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Ocriplasmin for Symptomatic Vitreomacular Adhesion

Policy Number: MP-535

Latest Review Date:  March 2020

Category:  Surgery  

Policy Grade: C   


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

  • Individual's age is equal to or greater than 18 years;
  • Optical coherence tomography (OCT) demonstrates all of the following:
    • There is vitreous adhesion within 6-mm of the fovea (center of macula); and
    • There is elevation of the posterior vitreous cortex (outer layer of the vitreous).
  • Individual has best-corrected visual acuity of 20/25 or less in the eye to be treated with ocriplasmin
  • Individual does not have any of the following:
    • Proliferative diabetic retinopathy;
    • Neovascular age-related macular degeneration;
    • Retinal vascular occlusion;
    • Aphakia;
    • High myopia (> −8 diopters);
    • Uncontrolled glaucoma;
    • Macular hole greater than 400 μm in diameter;
    • Vitreous opacification;
    • Lenticular or zonular instability;
    • History of retinal detachment in either eye;
    • Prior vitrectomy in the affected eye;
    • Prior laser photocoagulation of the macula in the affected eye;
    • Prior treatment with ocular surgery, intravitreal injection or retinal laser photocoagulation in the previous three months.

The use of intravitreal ocriplasmin is not medically necessary and is considered investigational in all other situations, including use of repeat injections of ocriplasmin.


Ocriplasmin (Jetrea) is a recombinant truncated form of human plasmin, a proteolytic enzyme that breaks down protein components at the vitreoretinal interface in the eye, used for symptomatic vitreomacular adhesion and vitreomacular traction. Ocriplasmin is injected into the affected eye (intravitreal) as a single dose and can induce vitreous liquefaction and separation from the retina.


Symptoms of vitreomacular adhesion (VMA) or vitreomacular traction can vary and may 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 standard treatment. Spontaneous release of VMA/VMT occurs in about 30% of cases over a period of 1 to 2 years, and observation is usually indicated because vitrectomy has risks and an almost certain occurrence of cataract in the years following the procedure.

Ocriplasmin is a recombinant product that is a shortened form of the protease plasmin. Early studies of ocriplasmin, conducted in patients scheduled to have vitrectomy, established doses that showed some effect in inducing posterior vitreous detachment. Studies by Benz et al (2010), de Smet et al (2009), and Stalmans et al (2010) led to the design and conduct of the pivotal clinical trials described in the Key Points section of this policy.


This policy is updated periodically with literature review using the MEDLINE database. The most recent literature update was performed through January 13, 2020.


For individuals who have symptomatic vitreomacular adhesion or vitreomacular traction who receive intravitreal injection of ocriplasmin, the evidence includes 2 large, double-blind, placebo-controlled, clinical trials and other supporting studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Results of principal randomized controlled trial, Randomized, Placebo controlled, Double-Masked, Multicenter Trial of Microplasmin Intravitreal Injection for Non-surgical Treatment of Focal Vitreomacular Adhesion (MIVI-TRUST), demonstrate an improvement in the resolution of VMA/VMT at 28 days (26.5% vs 10.1% of patients, NNT=6) and a lesser reduction in the proportion of patients undergoing vitrectomy (17.7% vs 26.6%, NNT=11). Results of these trials also showed a modest increase in the proportion of patients who had clinically significant gains in visual acuity (NNT=17) and visual function. The RCTs did not find a higher rate of important complications; however, post-marketing surveillance has identified some previously unknown adverse effects with this novel enzymatic treatment. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the net health outcome.


In 2013, the National Institute for Health and Care Excellence issued guidance on ocriplasmin for treating vitreomacular traction (VMT). The Institute recommended ocriplasmin as an option for treating VMT in adults, only if:

  • “an epiretinal membrane is not present and
  • “they have a stage II full-thickness macular hole with a diameter of 400 micrometres or less and/or
  • “they have severe symptoms.”

As of February 2017, this guidance was placed on the “static guidance list.”

American Academy of Ophthalmology

In 2019, the American Academy of Ophthalmology’s preferred practice pattern on the idiopathic epiretinal membrane and VMT the following:

“A Cochrane review of 932 eyes in four studes concluded that although ocriplasmin is useful in the treatment of symptomatic [vitreomacular adhesion], up to 20% of eyes treated with ocriplasmin will still require additional treatment with pars plana vitrectomy within 6 months. (I+, Good quality, Strong recommendation) There were more ocular adverse events in eyes in the ocriplasmin group than in the control treatment group (sham or placebo injection).”


Not applicable.


Intravitreal Injection, Ocriplasmin, Jetrea


In October 2012, ocriplasmin (Jetrea®, ThromboGenics Inc., Iselin, NJ) received U.S. Food and Drug Administration (FDA) approval for the treatment of symptomatic vitreomacular adhesion (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 three 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. Alcon has obtained exclusive distribution rights for Jetrea® in the U.S.


Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan.  FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.


