What's New in Ocular Drug Delivery: Advances in Suprachoroidal Injection since 2023

Abstract

Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing direct access to the choroid and retina while minimizing systemic exposure and side effects. This review examines the anatomical and physiological foundations of the SC space; evaluates delivery devices such as microcatheters, hypodermic needles, and microneedles; and discusses pharmacokinetic principles. Additionally, advancements in gene delivery through SC injections are explored, emphasizing their potential to transform ocular disease management. This review also highlights clinical applications in treating macular edema, diabetic macular edema, age-related macular degeneration, choroidal melanoma, and glaucoma. Overall, SC injections are emerging as a promising novel route for administering ophthalmic treatments, with high bioavailability, reduced systemic exposure, and favorable safety profiles. Key therapeutic agents such as triamcinolone acetonide, dexamethasone, AAV-based gene therapy, and axitinib have shown promise. The field of suprachoroidal injection is progressing rapidly, and this review article, while attempting to encapsulate most of the published preclinical and clinical studies, mainly focuses on those that are published within 2023 and 2024.

Keywords: choroid; cost-benefit analysis; humans; injections; intraocular; quality of life; retinal diseases; treatment outcome; visual acuity.

Figure 1

(A) Diagram of the three main suprachoroidal delivery systems: Microcatheter, hypodermic needle and microneedle. Created by Biorender. (B) Image of a lab-based microneedle for suprachoroidal delivery. Reprinted from Katz et al., 2024 [24]. Used under CC BY-NC-ND 4.0.

Figure 2

An overview of various ophthalmic medication administration routes. This figure illustrates a range of posterior segment administration methods in ophthalmic medicine, including suprachoroidal, intravitreal, and subretinal administration routes. Created with BioRender.com. Copyright © Kevin Y. Wu, 2024.

Figure 3

This figure illustrates the anatomical distribution and clearance pathways within suprachoroidal space. The red lines and red boxes highlight specific anatomical barriers that restrict fluid movement and protect the retina from systemic influences. Orange boxes represent different elimination pathways.

Figure 4

Comparison of changes in best-corrected visual acuity after SC injection of 4.0mg of triamcinolone acetate versus a sham injection from the PEACHTREE trial [129]. (A) Bar graph showing percent of patients gaining 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline at Week 24. (B) Graph showing mean ± standard error of the mean change from baseline in best-corrected visual acuity in ETDRS letters read at each visit. (C) Graph showing percent of patients reading 70 or more ETDRS letters (approximately 20/40 or better) at each visit. CLS-TA = triamcinolone acetonide formulation; LOCF = last observation carried forward. Used under CC BY-NC-ND 4.0.

Figure 5

Ultrasound biomicroscope images of hydrogel-injected eyes. (A) The red arrow indicates the approximate location of the injection site and the red dashed line roughly outlines the enlarged suprachoroidal space after injection of the hydrogels [168]. Used under CC BY-NC-ND 4.0. (B) The yellow arrow indicates the approximate injection site, and the yellow dashed line roughly outlines the expanded suprachoroidal space [169]. Used under CC BY-NC-ND 4.0.

Figure 6

This figure illustrates the clinical development stages of various therapeutic agents delivered via suprachoroidal injection for different ocular conditions. The progress of these therapies demonstrates ongoing advancements and the potential for new treatments for ocular diseases.