Ocriplasmin for Symptomatic Vitreomacular Adhesion - CAM 90330

Ocriplasmin 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.

Additional Information
2013 Clinical Input

Clinical input obtained in 2013 has suggested that not all of the MIVI-TRUST exclusion criteria should be absolute. However, there was no consensus on which criteria should be removed.

Vitreous is a gel-like fluid within the eye that adheres completely to the surface of the retina. The consistency of 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 vitreous and eventual separation of vitreous from the retina, a process called posterior vitreous detachment.

The process of vitreous detachment usually proceeds without incident, but sometimes the separation is incomplete. Adhesion usually remains at sites where the bonds between the vitreous and retina are the strongest. In some cases, the adhesion can cause visual symptoms. The traction caused by the adherent vitreous can cause deformation of the retina, edema, and full-thickness macular holes. Although the terms are sometimes used synonymously, the International Vitreomacular Traction Study Group has defined vitreomacular adhesion as adhesion at the macula without detectable changes in retinal morphology and vitreomacular traction as adhesion with retinal morphologic changes but without full-thickness defect.1 Both vitreomacular adhesion and vitreomacular traction can be focal or diffuse.

Symptoms of vitreomacular adhesion 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 vitreomacular adhesion and vitreomacular traction 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.2,3

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 Rationale section.4,5,6

Regulatory Status
On Oct. 17, 2012, ocriplasmin (Jetrea®; ThromboGenics) was approved by the FDA for the treatment of symptomatic vitreomacular adhesion.

A single intravitreal injection of ocriplasmin may be considered MEDICALLY NECESSARY for treatment of an eye with symptomatic vitreomacular adhesion or vitreomacular traction.

The use of intravitreal ocriplasmin is investigational/unproven therefore considered NOT MEDICALLY NECESSARY in all other situations, including use of repeat injections of ocriplasmin.

Policy Guidelines
The precise patient indications for treatment are uncertain. Eligibility criteria for the key randomized controlled trial included the following:

  • Individual's age is 18 years or older.
  • Optical coherence tomography demonstrates all of the following:
    • There is vitreous adhesion within 6 mm of the fovea (center of macula).
    • There is elevation of the posterior vitreous cortex (outer layer of the vitreous).
  • Individual has a 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 3 months.

Clinical input has suggested that not all trial exclusion criteria should be absolute. However, there was no consensus on the recommended exclusion criteria (see Supplementary Information section for clinical input).

See the Codes table for details.

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., Federal Employee Program) may dictate that certain U.S. Food and Drug Administration approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function, including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Intravitreal Injection for Vitreomacular Adhesion or Vitreomacular Traction
Clinical Context and Therapy Purpose

Prior to the availability of ocriplasmin, the only management options for individuals with symptomatic vitreomacular adhesion or vitreomacular traction were observation or vitrectomy. The potential benefit for the use of ocriplasmin at time of its approval was its relative simplicity of use and avoidance of vitrectomy surgery and associated complications of surgery. However, subsequent advances in vitrectomy technology have lowered surgical morbidity with more rapid patient recovery. High incidence of post vitrectomy cataract was also seen as a major disincentive. However, greater adoption of combined phacovitrectomy has obviated the risk of development of post-vitrectomy cataract. In addition, post-marketing data shows that the use of ocriplasmin is associated with short-term risk of vitreous floaters, photopsia and injection-related eye pain. Transient visual impairment has also been reported.

The purpose of intravitreal injection of ocriplasmin for patients with symptomatic vitreomacular adhesion or vitreomacular traction is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of intravitreal injection of ocriplasmin for patients with symptomatic vitreomacular adhesion or vitreomacular traction improve net health outcomes?

The following PICO was used to select literature to inform this review.

The relevant population of interest is patients with symptomatic vitreomacular adhesion or vitreomacular traction.

The treatment being considered is intravitreal injection of ocriplasmin.

The comparators of interest are observation and vitrectomy.

The general outcomes of interest are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity.

