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

Macular Edema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05038072
• Other study ID #: UDMS-Opthal-01-2021
• Status: Completed
• Phase: N/A
• Start date: July 25, 2019
• Est. completion date: February 28, 2021

Study information

• Verified date: August 2021
• Source: Damascus University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 28, 2021
• Est. primary completion date: November 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or nonpregnant female patients >18 years of age.

2. Has a clinical diagnosis of Retinal Vein Occlusion (RVO) in the study eye.

3. 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).

4. Central Subfield Thickness (CST) =310 microns measured by Spectral Domain Optical Coherence Tomography (SD-OCT) in the study eye.

Exclusion Criteria:

1. 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.

2. 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.

3. Macular laser photocoagulation treatment in the study eye.

4. Topical ophthalmic nonsteroidal anti-inflammatory drugs in the study eye within a month.

5. Any significant media opacity that could hinder the evaluation of the retina or ocular condition causing decreased vision other than RVO.

6. IOP >22 mm Hg, or history of steroid-induced ocular hypertension; uncontrolled glaucoma.

7. Past vitreoretinal or glaucoma surgery in the study eye.

8. Uncontrolled systemic disease that could hinder follow-up, immunodeficiency, or any other systemic contraindication for steroids.

Related Conditions & MeSH terms

• Edema
• Macular Edema
• Retinal Vein Occlusion

Intervention

Drug:
• suprachoroidal injection of Triamcinolone Acetonide.
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).

Locations

Country	Name	City	State
Syrian Arab Republic	Al Mouwasat University Hospital, Department of Ophthalmology	Damascus

Sponsors (1)

Lead Sponsor	Collaborator
Damascus University

Country where clinical trial is conducted

Syrian Arab Republic, 

References & Publications (10)

Campochiaro PA, Sophie R, Pearlman J, Brown DM, Boyer DS, Heier JS, Marcus DM, Feiner L, Patel A; RETAIN Study Group. Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study. Ophthalmology. 2014 Jan;121(1):209-219. doi: 10.1016/j.ophtha.2013.08.038. Epub 2013 Oct 7. — View Citation

Campochiaro PA, Wykoff CC, Brown DM, Boyer DS, Barakat M, Taraborelli D, Noronha G; Tanzanite Study Group. Suprachoroidal Triamcinolone Acetonide for Retinal Vein Occlusion: Results of the Tanzanite Study. Ophthalmol Retina. 2018 Apr;2(4):320-328. doi: 10.1016/j.oret.2017.07.013. Epub 2017 Sep 29. — View Citation

Chiang B, Jung JH, Prausnitz MR. The suprachoroidal space as a route of administration to the posterior segment of the eye. Adv Drug Deliv Rev. 2018 Feb 15;126:58-66. doi: 10.1016/j.addr.2018.03.001. Epub 2018 Mar 12. Review. — View Citation

Ciulla T, Pollack JS, Williams DF. Visual acuity outcomes and anti-VEGF therapy intensity in macular oedema due to retinal vein occlusion: a real-world analysis of 15 613 patient eyes. Br J Ophthalmol. 2020 Oct 14. pii: bjophthalmol-2020-317337. doi: 10.1136/bjophthalmol-2020-317337. [Epub ahead of print] — View Citation

Habot-Wilner Z, Noronha G, Wykoff CC. Suprachoroidally injected pharmacological agents for the treatment of chorio-retinal diseases: a targeted approach. Acta Ophthalmol. 2019 Aug;97(5):460-472. doi: 10.1111/aos.14042. Epub 2019 Jan 31. Review. — View Citation

Hancock SE, Wan CR, Fisher NE, Andino RV, Ciulla TA. Biomechanics of suprachoroidal drug delivery: From benchtop to clinical investigation in ocular therapies. Expert Opin Drug Deliv. 2021 Jun;18(6):777-788. doi: 10.1080/17425247.2021.1867532. Epub 2021 Jan 3. — View Citation

Moisseiev E, Loewenstein A, Yiu G. The suprachoroidal space: from potential space to a space with potential. Clin Ophthalmol. 2016 Jan 25;10:173-8. doi: 10.2147/OPTH.S89784. eCollection 2016. — View Citation

Spooner K, Fraser-Bell S, Hong T, Chang AA. Five-year outcomes of retinal vein occlusion treated with vascular endothelial growth factor inhibitors. BMJ Open Ophthalmol. 2019 Mar 29;4(1):e000249. doi: 10.1136/bmjophth-2018-000249. eCollection 2019. — View Citation

Wan CR, Kapik B, Wykoff CC, Henry CR, Barakat MR, Shah M, Andino RV, Ciulla TA. Clinical Characterization of Suprachoroidal Injection Procedure Utilizing a Microinjector across Three Retinal Disorders. Transl Vis Sci Technol. 2020 Oct 22;9(11):27. doi: 10.1167/tvst.9.11.27. eCollection 2020 Oct. — View Citation

Wan CR, Muya L, Kansara V, Ciulla TA. Suprachoroidal Delivery of Small Molecules, Nanoparticles, Gene and Cell Therapies for Ocular Diseases. Pharmaceutics. 2021 Feb 22;13(2). pii: 288. doi: 10.3390/pharmaceutics13020288. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.