Archived Policies - Other


Ocriplasmin for Symptomatic Vitreomacular Adhesion (VMA)

Number:OTH903.026

Effective Date:11-01-2015

End Date:07-31-2016

Coverage:

Medical policies are a set of written guidelines that support current standards of practice. They are based on current peer-reviewed scientific literature. A requested therapy must be proven effective for the relevant diagnosis or procedure. For drug therapy, the proposed dose, frequency and duration of therapy must be consistent with recommendations in at least one authoritative source. This medical policy is supported by FDA-approved labeling and nationally recognized authoritative references. These references include, but are not limited to: MCG care guidelines, Hayes, DrugDex (IIb level of evidence or higher), NCCN Guidelines (IIb level of evidence or higher), NCCN Compendia (IIb level of evidence or higher), professional society guidelines, and CMS coverage policy.

A single intravitreal injection of ocriplasmin may be considered medically necessary for treatment of an eye with symptomatic vitreomacular adhesion (VMA), when the following criteria have been met:

Individual's age is equal to or greater than 18 years; AND

Optical coherence tomography (OCT) demonstrates all of the following:

  1. There is vitreous adhesion within 6-mm of the fovea (center of macula); and
  2. There is elevation of the posterior vitreous cortex (outer layer of the vitreous); AND

Individual has best-corrected visual acuity of 20/25 or less in the eye to be treated with ocriplasmin; AND

Individual does not have any of the following:

  • Proliferative diabetic retinopathy, or
  • Neovascular age-related macular degeneration, or
  • Retinal vascular occlusion, or
  • Aphakia, or
  • High myopia (more than −8 diopters), or
  • Uncontrolled glaucoma, or
  • Macular hole greater than 400 μm in diameter or
  • Vitreous opacification, or
  • Lenticular or zonular instability, or
  • History of retinal detachment in either eye, or
  • Prior vitrectomy in the affected eye, or
  • Prior laser photocoagulation of the macula in the affected eye, or
  • Prior treatment with ocular surgery, intravitreal injection or retinal laser photocoagulation in the previous 3 months.

The use of intravitreal ocriplasmin is considered experimental, investigational and/or unproven in all other situations, including use of repeat injections of ocriplasmin.

Description:

The vitreous is a gel-like fluid within the eye that adheres completely to the surface of the retina. The consistency of the vitreous and its adhesion to the retina are maintained by several proteins including collagen, laminin, and fibronectin. With aging, the proteins in the vitreous break down, resulting in liquefaction of the vitreous and eventual separation of the vitreous from the retina, a process called posterior vitreous detachment (PVD).

The process of vitreous detachment usually proceeds without incident, but sometimes the separation is not complete. The adhesion usually remains at sites where the bonds between the vitreous and retina are the strongest. Adhesion at the macula is called vitreomacular adhesion (VMA). In some cases, VMA can cause visual symptoms. The traction caused by the adherent vitreous can cause deformation of the retina, edema, and macular holes. The retina may tear or detach. Symptoms can be variable, but can include diminished visual acuity, distorted vision (metamorphopsia) and central field defect.

Patients are usually observed until resolution or worsening, in which case vitrectomy is the only treatment. Although it is believed that only 10% of cases resolve spontaneously, observation is usually indicated because vitrectomy has risks and an almost certain occurrence of cataract in the years following vitrectomy. (1, 2)

Ocriplasmin (Jetrea®) is a recombinant product that is a shortened/truncated form of the human protease plasmin that breaks down protein components at the vitreoretinal interface in the eye. Ocriplasmin is injected into the affected eye (intravitreal) as a single dose and can induce vitreous liquefaction and separation from the retina. Its proposed use is for the treatment of symptomatic VMA. Early studies of ocriplasmin were conducted in patients who were scheduled to have vitrectomy and established doses that showed some effect in inducing PVD and the temporal course of the effect. Studies by Benz et al., de Smet et al., and Stalmans et al. led to the design and conduct of the pivotal clinical trials described in the Rationale section of this medical policy. (3-5)

Regulatory Status

Ocriplasmin (Jetrea®, ThromboGenics Inc., Iselin, NJ) received U.S. Food and Drug Administration (FDA) approval October 17, 2012 for the treatment of symptomatic VMA. There were no contraindications noted. In the Warnings and Precautions section of the prescribing information, it was noted that a higher percentage of subjects treated with ocriplasmin in the clinical trials had worsening of visual acuity of 3 or more lines than subjects in the control group. Transient injection-associated effects such as inflammation occurred in a higher percentage of subjects treated with ocriplasmin than control subjects.

Rationale:

This medical policy was created in January 2013, with literature review covering the period up to December 2013. The medical policy is based on a 2013 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment, (6) which included 2 randomized controlled trials (RCTs) of ocriplasmin versus standard treatment, and summarized the findings of these trials as follows:

Two trials met selection criteria. Only one trial had sufficient sample size to produce meaningful results. The smaller study’s results are consistent with the one large trial. The one large trial was a randomized double-blind placebo-controlled trial. Overall, 652 eyes were treated; 464 with ocriplasmin and 188 with placebo. The principal endpoint of the study, resolution of vitreomacular adhesion (VMA) at 28 days, occurred in 26.5% of ocriplasmin-treated patients and 10.1% of placebo-treated patients. Other 28-day secondary endpoints, posterior vitreal detachment and closure of macular holes, also favored ocriplasmin.