Follow-up of 12 months is desirable to assess outcomes and duration of results.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

  1. To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
  2. In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
  3. To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

Review of Evidence
Efficacy of Treatment

The evidence review was informed by a TEC Assessment (2013), which concluded that ocriplasmin is associated with higher rates of resolution of vitreomacular adhesions, closure of macular holes, lower rates of vitrectomy, and improvement in some measures of visual acuity, without increases in major adverse events, when compared with watchful waiting with vitrectomy as indicated.7 The Assessment concluded that use of ocriplasmin led to improvement in health outcomes.

Randomized Controlled Trials
The pivotal evidence supporting ocriplasmin for symptomatic vitreomacular adhesion are the RCT results published by Stalmans et al. (2012) for the Randomized, Placebo Controlled, Double-masked, Multicenter Trial of Microplasmin Intravitreal Injection for Non-surgical Treatment of Focal Vitreomacular Adhesion (MIVI-TRUST) study group.8 The study presented pooled results of 2 identically designed, double-blind, placebo-controlled, randomized trials. Patients enrolled in the trial met strict inclusion and exclusion criteria: they were not currently scheduled to have vitrectomy, but, according to assessment by their physicians, 84% were expected to need a vitrectomy if their conditions did not improve. Overall, 652 eyes were treated, 464 with ocriplasmin and 188 with placebo. The primary study endpoint (resolution of vitreomacular adhesion at 28 days) was met by 26.5% of ocriplasmin-treated patients and by 10.1% of placebo-treated patients (number needed to treat [NNT], 6.1).

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 varied depending on how data were analyzed but generally favored ocriplasmin. Measured as a categorical improvement of 3 or more lines on the Early Treatment of Diabetic Retinopathy Study chart, ocriplasmin-treated subjects showed greater improvement than placebo-treated subjects. Absolute gains in both groups were modest in the analysis that only considered those who did not undergo vitrectomy (9.7% and 3.7%, respectively). A higher proportion of patients in the ocriplasmin group had a clinically meaningful (≥ 5 point) improvement on 25-item National Eye Institute Visual Function Questionnaire scores (36.0% vs. 27.2%, p = 0.03), and fewer ocriplasmin-treated patients had a clinically meaningful worsening in their visual function compared with the placebo group (15.0% vs. 24.3%, p = 0.005).9 Resolution of vitreomacular adhesion at 28 days, regardless of treatment group, was associated with greater improvement in visual acuity at all time points (7.5-letter improvement vs. 2.1-letter improvement, p < 0.001).9 Serious adverse events in ocriplasmin-injected eyes (7.7%) did not differ significantly from placebo-injected eyes (10.7%).10 The most common adverse events reported in patients 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.

Novack et al. (2015) reported the results of a phase 2 randomized, sham-controlled trial which enrolled 100 patients with exudative age-related macular degeneration.11 The trial was primarily intended to evaluate the efficacy but also reported adverse events. Adverse events were higher in the ocriplasmin group, and serious adverse events in the study eye were observed in 10.7% of ocriplasmin-injected eyes compared with 0% in sham-treated eyes. The efficacy in releasing vitreomacular adhesions was numerically similar to the MIVI-TRUST trial, but the difference between active and sham treatments was not statistically significant (24.3% vs. 12.0%, p = 0.26); the phase 2 trial had insufficient power to detect a significant difference. Visual acuity was similar in both groups.

Dresner et al. (2016) reported results of a phase 2, sham-controlled, randomized trial that evaluated 22 pediatric patients scheduled to undergo vitrectomy.12 The trial was intended to test whether ocriplasmin would permit a faster surgical procedure and fewer complications. Use of ocriplasmin in pediatric patients is not currently recommended. The primary outcome was the proportion of eyes with posterior vitreous detachment at the beginning of vitrectomy or after suction. This outcome was observed in 50% of the ocriplasmin group and 62.5% of the placebo group. This result did not support any potential benefit of ocriplasmin.

