Retinal Function After Subconjunctival Injection of Carboplatin in Fibrin Sealant

Pardue, Machelle T.; Hejny, Charles; Gilbert, Jake A.; Phillips, M. Joseph; Geroski, Dayle H.; Edelhauser, Henry F.

doi:10.1097/00006982-200410000-00015

Cited by 29 publications

(12 citation statements)

References 20 publications

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“…However, in 2004, work by Pardue et al again found ERG responses suggestive of inner retinal toxicity but discovered no changes on light microscopy. In this study, subconjunctival carboplatin (12.2 µg/mL in basic salt solution or 25.1 µg/mL in fibrin sealant) in rabbits resulted in decreased b-wave amplitudes beginning at day 2 and resolving by 2 weeks [39]. While not always consistent with histopathologic correlation, the literature suggests carboplatin has a dose-dependent, inner retinal effect measurable by ERG starting at 10 µg in rabbits (equivalent of 5.88 µg/ml), which may be temporary at certain doses.…”

Section: Discussionmentioning

confidence: 73%

Electroretinogram Monitoring of Dose-Dependent Toxicity after Ophthalmic Artery Chemosurgery in Retinoblastoma Eyes: Six Year Review

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 73%

Electroretinogram Monitoring of Dose-Dependent Toxicity after Ophthalmic Artery Chemosurgery in Retinoblastoma Eyes: Six Year Review

et al. 2014

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“…Animal studies suggest a dose-dependent impact of carboplatin on the choroid and retina [50]. This dose dependent toxicity has been further corroborated by ERG findings in animal models [51]–[53] with an inner retina effect measurable by ERG. In humans, retinal toxicity was “dose-limiting” for intracarotid administration of carboplatin (mean 300 mg/m2) for treatment of brain tumors [54].…”

Section: Discussionmentioning

confidence: 70%

Carboplatin +/− Topotecan Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

et al. 2013

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PurposeCarboplatin administered systemically or periocularly can result in dramatic and prompt regression of retinoblastoma. However, both routes are rarely curative alone and have undesirable side effects. We aimed to assess the efficacy and toxicity of carboplatin +/− topotecan delivered by ophthalmic artery chemosurgery whereby chemotherapy is infused into the eye via the ophthalmic artery.MethodsThis retrospective, IRB-approved study investigated retinoblastoma patients whom received carboplatin +/− topotecan ophthalmic artery chemosurgery. Patient survival, ocular survival, hematologic toxicity, ocular toxicity, second cancer development and electroretinogram response were all evaluated.Results57 carboplatin +/− topotecan infusions (of 111 total) were performed in 31 eyes of 24 patients. The remaining infusions were melphalan-containing. All patients were alive and no patient developed a second malignancy at a median follow up of 25 months. The Kaplan-Meier estimate of ocular survival at two years was 89.9% (95% confidence interval [CI], 82.1–97.9%) for all eyes. Grade 3 or 4 neutropenia developed in two patients and one patient developed metastatic disease. By univariate analysis, neither increasing maximum carboplatin/topotecan dose nor cumulative carboplatin/topotecan dose was associated with statistically significant reduction in the electroretinogram responses.ConclusionCarboplatin +/− topotecan infusions are effective for ophthalmic artery chemosurgery in retinoblastoma: they demonstrate low hematologic and ocular toxicity and no statistically significant influence on electroretinogram responses, and used in conjunction with melphalan-containing OAC, demonstrate excellent patient survival and satisfactory ocular survival.

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“…At 1, 2, and 4 weeks post-injection, ERG recordings were performed, as previously described [17]. Rats were dark-adapted overnight and then prepared under dim red lights.…”

Section: Methodsmentioning

confidence: 99%

Targeting retinal and choroid neovascularization using the small molecule inhibitor carboxyamidotriazole

Afzal

Caballero

Palii

et al. 2010

Brain Research Bulletin

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Neovascular ocular diseases as exemplified by proliferative diabetic retinopathy(PDR), exudative age-related macular degeneration (AMD), and retinopathy of prematurity (ROP) are severe diseases affecting all age groups in the US. We asked whether a small molecule, carboxyamidotriazole (CAI) known for its anti-angiogenic and anti-tumor effects and its ability to be administered orally in humans, could have anti-angiogenic effects in ocular in vitro and in vivo angiogenesis models. The anti-proliferative effects of CAI were examined by BrdU incorporation using human retinal and dermal endothelial cells and human pigment epithelial cells. The effect of CAI was determined using the Matrigel tube formation assay. The mouse model of choroidal neovascularization (CNV) initiated by laser rupture of Bruch’s membrane was used to quantify in vivo effects of aqueous beta-hydroxypropyl cyclodextrin (bHPCD) formulations of CAI on neovascularization. The pharmacokinetics (PK) of CAI after intravitreal administration bHPCD-CAI were studied undertaken in rabbit. The intravitreal toxicology of bHPCD-CAI was also examined in rat ocular tissue. We observed that CAI treatment of human endothelial cells decreased cell proliferation in a dose dependent manner. In the in vivo tests bHPCD-CAI treatment reduced choroidal neovascular lesion volume, also in a dose-dependent manner. The intravitreal PK of bHPCD-CAI demonstrated that highly efficacious concentrations of CAI are reached in the vitreous compartment. No ocular toxicology was observed with intravitreous injection of CAI. These studies support the potential of developing intravitreal CAI in an bHPCD ocular formulation for treatment of proliferative retinopathies in humans.

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Retinal Function After Subconjunctival Injection of Carboplatin in Fibrin Sealant

Abstract: Subconjunctival delivery of carboplatin in fibrin sealant or BSS does not have a toxic effect on retinal function or structure in a non-tumor-bearing rabbit model at the doses used in this study at 3 weeks' follow-up.

Cited by 29 publications

References 20 publications

Electroretinogram Monitoring of Dose-Dependent Toxicity after Ophthalmic Artery Chemosurgery in Retinoblastoma Eyes: Six Year Review

Electroretinogram Monitoring of Dose-Dependent Toxicity after Ophthalmic Artery Chemosurgery in Retinoblastoma Eyes: Six Year Review

Carboplatin +/− Topotecan Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

Targeting retinal and choroid neovascularization using the small molecule inhibitor carboxyamidotriazole

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