Pending Policies - Other


Suprachoroidal Delivery of a Pharmacologic Agent

Number:OTH903.035

Effective Date:11-01-2018

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. (2)

The SCS™ microinjector (Clearside Biomedical Inc. Alpharetta, GA) is a microneedle being developed for injection into the suprachoroidal space. The device is currently undergoing phase 2 and phase 3 clinical trials for the treatment of diabetic macular edema; retinal vein occlusion (RVO) and uveitis (macular edema associated with non-infectious uveitis). To date, the SCS™ microinjector (Clearside Biomedical Inc. Alpharetta, GA) has not yet received FDA approval. (3)

Rationale:

This policy was created in November 2016 and has been updated periodically with searches of the MEDLINE database. Following is a summary of the key literature through September 6, 2018.

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. (4) 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. (5) 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. (6) 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. (7) 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.

In 2016, Goldstein et al. (8) performed a phase I/II open-label, clinical trial to evaluate the safety, tolerability, and preliminary efficacy of suprachoroidal injection of triamcinolone acetonide in patients with non-infectious uveitis. A single suprachoroidal injection of 4-mg triamcinolone in 100 μl was performed in the study eye of patients with non-infectious intermediate, posterior, or pan uveitis, and follow-up obtained for 26 weeks. A total of 9 individuals with chronic uveitis were enrolled. There were 38 reported adverse events; most were mild or moderate in severity. Approximately 50% of the adverse events were ocular. The most common events were reported by 4 subjects who experienced ocular pain at or near the time of the injection. All systemic adverse events were unrelated to the study drug. No steroid-related increases in intra-ocular pressure were observed and no subject required intra-ocular pressure lowering medication. All 8 subjects had improvements in visual acuity; 4 subjects, who did not need additional therapy, had on average a greater than 2-line improvement in visual acuity through week 26; 3 of 4 had macular edema at baseline, and 2 of 3 had at least a 20% reduction in macular edema at week 26. The authors concluded that the safety and preliminary efficacy data support further investigations of suprachoroidal administered triamcinolone as a therapeutic option for the treatment of non-infectious uveitis.

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)

160

January 18, 2018

(completed, no study results posted)

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)

NCT03203447 (13)

Suprachoroidal Injection of Triamcinolone Acetonide With IVT Anti-VEGF in Subjects with Macular Edema Following RVO (TOPAZ)

460

August 2019 (Recruiting)

Table Key: NCT NationalClinical Trial

Practice Guidelines and Position Statements

The 2015 Guidelines of the American Academy of Ophthalmologists (14) do not include suprachoroidal delivery as a method for delivering drugs to the posterior regions of the eye.

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 outcomes. 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) – July 1, 2008. Available at <http://www.accessdata.fda.gov> (accessed September 6, 2018).

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. Alpharetta, GA. 2018. Available at <http://clearsidebio.com> (accessed September 6, 2018).

4. 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):135-143. PMID 18275911

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

6. 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

7. Pearce W, Hsu J, Yeh S, et al. Advances in drug delivery to the posterior segment. Curr Opin Ophthalmol. 2015 May; 26(3):233-9. PMID 25759965

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 Dec 14;5(6):14. PMID 27980877

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); 2016 October. Available at <http://clinicaltrials.gov> (accessed September 6, 2018). NCT02595398

11. Suprachoroidal Injection of Triamcinolone Acetonide in Subjects with Macular Edema Following Non-Infectious Uveitis (DOGWOOD). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Bethesda, MD: National Library of Medicine (US); 2016 Mar. Available at <http://clinicaltrials.gov> (accessed September 6, 2018). NCT 02255032

12. Safety Study of Suprachoroidal Triamcinolone Acetonide Via Microneedle to Treat Uveitis. In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine (US). 2016 July. Available at <http://clinicaltrials.gov> (accessed September 6, 2018). NCT01789320

13. Suprachoroidal Injection of Triamcinolone Acetonide With IVT Anti-VEGF in Subjects with Macular Edema Following RVO (TOPAZ). In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine (US). 2018 August 22. Available at <http://clinicaltrials.gov> (accessed September 6, 2018). NCT03203447

14. American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern® Guidelines. Age-related Macular Degeneration. American Academy of Ophthalmology. (2008, updated 2015 Jan). Available at <http://www.aao.org> (accessed September 6, 2018).

15. 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
11/1/2018 Document updated with literature review. Coverage unchanged. Added references 8,13,14.
10/15/2017 Reviewed. No changes.
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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