Observational Studies
Steel et al. (2021) reported the results of the INvestigation of Jetrea in Patients with Confirmed Vitreomacular Traction (INJECT), a phase 4, multicenter, prospective observational study, which enrolled 452 patients.13 Patients were ≥ 18 years, had vitreomacular traction, received ocriplasmin 0.125 mg, and were followed up for 12 months. At day 28, the rate of non-surgical vitreomacular traction resolution was 40.7% in the overall group, and the rate of nonsurgical macular hole closure was 36% in the group with macular holes. At month 12, the rate of best correlated visual acuity gain was 36.8% in the overall group and 59.6% in the group with macular holes. About 29.1% of patients in the overall group and 55.6% in the group with macular holes underwent vitrectomy.

Khanani et al. (2019) reported on Ocriplasmin Research to Better Inform Treatment (ORBIT), a phase 4 multicenter, prospective, observational study.14 Participants included patients aged ≥ 18 years who had symptomatic vitreomacular adhesion/vitreomacular traction and were treated with a single intravitreal injection of ocriplasmin 0.125 mg. A total of 539 patients were enrolled in the study, but only 480 had confirmed vitreomacular adhesion/vitreomacular traction at baseline. Patients were followed up by physicians for up to 12 months. Results showed that at week 1, 27.7% (95% CI, 23.7 to 31.9) of patients achieved nonsurgical resolution without subsequent vitrectomy. By 1 year, 59.0% (95% CI, 54.4 to 63.4) had nonsurgical resolution. The mean time to resolution without subsequent vitrectomy was 13 days. Rate of nonsurgical closure of full-thickness macular hole at 1 week was 17.8% (95% CI, 11.4 to 25.9); at month 3, 32.2% (95% CI, 23.9 to 41.4) of patients saw full-thickness macular hole closure. For visual acuity, the majority (65.6%) of measurements were obtained using the maximum from the Snellen Equivalent and Pinhole tests. At months 10 and 12, 48.2% (95% CI, 34.7 to 62.0) of patients gained ≥ 2 Early Treatment of Diabetic Retinopathy Study lines from baseline. For the 28.5% of patients who underwent vitrectomy during the study, the median time to vitrectomy was 63.0 days. Four hundred five ocular adverse drug reactions were reported in 165 patients, 45 of them serious. Study limitations included the varying follow-up visit schedules among the treating physicians, possible confounding due to the inclusion of patients with prior or concomitant medications, and lack of standardization of visual acuity measurements across studies.

In 2016, results were posted on ClinicalTrials.gov of the industry-sponsored, phase 4 study officially titled, “Assessment of Anatomical and Functional Outcomes in Patients Treated With Ocriplasmin for Vitreomacular Traction/Symptomatic Vitreomacular Adhesion (VMT/sVMA)” (NCT02035748).15 The open-label, single group assignment study enrolled 628 patients with vitreomacular traction or vitreomacular adhesion, but 160 participants left the study before treatment; the analysis included the remaining 468 participants. All participants received a single dose of ocriplasmin 0.125 mg in a 0.1 mL volume administered by intraocular injection. At day 28, 47.4% of participants had nonsurgical resolution of focal VMT/VMA as measured by Central Reading Center Spectral Domain Optical Coherence Tomography. A secondary outcome was nonsurgical change from baseline in best-corrected visual acuity at 4 meters, assessed using Early Treatment of Diabetic Retinopathy Study testing. Gain in letters at day 28 was 1.7 (standard deviation [SD] = 6.70); at day 90, gain was 3.0 (SD = 7.07); and at day 180, it was 3.5 (SD = 7.77). Adverse events were reported in 46 (9.83%) participants, the 2 most common being development of macular hole (1.71%) and a reduction in visual acuity (1.07%).

Adverse Events
Hahn et al. (2015), in a report commissioned by the American Society of Retina Specialists, assessed adverse events based on regulatory reports of 999 injections administered during clinical trials and voluntary reports of adverse events from 4387 doses administered postmarketing.16 This report described the incidence, in a small percentage of patients, of significant and permanent vision loss, electroretinogram changes, dyschromatopsia, retinal tear/detachment, lens subluxation, impaired pupillary reflex, loss or disruption of the ellipsoid zone, vascular attenuation or vasoconstriction, and nyctalopia (night blindness). The rates of these adverse events could not be determined with certainty due to the voluntary and possibly incomplete nature of reporting.