CPT Codes


Intravitreal injection of a pharmacologic agent (separate procedure)




Injection, ocriplasmin, 0.125 mg


  1. Assessment of Patients Treated With JETREA for Vitreomacular Traction (NCT02035748). U.S. National Library of Medicine. Updated October 12, 2016. Accessed March 3, 2020.
  2. 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.
  3. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Ocriplasmin for symptomatic vitreomacular adhesion. TEC Assessments 2013; Volume 28, Tab TBA.
  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):1349-1355, 1355 e1341-1342.
  5. Chatziralli I, Theodossiadis G, Xanthopoulou P, et al. Ocriplasmin use for vitreomacular traction and macular hole: A meta-analysis and comprehensive review on predictive factors for vitreous release and potential complications. Graefes Arch Clin Exp Ophthalmol. Jul 2016; 254(7):1247-1256.
  6. Drenser K, Girach A, Capone A, Jr. A randomized, placebo-controlled study of intravitreal ocriplasmin in pediatric patients scheduled for vitrectomy. Retina. Sep 21 2015.
  7. Duker JS, Kaiser PK, Binder S, et al. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology. Dec 2013; 120(12):2611-2619.
  8. Flaxel CJ, Adelman RA, Bailey ST et al. Idiopathic Epiretinal Membrane and Vitreomacular Traction Preferred Practice Pattern(R). Ophthalmology. 2020 Feb;127(2).
  9. Folk JC, Adelman RA, Flaxel CJ, et al. Idiopathic epiretinal membrane and vitreomacular traction Preferred Practice Pattern® guidelines. Ophthalmology. Jan 2016; 123(1):P152-181.
  10. Gandorfer A, Benz MS, Haller JA, et al. Association between anatomical resolution and functional outcomes in the mivi-trust studies using ocriplasmin to treat symptomatic vitreomacular adhesion/vitreomacular traction, including when associated with macular hole. Retina. Jun 2015; 35(6):1151-1157.
  11. Hahn P, Chung MM, Flynn HW, Jr., et al. Safety profile of ocriplasmin for symptomatic vitreomacular adhesion: A comprehensive analysis of premarketing and post-marketing experiences. Retina. Jun 2015; 35(6):1128-1134.
  12. Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol 1995; 119(1):55-61.
  13. 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.
  14. Kaiser PK, Kampik A, Kuppermann BD, et al. Safety profile of ocriplasmin for the pharmacologic treatment of symptomatic vitreomacular adhesion/traction. Retina. Jun 2015; 35(6):1111-1127.
  15. Khanani AM, Duker JS, Heier JS et al. Ocriplasmin Treatment Leads to Symptomatic Vitreomacular Adhesion/Vitreomacular Traction Resolution in the Real-World Setting: The Phase IV ORBIT Study. Ophthalmol Retina. 2019 Jan;3(1).
  16. National Institute of Health and Care Excellence (NICE). Ocriplasmin for treating vitreomacular traction. 2013; TA297: // Accessed February 16, 2018.
  17. Novack RL, Staurenghi G, Girach A, et al. Safety of intravitreal ocriplasmin for focal vitreomacular adhesion in patients with exudative age-related macular degeneration. Ophthalmology. Apr 2015; 122(4):796-802.
  18. Ocriplasmin for treating vitreomacular traction. National Institute for Health and Care Excellence. Updated February 16, 2017. Accessed February 4, 2020.
  19. Shah SP, Jeng-Miller KW, Fine HF, et al. Post-marketing survey of adverse events following ocriplasmin. Ophthalmic Surg Lasers Imaging Retina. Feb 2016; 47(2):156-160.
  20. 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.
  21. 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.
  22. Tzu JH, John VJ, Flynn HW, Jr., et al. Clinical Course of Vitreomacular Traction Managed Initially by Observation. Ophthalmic Surg Lasers Imaging Retina. May 1 2015; 46(5):571-576.
  23. Varma R, Haller JA, Kaiser PK. Improvement in Patient-Reported Visual Function After Ocriplasmin for Vitreomacular Adhesion: Results of the Microplasmin for Intravitreous Injection-Traction Release Without Surgical Treatment (MIVI-TRUST) Trials. JAMA Ophthalmol. Jun 11 2015.


Medical Policy Panel, July & August 2013

Medical Policy Group, August 2013 (2): New policy

Medical Policy Administration Committee, August 2013

Available for comment August 22 through October 5, 2013

Medical Policy Group, January 2014 (1): 2014 Coding Update: new HCPCS code, J7316, added to coding section, effective 01/01/2014; deleted code C9298 moved to previous coding section, effective 01/01/2014

Medical Policy Panel, August 2014

Medical Policy Group, August 2014 (1): Update to Key Points and References; no change to policy statement

Medical Policy Panel, March 2016

Medical Policy Group, March 2016 (6):  Updates to Description, Key Points and References; no change to policy statement

Medical Policy Panel, March 2017

Medical Policy Group, March 2017 (6): Updates to Description, Key points, Summary, Practice Guidelines and References. No change to policy intent.

Medical Policy Panel, March 2018

Medical Policy Group, March 2018 (6): Updates to Description, Key points, Practice Guidelines and References. No change to policy intent.

Medical Policy Panel, March 2019

Medical Policy Group, March 2019 (6): Updates to Description and Key Points. No change to policy statement.

Medical Policy Panel, March 2020

Medical Policy Group, March 2020 (6): Updates to Key Points, Practice Guidelines and References.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.


Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.