Suppression of corticosteroid-induced ocular hypertension in sheep by anecortave.

Abstract

OBJECTIVE:

To confirm the ocular hypotensive effects of anecortave acetate on an ovine model for steroid-induced ocular hypertension. Eyes of normal sheep exhibit a robust steroid-induced ocular hypertensive response. Recent observations in an uncontrolled, interventional case series indicated that anecortave elicited hypotensive effects when administered as a sub-Tenon depot in the eyes of a small sample of patients with glaucoma.

METHODS:

Intraocular pressure (IOP) was monitored by Perkins applanation tonometry in 16 normal sheep receiving topically administered prednisolone acetate, 0.5%, in both eyes, 3 times daily, a protocol that doubled IOP within 12 days. Half of the sheep had received a unilateral sub-Tenon injection of anecortave in 1 eye prior to the initiation of the bilateral prednisolone instillations, while the 8 remaining sheep received the unilateral anecortave sub-Tenon depot after the IOP was maximally elevated by the prednisolone instillations.

RESULTS:

In these 2 sets of experiments, the presence of the anecortave depot suppressed the steroid-induced IOP elevation and reverted the elevated IOP to baseline levels. Measurements of aqueous outflow facility indicated that eyes treated with prednisolone plus anecortave exhibited a 5.8-fold higher outflow facility than the fellow eyes solely exposed to prednisolone, indicating that anecortave prevented the increase in outflow resistance produced by the corticosteroid.

CONCLUSION:

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

• Authors: Oscar A Candia, Rosana Gerometta, J Cameron Millar, Steven M Podos
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 128 Issue 3 Pg. 338-43 (Mar 2010) ISSN: 1538-3601 [Electronic] United States
• PMID: 20212205 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Glucocorticoids
• Pregnadienediols
• prednisolone acetate
• Prednisolone
• anecortave acetate

Topics

• Administration, Topical
• Angiogenesis Inhibitors (administration & dosage)
• Animals
• Aqueous Humor (metabolism)
• Disease Models, Animal
• Female
• Glucocorticoids (toxicity)
• Injections
• Intraocular Pressure (drug effects)
• Ocular Hypertension (chemically induced, prevention & control)
• Prednisolone (analogs & derivatives, toxicity)
• Pregnadienediols (administration & dosage)
• Sheep
• Tonometry, Ocular