Shah et al. (2016) surveyed 2465 retinal physicians about ocriplasmin use and adverse events-270 (11%) completed questionnaires (reporting on 1056 treated eyes).17 The most common adverse events reported included acute visual acuity decline (17.0%), retinal detachment or submacular fluid (10.2%), dyschromatopsia (9.1%), progression to macular hole (8.7%), retinal detachment (2.7%), retinal tear (2.0%), and afferent pupillary defect (1.8%). Reported adverse event rates were higher than those in clinical trial data (e.g., incidence of decline in visual acuity in trials was 7.7%). However, the survey-based estimates would likely be influenced by the high rate of physician nonresponse.

Finally, Chatziralli et al. (2016) conducted a meta-analysis ocriplasmin for vitreomacular traction.18 Results from 19 studies included pooled-RCT, cohort, case-control, or cross-sectional designs. No study quality (risk of bias) appraisal was performed. Factors predictive for vitreomacular traction release were adhesion diameter, age less than 65 years, female, and lack of a phakic lens. The pooled rate of macular hole closure was 33% (95% CI, 26% to 39%; I2 = 0%; 13 studies). Adverse event rates were summarized for 874 eyes, including acute decrease in visual acuity (17.4%), subretinal fluid (8.8%), dyschromatopsia (0.9%), progression to macular hole (5.0%), retinal detachment/tear (1.8%), and afferent pupillary defect (0.1%). Except for decreased acute visual acuity, adverse event rates were considerably lower than those from the Shah survey. While some factors were associated with response, implications are limited by the study-level nature of the meta-analysis.

Summary of Evidence
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 trials and other supporting studies. Relevant outcomes are symptoms, change in disease status, functional outcomes, quality of life, and treatment-related morbidity. Results of the pivotal randomized controlled trial, MIVI-TRUST , demonstrated an improvement in the resolution of vitreomacular adhesion and vitreomacular traction at 28 days (26.5% of ocriplasmin patients vs. 10.1% of placebo patients; NNT, 6) and a lesser reduction in the proportion of patients undergoing vitrectomy (17.7% of patients vs. 26.6% of patients; NNT, 11). Results of this and other trials have also shown an increase in the proportion of patients who had clinically significant gains in visual acuity (NNT, 17) and visual function. The RCTs did not find higher rates of important complications; however, postmarketing surveillance has identified some previously unknown adverse events for this enzymatic treatment. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Clinical Input From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 1 physician specialty society and 1 academic medical center while this policy was under review in 2013. Input suggested that not all of the MIVI-TRUST trial exclusion criteria should be absolute. However, there was no consensus on which exclusion criteria should be removed. Individual reviewers suggested removing the following criteria: macular hole greater than 400 μm, proliferative diabetic retinopathy, vitreous opacification, aphakia, high myopia, neovascular age-related macular degeneration, history of retinal detachment, and uncontrolled glaucoma. In addition, it was suggested that ocriplasmin might be beneficial for the treatment of macular holes and vitreous hemorrhage.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in Supplemental Information if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

National Institute for Health and Care Excellence
In 2013, the National Institute for Health and Care Excellence issued guidance on ocriplasmin for treating vitreomacular traction.19 The Institute recommended ocriplasmin as an option for treating vitreomacular traction 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.”20

American Academy of Ophthalmology
In 2019, the American Academy of Ophthalmology’s preferred practice pattern on the idiopathic epiretinal membrane and vitreomacular traction21 stated the following:

“A Cochrane review of 932 eyes in four studies 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).”22

U.S. Preventive Services Task Force Recommendations
Not applicable

Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in February 2022 did not identify any ongoing or unpublished trials that would likely influence this review.


