This document addresses the use of ocriplasmin (Jetrea, ThromboGenics® Inc., Iselin, NJ), a recombinant truncated form of human plasmin (proteolytic enzyme) that breaks down protein components such as laminin, fibronectin and collagen in the vitreous body and vitreoretinal interface (VRI) 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.
Note: For additional information, please refer to the following documents:
A single intravitreal injection of ocriplasmin is considered medically necessary for treatment of an eye* with symptomatic vitreomacular adhesion (VMA) when all of the following criteria are met:
*Note: For treatment of bilateral VMA, a waiting period of at least 7 days is recommended before treatment of the contralateral eye.
Investigational and Not Medically Necessary:
Repeat intravitreal injection of ocriplasmin in the affected eye is considered investigational and not medically necessary.
The use of intravitreal ocriplasmin is considered investigational and not medically necessary for any other condition not meeting the medically necessary criteria above.
Posterior vitreous detachment (PVD) is generally a benign process associated with aging. With age, the vitreous liquefies and the adhesion between the vitreous and the retina weakens (Sebag, 2012). VMA is a condition in which the vitreous gel adheres in an abnormally strong manner to the retina. This may cause increased traction, tangential forces, or both resulting in vitreomacular traction and may become symptomatic. Symptoms typically include metamorphopsia (distorted vision), blurring of visual acuity and defects in the central visual field. Macular distortion, edema and the formation of macular holes may result from vitreomacular traction. Posterior segment OCT produces high-resolution, three-dimensional images that allow measurement of the retina and surrounding tissue and is utilized to assess and document the status of the VMA. In symptomatic VMA, the posterior vitreous cortex separates from the back of the eye, appearing elevated when compared to the adhesion in the central macular area. The movement of the separating vitreous cortex pulls on the macular adhesion, which creates the traction and resulting symptoms. Stalmans and colleagues (2012) suggested that VMA:
May play a role in the progression of diabetic retinopathy and age-related macular degeneration. Vitrectomy is the only treatment for vitreomacular traction and macular holes, and because it poses certain risks (infection, retinal detachment, hemorrhage, and cataract), it is usually withheld until loss of vision has become clinically significant.
In October 2012, the U.S. Food and Drug Administration (FDA) approved ocriplasmin (Jetrea) for the treatment of symptomatic vitreomacular adhesion. Ocriplasmin is a recombinant form of human plasmin that breaks down protein components such as laminin, fibronectin and collagen in the vitreous body and VRI in the eye. These proteins are responsible for VMA (Product Information Label, 2014; Sebag, 2012; Stalmans, 2012). The breakdown of these proteins allows a better separation between the vitreous and macula and can reduce the chances that tugging will occur.
In two industry sponsored multi-center, phase III, randomized, double-blind, placebo-controlled trials, 652 adults with symptomatic VMA provided data on the safety and effectiveness of ocriplasmin. A total of 464 participants were randomized to the treatment group which received a single injection of ocriplasmin and 188 were randomized to the placebo group, receiving a sham injection without the active ingredient. Participants were evaluated and the primary endpoint was resolution of VMA at day 28, which occurred in 26.5% of the participants treated with ocriplasmin compared with 10.1% of those who received placebo (p<0.001). There was a significant difference in the total PVD achieved at day 28 (13.4% for ocriplasmin vs. 3.7% for placebo; p<0.001) and nonsurgical closure of macular holes (40.6% for ocriplasmin vs. 10.6% for placebo; p<0.001). There were instances of persistent VMA which resulted in subsequent vitrectomy during the study. There were fewer participants from the ocriplasmin treatment group compared to the placebo group that required vitrectomy (17.7% vs. 26.6%; odds ratio [OR], 0.61; 95% confidence interval [CI], 0.40 to 0.94; p=0.02). A secondary endpoint of best corrected visual acuity of 3 or more lines on the eye chart without vitrectomy was improved with ocriplasmin treatment compared to placebo 9.7% versus 3.7% (OR, 2.89; 95% CI, 1.26 to 7.76; p=0.008). The most common side effects reported in individuals treated with ocriplasmin included eye floaters; bleeding of the conjunctiva, eye pain; flashes of light (photopsia); blurred vision; vision loss; retinal edema (swelling); and macular edema (Stalmans, 2012).
A retrospective case series reported outcomes of 17 individuals with symptomatic VMA treated with ocriplasmin at a single center. At day 28, a total of 8 out of 17 eyes had a 47.1% overall response rate to treatment with ocriplasmin (Singh, 2014). The secondary outcome of improved visual acuity after ocriplasmin therapy showed a non-significant trend (p=0.29) for those with release of the VMA compared to those without VMA release. The authors noted positive predictors associated with VMA release included no epiretinal membrane at baseline, VMA diameter ≤ 1500 µm and phakic lens status. Limitations of the published data noted the small number, retrospective nature and variations in the follow-up schedule and potential for bias. The authors recommended further study to clarify and quantify the effects of ocriplasmin injections on the eye structures.
