April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Ocular Effects of Maleic Acid Administration in Rabbits Following Intravitreal Injection
Author Affiliations & Notes
  • S. A. Aguirre
    DSRD, Pfizer Inc, San Diego, California
  • W. Collette, III
    DSRD, Pfizer Inc, San Diego, California
  • H. Younis
    DSRD, Pfizer Inc, San Diego, California
  • H. J. Gukasyan
    DSRD, Pfizer Inc, San Diego, California
  • W. Huang
    DSRD, Pfizer Inc, San Diego, California
  • Footnotes
    Commercial Relationships  S.A. Aguirre, Pfizer Inc, E; W. Collette, III, Pfizer Inc, E; H. Younis, Pfizer Inc, E; H.J. Gukasyan, Pfizer Inc, E; W. Huang, Pfizer Inc, E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5105. doi:
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    • Get Citation

      S. A. Aguirre, W. Collette, III, H. Younis, H. J. Gukasyan, W. Huang; Ocular Effects of Maleic Acid Administration in Rabbits Following Intravitreal Injection. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5105.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : The objective of this work was to characterize the tolerability/toxicity of maleic acid formulated as an excipient following intravitreal dosing in Dutch Belted rabbits.

Methods: : Female Dutch Belted rabbits were anesthetized and prepared for sterile injection. Maleic acid was formulated with 0.7% NaCl and the concentrations and conditions tested included; 18 mM or 0.2 mg/eye, pH 3.0, 300 mOsm, 43 mM or 0.5 mg/eye, pH 3.1, 332 mOsm, 86 mM or 1.0 mg/eye, pH 3.1, 334 mOsm, and 172 mM or 2 mg/eye, pH 3.1, 337 mOsm. Rabbits were given a single intravitreal 100 µl bolus of 0.7% NaCl or a maleic acid formulation in an area 3 mm above the corneal limbus in the superior temporal quadrant of the globe. Ophthalmic examinations were performed using direct and indirect ophthalmoscopy. On day 4 or 8, eyes were fixed in 6% glutaraldehyde solution and processed to slides for histological examination.

Results: : Rabbits dosed with ≥0.2 mg/eye developed a dose-related ocular irritation reaction that included conjunctival redness, eyelid swelling (chemosis), and scleral swelling near the injection site. The irritation reaction was mild to moderate the day after dosing and subsided to minimal on days six to eight post-dose. Indirect ophthalmolscopic examination revealed retinal vessel dilatation, retinal discoloration, retinal detachment, and abnormality in the medullary rays in rabbits given 2 mg/eye maleic acid. Histopathologic examination revealed a dose-related retinal degeneration in rabbits given ≥0.5 mg/eye and optic nerve axonal swelling (spheroids) in a rabbit given at 2.0 mg/eye. The 0.2 mg/eye dose was the no adverse effect level.

Conclusions: : Conjunctival redness, eyelid swelling (chemosis), scleral swelling near the injection site and retinal degeneration were dose-related in rabbits given ≥ 0.5 mg/eye maleic acid in the vitreous chamber and optic nerve degeneration occurred in rabbits given 2.0 mg/eye maleic acid. Applications of maleic acid as a dosage form buffer or counter ion in intravitreal injections may require further, careful study in light of these results.

Keywords: vitreous • injection 

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