Ocular Safety of Intravitreal Ethylene Diamine Tetra Acetic Acid (EDTA): An Experimental Feasibility Study

Amin Zand1 *, Khalil Ghasemi Falavarjani2 , Mozhgan Rezaei Kanavi3

  1. Department of Ophthalmology, Shafa Hospital, Kerman University of Medical Sciences, Kerman, Iran
  2. Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
  3. Stem cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran

Abstract: To determine any observable toxicity signs of intravitreal ethylene diamine tetra acetic acid (EDTA, an antioxidative and potential neuroprotective drug) in rabbit eyes, and provide a baseline for setting dose levels in future studies.

Methods: Ten New Zealand albino rabbits were divided into five groups. Right eyes of the animals in each group received intravitreal injection of one of the dilutions of EDTA (112.5, 225, 450, 900 and 1800 µg /0.1 mL). Fellow eyes received either intravitreal injection of 5% dextrose water (5 eyes) or no injection (5 eyes). In addition to clinical examinations, electroretinography (ERG) was performed at the baseline and on day 28. The enucleated eyes were subjected to hematoxylin and eosin (H&E) staining, immunohistochemistry for glial fibrillary acidic protein (GFAP) and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test.

Results: Clinical examinations, H&E staining and TUNEL assay were unremarkable. ERG test did not exhibit any significant alteration compared to the baseline values, except a significant decrease in just one of the measurements of eyes injected with 225 µg EDTA. The mean scores of GFAP immune reactivity in the eyes injected with 112.5 and 225 µg EDTA indicated a non-significant reaction. The mean GFAP scores in higher doses were significant.

Conclusion: This study suggests intravitreal EDTA with the dose threshold of < 450 µg can be investigated for confirmation of the safe dose and evaluating potential neuroprotective effects of the drug on intraocular structures.





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