the oncology service at Charité, Berlin and Helmholtz-Zentrum, Berlin between 05/1998 and 11/2008 regarding the development and risk factors of NVG. Patients with tumor resection, salvage proton beam therapy for recurrent disease and known glaucoma of other origin were excluded from the cohort., Results: Of the 629 patients matching the inclusion criteria, 20.8% developed neovascularization of the iris after a mean time of 2.0 years (range 0.45 to 8.4 years) after PBT. Forty-seven percent of the patients with a neovascularization of the iris developed NVG after a mean time of 2.0 years after PBT, ranging from 5 months to 11.6 years. Univariate analysis revealed tumor height [p < 0.001, hazard ratio (HR): 2.71, 95% confidence interval (CI): 1.36-5.35 for tumors >6 mm ≤9 mm and 11.32 (4.03-31.73) for tumors >9 mm], distance of the tumor to the optic disc (p < 0.001, HR: 0.43, 95% CI: 0.24-0.77 for >0 mm ≤3 mm and HR: 0.13, 95% CI: 0.04-0.37 for >3 mm), dose to the ciliary body (p < 0.001, HR: 9.21, 95% CI: 5.08-16.71 (21-40 cobalt gray equivalents (CGE), HR 27.23, 95% CI: 6.33-116.97 (41-60 CGE)), dose to the optic disc (p < 0.001, HR: 3.53, 95% CI: 1.11-11.27 (21-40CGE), HR: 5.37, 95% CI: 2.72-10.63 (41-60CGE)), the irradiated length of the optic nerve (p < 0.001, HR: 4.48, 95% CI: 2.47-8.13) and diabetes mellitus (p < 0.05, HR: 2.53, 95% CI: 1.4-4.5) were found to be risk factors for the development of NVG. Multivariate regression analysis identified the dose to the ciliary body [p < 0.001, HR: 4.39, 95% CI: 2.28-8.44 (21-40 CGE), HR: 11.04, 95% CI: 1.97-61.69 (41-60 CGE)], the irradiated length of the optic nerve (p < 0.001, HR: 3.88, 95% CI: 2.11-7.16), the existence of diabetes mellitus (p < 0.01, HR: 1.28, 95% CI: 1.24-4.21) and tumor height [p < 0.05, HR: 2.28, 95% CI: 1.17-4.83 (>6 mm ≤9 mm), HR: 3.74, 95% CI: 1.05-13.23, (>9 mm)] to be independent risk factors for the development of NVG., Conclusions: In the present analysis we found tumor height, dose to the ciliary body, irradiated length of the optic nerve and diabetes mellitus to be risk factors for the development of NVG. Whenever possible, critical structures of the anterior and posterior segment should be spared by beam shaping or changing of the beam entry angle.

Purpose: This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures., Design: Retrospective cohort study., Methods: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included., Results: A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years)., Conclusion: This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To evaluate long-term outcomes of proton beam radiotherapy in the treatment of choroidal melanoma of the intermediate zone of the fundus., Design: Retrospective interventional single-center study., Methods: The study was a retrospective analysis with long-term follow-up of 62 patients with a minimum tumor-to-disc and tumor-to-fovea distance of 2 mm of choroidal melanoma in the intermediate zone of the fundus. Mean values of tumor prominence, largest basal diameter, and tumor distances to the optic disc and fovea were 7.6, 12.8, 5.2, and 4.6 mm, respectively. All patients were irradiated with a total proton dose of 60 cobalt gray equivalents., Results: After proton beam radiotherapy, 71.0% of the patients received subsequent endoresection of the tumor. Only 18 patients (29.0%) did not require additional tumor resection and were analyzed as a separate group. For the total of patients, the median follow-up time was 70.3 months. The 5-year Kaplan-Meier rates of local tumor relapse, enucleation, and distant metastasis were 3.9%, 3.7%, and 13.4%, respectively. Cataract surgery was the most frequent secondary treatment in our cohort., Conclusions: In this study we demonstrate the effectiveness of proton beam irradiation in tumor control and preservation of the globe in the analyzed patients. The rate of metastasis was not higher than previously described. Nevertheless, consecutive tumor surgery is frequently required to maintain the eye in patients with large-sized choroidal melanomas. In conclusion, proton beam radiotherapy allows preservation of the eye in mid-zone choroidal melanomas., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The aim of this retrospective study was to determine the efficacy of proton beam irradiation in choroidal hemangioma in a long-term follow-up., Patients and Methods: A total dose of 20 Cobalt Gray equivalent (CGE) was administered to 50 eyes of 50 patients from September 1998 to September 2010. All treated patients presented with a symptomatic tumor. Nine patients were pre-treated by photodynamic therapy (PDT). Visual outcome, tumor regression, and complications resulting from radiation were investigated., Results: The mean follow-up was 55.4 months (range 13-132). Tumor thickness decreased in all patients. Retinal re-attachment was achieved without evidence of tumor leakage. Visual acuity improved by two lines after one year in 43.4 % of patients and after two years in 36.8 % of patients. During the 55.4 months of long-term follow-up the visual acuity improved from 6/15 to 6/12 after proton therapy. Twenty-three patients (46.0 %) developed radiation retinopathy. According to the Finger classification of 2004, 21 patients (42.0 %) showed a stage 1 or 2 (functionally not relevant) retinopathy, and two patients (4.0 %) presented a stage 3 or 4 (functionally relevant) retinopathy. Further complications included sicca syndrome in nine cases, cataract formation in 10 cases, and radiation optic neuropathy in four cases., Conclusion: Proton therapy with 20 CGE is an efficient primary therapy in choroidal hemangioma and is very effective as a secondary treatment after PDT.

