Anecortave
acetate (AL-3789) (Alcon Laboratories, Inc.) is a cortisene –a derivative of
cortisol.
Anecortave is
formulated by replacing the hydroxyl group at carbon 9 of the cortisol molecule
with a double bond between carbons 9 and 11 and the addition of an acetate
group at carbon 21.
This renders
Anecortave devoid of glucocorticoid receptor agonist activity.
Anecortave
acetate has two inherent pharmacological activities; it has antiangiogenic
properties through inhibition of the angiogenic proteolytic cascade, and it has
IOP-lowering activity.
It has been
studied mostly in models of neovascular Age-related macular degeneration (AMD).
In these models
it is given by posterior juxtascleral depot injection.
The agent has
angiostatic activity by inhibition of proteases that degrade the extracellular
matrix, thus blocking migration of vascular endothelial cells.
It has no glucocorticoid
receptor-mediated biological activity.
Anecortave
acetate does not reduce inflammation, elevate IOP, or cause cataracts.
In glaucoma it
has been given by anterior juxtascleral depot (AJD). It exerts its effect
locally, migrating through sclera over approximately 270°, and acting at the
level of the trabecular meshwork (TM) and ciliary body, for a prolonged period.
Robin et al
have described the delivery of this medication in the sub-Tenon’s space,
creating a circumferential deposition surrounding the limbus. IOP was lowered
by 40–50% at 4 weeks in eyes with baseline IOP ranging from 23 to 52 mmHg on a
prostaglandin analogue. In six out of seven eyes, Anecortave acetate produced a
rapid and substantial reduction in IOP, dropping by 9.5 mmHg after 1 week and
by 12.7 mmHg at 4 weeks. This IOP lowering from a single injection lasted for
at least 3 months and up to 19 months.
Prata
demonstrated at least 30% IOP reduction lasting for at least 3 months after a single
injection of Anecortave.
Callanan has also
reported good IOP reduction following Anecortave injection. Doses of 12 mg, 24
mg, or 30 mg were given every 4 months.
Landry has also
reported more than 30% IOP reduction with this injection.
In a series of
steroid-induced glaucoma a rapid and sustained reduction in IOP was
demonstrated by 1 week in all patients, and no adverse events were noted. By 1
month, seven of eight had IOP that remained reduced by over 30%.
The mechanism
for Anecortave acetate’s IOP lowering is not fully understood at present.
Elevated plasminogen
activator inhibitor-1 has been induced in cultured TM cells and found to be
inhibited by simultaneous addition of Anecortave desacetate in the culture
medium. This suggests the mechanism for this agent’s ability to lower IOP in
patients with glaucoma and steroid-induced ocular hypertensive patients.
REFERENCES:
Robin AL, Suan EP, Sjaarda RN, Callanan DG, Defaller J; Alcon
Anecortave Acetate for IOP Research Team. Reduction of intraocular pressure
with anecortave acetate in eyes with ocular steroid injection-related glaucoma.
Arch Ophthalmol. 2009 Feb;127(2):173-8. doi: 10.1001/archophthalmol.2008.595.
PMID: 19204235.
Stalmans I, Callanan DG, Dirks MS, Moster MR, Robin AL, Van
Calster J, Scheib SA, Dickerson JE Jr, Landry TA, Bergamini MV. Treatment of
steroid-induced elevated intraocular pressure with anecortave acetate: a
randomized clinical trial. J Ocul Pharmacol Ther. 2012 Dec;28(6):559-65. doi:
10.1089/jop.2012.0063. Epub 2012 Aug 3. PMID: 22860637; PMCID: PMC3505827.
T. A. Landry, J. Dickerson, J. C. Merriam; The Use of
Anecortave Acetate for Refractory, Complex Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1206.
Prata TS, Tavares IM, Mello PAA, Tamura CY, Belfort R Jr.
Anterior juxtascleral depot of anecortave acetate: intraocular pressure
reduction in different types of glaucoma. Association for Research in
Vision and Ophthalmology (ARVO); abstract 2008 E-1205, poster A47.
Callanan D, Fuller C, Landry TA, Dickerson JE, Bergamini MVW. Prophylactic anecortave acetate in patients with a retisert implant. Association for Research in Vision and Ophthalmology (ARVO) 2008; abstract 2008 E-5630
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