Ocular safety of repeated intravitreal injections of Carboplatin and Digoxin: A preclinical study on the healthy rabbits

Khodabande, Alireza; Ghassemi, Fariba; Amoli, Fahimeh Asadi; Riazi-Esfahani, Hamid; Mahmoudzadeh, Raziyeh; Mehrpour, Mohammad; Valipour, Niloufar

doi:10.1002/prp2.814

Cited by 4 publications

(3 citation statements)

References 45 publications

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“…It was speculated that the molecular type and structure of conbercept were related to its effects on the fellow eye. Khodabande et al (2021) found some electroretinography changes in contralateral rabbits’ eyes in the unilateral intravitreal injection of digoxin and carboplatin. They proposed it might be related to the repeated intravitreal injection of the agents that cause damage to the ocular-blood barrier.…”

Section: Discussionmentioning

confidence: 90%

A Study on the Drug Concentration in Fellow Eyes After Unilateral Intravitreal Injection of Conbercept Into New Zealand Rabbit Eyes

et al. 2021

Front. Pharmacol.

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Intravitreal injections of anti-vascular endothelial growth factor (VEGF) have become increasingly popular in the treatment of ocular diseases. However, few studies have determined the efficiency of unilateral intravitreal anti-VEGF injection in the fellow eye. Herein, we performed a study to investigate the drug concentration in fellow eyes and venous serum after unilateral intravitreal injection of conbercept into rabbit eyes. This is an experimental animal study. Thirty male New Zealand rabbits (60 eyes) were used. One eye of each rabbit was intravitreally injected with 0.5 mg of conbercept. Both eyes from six rabbits were enucleated on days 1, 3, 7, 14, and 30. Conbercept concentrations were measured in the serum, aqueous humor, and vitreous humor. We found conbercept was detected in the fellow eyes and serum of rabbits. Conbercept concentrations in the vitreous humor of the fellow eyes increased from 74.11 ng/ml on day 1 to 246.69 ng/ml on day 3 and then declined to 69.11 ng/ml after 30 days. The concentration in the aqueous humor peaked on day 1 with a concentration of 244.82 ng/ml and declined to 40.13 ng/ml after 30 days. The maximum conbercept concentrations in the aqueous humor and vitreous humor of fellow eyes were similar, which were 0.2 and 1.3% of those of the injected eye, respectively. A peak concentration of 102.49 ng/ml was achieved in the venous serum 1 day after intravitreal injection of conbercept, which was 0.08 and 0.5% of those of the maximum conbercept concentrations in the vitreous humor and aqueous humor of the injected eye, respectively, and 41.5 and 41.8% of the maximum conbercept concentrations in the vitreous humor and aqueous humor of the non-injected eye, respectively. In conclusion, after intravitreal injection of 0.5 mg of conbercept into rabbit eyes, very small amounts of conbercept were detected in the fellow non-injected eyes and venous serum.

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Section: Discussionmentioning

confidence: 90%

A Study on the Drug Concentration in Fellow Eyes After Unilateral Intravitreal Injection of Conbercept Into New Zealand Rabbit Eyes

et al. 2021

Front. Pharmacol.

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“…Nonetheless, OAC may not be the optimal route for digoxin due to low intravitreal levels and systemic exposure related to cardiotoxicity; IVi may be preferable. In rabbits, IVi of digoxin resulted in levels well above the IC 50 and plasma concentrations far below the concentrations related to cardiac toxicity in humans; however, the injected dose was toxic to the retina (110,111).…”

Section: Drug Discovery In Retinoblastomamentioning

confidence: 89%

Treatment of Retinoblastoma: What Is the Latest and What Is the Future

et al. 2022

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The management of retinoblastoma, the most common intraocular malignancy in children, has changed drastically over the last decade. Landmark developments in local drug delivery, namely, safer techniques for intravitreal chemotherapy injection and ophthalmic artery chemosurgery, have resulted in eye globe salvages that were not previously attainable using systemic chemotherapy or external beam irradiation. Novel drugs, oncolytic viruses, and immunotherapy are promising approaches in the treatment of intraocular retinoblastoma. Importantly, emerging studies of the pattern of tumor dissemination and local drug delivery may provide the first steps toward new treatments for metastatic disease. Here, we review recent advances in retinoblastoma treatment, especially with regard to local drug delivery, that have enabled successful conservative management of intraocular retinoblastoma. We also review emerging data from preclinical and clinical studies on innovative approaches that promise to lead to further improvement in outcomes, namely, the mechanisms and potential uses of new and repurposed drugs and non-chemotherapy treatments, and discuss future directions for therapeutic development.

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“…While an effective research tool, safely translating the cardiac glycoside digoxin to patients with ocular disease has proven to be challenging due in part to its complex pharmacokinetic profile and narrow therapeutic index ( 39 ). Indeed, intraocular administration of digoxin in rabbits at therapeutic doses has been reported to result in retinal toxicity ( 51 , 52 ). Similar observations were made following intraocular administration of the chemotherapeutic agent doxorubicin ( 53 , 54 ).…”

Section: Discussionmentioning

confidence: 99%

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice

Zhang¹,

Sharma²,

Dinabandhu³

et al. 2023

Journal of Clinical Investigation

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Statistical analysis was performed with Microsoft Excel, version 16.0.16327.20248, or Prism, version 8.0, software (GraphPad). Statistical differences between 2 or multiple heterogenous groups were determined by unpaired Student's t test or 1-way or 2-way ANOVA. Analysis of data was performed using Excel.Study approval. All animal experiments were performed in accordance with the Animal Care and Use Program at Johns Hopkins University and were approved by the Institutional Animal Care and Use Committee (IACUC). All studies involving patients or patient tissue were approved by the Institutional Review Board of Johns Hopkins University School of Medicine. All participants provided written informed consent prior to enrolment in the study.

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Ocular safety of repeated intravitreal injections of Carboplatin and Digoxin: A preclinical study on the healthy rabbits

Cited by 4 publications

References 45 publications

A Study on the Drug Concentration in Fellow Eyes After Unilateral Intravitreal Injection of Conbercept Into New Zealand Rabbit Eyes

A Study on the Drug Concentration in Fellow Eyes After Unilateral Intravitreal Injection of Conbercept Into New Zealand Rabbit Eyes

Treatment of Retinoblastoma: What Is the Latest and What Is the Future

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice

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