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Published on: January 22, 2018
Evaluation of the toxicity of subretinal triamcinolone acetonide in the rabbit
Igor Kozak1, Lingyun Cheng, Tim Mendez
1Jacobs Retina Center, University of California at San Diego, Shiley Eye Center, La Jolla, California 92036-0946, USA.
Purpose:
Subretinal triamcinolone acetonide (TCA) might be a useful adjuvant in the treatment of subretinal neovascularization. The purpose of this study was to test the toxicity of subretinal TCA in the rabbit eye.
Methods:
Sixteen New Zealand rabbits were vitrectomized and injected with either decanted TCA solution or vehicle. The concentration of injected TCA was 2 mg, and the delivered volume was 10 microL. Rabbits were examined on days 1, 3, and 7 and then once a week up to 3 months after surgery. Optical coherence tomography was performed at months 1, 2, and 3. After the last examination, which included electroretinography, the rabbits were killed, and the eyes were enucleated for histopathologic analysis.
Results:
Subretinal TCA appeared as a white circumscribed deposit. As the drug disappeared, areas of hyperpigmentation were seen adjacent to the drug deposit. Electroretinography tracings were normal, indicating no widespread toxic effect. Histologic analysis revealed areas of absence and/or hyperpigmentation of the retinal pigment epithelium and damage to photoreceptors and the outer nuclear layer of the retina.
Conclusion:
Subretinal injection of TCA crystals can be toxic to the outer retina and retinal pigment epithelium. Whether the potential beneficial effect of such a high-dose steroid in limiting subretinal inflammation, angiogenesis, and proliferation outweighs toxicity can only be determined from a clinical trial.
Insights
Subretinal triamcinolone acetonide (TCA) showed toxicity to the outer retina and retinal pigment epithelium in rabbits. Further clinical trials are needed to determine if its benefits outweigh these risks.
Area of Science:
- Ophthalmology
- Retinal Diseases
- Pharmacology
Background:
- Subretinal neovascularization requires effective treatments.
- Subretinal triamcinolone acetonide (TCA) is a potential therapeutic agent.
Purpose of the Study:
- To evaluate the toxicity of subretinal TCA in a rabbit eye model.
- To assess the safety of subretinal TCA for treating subretinal neovascularization.
Main Methods:
- Vitrectomy and subretinal injection of TCA or vehicle in New Zealand rabbits.
- Weekly examinations, optical coherence tomography, and electroretinography over 3 months.
- Histopathologic analysis of enucleated eyes post-mortem.
Main Results:
- Subretinal TCA deposits led to retinal pigment epithelium hyperpigmentation.
- Electroretinography indicated no widespread toxic effects.
- Histology confirmed damage to photoreceptors and outer nuclear layer.
Conclusions:
- Subretinal TCA crystals can cause toxicity to the outer retina and retinal pigment epithelium.
- Clinical trials are necessary to weigh the therapeutic benefits against observed toxicity.
