April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Anecortave Acetate Suppresses and Reduces Corticosteroid-Induced Ocular Hypertension in Sheep
Author Affiliations & Notes
  • C. Millar
    Glaucoma Research, Mail Code R9/11, Alcon Research Ltd, Fort Worth, Texas
  • O. A. Candia
    Ophthalmology & Structural and Chemical Biology,
    Mount Sinai School of Medicine, New York, New York
  • R. Gerometta
    Departmento de Oftalmologia, Universidad Nacional Del Nordeste, Corrientes, Argentina
  • S. M. Podos
    Departments of Ophthalmology and Neuroscience,
    Mount Sinai School of Medicine, New York, New York
  • Footnotes
    Commercial Relationships  C. Millar, Alcon Research, Ltd., E; O.A. Candia, Alcon Research, Ltd., C; R. Gerometta, Alcon Research, Ltd., C; S.M. Podos, Alcon Research, Ltd., C.
  • Footnotes
    Support  Alcon Research, Ltd.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 584. doi:
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    • Get Citation

      C. Millar, O. A. Candia, R. Gerometta, S. M. Podos; Anecortave Acetate Suppresses and Reduces Corticosteroid-Induced Ocular Hypertension in Sheep. Invest. Ophthalmol. Vis. Sci. 2010;51(13):584.

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

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Abstract

Purpose: : To corroborate the ocular hypotensive effects of anecortave acetate (AL-3789, Alcon Research, Ltd.) on an ovine model of steroid-induced ocular hypertension. Eyes of normal sheep exhibited a robust steroid-induced ocular hypertensive response. Recent observations in an uncontrolled, interventional case series indicated that anecortave acetate elicited hypotensive effects when administered as a sub-Tenon depot in the eyes of a small sample of glaucoma patients. We sought to investigate this phenomenon further in sheep.

Methods: : Intraocular pressure (IOP) was monitored by Perkins applanation tonometry in 16 normal sheep receiving topically administered 0.5% prednisolone acetate in both eyes, three times daily, a protocol that approximately doubled IOP within 12 days. Half of the sheep had received a unilateral sub-Tenon injection of anecortave acetate in one eye prior to initiation of the bilateral prednisolone instillations; while the 8 remaining sheep received the unilateral anecortave acetate sub-Tenon depot after the IOP was maximally elevated by the prednisolone instillations.

Results: : In these two sets of experiments, the presence of the anecortave acetate depot prevented the steroid-induced IOP elevation, normally to 26.4+/-0.7mmHg (Mean+/-SEM, n=8, P<1x10-6), and reversed the elevated IOP to baseline levels (10.4+/-0.8mmHg, n=8) respectively. Measurements of aqueous outflow facility indicated that eyes treated by the combined presence of prednisolone plus anecortave acetate exhibited a 5.8-fold higher outflow facility than that of the fellow eyes solely exposed to prednisolone (0.46+/-0.15 microliters/min/mmHg vs. 0.08+/-0.02 microliters/min/mmHg, n=9, P<0.01); indicating that anecortave acetate prevented the increase in outflow resistance produced by the corticosteroid.

Conclusions: : Elucidation of the mechanisms of action of anecortave acetate in animal models may prove relevant to the design of novel interventions for the management of primary open-angle glaucoma.

Keywords: intraocular pressure • outflow: trabecular meshwork 
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