Subject:
Suprachoroidal Delivery of Pharmacologic Agents
Description:
_______________________________________________________________________________________
IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
__________________________________________________________________________________________________________________________
Delivery of pharmacologic agents to the suprachoroidal space is being investigated for treatment of posterior eye segment diseases.
Background
The structure of the eye is classified under 2 subheadings: (1) anterior segment and (2) posterior segment. The anterior segment consists of the front one-third of the eye and includes the pupil, cornea, iris, ciliary body, aqueous humor, and lens; the posterior segment consists of the back two-thirds of the eye and includes the vitreous humor, retina, choroid, macula, and optic nerve. Posterior segment ocular diseases (eg, 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
- Suprachoroidal injections
- Intravitreal surgery
- Intravitreal injections
- Intracameral surgery
- Intracameral injections
- Subretinal injection
- Invasive periocular and scleral modes of drug administration
- Intrascleral surgery
- Episcleral surgery
- Periocular injections
- Subconjuctival injections
- Transscleral diffusion from controlled release systems
- Noninvasive methods
- Topical administration on the eye
- Systemic administration
- Intravenous infusion and injection
- 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 levels of drugs to the retina has prompted vision scientists to continue to explore alternative routes of administration.
One potential advantage of suprachoroidal injection would be the ability to minimize systemic adverse effects while delivering higher local tissue levels of drugs. This proposed benefit assumes that high local levels lead to improved outcomes. Weighed against this potential benefit is the risk of localized tissue damage from the microcannula. 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 diseases of the retina.
Regulatory Status
The iTRACK™ (iScience Interventional), 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. 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 (eg, sustained-release hydrogels and
microparticles) in development, none of which is currently FDA-approved. (2)
Related Policies
- Photodynamic Therapy for Choroidal Neovascularization (Policy #027 in the Treatment Section)
- Transpupillary Thermotherapy for Treatment of Choroidal Neovascularization (Policy #126 in the Treatment Section)
- Intraocular Radiation Therapy for Age-Related Macular Degeneration (Policy #076 in the Radiology Section)
- Angiogenic Inhibitors for the Treatment of Ophthalmic Macular Conditions (Policy #080 in the Treatment Section)
Policy:
(NOTE: For Medicare Advantage, Medicaid and FIDE-SNP, please refer to the Coverage Sections below for coverage guidance.)
Suprachoroidal delivery of a pharmacologic agent is considered investigational.
Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
Medicaid Coverage:
For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.
FIDE-SNP Coverage:
For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.
[RATIONALE: The most recent literature search was performed through January 2018.
When this policy was created, searches of the MEDLINE database did not identify any clinical studies on the suprachoroidal delivery of pharmacologic agents. One 2007 review discussed industry-funded tests of the suprachoroidal injection technique in pig eyes.(3) 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 of 94), scleral ectasia (4 of 94), choroidal blood flow abnormalities (4 of 94), and inflammation (6 of 94). Some cannula tip designs resulted in snag lesions in the pigment epithelium, and the suprachoroidal space was found to separate from the sclera following injection of sodium hyaluronate but returned to a normal position after 1 month. Clinical trials in humans were reported to be ongoing.
A 2008 review by Del Amo and Urtti discussed the emerging methods of ocular drug delivery, which include polymeric-controlled release injections and implants; nanoparticulates; microencapsulated cells; iontophoresis; and gene therapy.(4) The authors note the biggest drug delivery challenge is to develop effective methods for posterior segment therapies that would also be applicable for outpatient use.
Periodic literature has identified 2 small studies from the same group of investigators. One was a prospective case series (2012) that used a microcatheter (iTRACK) for suprachoroidal drug delivery for the treatment of advanced, chronic macular edema with large subfoveal hard exudates in 6 eyes of 6 patients.(5) The subfoveal hard exudates were reported to be almost completely resolved at 1 to 2 months following a single suprachoroidal infusion of bevacizumab and triamcinolone, with no surgical or postoperative complications.
In 2012, these investigators also published an industry-sponsored retrospective analysis of 21 eyes of 21 patients with choroidal neovascularization secondary to age-related macular degeneration that were 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 the 6-month follow-up (0.98 logMAR [minimum angle of resolution] at baseline, 0.92 logMAR at 1 month and 0.93 logMAR at 6 months; lower scores indicate improvement). There was a significant decrease in central foveal thickness (407.2 mm at baseline to 333.3 mm at 1 month). There was no visible evidence of retinal or choroidal tissue trauma in this safety and feasibility study.
Summary of Evidence
Controlled clinical trials are needed to evaluate the safety and efficacy of suprachoroidal drug administration compared to the standard of care. Evidence to date consists of 2 small case series from the same group of investigators in Europe. Current evidence is insufficient to determine whether suprachoroidal delivery of pharmacologic agents improves the net health outcome. Thus, this procedure is considered investigational.
SUPPLEMENTAL INFORMATION
Practice Guidelines and Position Statements
No guidelines or statements were identified.
U.S. Preventive Services Task Force Recommendations
Not applicable.]
________________________________________________________________________________________
Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
___________________________________________________________________________________________________________________________
Index:
Suprachoroidal Delivery of Pharmacologic Agents
iTRACK
References:
1. U.S. Food and Drug Administration. Center for Devices and Radiological Health. Summary of Safety and Effectiveness: iScience Surgical Ophthalmic Microcannula (iTRACK) - June 22, 2004. Available online at: http://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm?db=pmn&id=K041108. Last accessed November 2013.
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. Olsen T. Drug delivery to the suprachoroidal space shows promise. Retina Today; March/April 2007. 2007. Available online at: http://www.retinatoday.com/Html%20Pages/0307/0307_feature_olsen.pdf. Last accessed November 2013.
4. Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug discovery today 2008; 13(3-4):135-43.
5. Rizzo S, Ebert FG, Bartolo ED et al. Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates. Retina (Philadelphia, Pa.) 2012; 32(4):776-84.
6. Tetz M, Rizzo S, Augustin AJ. Safety of submacular suprachoroidal drug administration via a microcatheter: retrospective analysis of European treatment results. Ophthalmologica. Journal international d'ophtalmologie. International Journal of Ophthalmology. Zeitschrift fur Augenheilkunde 2012; 227(4):183-9.
7. 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.
8. Pearce W, Hsu J, Yeh S. Advances in drug delivery to the posterior segment. Curr Opin Ophthalmol. 2015;26(3):233-239.
9. Kim YC, Oh KH, Edelhauser HF, et al. Formulation to target delivery to the ciliary body and choroid via the suprachoroidal space of the eye using microneedles. Eur J Pharm Biopharm. 2015 May 31 [Epub ahead of print].
10. Habot-Wilner Z, Noronha G, Wykoff CC. Suprachoroidally injected pharmacological agents for the treatment of chorio-retinal diseases: a targeted approach. Acta Ophthalmol. 2019 Jan 31. doi: 10.1111/aos.14042. [Epub ahead of print] .
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
_________________________________________________________________________________________
Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
____________________________________________________________________________________________________________________________ |