Posterior Segment Drug Delivery
Suprachoroidal Drug Delivery – A New Approach for the Treatment of Severe Macular Diseases
Constanze Augustin,1 Albert Augustin,2 Manfred Tetz3 and Stanislao Rizzo4
1. Medical student; 2. Professor and Chair; 3. Professor and Chair, Berlin Eye Research Institute; 4. Professor and Chair, UO Chirurgia Oftalmica, Azienda Ospedaliera-Universitaria Pisana
Abstract
In this article, we review recent research in suprachoroidal drug administration for the treatment of advanced, refractory, retinal disease. A microcatheter (iTRACK™ 400) has been used to access and deliver drugs to the suprachoroidal space. This technology has been investigated in several animal models as well as in patients with advanced disease stages and/or who are unresponsive to conventional treatments. In groups with either age-related macular degeneration (AMD) and/or macular oedema resulting from other diseases, significant effects were achieved by using this technology to apply steroids and/or anti-vascular endothelial growth factor (VEGF) drugs, with no surgical or postoperative complications observed. Suprachoroidal drug administration directly adjacent to the choroid in the submacular region might therefore be a potential treatment for many retinal diseases. Human pilot studies in patients with advanced, refractory retinal disease that is unresponsive to conventional treatments showed some increase in residual vision and significant reduction of macular oedema, with few complications. Prospective trials are necessary to confirm the pilot results obtained by different research groups.
Keywords Age-related macular degeneration, exudates, macular oedema, microcatheter, suprachoroidal space
Disclosure: The authors have no conflicts of interest to declare. Received: 13 September 2011 Accepted: 6 December 2011 Citation: European Ophthalmic Review, 2012;6(1):25–7 Correspondence: Albert J Augustin, Department of Ophthalmology, Staedtisches Klinikum Karlsruhe, Moltkestraße 90, 76133 Karlsruhe, Germany. E:
albertjaugustin@googlemail.com
Intravitreal drugs are currently approved for the treatment of both age-related macular degeneration (AMD) and macular oedema resulting from diabetes or vein occlusion. However, the major drawback of these drugs and/or an intravitreal monotherapy strategy is the need for repeated injections, with most of the drugs requiring injections on a monthly to bimonthly basis. In addition, some of the disease stages do not respond adequately to treatment. Thus, there is currently a medical need for new innovative technologies that reduce the requirement for repeated injections and optimise treatment safety. Moreover, to reduce the risk of adverse effects, exposure of the anterior segment should be limited, which can be achieved by a suprachoroidal approach.
In a rabbit model using dynamic contrast-enhanced magnetic resonance imaging, it has been shown that intrascleral catheter infusions expand the suprachoroidal layer. The model drug, gadolinium-diethylenetriaminopentaacetic acid, was rapidly delivered to the macula with limited anterior segment exposure.1
However,
several other approaches to get the drug nearer to the target without diminishing safety did not show convincing results.2
Finally, using a porcine model, Olsen and co-workers demonstrated that the suprachoroidal space might be the ideal reservoir for sustained-release formulations. Here, a steep concentration gradient can be established for drug diffusion to the target. The authors
© TOUCH BRIEFINGS 2012
directly accessed the posterior segment through the suprachoroidal space by using either a rigid or flexible cannula. Interestingly, by positioning a triamcinolone acetonide depot into the suprachoroidal space, pharmacokinetic studies showed local drug concentrations in both the choroid and retina that were high enough to exert positive effects. In addition, the drug stayed in place for up to four months and an excellent safety profile was also demonstrated.3
Thus,
suprachoroidal administration or targeted delivery of drugs directly to the suprachoroidal space might be of combined clinical benefit.
Method
The use of a microcatheter (iTRACK™ 400) to access and deliver drugs to the suprachoroidal space was first investigated in a porcine model by Olsen et al.4
These authors evaluated posterior drug administration by catheterising the suprachoroidal space in 93 out of 94 pigs. Triamcinolone acetonide was injected into the suprachoroidal space to characterise the pharmacokinetics and pharmacodistribution of steroid administration. Fluorescein angiography, fundus examination and histopathology were performed to investigate the safety of the procedure.
Subsequent to publication of the work by Olsen et al., patients with advanced, refractory AMD were treated in a pilot study by Chang and co-workers (Chang et al., oral presentation summarised in Augustin and Rizzo).4
25
In the study, patients were selected who had choroidal
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68