Medical Policy

 

Subject: Suprachoroidal Injection of a Pharmacologic Agent
Document #: SURG.00101 Publish Date:    10/17/2018
Status: Reviewed Last Review Date:    09/13/2018

Description/Scope

This document addresses the use of an injection of a pharmacologic agent into the suprachoroidal space.

Position Statement

Investigational and Not Medically Necessary:

Suprachoroidal injection of a pharmacologic agent is considered investigational and not medically necessary for all indications.

Rationale

Injection into the suprachoroidal space has been proposed as a method to effectively deliver pharmacologic agents to the posterior segment of the eye. The posterior segment of the eye, including the retina, macula and optic nerve, is difficult to access due to the recessed position within the orbital cavity. Local delivery of pharmacologic agents to the posterior segment of the eye is essential in the management of diseases or degenerations of the retina and optic nerve. Current local drug delivery techniques to access the posterior segment are intravitreal injections, periocular injections and intravitreal implants.

At this time, published, peer-reviewed literature is limited. In a 2012 retrospective analysis by Tetz and colleagues, the authors reported on the safety and feasibility of delivering bevacizumab in combination with triamcinolone acetonide via a microcatheter to the suprachoroidal space of individuals with age-related macular degeneration unresponsive to conventional therapy. Conventional therapy included intravitreal injections of bevacizumab and/or ranibizumab, pegaptanib, and photodynamic therapy. A total of 21 participants were included in the review. The average best-corrected visual acuity was 0.98 logMAR which is characteristic of advanced macular degeneration. At the 1-month visit, the mean best-corrected visual acuity was 0.92 logMAR; at 3 months the mean best-corrected visual acuity was 0.96 logMAR, and at 6 months it was 0.93 logMAR. Central subfield foveal thickness showed an initial decrease at 1 month, then trended to preoperative levels at 6 months following insertion. Following the insertion of the microcatheter, 1 participant experienced an elevated intraocular pressure at the 3-month visit which returned to the preoperative level at 6 months following temporary glaucoma medication therapy. The authors conclude that further studies are necessary on larger participant groups to compare suprachoroidal injection to conventional intravitreal injections.

Another 2012 study by Rizzo and colleagues reported on the use of suprachoroidal injection. This prospective, noncomparative, interventional study evaluated the safety, feasibility, and preliminary efficacy of a single suprachoroidal injection of bevacizumab and triamcinolone to 6 participants with subfoveal hard exudates. Main outcome measures included best-corrected visual acuity, vascular leakage, macular thickness, extent of subfoveal hard exudates, and complications. Diagnoses of the participants included: 3 eyes with central retinal vein occlusion, 1 with branch retinal vein occlusion, and 2 with chronic diabetic macular edema. All participants had advanced macular edema with massive subfoveal hard exudate plaques, which had been unresponsive to previous treatment which included focal laser and/or intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. The mean follow-up was 12 months. Best-corrected visual acuity improved by ≥ 2 lines in 4 eyes and remained unchanged in 2 eyes. Mean macular thickness and macular volume decreased from baseline to the final follow-up visit. At 1 to 2 months following the injection, there was almost complete resolution of subfoveal hard exudates in all participants with reduced macular edema. There were no reported surgical or postoperative complications. Insertion of a microcatheter into the suprachoroidal space can be challenging. In this particular study, limitations include the lack of a control group and small sample size. Further clinical studies with larger group sizes are necessary.

In a 2016 study by Goldstein and colleagues, the authors evaluated the safety, tolerability, and preliminary efficacy of suprachoroidal injection of triamcinolone acetonide in subjects with noninfectious uveitis. Participants received a single suprachoroidal injection of triamcinolone acetonide in the study eye on day 1 with observation for 26 weeks. The participants were allowed to receive additional therapy at the investigator’s discretion for lack of efficacy at any point during the study. A total of 8 participants received the initial injection and completed the 26-week follow-up. At least 1 adverse event was reported by all participants with a total of 38 adverse events reported overall. The most common adverse event was ocular pain at or near the time of the injection. The adverse events were reported as mild to moderate in 89% of participants, 22 of 38 of the adverse events were ocular events with systemic events being reported in 8 participants which were unrelated to the study medication. There were no increases in intraocular pressure. All 8 participants had improvements in visual acuity. Four of the participants, who did not require additional therapy, had on average a greater than 2-line improvement in visual acuity through week 26. Three of 4 had macular edema at baseline, and 2 of 3 had at least a 20% reduction in macular edema at week 26. This study has several limitations including a small group size of 8 participants and its open-label, single administration design. Suprachoroidal injection is a novel technique that requires physicians to learn the technique and relies on investigator experience to ensure accuracy of the delivery. Further research with controlled studies, masked centralized evaluations, and repeated injections with larger sample sizes are necessary.

