期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 60, 期 4, 页码 954-964出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.18-25346
关键词
retinoblastoma; intra-arterial chemotherapy; animal models; toxicity
资金
- Knights Templar Eye Foundation
- Vanderbilt Faculty Research Scholars program
- Research to Prevent Blindness Foundation
- National Eye Institute [NIH/NEI 5K08EY027464-02]
- Research to Prevent Blindness to the Vanderbilt Department of Ophthalmology and Visual Sciences
- Department of Veterans Affairs Senior Research Career Scientist Award
- Vanderbilt Ingram Cancer Center Support Grant [CA68485, P41 GM103391-06]
- National Center for Advancing Translational Sciences [UL1RR024975-01, 2 UL1 TR000445-06]
PURPOSE. To use our intra-arterial chemotherapy (IAC) rabbit model to assess the impact of IAC procedure, drug, dose, and choice of technique on ocular structure and function, to study the nature and etiology of IAC toxicity, and to compare to observations in patients. METHODS. Rabbits received IAC melphalan (0.4-0.8 mg/kg), carboplatin (25-50 mg), or saline, either by direct ophthalmic artery cannulation, or with a technique emulating nonocclusion. Ocular structure/function were assessed with examination, electroretinography (ERG), fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography, prior to and 5 to 6 weeks after IAC. Blood counts were obtained weekly. We reviewed our last 50 IAC treatments in patients for evidence of ocular or systemic complications. RESULTS. No toxicity was seen in the saline control group. With standard (0.4 mg/kg) melphalan, no vascular/microvascular abnormalities were seen with either technique. However, severe microvascular pruning and arteriolar occlusions were seen occasionally at 0.8 mg/kg doses. ERG reductions were dose-dependent. Histology showed melphalan dose-dependent degeneration in all retinal layers, restricted geographically to areas of greatest vascular density. Carboplatin caused massive edema of ocular/periocular structures. IAC patients experienced occasional periocular swelling/rash, and only rarely experienced retinopathy or vascular events/hemorrhage in eyes treated multiple times with triple (melphalan/carboplatin/topotecan) therapy. Transient neutropenia occurred after 46% of IAC procedures, generally after triple therapy. CONCLUSIONS. IAC toxicity appears to be related to the specific drug being used and is dose-dependent, rather than related to the IAC procedure itself or the specific technique selected. These rabbit findings are corroborated by our clinical findings in patients.
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