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Purpose: Injection of pharmacotherapy into the suprachoroidal space, between the sclera and choroid, is an alternative delivery technique developed with the rationale of providing higher drug concentrations to posterior ocular structures compared with other intraocular and periocular injection procedures. This study was conducted to evaluate the safety and efficacy of suprachoroidally injected triamcinolone acetonide formulation (CLS-TA), a suspension of triamcinolone acetonide, in improving vision among patients with noninfectious uveitis complicated by macular edema (ME)., Design: Phase 3 masked, randomized trial., Participants: One hundred sixty patients with ME secondary to noninfectious uveitis. Patients were required to have a best-corrected visual acuity (BCVA) of 5 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent, 20/800) and 70 or fewer ETDRS letters read (Snellen equivalent, 20/40) in the study eye., Methods: Patients were randomized 3:2 to suprachoroidally injected CLS-TA or sham treatment, with administrations at day 0 and week 12., Main Outcome Measures: The primary end point was improvement from baseline of 15 or more ETDRS letters in BCVA at week 24. The secondary end point was reduction from baseline in central subfield thickness (CST) at week 24., Results: In the CLS-TA arm, 47% of patients gained 15 or more ETDRS letters in BCVA versus 16% in the control arm (P < 0.001), meeting the primary end point. Mean reductions in CST from baseline were 153 μm versus 18 μm (P < 0.001). No serious adverse events (AEs) related to treatment were reported. Corticosteroid-associated AEs of elevated intraocular pressure occurred in 11.5% and 15.6% of the CLS-TA and control groups, respectively. Cataract AE rates were comparable (7.3% and 6.3%, respectively)., Conclusions: Patients in the CLS-TA study arm experienced clinically significant improvement in vision relative to the sham procedure, demonstrating the efficacy of suprachoroidal injection of CLS-TA for the treatment of ME in a vision-threatening disorder., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis., Methods: Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography., Results: Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure., Conclusion: A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

Background and Objective: To study anatomic changes in the suprachoroidal space (SCS) following suprachoroidal injection of CLS-TA, triamcinolone acetonide injectable suspension., Patients and Methods: Eyes with diabetic macular edema receiving CLS-TA were imaged serially using anterior segment spectral-domain optical coherence tomography to examine the SCS., Results: At the final imaging session, the SCS was not significantly different in study eyes (n = 14; 8.4 μm) compared to fellow eyes (n = 10; 8.1 μm; P = .698). Two eyes were imaged immediately before and 30 minutes after suprachoroidal injections; in these eyes, mean suprachoroidal width increased significantly following CLS-TA injection, 9.9 μm to 75.1 μm (P < .001), and subsequently returned to 14.9 μm 1 month after the final injection (P = .221)., Conclusion: Suprachoroidal CLS-TA injection caused a measurable increase in the SCS, which returned to preinjection levels by 1 month following injection with no apparent lasting impact on SCS anatomy. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:692-697.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To evaluate choroidal and suprachoroidal changes following suprachoroidal injection of triamcinolone acetonide injectable suspension (CLS-TA), in eyes with macular edema due to retinal vein occlusion (RVO)., Design: Prospective cohort study within a randomized, controlled phase 2 clinical trial., Methods: Enhanced depth imaging optical coherence tomography (EDI-OCT) images were analyzed from 38 eyes of 38 treatment-naïve patients with macular edema due to RVO, enrolled in the prospective Suprachoroidal Injection of Triamcinolone Acetonide with Intravitreal Aflibercept in Subjects with Macular Edema Due to Retinal Vein Occlusion (TANZANITE) study who received either a suprachoroidal injection of CLS-TA with an intravitreal injection of aflibercept (combination arm) or only an intravitreal injection of aflibercept (monotherapy arm), followed by monthly intravitreal aflibercept injections in both arms based on pro re nata criteria., Results: Macular choroidal thickness measured to the outer choroidal vessel lumen (vascular choroidal thickness, VCT), outer choroid stroma (stromal choroidal thickness, SCT), or inner scleral border (total choroidal thickness, TCT) showed no significant changes over 3 months in both study arms (P = .231-.342). Eyes that received combination therapy showed a trend toward thickening of the suprachoroidal space (SCS) compared with monotherapy alone (13.4 μm vs 5.3 μm at 3 months; P = .077). In the 15 eyes that demonstrated a visible SCS at baseline, the SCS expanded significantly after suprachoroidal CLS-TA injection (16.2 μm to 27.8 μm at 3 months; P = .033)., Conclusions: Suprachoroidal injection of CLS-TA does not alter choroidal thickness in eyes with macular edema due to RVO, but may result in expansion of the SCS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Delivery of pharmaceuticals to the posterior segment presents challenges that arise from the anatomy and clearance pharmacokinetics of the eye. Systemic and several local administration options [topical, periocular, intravitreal (IVT) and subretinal] are in clinical use, each with a unique benefit to risk profile shaped by factors including the administered agent, frequency of dosing, achievable pharmaceutical concentrations within posterior segment structures versus elsewhere in the eye or the body, invasiveness of the procedure and the inherent challenges with some administration methods. The use of the suprachoroidal space (SCS), which is the region between the sclera and the choroid, is being explored as a potential approach to target pharmacotherapies to the posterior segment via a minimally invasive injection procedure. Preclinical data on agents such as vascular endothelial growth factor inhibitors and triamcinolone acetonide (TA) indicate that administration via suprachoroidal injection results in more posterior distribution of the pharmacologic agent, with higher exposure to the sclera, choroid, retinal pigment epithelium cells and retina, and lesser exposure to the anterior segment, than observed with IVT administration. Based in part on these findings, clinical trials have explored the efficacy and safety of suprachoroidal administration of pharmacologic therapies in conditions affecting the posterior segment. Data on a proprietary formulation of TA administered by suprachoroidal injection show improvement in anatomic and visual outcomes in subjects with noninfectious uveitis, with the potential to mitigate the known risks of cataract and increased intraocular pressure (IOP) associated with the use of intraocular corticosteroids. Suprachoroidal administration appears to be a promising treatment modality and is also in the early stages of investigation for other possible applications, such as injection of antiglaucoma agents into the anterior SCS for long‐lasting control of elevated IOP, and as a mode of delivery for gene‐ or cell‐based therapies for retinal disorders. [ABSTRACT FROM AUTHOR]