Secondary outcomes measured beyond 28 days were also better in ocriplasmin-treated eyes. By 6 months, 17.7% of ocriplasmin-treated subjects had undergone vitrectomy versus 26.6% of placebo-treated subjects. Visual improvement results varied depending on how the data were analyzed, but generally favored ocriplasmin. Measured as categorical improvement of 3 or more lines on the Early Treatment of Diabetic Retinopathy (ETDRS) chart, ocriplasmin-treated subjects had higher success rates than placebo-treated subjects. Absolute gains in both groups were modest, particularly in the analysis where improvement was only counted in those who did not undergo vitrectomy (9.7% and 3.7%, respectively). Major adverse events were not significantly different between the 2 groups.

Conclusion: The one large RCT of ocriplasmin shows that ocriplasmin is associated with higher rates of resolution of VMAs, closure of macular holes, lower rates of vitrectomy and improvement in some measures of visual acuity, without increases in major adverse events, when compared to watchful waiting with vitrectomy as indicated. This demonstrates improvement in health outcomes.

Literature review

The principal evidence supporting ocriplasmin for symptomatic VMAs is the published study by Stalmans et al. (7) The study presents pooled results of 2 identically designed double-blind placebo-RCTs. Patients enrolled in the study met strict inclusion and exclusion criteria listed in the coverage statement. They were not currently scheduled to have vitrectomy, but according to assessment by their physician, 84% were expected to need vitrectomy if their condition did not improve. Overall, 652 eyes were treated; 464 with ocriplasmin and 188 with placebo. The principal endpoint of the study, resolution of VMAs at 28 days, occurred in 26.5% of ocriplasmin-treated patients and 10.1% of placebo-treated patients. Other 28-day secondary endpoints, posterior vitreal detachment and closure of macular holes, also favored ocriplasmin.

Secondary outcomes measured beyond 28 days were also better in ocriplasmin-treated eyes. By 6 months, 17.7% of ocriplasmin-treated subjects had undergone vitrectomy versus 26.6% of placebo-treated subjects. Visual improvement results varied depending on how the data were analyzed, but generally favored ocriplasmin. Measured as categorical improvement of 3 or more lines on the Early Treatment of Diabetic Retinopathy (ETDRS) chart, ocriplasmin-treated subjects had higher success rates than placebo-treated subjects. Absolute gains in both groups were modest, particularly in the analysis where improvement was only counted in those who did not undergo vitrectomy (9.7% and 3.7%, respectively).

Major adverse events were not significantly different between the 2 groups. The most common side effects reported in individuals treated with ocriplasmin include eye floaters; bleeding of the conjunctiva, eye pain; flashes of light (photopsia); blurred vision; vision loss; retinal edema (swelling); and macular edema.

Conclusions: This clinical trial of ocriplasmin in patients with symptomatic VMAs demonstrates that it resolves VMAs and lessens the need for vitrectomy in a proportion of patients, although some patients resolve VMA without ocriplasmin and vitrectomy is still needed in some patients despite treatment with ocriplasmin.

Summary

Ocriplasmin is a novel treatment for VMAs. One large double-blind placebo-RCT and other earlier supporting studies demonstrate that ocriplasmin resolves VMAs and prevents the need for vitrectomy in a proportion of the patients treated, without a higher rate of important complications. Improvements in visual acuity are modest. Therefore, ocriplasmin may be considered medically necessary for the treatment of symptomatic VMAs when clinical criteria are met.

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

67028

HCPCS Codes

J7316

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 have a national Medicare coverage position.

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. Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol 1995; 119(1):55-61.

2. Jackson TL, Donachie PH, Sparrow JM et al. United Kingdom National Ophthalmology Database Study of Vitreoretinal Surgery: Report 1; Case mix, complications, and cataract. Eye (Lond) 2013; 27(5):644-51.

3. Benz MS, Packo KH, Gonzalez V et al. A placebo-controlled trial of microplasmin intravitreous injection to facilitate posterior vitreous detachment before vitrectomy. Ophthalmology 2010; 117(4):791-7.

4. de Smet MD, Gandorfer A, Stalmans P et al. Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial. Ophthalmology 2009; 116(7):1349-55, 55 e1-2.

5. Stalmans P, Delaey C, de Smet MD et al. Intravitreal injection of microplasmin for treatment of vitreomacular adhesion: results of a prospective, randomized, sham-controlled phase II trial (the MIVI-IIT trial). Retina 2010; 30(7):1122-7.

6. Ocriplasmin for Symptomatic Vitreomacular Adhesion. Chicago, Illinois: Blue Cross Blue Shield Association Technology Evaluation Center. (August 2013) Volume 28, Tab 5.

7. Stalmans P, Benz MS, Gandorfer A et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med 2012; 367(7):606-15.

8. Drugs @ FDA – Drug Approval Package: Jetrea (ocriplasmin) Intravitreal Injection. Food and Drug Administration (2012 December 4). Available at <http://www.fda.gov> (accessed – 2013 December 9).

9. Ocriplasmin for Symptomatic Vitreomacular Adhesion. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (August 2013) Other/Vision 9.03.30.

Policy History:

Date Reason
11/1/2015 Reviewed. No changes.
1/1/2014 New medical document. A single intravitreal injection of ocriplasmin may be considered medically necessary for treatment of an eye with symptomatic vitreomacular adhesion (VMA), when specified clinical criteria has been met. Otherwise, the use of intravitreal ocriplasmin is considered experimental, investigational and/or unproven in all other situations, including use of repeat injections of ocriplasmin.

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