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 steroidinduced 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.

Intraocular pressure measurement in sheep using an applanation tonometer

“…There are quite a few studies using applanation tonometry in animals (Priehs et al, 1990;Miller et al, 1990;Miller et al, 1991;Dziezyc et al, 1992;Passaglia et al, 2004;Candia et al, 2010;Gerometta et al, 2010;Ribeiro et al, 2010;Rusanen et al, 2010), but we found no reports on the assessment of the mean IOP in healthy sheep using the applanation tonometer Tonopen XL e . The purpose of this study was to determine the mean IOP in healthy adult sheep using applanation tonometry with Tonopen XL e .…”

“…The MacKay-Marg applanation tonometer, which is considered the golden standard in Veterinary Medicine, has no longer been manufactured. A portable Mackay-Marg-type tonometer (Tonopen) has been widely used among veterinary ophthalmologists and has been assessed in dogs, cats, horses, and in some extent in sheep (Miller et al, 1990;Priehs et al, 1990;Miller et al, 1991;Dziezyc et al, 1992;Passaglia et al, 2004;Candia et al, 2010;Gerometta et al, 2010;Rusanen et al, 2010); however, a controlled study measuring the baseline IOP in healthy sheep, using applanation tonometry with Tonopen XL e , has not yet been reported.…”

Model systems for the study of steroid-induced IOP elevation

“…Adenovirally (AdV) mediated MMP1 overexpression lead to a reversal of steroid-induced IOP elevation (Gerometta et al, 2010). Similarly, treatment with anterior juxtascleral administration of anecortave acetate has been shown to prevent IOP elevation in sheep (Candia et al, 2010). The sheep model has also been used to determine that tPA can prevent as well as reverse steroid-induced IOP elevation (Candia et al, 2014; Gerometta et al, 2013).…”

Intraocular pressure elevation in uveitis

“…In addition, anecortave depot also reverted elevated IOP to baseline levels in the eyes of normal sheep who received the injection after IOP elevation [72].…”