Cannulation of the Suprachoroidal Space: A Novel Drug Delivery Methodology to the Posterior Segment

Olsen, Timothy W.; Feng, Xu; Wabner, Kathy; Conston, Stanley R.; Sierra, David H.; Folden, David V.; Smith, Morton E.; Cameron, J. Douglas

doi:10.1016/j.ajo.2006.05.045

Cited by 150 publications

(134 citation statements)

References 18 publications

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“…Determination of the dosage of triamcinolone and bevacizumab had been based on the dose and volume of drug used for intravitreal administration of bevacizumab or triamcinolone in other studies [7,10,11,12] and previous investigations of the administration of drugs to the suprachoroidal space [9]. The operational steps included priming the microcatheter with the bevacizumab injectate prior to insertion into the suprachoroidal space.…”

Section: Methodsmentioning

confidence: 99%

“…The use of a microcatheter to access and deliver therapeutic agents to the suprachoroidal space for targeted treatment of posterior segment disease has been investigated in animals by Olsen et al [9]. These authors observed that the administration of therapeutic agents to the suprachoroidal space to treat posterior segment disease may be desirable to allow for direct drug exposure to the choroid, potentially increasing local tissue drug levels and drug efficacy.…”

Section: Introductionmentioning

confidence: 99%

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Safety of Submacular Suprachoroidal Drug Administration via a Microcatheter: Retrospective Analysis of European Treatment Results

2012

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Purpose: To investigate the safety and feasibility of using a microcatheter for drug delivery in the suprachoroidal space in eyes with advanced, exudative, age-related macular degeneration (AMD) unresponsive to conventional therapy. Procedures: A unique microcatheter was used to deliver a drug combination consisting of bevacizumab and triamcinolone to the submacular suprachoroidal space. Twenty-one eyes of 21 patients with choroidal neovascularization (CNV) secondary to advanced, exudative AMD were followed over a 6-month postprocedure period. Results: The microcatheter was successfully and atraumatically inserted into the suprachoroidal space of all eyes. No serious intraoperative or postoperative complications including suprachoroidal hemorrhages were encountered. Postsurgically, complications consisted of 1 eye experiencing a transient elevation in intraocular pressure at 3 months, which was medically controlled, and 2 eyes (10.5%) with an apparent increase in nuclear sclerotic cataracts. Conclusions: Suprachoroidal drug administration was achieved without serious complication using a novel microcatheter. Direct drug delivery to the choroid can potentially increase local tissue drug levels and drug efficacy for the treatment of AMD and other diseases associated with CNV.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety of Submacular Suprachoroidal Drug Administration via a Microcatheter: Retrospective Analysis of European Treatment Results

2012

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“…Recently, this microcatheter is challenged to use for suprachoroidal drug delivery (Olsen, 2007, Rizzo et al, 2010. The pharmacokinetic study of suprachoroidal delivery of TA in pigs has shown that TA remained in the ocular tissues for at least 120 days, and the systemic exposure was very low (Olsen et al, 2006). In contrast, the study to compare the pharmacokinetics of bevacizumab between intravitreal and suprachoroidal injections to pigs (Olsen et al, 2011) reported that the profile of intravitreal injections of bevacizumab was more sustained than that of suprachoroidal injections at the same dosage level.…”

Section: Microcathetermentioning

confidence: 92%

Clinical Application of Drug Delivery Systems for Treating AMD

Kuno¹,

Fujii²

2012

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“…Surgical steps, such as conjunctival peritomy, eye rotation, choroidal exposure via a sclerotomy, and needle puncture of the choroid are all standard techniques used for decades in retinal detachment drainage procedures. 24 With regard to suprachoroidal cannulation, Olsen and colleagues 25 described a microcatheter for (1) insertion into the suprachoroidal space, (2) advancement to the macular region, and (3) delivery of a therapeutic product to the suprachoroidal space. El Rayes and Elborgy 26 used suprachoroidal cannulation to create an internal buckle for retinal detachments by injecting a long-lasting viscoelastic through an olive tip cannula.…”

Section: Discussionmentioning

confidence: 99%

A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

Smet¹,

Lynch

Dejneka

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. This study evaluated a new subretinal method for delivery of human or pig umbilical tissue-derived cells (hUTC or pUTC, respectively) using a novel subretinal injection cannula and suprachoroidal approach in Göttingen minipig eyes. hUTC (palucorcel) are currently under development for treating geographic atrophy in humans.METHODS. Twenty-four Göttingen minipigs (divided into eight groups) were subretinally administered palucorcel, pUTC, or vehicle. In some cases, fluorescently labeled cells and vehicle were administered. Conjunctival cutdown and sclerotomy were performed, then a flexible cannula containing a microneedle was inserted and advanced into the suprachoroidal space. The microneedle was deployed and visualized; 50 lL cells (target concentration, 11.2 3 10 6 cells/mL [560,000 cells/eye]) or vehicle was injected subretinally. Safety outcomes were evaluated.RESULTS. For all animals, cells and vehicle were successfully administered. Labeled cells or fluorescent vehicle were contained in the subretinal bleb, without leakage into the vitreous. No retinal detachment or vitreous traction band was identified by ophthalmologic examination. At all time points, observed microscopic changes were attributable to experimental procedures. On histopathology immediately after injection, localized retinal detachments were seen, along with focal retinal, choroidal, and/or scleral discontinuities. A moderate inflammatory response was seen in a limited number of animals. In the allogeneic setting, no antibody responses were detectable. Anti-human UTC antibodies were detected in the xenogeneic setting.CONCLUSIONS. Palucorcel, pUTC, and vehicle were successfully administered to Göttingen minipigs using a novel subretinal injection cannula via a suprachoroidal surgical approach, with no significant adverse events; therefore, this technique appears to be feasible for further clinical development.

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Cannulation of the Suprachoroidal Space: A Novel Drug Delivery Methodology to the Posterior Segment

Cited by 150 publications

References 18 publications

Safety of Submacular Suprachoroidal Drug Administration via a Microcatheter: Retrospective Analysis of European Treatment Results

Safety of Submacular Suprachoroidal Drug Administration via a Microcatheter: Retrospective Analysis of European Treatment Results

Clinical Application of Drug Delivery Systems for Treating AMD

A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

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