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Suprachoroidal Delivery of Pharmacological Agents

Policy Number: MP-312

Last Review Date:  February 2022                                                   

Category:  Other      

POLICY:

Effective for dates of service on and after March 1, 2022:

Suprachoroidal delivery of a pharmacologic agent may be considered medically necessary for use with XIPERE™ (triamcinolone acetonide injectable suspension).

Suprachoroidal delivery of a pharmacologic agent is considered investigational in all other situations.

Effective for dates of service prior to March 1, 2022:

Suprachoroidal delivery of a pharmacologic agent is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

The delivery of pharmacologic agents to the suprachoroidal space has been investigated for the treatment of posterior eye segment disease. Two of the most posterior eye segment diseases are age-related macular degeneration and diabetic neuropathy. The posterior eye segment structures included the vitreous humor, retina, choroid, macula, and optic nerve.

The suprachoroidal delivery of a pharmacologic agent method uses a microcannula system that combines a drug delivery channel with a fiber optic light source for localization of the cannula tip. There are identified advantages and risks associated with this drug delivery method. One potential advantage of suprachoroidal injection is the ability to minimize systemic side-effects while delivering high local tissue levels of drugs.  A potential risk associated with utilizing this drug delivery method is the possibility localized tissue damage caused by the microcannula.

There exists various methods of invasive and noninvasive delivery of ocular medications. Some examples of invasive drug administration to intraocular cavities include: Suprachoroidal injections, Intravitreal surgery, Intravitreal injections, Intracameral surgery, Subretinal injection, and Intracameral injections. Some examples of invasive periocular and scleral modes of drug administration include: intrascleral surgery, episcleral surgery, periocular injections, subconjunctival injections, and transscleral diffusion from controlled release systems. There are several noninvasive method choices, such as topical administration on the eye, systemic administration (e.g. intravenous infusion or injection), and oral delivery. It is important to choose the delivery method that will most positively affect the net health outcomes of the patient with minimal risk of adverse effect.

The most widely used method of ocular drug delivery is topical or systemic. Topical application has remained the most preferred delivery route due to ease of administration. Topical application is useful in the treatment of disorders affecting the anterior segment of the eye. Although topical and systemic routes are convenient, they lack bioavailability and can fail to deliver therapeutic levels of drugs to the retina and posterior segment structures has prompted exploration of alternative routes of ocular drug administration.

KEY POINTS:

This policy has been updated with a review of literature performed through February 7, 2022.

Summary of Evidence

There is inadequate evidence regarding the clinical utility of suprachoroidal injection of pharmacologic agents for the treatment of any ophthalmologic condition. Clinical outcome studies published in peer-reviewed medical literature are needed to determine the value of this drug delivery method in the management of patients with diseases of the posterior segment of the eye. There is a paucity of well-designed clinical trials and scientific evidence to validate that this technology improves net health outcomes and is, therefore, considered investigational.

The drug, XIPERE™ (triamcinolone acetonide), is indicated for use in the treatment of macular edema associated with uveitis. This drug is only available in SCS (suprachoroidal space) injectable form. When the drug is appropriate for use, the suprachoroidal injection of a pharmacologic agent is also deemed appropriate.

Practice Guidelines and Position Statements

No guidelines or statements were identified.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Suprachoroidal delivery system, iTrack™, suprachoroidal delivery of pharmacological agents, SCS Microinjector®, Xipere™

APPROVED BY GOVERNING BODIES:

The iScience Surgical Ophthalmic Microcannula, or iTRACK™, is a flexible microcannula designed to allow atraumatic cannulation of spaces in the eye such as the anterior chamber and posterior segment, for infusion and aspiration of fluids during surgery, including saline and viscoelastics. The microcannula incorporates an optical fiber to allow transmission of light to the microcannula tip for surgical illumination and guidance. The iScience Surgical Ophthalmic Microcannula is indicated for fluid infusion and aspiration, as well as illumination, during surgery. This device received 501(k) clearance from the U.S. FDA in 2004.

XIPERE™ is administered with a SCS Microinjector®. XIPERE™ is a sterile, preservative-free, injectable suspension of triamcinolone acetonide, a synthetic corticosteroid for use with the SCS Microinjector®. The SCS Microinjector® is a piston syringe and a needle approximately 1 mm in length (900-µm and 1100-µm needles are included) for conducting the suprachoroidal injection. XIPERE™ received clearance from the FDA on October 22, 2021.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity. Special benefit consideration may apply.  Refer to member’s benefit plan.

