Suprachoroidal space: Promising route for retinal drug delivery

Retinal vein occlusions (RVOs) are a frequent cause of retinal vascular disease in patients older than 50 years. They can result in vascular congestion, damage to vessel endothelium, and the release of inflammatory cytokines-triggering macular edema and decreased vision.

Primary therapies for patients with RVO include intraocular injections of anti-vascular endothelial growth factor (VEGF) drugs and steroids.

However, use of intravitreal steroids has been limited due to risks of cataract formation and IOP elevations. These potential adverse effects have led investigators to look for alternative approaches for delivering drugs to the retina, said Glenn Yiu, MD.

The suprachoroidal space is an exciting, new route for ocular drug delivery, said Dr. Yiu, assistant professor of ophthalmology, University of California, Davis School of Medicine, Sacramento, CA.

Animal models

Experimental animal studies showed that administering triamcinolone acetonide-a steroid with anti-inflammatory properties-into the suprachoroidal space of rabbit and pig eyes (using microneedles inserted anteriorly near the limbus) resulted in higher concentrations of the drug in the posterior retina than anterior segment structures such as the lens or trabecular meshwork, allowing treatment of ocular inflammation with lower risks of cataracts and IOP elevation.

However, while the pharmacokinetics of suprachoroidal drug delivery have been investigated in animal models, the ocular distribution and anatomic effects in human patients have not been thoroughly explored.

Enhanced-depth imaging OCT

A study recently published in the American Journal of Ophthalmology (2018;186:144-151) set out to evaluate the choroidal and suprachoroidal changes after suprachoroidal injection of triamcinolone acetonide using enhanced-depth imaging optical coherence tomography (EDI-OCT) in patients enrolled in the TANZANITE study.

The Suprachoroidal Injection of Triamcinolone Acetonide with Intravitreal Aflibercept in Subjects with Macular Edema due to Retinal Vein Occlusion (TANZANITE) study was a prospective, randomized, phase II, multicenter clinical trial that compared the effects of a single suprachoroidal injection of triamcinolone acetate suspension (CLS-TA, Clearside Biomedical) delivered using microneedles and an intravitreal injection of aflibercept (Eylea, Regeneron Pharmaceuticals) versus intravitreal aflibercept alone in eyes with RVO and macular edema.

Both the combination and monotherapy groups were then followed monthly and received additional intravitreal injections of aflibercept as needed over 3 months based on pre-defined re-treatment criteria.

Suprachoroidal space expansion

Though no significant changes were seen in choroidal thickness in either arm over the 3 months of the study, Dr. Yiu noted there was a trend toward suprachoroidal space expansion in the eyes in the combination group which received the suprachoroidal triamcinolone injections compared with the monotherapy arm (13.4 versus 5.3 μm, respectively) (p = 0.077).

When they examined only eyes in which the suprachoroidal space could be clearly seen on EDI-OCT images at baseline, they found the suprachoroidal expansion was significant (16.2 versus 27.8 μm) (p = 0.033) across months 1 to 3 of the study.

Although IOP increases developed in four eyes that received the combination treatment, two of these had pre-existing glaucoma. The suprachoroidal spaces in these patients did not differ significantly from the others.

Diving deeper

According to Dr. Yiu, this is the first study to show an anatomic change in the suprachoroidal space that may correspond to the effects of suprachoroidal drug delivery.

Nevertheless, Dr. Yiu cautions that it is unclear if the expansion represents persistent drug remaining in the suprachoroidal space or mechanical or pharmacologic changes caused by the drug injection.

Preclinical animal studies have shown a 90-day window when suprachoroidally injected triamcinolone can be detected. The possibility that OCT imaging may be used to follow suprachoroidal drug delivery is intriguing.

"Our findings provide novel insights into the ocular distribution and anatomic effects of suprachoroidal injection of triamcinolone acetonide suspension in patients with macular edema due to RVO. The suprachoroidal space influences both posterior and anterior segment disease processes, and continues to be a target for new interventions, including glaucoma drainage devices, IOP monitoring, and injections of pharmacologic agents. The advantages of suprachoroidal drug administration include the reduction of anterior segment exposure, lower risk of cataracts and glaucoma, and potentially more targeted or sustained drug delivery for treatment of retinal conditions," the investigators commented.

Disclosures:

Glenn Yiu, MD, PhD
E: gyiu@ucdavis.edu
This article was reviewed by Dr. Yiu. Dr. Yiu has no financial interest in any aspect of this report.