Purpose: To analyze the functional outcome with regard to the development of visual acuity and radiation-induced optic neuropathy of patients with parapapillary choroidal melanoma treated with proton beam therapy., Design: Clinical case series, retrospective study., Methods: We evaluated 147 consecutive patients with parapapillary choroidal melanoma who received proton beam therapy as primary tumor treatment at the Helmholtz Center in Berlin from 1998 to 2005. A cumulative dose of 60 Cobalt Gray Equivalents (CGE) was delivered to the tumor and the optic disc received a minimum of 50 CGE. Kaplan-Meier analysis was used to assess ocular outcome and survival rates. For trend analysis of functional development, Wilcoxon-Mann-Whitney U test was used to compare the medians of 2 groups and Kruskal-Wallis test was used in the case of more than 2 groups., Results: The mean follow-up time was 6.5 years (range 0.3-11.7 years). The most common side effects were radiation-induced optic neuropathy, retinopathy, and cataract. The median visual acuity before and within the first year after therapy was 0.4 logMAR (20/50), lapsing to 1.3 logMAR (20/400) after 3 years and 1.4 logMAR (20/500) after 5 years. During follow-up, no light perception developed in 17 cases (11.6%), mostly attributed to radiation-induced retinopathy, optic neuropathy, and secondary glaucoma. Enucleation was carried out in 14 patients (9.5%) because of local recurrence or severe side effects., Conclusion: Radiation-induced optic neuropathy is an expected issue after proton beam therapy of parapapillary choroidal melanoma, and visual impairment is common during long-term follow-up, but some useful vision can be preserved in a considerable number of patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to compare, on a retrospective basis, the results of therapy in patients with uveal hemangioma treated with photon or proton irradiation at a single center., Methods: From 1993 to 2002 a total of 44 patients were treated. Until 1998 radiotherapy was given with 6 MV photons in standard fractionation of 2.0 Gy 5 times per week. In 1998 proton therapy became available and was used since then. A dose of 20 to 22.5 Cobalt Gray Equivalent (CGE) 68 MeV protons was given on 4 consecutive days. Progressive symptoms or deterioration of vision were the indications for therapy., Results: Of the 44 patients treated, 36 had circumscribed choroidal hemangiomas and 8 had diffuse choroidal hemangiomas (DCH) and Sturge-Weber syndrome. Of the patients, 19 were treated with photons with a total dose in the range of 16 to 30 Gy. A total of 25 patients were irradiated with protons. All patients with DCH but 1 were treated with photons. Stabilization of visual acuity was achieved in 93.2% of all patients. Tumor thickness decreased in 95.4% and retinal detachment resolved in 92.9%. Late effects, although generally mild or moderate, were frequently detected. In all, 40.9% showed radiation-induced optic neuropathy, maximum Grade I. Retinopathy was found in 29.5% of cases, but only 1 patient experienced more than Grade II severity. Retinopathy and radiation-induced optic neuropathy were reversible in some of the patients and in some resolved completely. No differences could be detected between patients with circumscribed choroidal hemangiomas treated with protons and photons. Treatment was less effective in DCH patients (75%)., Conclusions: Radiotherapy is effective in treating choroidal hemangiomas with respect to visual acuity and tumor thickness but a benefit of proton therapy could not be detected. Side effects are moderate but careful monitoring for side effects should be part of the follow-up procedures.