Comparison of Suprachoroidal Drug Delivery with Subconjunctival and Intravitreal Routes Using Noninvasive Fluorophotometry

Abstract

PurposeTo determine whether exposure of sodium fluorescein (NaF) to the choroid-retina region in the posterior segment of the eye is greater with suprachoroidal injection when compared to intravitreal and transscleral routes.MethodsSuprachoroidal injection, a new approach for drug delivery to the posterior segment of the eye was validated using a 34 G needle and Indian ink injections in Sprague Dawley rats, followed by histology. Delivery of NaF was compared in Sprague Dawley rats after suprachoroidal, posterior subconjunctival, or intravitreal injections. NaF levels were monitored noninvasively up to 6 hours using Fluorotron Master™, an ocular fluorophotometer Pharmacokinetic parameters were estimated using WinNonlin.ResultsHistological analysis indicated localization of India ink to the suprachoroidal space below sclera, following injection. NaF delivery to choroid-retina was in the order: suprachoroidal > intravitreal >posterior subconjunctival injection. Peak NaF concentration (Cmax) in choroid-retina was 36-fold (p = 0.001) and 25-fold (p = 0.001) higher after suprachoroidal (2744±1111 ng/ml) injection when compared to posterior subconjunctival (76±6 ng/ml) and intravitreal (108±39 ng/ml) injections, respectively. NaF exposure (AUC0–360min) to choroid-retina after suprachoroidal injection was 6-fold (p = 0.001) and 2-fold (p = 0.03) higher than posterior subconjunctival and intravitreal injections, respectively. Choroid-retina Tmax was observed immediately after dosing with suprachoroidal injections and at 10 and 27.5 minutes, respectively, with subconjunctival and intravitreal injections.ConclusionsSuprachoroidal injections are feasible in a rat model. Suprachoroidal injections resulted in the highest bioavailability, that is, the extent and rate of delivery of NaF to choroid-retina, when compared to intravitreal and posterior subconjunctival injections. Ocular fluorophotometry is useful for noninvasive monitoring of NaF in rats following administration by various routes including suprachoroidal route.

Circumferential flow of particles in the suprachoroidal space is impeded by the posterior ciliary arteries

“…The SCS is an attractive site of drug delivery targeted to the chorioretina (Chen et al, 2015; Einmahl et al, 2002; Gilger et al, 2013; Kadam et al, 2013; Olsen et al, 2006; Patel et al, 2012; Patel et al, 2011; Tyagi et al, 2012; Tzameret et al, 2014; Wang et al, 2012). However, targeting within the SCS is important as well, since sites of disease are often localized to specific regions of the chorioretina, such as localization of AMD to the macula and localization of tumors at their sites of growth.…”

“…Suprachoroidal delivery is being explored as a targeted ophthalmic drug delivery technique to treat posterior segment diseases that affect choroidal, retinal pigment epithelial, and/or retinal tissues (Chen et al, 2015; Einmahl et al, 2002; Gilger et al, 2013; Kadam et al, 2013; Olsen et al, 2006; Patel et al, 2012; Patel et al, 2011; Tyagi et al, 2012; Tzameret et al, 2014; Wang et al, 2012). The suprachoroidal space (SCS), which is a potential space between the sclera and choroid, is an attractive drug delivery site because it is directly adjacent to the diseased tissue in many posterior segment diseases, including age-related macular degeneration (AMD) and posterior uveitis (Ambati and Fowler, 2012; Gilger et al, 2013; Kim et al, 2014a).…”

Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model

“…The current study was designed to compare traditional subtenon drug delivery with the emerging technique of suprachoroidal drug delivery in the context of medical care of posterior segment eye diseases. Thus far, when comparing suprachoroidal drug delivery with intravitreal or transscleral drug delivery, drug level was computed from the mixture of choroid and retina for suprachoroidally injected eyes [20,11,12]. This can lead to an inflated drug level because the drug delivered to suprachoroidal space was sampled into the complex of choroid and retina.…”

“…Suprachoroidal cannulation and drug delivery were also reported to be damaging to the outer retina, including photoreceptors, in the primate eye model [10]. The most recent studies from Tyagi et al and Patel et al were encouraging and a good safety profile was depicted using a 34 gauge needle or a microneedle for the suprachoroidal injection [11,12].…”

“…For example, the amount of Avastin reaching the retina from suprachoroidal delivery was limited and cleared more quickly compared with intravitreal delivery [13]. In contrast, sodium fluorescein seems to behave differently [11,12]. Though suprachoroidal delivery may be different from subtenon and intravitreal routes, a sustained drug delivery formulation is equally important for all these ocular delivery routes.…”