CURRENT CODING:

CPT Codes

0465T 

  Suprachoroidal injection of a pharmacologic agent (does not include supply of medication) 

PREVIOUS CODING:

CPT Codes

67299

Unlisted procedure, posterior segment

REFERENCES:

  1. Abarca EM, Salmon JH, Gilger BC. Effect of choroidal perfusion on ocular tissue distribution after intravitreal or suprachoroidal injection in an arterially perfused ex vivo pig eye model. J Ocul Pharmacol Ther. 2013; 29(8):715-722.
  2. Bausch + Lomb and Clearside Biomedical announce FDA approval of Xipere™ (triamcinolone acetonide injectable suspension) for suprachoroidal use for the treatment of macular edema associated with uveitis. News release. Bausch Health Companies Inc. and Clearside Biomedical, Inc. https://www.prnewswire.com/news-releases/bausch–lomb-and-clearside-biomedical-announce-fda-approval-of-xipere-triamcinolone-acetonide-injectable-suspension-for-suprachoroidal-use-for-the-treatment-of-macular-edema-associated-with-uveitis-301407260.html. Accessed February 7, 2022.
  3. Chen M, Li X, Liu J, et al. Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model. J Control Release. 2015; 203:109-117.
  4. 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; 126:58-66.
  5. Del Amo EM, Urtti A.  Current and future ophthalmic drug delivery systems.  A shift to the posterior segment.  Drug Discov Today. 2008 Feb; 13(3-4):135-43.
  6. Emami-Naeini P, Yiu G. Medical and Surgical Applications for the Suprachoroidal Space. Int Ophthalmol Clin. 2019 Winter; 59(1):195-207. 
  7. Gilger BC, Mandal A, Shah S, et al. Episcleral, intrascleral, and suprachoroidal routes of ocular drug delivery -recent research advances and patents. Recent Pat Drug Deliv Formul. 2014; 8(2):81-91.
  8. Goldstein DA, Do D, Noronha G, et al. Suprachoroidal corticosteroid administration: A novel route for local treatment of noninfectious uveitis. Transl Vis Sci Technol. 2016; 5(6):14.
  9. Gu B, Liu J, Li X, et al. Real-time monitoring of suprachoroidal space (SCS) following SCS injection using ultra-high resolution optical coherence tomography in guinea pig eyes. Invest Ophthalmol Vis Sci. 2015; 56(6):3623-3634.
  10. Habot-Wilner Z, Noronha G, Wykoff CC, et al. Suprachoroidally injected pharmacological agents for the treatment of chorio-retinal diseases: A targeted approach. Acta Ophthalmol. 2019; 97(5):460-472.
  11. Hartman RR, Kompella UB. Intravitreal, subretinal, and suprachoroidal injections: Evolution of microneedles for drug delivery. J Ocul Pharmacol Ther. 2018; 34(1-2):141-153.
  12. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  13. iScience Interventional. iTrack™ Microcatheter [website]. Menlo Park, CA: iScience Interventional; 2008. Available at: http://www.iscienceinterventional.com/US/itrack.htm. Accessed January 4, 2022.
  14. Jung JH, Chae JJ, Prausnitz MR. Targeting drug delivery within the suprachoroidal space. Drug Discov Today. 2019 Aug; 24(8):1654-1659. 
  15. Kadam RS, Williams J, Tyagi P, et al. Suprachoroidal delivery in a rabbit ex vivo eye model: Influence of drug properties, regional differences in delivery, and comparison with intravitreal and intracameral routes. Mol Vis. 2013; 19:1198-1210.
  16. Khurana RN, Merrill P, Yeh S, et al. Extension study of the safety and efficacy of CLS-TA for treatment of macular oedema associated with non-infectious uveitis (MAGNOLIA). Br J Ophthalmol. 2021;0:0-6
  17. Kim YC, Oh KH, Edelhauser HF, Prausnitz MR. Formulation to target delivery to the ciliary body and choroid via the suprachoroidal space of the eye using microneedles. Eur J Pharm Biopharm. 2015; 95(Pt B):398-406.
  18. Olsen TW, Feng X, Wabner K, et al. Cannulation of the suprachoroidal space: A novel drug delivery methodology to the posterior segment. Am J Ophthalmol. 2006; 142(5):777-787.
  19. Park, B. Xipere for Suprachoroidal Use Approved for Macular Edema Associated With Uveitis. Oct 25, 2021. Retrieved from: https://www.empr.com/home/news/xipere-for-suprachoroidal-use-approved-for-macular-edema-associated-with-uveitis/. Accessed February 3, 2022.
  20. Patel SR, Lin AS, Edelhauser HF, Prausnitz MR. Suprachoroidal drug delivery to the back of the eye using hollow microneedles. Pharm Res. 2011; 28(1):166-176.
  21. Pearce W, Hsu J, Yeh S. Advances in drug delivery to the posterior segment. Curr Opin Ophthalmol. 2015; 26(3):233-239.
  22. Rai Udo J, Young SA, Thrimawithana TR, et al. The suprachoroidal pathway: A new drug delivery route to the back of the eye. Drug Discov Today. 2015; 20(4):491-495.
  23. Rizzo S, Ebert FG, Bartolo ED et al. Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates. Retina 2012; 32(4):776-84.
  24. Tayyab H, Ahmed CN, Sadiq MAA. Efficacy and safety of suprachoroidal triamcinolone acetonide in cases of resistant diabetic macular edema. Pak J Med Sci. 2020; 36(2):42-47.
  25. Tetz M, Rizzo S, Augustin AJ. Safety of submacular suprachoroidal drug administration via a microcatheter: retrospective analysis of European treatment results. Ophthalmologica 2012; 227(4): 183-9.
  26. Venkatesh P, Takkar B. Suprachoroidal injection of biological agents may have a potential role in the prevention of progression and complications in high myopia. Med Hypotheses. 2017; 107:90-91.
  27. Willoughby AS, Vuong VS, Cunefare D, et al. Choroidal changes after suprachoroidal injection of triamcinolone acetonide in eyes with macular edema secondary to retinal vein occlusion. Am J Ophthalmol. 2018; 186:144-151.
  28. U.S. Food and Drug Administration (FDA). iScience surgical ophthalmic microcannula. 510(k) Summary. K041108. iScience Surgical Corporation, Redwood City, CA. Rockville, MD: FDA; June 22, 2004. Accessed: January 4, 2022.
  29. XIPERE™ [prescribing information]. Alpharetta, GA: Clearside Biomedical, Inc.; 2021.
  30. Yeh S, Khurana RN, Shah M, et al. Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis: phase 3 randomized trial. Ophthalmology. 2020: 127(7):948-955.

