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

Puneet Tyagi,Rajendra S Kadam,Uday B Kompella,Tiansen Li

doi:10.1371/journal.pone.0048188

Puneet Tyagi, Rajendra S Kadam + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0048188

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Journal: PloS one	Publication Date: Oct 31, 2012
Citations: 92	License type: CC BY 4.0

Affiliation: University of Colorado Anschutz Medical Campus

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.

Highlights

Diseases of the posterior segment of the eye are responsible for severe vision loss and blindness in the developed countries
10% of the subjects suffering from age related macular degeneration (AMD) are diagnosed with the growth of abnormal or leaky blood vessels in the choroid below the retina, a condition known as wet AMD or choroidal neovascularization (CNV)
Suprachoroidal injection resulted in widening of suprachoroidal space as compared to control eyes (Figure 1D), which might be due to the pressure created by the India ink injection

Summary

Introduction

Diseases of the posterior segment of the eye are responsible for severe vision loss and blindness in the developed countries. As of 2008, AMD is prevalent in 8 million in the USA and is expected to increase to 12 million by 2020 [1]. CNV is primarily responsible for significant loss of vision and blindness in AMD patients. Diabetic retinopathy is prevalent in 4.1 million people in the United States, with nearly 22% (0.9 million) of diabetic patients having vision threatening diabetic retinopathy [2]. Despite the severity and increasing prevalence of back of the eye diseases, conventional drug delivery methods are either inefficient in delivering required amount of drug to the site of action or highly invasive to the vitreous humor, with significant side effects

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