  1. 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. PMID 24053995
  2. Tzu JH, John VJ, Flynn HW, et al. Clinical Course of Vitreomacular Traction Managed Initially by Observation. Ophthalmic Surg Lasers Imaging Retina. May 2015; 46(5): 571-6. PMID 26057761
  3. 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). May 2013; 27(5): 644-51. PMID 23449509
  4. Benz MS, Packo KH, Gonzalez V, et al. A placebo-controlled trial of microplasmin intravitreous injection to facilitate posterior vitreous detachment before vitrectomy. Ophthalmology. Apr 2010; 117(4): 791-7. PMID 20138368
  5. 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. Jul 2009; 116(7): 1349-55, 1355.e1-2. PMID 19447497
  6. 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. Jul-Aug 2010; 30(7): 1122-7. PMID 20616687
  7. Blue Cross and Blue Shield Association. Ocriplasmin for symptomatic vitreomacular adhesion. Technol Eval Cent Assess Program Exec Summ. Aug 2013; 28(5): 1-3. PMID 24066370
  8. Stalmans P, Benz MS, Gandorfer A, et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes. N Engl J Med. Aug 16 2012; 367(7): 606-15. PMID 22894573
  9. 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): 1151-7. PMID 25741816
  10. 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): 1111-27. PMID 25635577
  11. 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. PMID 25435217
  13. Steel DHW, Patton N, Stappler T, et al. OCRIPLASMIN FOR VITREOMACULAR TRACTION IN CLINICAL PRACTICE: The INJECT Study. Retina. Feb 01 2021; 41(2): 266-276. PMID 32496343
  14. 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. Jan 2019; 3(1): 32-41. PMID 30935657
  15. Assessment of Patients Treated With JETREA for Vitreomacular Traction (NCT02035748). U.S. National Library of Medicine. Updated October 12, 2016. https://clinicaltrials.gov/ct2/show/results/NCT02035748. Accessed February 25, 2022.
  16. Hahn P, Chung MM, Flynn HW, et al. SAFETY PROFILE OF OCRIPLASMIN FOR SYMPTOMATIC VITREOMACULAR ADHESION: A Comprehensive Analysis of Premarketing and Postmarketing Experiences. Retina. Jun 2015; 35(6): 1128-34. PMID 25635575
  17. 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): 156-60. PMID 26878449
  18. 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): 1247-56. PMID 27137631
  19. National Institute for Health and Care Excellence (NICE). Ocriplasmin for treating vitreomacular traction [TA297]. 2017; https://www.nice.org.uk/guidance/ta297. Accessed February 25, 2022.
  20. Ocriplasmin for treating vitreomacular traction. National Institute for Health and Care Excellence. https://www.nice.org.uk/guidance/ta297/evidence/review-decision-february-2017-4365648541?tab=evidence. Updated February 16, 2017. Accessed February 25, 2022.
  21. Flaxel CJ, Adelman RA, Bailey ST, et al. Idiopathic Epiretinal Membrane and Vitreomacular Traction Preferred Practice Pattern(R). Ophthalmology. Feb 2020; 127(2): P145-P183. PMID 31757497
  22. Neffendorf JE, Kirthi V, Pringle E, et al. Ocriplasmin for symptomatic vitreomacular adhesion. Cochrane Database Syst Rev. Oct 17 2017; 10: CD011874. PMID 29040800

Coding Section

Codes Number Description
CPT 67028 Intravitreal injection of a pharmacologic agent (separate procedure)
HCPCS J7316 Injection, ocriplasmin, 0.125 mg
ICD-10-CM H43.821-H43.829 Vitreomacular adhesion code group
ICD-10-PCS   ICD-10-PCS codes are only used for inpatient services.
  3E0C3TZ Administration, physiological systems and anatomical regions, introduction, eye, percutaneous, destructive agent
Type of service Ophthalmology  
Place of service Inpatient/Outpatient

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.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

History From 2014 Forward

09/29/2022 Annual Review. No change to policy intent.


Annual review, on change to policy intent. Updating background, regulatory status, rationale and references. 


Annual review, no change to policy intent. Updating background, coding, rationale and references. 


Annual review, no change to policy intent. Updating rationale. 


Annual review, no change to policy intent. Updating rationale.


Annual review, no change to policy intent. Updating background, description, regulatory status, rationale and references. 


Annual review, no change to policy intent. Updating rationale and references. 


Change Category from Medicine to Prescription Drug 


Annual review, no change to policy intent. Updated background, description, rationale, references and coding. 


Annual review. Updating rationale, references and supplemental information. Adding ICD 9 & 10. No change to policy intent.



Complementary Content