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Purpose The Collaborative Ocular Melanoma Study (COMS) established iodine-125 (I-125) plaque brachytherapy for eye preserving treatment of medium-sized choroidal melanomas in the United States. Eye Physics I-125 plaque treatment modeled with Plaque Simulator (PS) software yields similar results to COMS. Herein, we report results from a series of 15 patients treated with ruthenium-106 (Ru-106) plaque brachytherapy using PS pretreatment modeling for plaque localization and dosimetry. Methods and Materials Fifteen patients with medium-sized choroidal melanomas (2.84–5.5 mm in apical height and a basal diameter of 7.8–12.6 mm) treated with ruthenium brachytherapy from 2003 to 2005 were evaluated retrospectively. Baseline and followup data were evaluated for tumor height, best corrected visual acuity, radiation retinopathy, radiation optic neuropathy, postradiation cataract formation, diplopia, and ptosis. Tumor response for both Ru-106 and I-125 plaques planned using the same PS pretreatment modeling was evaluated and compared. Results Isotope-specific radiation profiles were compared, and rates of local treatment failure (0%), optic neuropathy (6.7%), retinopathy (20%), and cataracts (33%) were evaluated. Five year–treated tumor heights were approximately 0.61 ± 0.29 (I-125, n = 16) and 0.53 ± 0.17 (Ru-106, n = 6) of their heights at diagnosis. Conclusions This patient subset had background characteristics very similar to those of the COMS and patients treated at our institution with I-125 plaques. Treatment response was equivalent although radiation complications occurred slightly less frequently in the Ru-106 group compared with those treated with I-125. Image-guided three-dimensional pretreatment modeling for plaque localization and dosimetry seems to work equally as well for Ru as for I-125 plaques and justifies more extensive investigation. [ABSTRACT FROM AUTHOR]