Archived Policies - Other


Suprachoroidal Delivery of a Pharmacologic Agent

Number:OTH903.035

Effective Date:01-01-2017

End Date:10-14-2017

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Suprachoroidal delivery of a pharmacologic agent is considered experimental, investigational and/or unproven.

Description:

The structure of the eye is classified under 2 subheadings: anterior segment and posterior

segment. The anterior segment comprises the front one-third of the eye and includes the pupil, cornea, iris, ciliary body, aqueous humor, and lens; the posterior segment comprises the back two-thirds of the eye and includes the vitreous humor, retina, choroid, macula, and optic nerve. Posterior segment ocular diseases (e.g., age-related macular degeneration, diabetic neuropathy) are the most prevalent causes of visual impairment. The following is a list of the various routes for ocular drug administration:

Invasive drug administration to intraocular cavities:

o Suprachoroidal injections;

o Intravitreal surgery;

o Intravitreal injections;

o Intracameral surgery;

o Intracameral injections;

o Subretinal injection.

Invasive periocular and scleral modes of drug administration:

o Intrascleral surgery;

o Episcleral surgery;

o Periocular injections;

o Subconjunctival injections;

o Transscleral diffusion from controlled release systems.

Noninvasive methods:

o Topical administration on the eye.

Systemic administration:

o Intravenous infusion and injection;

o Oral.

Many ocular diseases are treated with either topical or systemic medications. 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, lack of bioavailability and failure to deliver therapeutic drug levels to the retina has prompted vision scientists to explore alternative routes of administration.

A potential advantage of suprachoroidal injection would be the ability to minimize systemic adverse effects while delivering higher drug levels to local tissues. This proposed benefit assumes that high drug local levels lead to improved outcomes. Weighed against this potential benefit is the risk of localized tissue damage from microcannulae. A microcannula system combines a drug delivery channel with a fiberoptic light source for localization of the cannula tip. This technique is being investigated for the treatment of subchoroidal neovascularization related to retinal diseases.

Regulatory Status

The iTRACK™ (Ellex, Adelaide, South Australia), which is a flexible microcannula designed to allow atraumatic cannulation of spaces in the eye for infusion and aspiration of fluids during surgery, received 510(k) marketing clearance from the U.S. Food and Drug Administration (FDA) in 2004. The microcannula incorporates an optical fiber to allow transmission of light to the microcannula tip for surgical illumination and guidance. The microcannula “is indicated for fluid infusion and aspiration, as well as illumination, during surgery.” (1) In a review of patented ocular drug delivery devices, Gilger et al. (2014) describe several suprachoroidal drug delivery devices and products (e.g., sustained-release hydrogels and microparticles) in development, none of which is currently FDA-approved. (2)

Clearside Biomedical (3) is developing several ocular drugs that are administered in the suprachoroidal space (SCS) including the SCS™ microinjector with ZupradaTM for the treatment of macular edema associated with noninfectious uveitis. The CLS-1001 consists of a “suprachoroidal space injection of Zuprata, our proprietary, preservative-free formulation of the corticosteroid triamcinolone acetonide (TA) specifically designed to be administered through our SCS™ microinjector” for treatment of patients with non-infectious uveitis. Clearside’s products (3) are not yet approved by the FDA.

Rationale:

This policy was created in November 2016 with the most recent literature search through October 31, 2016.

In 2007, Olsen et al. discussed industry-funded tests of the suprachoroidal injection technique in pig eyes. (4) Triamcinolone (3 mg) was found to remain at detectable levels in the posterior tissues of the pig eye for up to 120 days. Adverse events included infection (2/94), scleral ectasia (4/94), choroidal blood flow abnormalities (4/94), and inflammation (6/94). Some cannula tip designs resulted in snag lesions in the pigment epithelium, and the suprachoroidal space was found to separate from the sclera after injection of sodium hyaluronate but returned to a normal position after 1 month.

A 2008 review by Del Amo and Urtti discussed emerging methods of ocular drug delivery, which include polymeric-controlled release injections and implants; nano particulates; microencapsulated cells; iontophoresis; and gene therapy. (5) The authors noted that the biggest drug delivery challenge is to develop effective posterior segment therapies for use in the outpatient setting.

Periodic literature searches have identified 2 small studies from a single group of investigators. One was a prospective case series (2012) that used a microcatheter (iTRACK™) for suprachoroidal drug delivery to treat advanced, chronic macular edema with large subfoveal hard exudates in 6 eyes of 6 patients. (6) Subfoveal hard exudates were reported to be almost completely resolved at 1 to 2 months after a single suprachoroidal infusion of bevacizumab and triamcinolone, with no surgical or postoperative complications.

In 2012, these investigators published an industry-sponsored retrospective analysis of 21 eyes of 21 patients with choroidal neovascularization secondary to age-related macular degeneration treated with bevacizumab and triamcinolone using the iTRACK™ microcatheter. (7) Patients were included in the analysis if they had been unresponsive to at least 3 prior treatments, including thermal laser photocoagulation, photodynamic therapy, or intravitreal injections of pegaptanib, bevacizumab, or ranibizumab. Best-corrected visual acuity did not improve significantly from baseline through 6-month follow-up (baseline logMAR [minimum angle of resolution], 0.98; logMAR at 1 month, 0.92; logMAR at 6 months, 0.93; lower scores indicate improvement). There was a significant decrease in central foveal thickness (from 407 µm at baseline to 333 µm at 1 month). There was no visible evidence of retinal or choroidal tissue trauma in this safety and feasibility study.

