Abstract
PurposeTo report electroretinogram responses of retinoblastoma children under anesthesia before and after treatment with chemotherapeutic drugs (melphalan, topotecan, carboplatin) delivery by ophthalmic artery chemosurgery (OAC).MethodsA cohort study of 81 patients with retinoblastoma treated with OAC. All patients treated with OAC at our center through May 2012 for whom the requisite ERG data were available are included in the analysis. This study recorded the ERG 30 Hz flicker amplitude response changes from baseline, at 3 and 12 months following OAC treatment completion. Both univariate and multivariate linear regression models were evaluated, with generalized estimating equations to correct for correlations within patients. Independent numerical variables included maximum doses and cumulative doses of melphalan, topotecan and carboplatin.ResultsBy univariate analysis, both melphalan and topotecan appear to be associated with changes in ERG amplitude at both 3 and 12 months; but for the most part, these changes are minimal and likely clinically insignificant. By multivariate analysis, maximum and cumulative melphalan have a modest, temporary effect on the ERG amplitude change, which is apparent at 3 months but no longer evident at 12 months after completing treatment. By multivariate analysis, topotecan and carboplatin do not appear to adversely effect the change in ERG response.ConclusionMelphalan has the strongest, and carboplatin the weakest association with reduction in ERG response amplitudes; but for the most part, these changes are minimal and likely clinically insignificant. These conclusions apply only over the dose ranges used here, and should be applied with caution.
Highlights
Seven years ago, we first started treating retinoblastoma with ophthalmic artery chemosurgery (OAC), with the initial intent to save eyes with extensive retinoblastoma destined for enucleation
The elevated local dose– reported to be three-fold the plasma dose in non-tumor bearing animals receiving OAC with melphalan [1], and 10-fold the dose compared to periocularly administered topotecan [2]– raises concern for ocular toxicity since prior animal studies have demonstrated dose-related retinal toxicity
We have previously reported on the ERG findings of our first 10 patients, demonstrating that ERG responses can persist and even recover at 3–14 months following OAC with mostly one, and two drugs [4]
Summary
We first started treating retinoblastoma with ophthalmic artery chemosurgery (OAC), with the initial intent to save eyes with extensive retinoblastoma destined for enucleation. This treatment consists of introducing a micro-catheter into the femoral artery and advancing it to the orifice of the ophthalmic artery where chemotherapy is injected. It allows for concentrated, localized administration of chemotherapy to the eye while minimizing systemic exposure and limiting systemic toxicity. We have briefly summarized our ERG findings, including eyes with .50% retinal detachment [5,6,7]
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