Posterior juxtascleral delivery of anecortave acetate for treatment of age-related macular degeneration
A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha in Vitreoretinal Surgical Techniques, 2019
A number of pharmacologic agents designed to inhibit blood vessel growth are currently being evaluated for the treatment of exudative ARMD. The effective use of these agents relies upon their local administration into the sub-retinal space. Two of them – pegaptanib sodium (Macugen, Eyetech Pharmaceuticals, Inc., New York) and ranibizumab (Lucentis, Genentech, Inc., South San Francisco), both of which are inhibitors of vascular endothelial growth factor (VEGF) – are currently administered by intravitreal injection, although this technique carries the risk of retinal detachment and endophthalmitis.2 An alternative route of administration – transscleral drug delivery via a posterior juxtascleral depot – has been developed for use in clinical trials of the angiostatic cortisene anecortave acetate (Retaane, Alcon Research Ltd, Fort Worth), which is now being evaluated for inhibition of CNV in exudative ARMD and for reduction of the risk of developing exudative ARMD. This compound has been shown to inhibit new blood vessel growth in several in vitro and in vivo models of neovascularization,3,4 and has demonstrated efficacy in the treatment of CNV in patients with progressive ARMD.5,6 To maximize drug delivery to the subretinal space from the posterior juxtascleral depot, a unique curved, blunt-tipped cannula has been developed for placement of the drug in the macular region. This technique provides the targeted effective drug concentration of anecortave acetate to the retina and choroid for an extended duration to maximize drug effect.
Age-Related Macular Degeneration Drug Delivery
Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson in Intraocular Drug Delivery, 2006
Anecortave acetate is a synthetic steroid derivative which is thought to inhibit blood vessel growth by inhibiting the proteases necessary for vascular endothelial cell migration (54,55). It inhibits both urokinase-like plasminogen activator and matrix metalloproteinase-3 (56). Anecortave acetate has been specifically modified to eliminate its in vivo corticoid activity (57). It is administered posterior to the eye as a juxtascleral depot injection onto the outer surface of the sclera near the macula, using a specially designed cannula (see Chapter 5) (57).
Scleral Inflammation around Collector Channels in Eyes with Primary Open-Angle Glaucoma
Published in Ocular Immunology and Inflammation, 2021
Maximilian Schultheiss, Bogomil Voykov, Maren Klemm, Ulrich Gross, Heinz-Peter Schultheiss, Martin S. Spitzer, Maria Casagrande
Nevertheless, in POAG-biopsies inflammation exists and this raises several questions. What does the inflammation mean? It is possible that in most patients POAG is a consequence of a subclinical inflammatory process, which does not result in an obvious ocular inflammation observable in slit-lamp examination, but induces an increase in AH outflow resistance. In studies, anecortave acetate, applied as a juxtascleral depot, was found to have a hypotensive effect in steroid-induced elevated intraocular pressure, POAG, and closed-angle glaucoma.26–29 This hypotensive effect was found to be statistically significant over a course of up to 6 months27 with an IOP reduction of about 30% throughout the studies.26–28 Anecortave acetate is an angiostatic cortisone derived from glucocorticoid cortisol acetate, but lacking glucocorticoid activity.30 The mechanism by which anecortave acetate can lower intraocular pressure is not fully understood.27 It is known that it possesses angiostatic activity by inhibiting proteases.27 Elevated TGF-beta can increase the messenger ribonucleic acid (mRNA) and protein expression of plasminogen activator inhibitor-1 (PAI-1) in TM cells.27 In cultured cells, anecortave acetate inhibited this PAI-1 expression.27 The actuality of anecortave acetate having a hypotensive effect and regarding its inhibitory function of proteases, the findings in this study could be an explanation for this effect on IOP in glaucoma patients. Vice versa, the fact that anecortave acetate can have a hypotensive effect by this mechanism can support the relevance of our findings and supports the hypothesis that the immune system influences the AH outflow resistance.
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