Novack and colleagues (2015) reported results from a phase II trial that was double-masked, and performed at multiple centers. A total of 100 individuals with exudative age-related macular degeneration were enrolled with 75 participants randomized to injection with ocriplasmin and 25 assigned to the sham control arm. Although the primary endpoint of VMA release by day 28 was achieved in 24.3% of the treatment group compared to 12.3% in the sham group, the difference was not statistically significant between the groups (p=0.262). The authors noted the sample size lacked power to demonstrate statistical significance. The safety and efficacy of ocriplasmin to treat VMA in individuals with wet age-related macular degeneration continue to be investigated.
Wong and colleagues (2012) described the development and role of microplasmin and ocriplasmin in the adult and pediatric populations along with pediatric vitreoretinal surgery. The authors noted there are differences in the physiology and anatomy of vitreoretinopathies characterized by stronger vitreoretinal adhesions between the vitreous cortex and the internal limiting membrane of the retina in the pediatric population. This difference makes induction of PVD during vitrectomy extremely difficult. The authors noted a phase II randomized, placebo-controlled trial to investigate the safety and efficacy of ocriplasmin as an adjunct to vitrectomy in the pediatric population. However, at this time the pediatric data have not been published.
The use of ocriplasmin in the pediatric population is not recommended in the FDA product information label (2016). Additional information from the label includes:
A single center, randomized, placebo controlled, double masked clinical study to investigate the safety and efficacy of a single intravitreal injection of 0.175 mg ocriplasmin in pediatric subjects as an adjunct to vitrectomy was conducted in 24 eyes of 22 patients. There were no statistical or clinical differences between groups for the induction of total macular PVD, any of the secondary endpoints or adverse events.
Additionally, ongoing studies are investigating the optimal timing (early/asymptomatic individuals), treatment of other indications such as neovascular age-related macular degeneration and the use of multiple intravitreal injections to one affected eye.
VMA can contribute to eye problems if the vitreous starts to move away from the macula . This movement can lead to damage of the macula due to traction (for example, pulling or tugging) on the macula, including a macular hole (Sebag, 2012; Stalmans, 2012).
Warning, precautions and adverse reactions from the FDA Product Information Label (2016) include the following:
Warnings and Precautions:
Aphakia: The absence of the lens of an eye, resulting from a congenital condition or as a result of trauma or surgery.
Central retina: A circular retinal field of approximately 6 mm around the fovea.
Contralateral: A term relating to a corresponding part on the opposite side of the body.
Fovea: Center of the macula region of the eye responsible for sharp central vision.
Glaucoma: A disease characterized by destruction of the nerve fiber layer of the optic disc.
Intravitreal or intravitreous: In the vitreous, the clear, jelly-like substance that fills the posterior segment of the eye.
Lenticular or zonular instability: Instability of the eye lens.
Macula: A part of the retina responsible for reading vision.
Myopia: A condition in which the visual images come to a focus in front of the retina of the eye resulting especially in defective vision of distant objects.
Neovascular age-related macular degeneration (AMD): A slowly progressive, painless disease affecting the macula that blurs the sharp, central vision needed for "straight-ahead" activities such as reading, sewing, and driving. AMD occurs when abnormal blood vessels behind the retina start to grow under the macula. These new blood vessels tend to be very fragile and often leak blood and fluid which thickens the macula and damages the photoreceptors.
Vitrectomy: The surgical removal of the vitreous.
Vitreous body: A transparent jelly-like substance that fills the posterior segment of the eye, delimited by the hyaloid membrane.
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 may be Medically Necessary when criteria are met:
|67028||Intravitreal injection of a pharmacologic agent [when specified as intravitreal injection of ocriplasmin, in conjunction with the HCPCS code listed below]|
|J7316||Injection, ocriplasmin, 0.125 mg [Jetrea]|
When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Websites for Additional Information|
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.
|Reviewed||01/25/2018||Medical Policy & Technology Assessment Committee (MPTAC) review. The document header wording updated from “Current Effective Date” to “Publish Date.”|
|Reviewed||02/02/2017||MPTAC review. Updated Description, Background, Definitions and Websites sections. Updated formatting in Position Statement section.|
|Reviewed||02/04/2016||MPTAC review. Updated Rationale and References sections. Removed ICD-9 codes from Coding section.|
|Reviewed||02/05/2015||MPTAC review. Updated Rationale, References and Definitions sections.|
|Revised||02/13/2014||MPTAC review. Clarified medically necessary optical coherence tomography is done on the posterior segment. Clarified visual acuity criterion. Updated Rationale, References and Websites sections.|
|01/01/2014||Updated Coding section with 01/01/2014 HCPCS changes; removed C9298 deleted 12/31/2013.|
|New||02/14/2013||MPTAC review. Initial document development.|