A 2018 randomized, controlled phase 2 trial by Willoughby and colleagues evaluated the changes in choroidal thickness over a 3-month period comparing intravitreal aflibercept with and without a single suprachoroidal injection. A total of 46 participants with macular edema due to retinal vein occlusion were randomized to either a single intravitreal injection of aflibercept followed by either a single suprachoroidal injection of CLS-TA suspension (combination arm) or a sham suprachoroidal injection (monotherapy arm). After initial treatment, participants were examined on a monthly basis. Additional intravitreal aflibercept was given if there was any fluid with central subfield thickness (CST) > 340 mm, any vision loss of 10 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters from the prior visit, or vision loss of 10 or more letters from the best data from any prior visit accompanied by an increase in fluid of at least 50 mm. Mean central vascular choroidal thickness; stromal choroidal thickness, and total choroidal thickness showed no significant change over the 3 months after treatment in either the combination arm or the monotherapy arm. There was also no significant correlation between the change in retinal thickness and any choroidal thickness measurements in either arm or at any visit. In the participants who received combination therapy there was a trend toward thickening of the suprachoroidal space compared with monotherapy alone. There were 15 eyes that demonstrated a visible suprachoroidal space at baseline and that suprachoroidal space expanded after the suprachoroidal injection. Without a control arm, there is no way to conclude whether the expansion of the suprachoroidal space was due to the physical volume effect of the suprachoroidal fluid injection or a pharmacologic effect of the CLS-TA drug suspension. With this new route for ocular drug delivery, there are concerns including a learning curve for the more complex technique, inadvertent intravitreal administration, or failed delivery if the microneedle is not completely orthogonal to the ocular contour. Further investigation is necessary.

There is a need for additional studies to determine whether this technique is superior to other currently available treatment options for posterior segment disease.

Background/Overview

The suprachoroidal space is a potential space in the eye that is located between the choroid, and the sclera, the outer layer of the eye. The suprachoroidal space extends from the anterior portion of the eye near the ciliary body to the posterior end of the eye near the optic nerve. Normally the suprachoroidal space is not evident due to the close apposition of the choroid to the sclera from the intraocular pressure of the eye. Since there is no substantial attachment of the choroid to the sclera, the tissues separate to form the suprachoroidal space when fluid accumulation or other conditions occur. The suprachoroidal space provides a potential route of access from the anterior region of the eye to treat the posterior region. Suprachoroidal injection of a pharmacologic agent has been proposed as an alternative to intravitreal and periocular injections. Clinical trials are in progress studying the safety and efficacy of suprachoroidal injections compared to other available treatment options as well as studying the current devices used to inject into the suprachoroidal space.

Definitions

Choroid: The vascular layer of the eye that lies between the retina and the sclera. It provides nourishment to outer layers of the retina.

Sclera: The dense fibrous opaque white outer coat enclosing the eyeball.

Suprachoroidal: Of, relating to, or being the layer of loose connective tissue situated between the choroid and sclera.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When Services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

CPT

 

0465T

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

 

 

ICD-10 Diagnosis

 

 

All diagnoses

References

Peer Reviewed Publications:

  1. del Amo EM, Rimpelä AK, Heikkinen E, et al. Pharmacokinetic aspects of retinal drug delivery. Prog Retin Eye Res. 2017; 57:134-185.
  2. 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.
  3. Rizzo S, Ebert FG, Bartolo ED, et al. Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates. Retina. 2012; 32(4):776-784.
  4. 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.
  5. 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.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. U.S. Food and Drug Administration 510(k) Premarket Notification Database. iScience Surgical Ophthalmic Microcannula. Summary of Safety and Effectiveness. No. K041108. Rockville, MD: FDA. June 22, 2004. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf4/k041108.pdf. Accessed on August 1, 2018.
Index

Suprachoroidal Injection

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Reviewed

09/13/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Rationale, Background/Overview, References, and Index sections.

Reviewed

11/02/2017

MPTAC review. The document header wording updated from “Current Effective Date” to “Publish Date.”

Reviewed

11/03/2016

MPTAC review. Updated Coding section with 01/01/2017 CPT changes; removed 67299 NOC code.

Reviewed

11/05/2015

MPTAC review. Updated Rationale. Removed ICD-9 codes from Coding section.

Reviewed

11/13/2014

MPTAC review.

Reviewed

11/14/2013

MPTAC review. Updated Rationale and References. Updated Coding section with 01/01/2014 CPT changes; removed 0186T deleted 12/31/2013.

Reviewed

11/08/2012

MPTAC review. Updated Rationale.

Reviewed

11/17/2011

MPTAC review. Updated Index.

Reviewed

11/18/2010

MPTAC review.

Reviewed

11/19/2009

MPTAC review. Updated References.

Reviewed

11/20/2008

MPTAC review. Updated Coding and Background/Overview sections.

New

11/29/2007

MPTAC review. Initial document development.