The Use of Suprachoroidal Triamcinolone Acetonide to Treat Macular Edema in Retinal Vein Occlusion

Study Overview
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Brief Summary
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This prospective non-randomized open-label interventional study aimed to evaluate feasibility in regard to potential efficacy and safety of triamcinolone acetonide (TA) injected in the suprachoroidal space (SCS) as a promising therapeutic route that provides a better bioavailability, longer sustained duration of action, and thus improved patients' compliance for the treatment of macular edema due to retinal vein occlusion (RVO).

Detailed Description
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Management of Macular Edema (ME) associated with Retinal Vein Occlusion (RVO) still poses a therapeutic challenge taking into account its complicated etiopathogenesis. Despite improved visual and anatomical outcomes achieved by intravitreal injections of antiangiogenics and steroids, these treatments are still associated with non-responders, tachyphylaxis, rebound phenomenon, high re-injection, and adverse events rates, which underscore the importance of addressing new approaches to formulate treatment strategies. Delivery of therapeutic agents into the suprachoroidal space (SCS) provides a novel alternative approach that has theoretical appeal, as it dominantly targets chorioretinal tissues with the posterior and circumferential spread of the drug administered while relatively sparing the unaffected anterior segment of the eye and the vitreous chamber, thus minimizing risks associated with off-target effects, which potentiates safety. This was well translated in preclinical and clinical studies through microinjector, which has been shown to provide a safe, minimally invasive, and reliable method of targeting SCS. In addition, sustained duration and favorable pharmacokinetics have been observed for small molecule suspensions including Triamcinolone Acetonide (TA), with the potential to reduce treatment burden.

Official Title
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Suprachoroidal Triamcinolone Acetonide for the Treatment of Macular Edema Associated With Retinal Vein Occlusion: A Pilot Study

Conditions
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Macular Edema, Retinal Vein Occlusion

Intervention / Treatment
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* Drug: suprachoroidal injection of Triamcinolone Acetonide.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or nonpregnant female patients >18 years of age. Has a clinical diagnosis of Retinal Vein Occlusion (RVO) in the study eye. Best-Corrected Visual Acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score ≥ 20 (20/400 Snellen equivalent), and ≤75 in the study eye (20/32 Snellen equivalent). Central Subfield Thickness (CST) ≥310 microns measured by Spectral Domain Optical Coherence Tomography (SD-OCT) in the study eye. Exclusion Criteria: Intravitreal (IVT) injection of anti-VEGF: Bevacizumab (Avastin; Genentech, South San Francisco, CA, USA/Roche, Basel, Switzerland) or ranibizumab (Lucentis; Genentech Inc., South San Francisco, CA, USA) within 1 month and aflibercept (Eylea®; Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA, and Bayer HealthCare Pharmaceuticals, Berlin, Germany) within 2 months in the study eye. Intraocular or periocular corticosteroid injection within 3 months, dexamethasone implant (Ozurdex, Allergan, Dublin, Ireland) within 6 months, Retisert (Bausch and Lomb, Bridge water, NJ) within 1 year, or fluocinolone acetonide implant (Iluvien, Alimera Sciences, Alpharetta, GA) within 3 years in the study eye. Macular laser photocoagulation treatment in the study eye. Topical ophthalmic nonsteroidal anti-inflammatory drugs in the study eye within a month. Any significant media opacity that could hinder the evaluation of the retina or ocular condition causing decreased vision other than RVO. IOP >22 mm Hg, or history of steroid-induced ocular hypertension; uncontrolled glaucoma. Past vitreoretinal or glaucoma surgery in the study eye. Uncontrolled systemic disease that could hinder follow-up, immunodeficiency, or any other systemic contraindication for steroids.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4 mg Triamcinolone Acetonide (TA)/ Suprachoriodal Injection<br>Suprachoroidal injection of 4 mg in 100 μL of TA was administered as a single injection. | Drug: suprachoroidal injection of Triamcinolone Acetonide.<br>* 4 mg /0.1 ml TA was injected in the SCS using an individualized microinjector according to scleral thickness measured by anterior segment OCT (AS-OCT) at the injection point (4 mm from the limbus in the inferotemporal quadrant).<br>* Other names: SCTA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with BCVA gain≥ 15 Letters at 3 months | Percentage of participants with ≥ 15 letter Improvement from Baseline Best corrected visual acuity (BCVA) using Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity score: BCVA refers to the measurement of the best possible vision that can be achieved following refraction. BCVA was assessed using a Snellen chart. The resultant measures were converted to Early Treatment of Diabetic Retinopathy Study ETDRS letter score. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement. | 3 months after injection | 
| Percentage of participants with IOP ≥20 mm Hg at 3 months | Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method that eye care professionals use to determine this. Tonometers in this study were calibrated to measure pressure in millimeters of mercury. | 3 months after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the BCVA | Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction. BCVA was assessed using a Snellen chart. The resultant measures were converted to ETDRS letter score. A positive change from baseline value represents an improvement in vision. | 1 week, 1 month, 2 months and 3 months after injection. | 
| Change in the CST | Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT) (Heidelberg Spectralis; Heidelberg Engineering, Germany). A negative change from baseline value represents a reduction in macular edema. | 1 week, 1 month, 2 months and 3 months after injection. | 
| Change in the Proportion of Participants with CST ≤ 320 μ | Central subfield thickness (CST) is the average macular thickness in the central circular area 1 mm in diameter centered around the fovea and is a diagnostic measurement applied to diagnose macular edema. CST was measured using spectral domain optical coherence tomography (SD-OCT) (Heidelberg Spectralis; Heidelberg Engineering, Germany). | 1 week, 1 month, 2 months and 3 months after injection. | 
| Change in the Percentage of Reduction in Excess Foveal Thickness (EFT) | Excess Foveal Thickness (EFT) was estimated by subtracting 310 µ from the central subfield thickness (CST). CST was measured using spectral domain optical coherence tomography (SD-OCT) (Heidelberg Spectralis; Heidelberg Engineering, Germany). | 1 week, 1 month, 2 months and 3 months after injection. | 
| Change in the Serious Treatment-Emergent Adverse Events (S-TEAEs) | Number of patients with Serious Treatment-Emergent Adverse Events (S-TEAEs): A treatment-emergent adverse event (TEAE) is the development of an undesirable medical condition or the worsening of a preexisting medical condition either in intensity or frequency after exposure to a pharmaceutical product. Ophthalmic Serious TEAEs include Endophthalmitis, intraocular inflammation, vitreal hemorrhage, retinal tear and Rhegmatogenous retinal detachment. These Adverse Events were evaluated through anterior and posterior segments examination using slit lamp biomicroscopy and indirect ophthalmoscopy. | 1 week, 1 month, 2 months and 3 months after injection. | 
| Change in the IOP | Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method that eye care professionals use to determine this. Tonometers in this study were calibrated to measure pressure in millimeters of mercury. | 1 week, 1 month, 2 months and 3 months after injection. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RVO, Macular Edema, Retinal Vein Occlusion, Suprachoroidal Space, Triamcinolone Acetonide, ME