POLICY HISTORY:

Medical Policy Group, December 2007 (2)

Medical Policy Administration Committee, January 2008

Available for comment January 5-February 20, 2008

Medical Policy Group, December 2008 (1) Update to Key Points and References; no change to policy statement

Medical Policy Group, December 2009 (1)

Medical Policy Group, December 2010 (1): Description updated, reference list updated.

Medical Policy Group, October 2011 (1): Update to Description, Key Points and References; no change in policy statement

Medical Policy Panel, December 2012

Medical Policy Group, January 2013 (1): Update to Key Points and References, no change to policy statement

Medical Policy Group, December 2013 (1): 2014 Coding Update: added unlisted code 67299, effective for use 01/01/2014; moved deleted code 0186T to Previous Coding section, effective 01/01/2014

Medical Policy Panel, December 2013

Medical Policy Group, January 2014 (1): Update to References with current literature search; no change to policy statement

Medical Policy Panel, December 2014

Medical Policy Group, February 2015 (6):  Update to Key Points, Approved by Governing Bodies and References; no change to policy statement. Effective January 1, 2015, policy reviewed by consensus.

Medical Policy Group, November 2019 (6): Updates to Description, Key Points, Governing Bodies, Current Coding (0465T) and References.

Medical Policy Group, January 2021 (6): Updates to Description, Key Points and References.

Medical Policy Group, January 2022 (9): Reviewed by consensus. References added. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, February 2022 (9): Reviewed by consensus. References added. No new published peer-reviewed literature available that would alter the coverage statement in this policy. Key Word added: SCS Microinjector®

Medical Policy Group, February 2022 (9):  Updates to Key Points, Approved By Governing Bodies, and References. Policy statement updated: "suprachoroidal delivery of a pharmacologic agent may be considered medically necessary for use with XIPERE™ (triamcinolone acetonide injectable suspension)" effective for dates of service on or after March 1, 2022. Key Word added: Xipere. Created previous coding section. Moved cpt code 67299 from current coding section to previous coding section.

Medical Policy Administration Committee, February 2022.

Available for comment March 1, 2022 through April 15, 2022. 


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.