In 2015, Pearce et al. (8) evaluated emerging drug delivery options to the posterior segment of the eye which would offer future treatment opportunities for vitreo-retinal disease. The authors summarized the advantages and limitations of the most commonly used ocular drug delivery methods, including vitreous dynamics, physician sustainability and patient preferences. Currently available, intra-vitreal, corticosteroid-release devices offer surgical and in-office management of retinal vascular disease and posterior uveitis. The suprachoroidal space offers a new anatomic location for the delivery of lower dose medications directly to the target tissue. Implantable drug reservoirs would potentially allow for less frequent intra-vitreal injections reducing treatment burdens and associated risks. Newer innovations in encapsulated cell technology offer promising results in early clinical trials. The authors concluded that although pars plana intra-vitreal injection remains the mainstay of therapy for many vitreo-retinal diseases, targeted delivery and implantable eluting devices are rapidly demonstrating safety and efficacy. They stated that these therapeutic modalities offer promising options for the vitreo-retinal therapeutic landscape.

UpToDate

In 2016, UpToDate (9) published an article on the treatment of uveitis. There is no mention of using suprachoroidal injections for the management of uveitis.

Ongoing and Unpublished Clinical Trials

Some unpublished trials that might influence this policy are listed in Table 1.

Table 1. Summary of Key Trials

NCT Number

Title

Estimated Enrollment

Date of Completion

NCT02595398 (10)

Suprachoroidal Injection of CLS-TA in Subjects with Macular Edema Associated with Non-infectious Uveitis (PEACHTREE)

150

July 2017

NCT02255032 (11)

Suprachoroidal Injection of Triamcinolone Acetonide in Subjects with Macular Edema Following Non-Infectious Uveitis (DOGWOOD)

22

January 2016

(completed, no study results posted)

NCT01789320 (12)

Safety Study of Suprachoroidal Triamcinolone Acetonide Via Microneedle to Treat Uveitis

11

March 2015

(completed, no study results posted)

Table Key: NCT NationalClinical Trial

Practice Guidelines and Position Statements

There are no guidelines or position statements that address the use of suprachoroidal drug delivery for the treatment of any indication.

Summary of Evidence

Delivery of pharmacologic agents to the suprachoroidal space is being investigated for the treatment of posterior eye segment diseases. Large randomized controlled clinical trials are needed to evaluate the safety and efficacy of suprachoroidal drug administration compared with the standard of care. Evidence to date comprises of small case series and review articles. Current evidence is insufficient to determine whether suprachoroidal delivery of pharmacologic agents improves overall net health outcome. Thus, this procedure is considered experimental, investigational and/or unproven.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

67299, 0465T

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. US Food and Drug Administration (FDA). Summary of Safety and Effectiveness: iScience Surgical Ophthalmic Microcannula (iTRACK) - June 22, 2004. Available at <http://www.accessdata.fda.gov>. (Accessed November 4, 2016).

2. 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. PMID 25001638.

3. Clearside Biomedical: Product Portfolio. Alpharetta, GA; 2016. Available at <http://clearsidebio.com>. (Accessed 11/1/2016).

4. Olsen, T. Drug delivery to the suprachoroidal space shows promise. Retina Today; March 2007. Available at <http://retinatoday.com>. (Accessed November 2, 2016).

5. Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov Today. Feb 2008; 13(3-4):135-143. PMID 18275911.

6. Rizzo S, Ebert FG, Bartolo ED, et al. Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates. Retina. Apr 2012; 32(4):776-784. PMID 21817959.

7. 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):183-189. PMID 22354263.

8. Pearce W. et al. Advances in drug delivery to the posterior segment. 2015 May; 26(3):233-9. PMID: 25759965.

9. Rosenbaum, James. Uveitis: Treatment. In: UpToDate Post TW (Ed), UpToDate, Waltham, MA. Topic last updated: August 3, 2016. Available at <http://www.uptodate.com> (Accessed November 2, 2016).

10. Clearside Biomedical, Inc. Suprachoroidal Injection of CLS-TA in Subjects with Macular Edema Associated with Non-infectious Uveitis (PEACHTREE). Bethesda MD: National Library of Medicine (US); October 2016. Available at < http://clinicaltrials.gov>. (Accessed November 1, 2016). NCT02595398.

11. Clearside Biomedical, Inc. Suprachoroidal Injection of Triamcinolone Acetonide in Subjects with Macular Edema Following Non-Infectious Uveitis (DOGWOOD). Bethesda, MD: National Library of Medicine (US); March 2016. Available at http://clinicaltrials.gov> (Accessed November 1, 2016). NCT 02255032.

12. Clearside Biomedical, Inc. Safety Study of Suprachoroidal Triamcinolone Acetonide Via Microneedle to Treat Uveitis. Bethesda, MD: National Library of Medicine (US). July 2016. Available at <http://clinicaltrials.gov> (Accessed November 1, 2016). NCT01789320.

13. Suprachoroidal Delivery of Pharmacologic Agents - Archived. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2014 December) Other 9.03.19.

Policy History:

Date Reason
1/1/2017 New Medical Document. Suprachoroidal delivery of a pharmacologic agent is considered experimental, investigational and/or unproven.

Archived Document(s):

Title:Effective Date:End Date:
Suprachoroidal Delivery of a Pharmacologic Agent10-15-201710-31-2018
Suprachoroidal Delivery of a Pharmacologic Agent01-01-201710-14-2017
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