Objective: This study aimed to evaluate the outcomes and predictive factors of I-125 radioactive plaque therapy for recurrent and refractory retinoblastoma (Rb) cases that failed primary systemic chemotherapy and focal therapies.

Methods: A retrospective study of 20 eyes with intraocular Rb treated with I-125 radioactive plaque therapy (Apex dose 45 Gy) from 2013 to 2023 was conducted. Data on tumor characteristics, treatments, and outcomes were collected over a follow-up period of at least one year.

Results: There were 11 (55%) males and 8 (40%) patients who had bilateral disease. All 20 treated eyes (100%) showed initial tumor regression, while long-term tumor control and eye salvage were achieved in 14 eyes (70%). Six eyes (30%) experienced uncontrollable tumor recurrence after a mean of 6 months (range: 3-12 months) after plaque therapy. Recurrence included main tumor activity in six eyes and additional resistant vitreous seeds in two of them. Poor predictive factors for eye salvage included Group D at diagnosis (p = 0.044), active vitreous seeds at the time of plaque therapy ((p = 0.045), tumor thickness >5.0 mm (p = 0.045), and tumor base dimension >12 mm (p = 0.023). Post-plaque complications included cataracts in seven eyes (35%), tumor hemorrhage in six eyes (30%), retinal detachment in four eyes (20%), radiation retinopathy in three eyes (15%), and neovascular glaucoma in one eye (5%). Five (83%) of those with tumor hemorrhage had plaque surgery performed within less than 6 months of the last cycle of systemic chemotherapy. At a mean follow-up of 36 months (range: 12-96 months), five eyes (25%) were enucleated, and high-risk pathological features were identified in three eyes, including post-laminar optic nerve infiltration (one eye) and massive choroidal invasion (two eyes). All patients were alive and free of metastasis except one patient (5%) whose parents refused enucleation and came back with extra-scleral extension and bone marrow metastasis and eventually passed away.

Conclusions: I-125 radioactive plaque therapy is a valuable salvage treatment for recurrent and refractory retinoblastoma, achieving tumor control and eye salvage in 70% of cases with an acceptable safety profile. However, the observed recurrence rate (30%) at an apex dose of 45 Gy suggests a need for dose optimization and individualized treatment strategies. Identifying high-risk features, such as Group D disease, active vitreous seeds, and larger tumors, is crucial for patient selection and outcome prediction. Future research should explore alternative dosing strategies, combination therapies, and improved predictive models to enhance long-term tumor control while minimizing complications.