The role of Intravitreal chemotherapy as an adjunctive treatment for retinoblastoma: a systematic review and single-arm meta-analysis.

Topic: evaluation of clinical outcomes of patients with retinoblastoma treated with intravitreal chemotherapy (IvitC).

Design: Systematic review and single-arm meta-analysis CLINICAL RELEVANCE: Clinical outcomes with IVitC vary across reports according to patient characteristics and concomitant treatment modalities, mainly intravenous chemotherapy (IVC) and intra-arterial chemotherapy (IAC). There are currently no large clinical trials or meta-analyses focusing on the topic.

Methods: A systematic search was conducted in MEDLINE, EMBASE and Cochrane. All articles reporting use of IVitC for RB and safety or efficacy outcomes were included regardless of publication date. Studies with fewer than 10 eyes were excluded. Enucleation rates (ER) were calculated using proportions and 95% confidence intervals (CIs). The analysis was performed using the Random Effects model in R Studio.

Results: 25 studies comprising 1082 eyes met inclusion criteria. Melphalan was exclusively used in 687 eyes (63.49%), 104 eyes received topotecan exclusively (9.61%), and the remaining 291 (26.90%) used a combination. General ER was 24.70% (95% CI 19.20-31.18%). Subgroup analysis showed an ER of 27.76% (95% CI 19.05-38.55%) for melphalan, 14.23% (95% CI 5.61-21.66%) for topotecan, and 23.82% (95% CI 11.95-41.87%) for combination therapy (p<0.05). It also revealed an ER of 21.54% (95% CI 15.57-29.01%) for studies that implemented IAC+IVitC versus 35.50% (95% CI 20.73-53.66%) for those who used IVC+IVitC (p<0.05). Pigmentary retinopathy rate was 36.56% (95% CI 24.61-50.44%) in subjects treated with melphalan and 2.42% (95% CI 0.70-8.01%) for those receiving topotecan (p<0.05). Other adverse events were cataract (17.76%) followed by vitreous hemorrhage (12.10%) and retinal detachment (5.62%). All studies, except one, were determined to have a serious risk of bias.

Conclusion: IVitC represents an effective strategy for retinoblastoma, especially when administered after IAC; however, melphalan retinal toxicity still poses a challenge. Results with topotecan are promising but scarce. Comparing both drugs is needed to define the best treatment strategy. This study is limited by the lack of large, randomized studies on this subject.