This Medical Policy is provided for informational purposes only.

If Members have any questions about the medical necessity of a service or procedure, they should discuss the question with their Network Provider or call a member of our Customer Service Team.

MEDICAL POLICY USE DISCLAIMER

  1. Medical Policy is used by Blue Cross & Blue Shield of Mississippi, A Mutual Insurance Company ("BCBSMS") as one set of guidelines (among other sets of guidelines) to assist BCBSMS in making benefit coverage decisions. BCBSMS utilizes Medical Policy adopted by our Medical Policy Advisory Committee ("MPAC") which is supported by the Blue Cross and Blue Shield Association Medical Policy, research and development. Medical Policies are the property of BCBSMS and any use of Medical Policy not agreed to by BCBSMS is strictly prohibited. The use of Medical Policy for purposes related to the health care of a BCBSMS plan member is permitted and is not a violation of the proprietary rights of BCBSMS.
  2. These Medical Policies are based on scientifically meritorious evidence provided through research for a particular medical technology. Medical Policy is also based on data from peer-reviewed scientific literature, from criteria developed by specialty societies and from guidelines adopted by other health care organizations.
  3. These Medical Policies apply to members/subscribers who have health insurance through BCBSMS. This Medical Policy also applies to Members of a self-insured group health plan for which Blue Cross & Blue Shield of Mississippi provides claims administration and persons covered by a Medicare Supplement policy offered by BCBSMS. This Medical Policy does not apply to any other individuals. Medical Policies may differ for Federal employees covered under the Federal Employees Health Benefits Plan.
  4. In the event of any conflict between this Medical Policy and any benefit plan, Summary Plan Description or other coverage document, the benefit plan, Summary Plan Description or other coverage document will govern.
  5. Medical technology is rapidly changing and these Medical Policies are subject to change without notice. Also, please be aware that as a result of ongoing changes being made to Medical Policy, BCBSMS cannot and does not guarantee that these Medical Policies are current.

BCBSMS Medical Policies are Subject to the Following Restrictions


This Medical Policy is provided for informational purposes only.

If Members have any questions about the medical necessity of a service or procedure, they should discuss the question with their Network Provider or call a member of our Customer Service Team.

MEDICAL POLICY USE DISCLAIMER

  1. Medical Policy is used by Blue Cross & Blue Shield of Mississippi, A Mutual Insurance Company ("BCBSMS") as one set of guidelines (among other sets of guidelines) to assist BCBSMS in making benefit coverage decisions. BCBSMS utilizes Medical Policy adopted by our Medical Policy Advisory Committee ("MPAC") which is supported by the Blue Cross and Blue Shield Association Medical Policy, research and development. Medical Policies are the property of BCBSMS and any use of Medical Policy not agreed to by BCBSMS is strictly prohibited. The use of Medical Policy for purposes related to the health care of a BCBSMS plan member is permitted and is not a violation of the proprietary rights of BCBSMS.
  2. These Medical Policies are based on scientifically meritorious evidence provided through research for a particular medical technology. Medical Policy is also based on data from peer-reviewed scientific literature, from criteria developed by specialty societies and from guidelines adopted by other health care organizations.
  3. These Medical Policies apply to members/subscribers who have health insurance through BCBSMS. This Medical Policy also applies to persons covered by the Mississippi Children's Health Insurance Program, Members of a self-insured group health plan for which Blue Cross & Blue Shield of Mississippi provides claims administration and persons covered by a Medicare Supplement policy offered by BCBSMS. This Medical Policy does not apply to any other individuals. Medical Policies may differ for Federal employees covered under the Federal Employees Health Benefits Plan.
  4. In the event of any conflict between this Medical Policy and any benefit plan, Summary Plan Description or other coverage document, the benefit plan, Summary Plan Description or other coverage document will govern.
  5. Medical technology is rapidly changing and these Medical Policies are subject to change without notice. Also, please be aware that as a result of ongoing changes being made to Medical Policy, BCBSMS cannot and does not guarantee that these Medical Policies are current.

BCBSMS Medical Policies are Subject to the Following Restrictions


This Medical Policy is provided for informational purposes only.

If Members have any questions about the medical necessity of a service or procedure, they should discuss the question with their Network Provider or call a member of our Customer Service Team.

MEDICAL POLICY USE DISCLAIMER

  1. Medical Policy is used by Blue Cross & Blue Shield of Mississippi, A Mutual Insurance Company ("BCBSMS") as one set of guidelines (among other sets of guidelines) to assist BCBSMS in making benefit coverage decisions. BCBSMS utilizes Medical Policy adopted by our Medical Policy Advisory Committee ("MPAC") which is supported by the Blue Cross and Blue Shield Association Medical Policy, research and development. Medical Policies are the property of BCBSMS and any use of Medical Policy not agreed to by BCBSMS is strictly prohibited. The use of Medical Policy for purposes related to the health care of a BCBSMS plan member is permitted and is not a violation of the proprietary rights of BCBSMS.
  2. These Medical Policies are based on scientifically meritorious evidence provided through research for a particular medical technology. Medical Policy is also based on data from peer-reviewed scientific literature, from criteria developed by specialty societies and from guidelines adopted by other health care organizations.
  3. These Medical Policies apply to members/subscribers who have health insurance through BCBSMS. This Medical Policy also applies to persons covered by the Mississippi Children's Health Insurance Program, Members of a self-insured group health plan for which Blue Cross & Blue Shield of Mississippi provides claims administration and persons covered by a Medicare Supplement policy offered by BCBSMS. This Medical Policy does not apply to any other individuals. Medical Policies may differ for Federal employees covered under the Federal Employees Health Benefits Plan.
  4. In the event of any conflict between this Medical Policy and any benefit plan, Summary Plan Description or other coverage document, the benefit plan, Summary Plan Description or other coverage document will govern.
  5. Medical technology is rapidly changing and these Medical Policies are subject to change without notice. Also, please be aware that as a result of ongoing changes being made to Medical Policy, BCBSMS cannot and does not guarantee that these Medical Policies are current.

BCBSMS Medical Policies are Subject to the Following Restrictions

Medical Policy Search
Printer Friendly Version Intravitreal Angiogenesis Inhibitors for Retinal Vascular Conditions

Intravitreal Angiogenesis Inhibitors for Retinal Vascular Conditions

 

DESCRIPTION

Angiogenesis inhibitors (e.g., ranibizumab, bevacizumab, pegaptanib) are being evaluated for the treatment of disorders of retinal circulation. Ophthalmic disorders affecting the retinal circulation include proliferative diabetic retinopathy, diabetic macular edema, and central or branch retinal vein occlusion.

Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of a variety of ocular vascular conditions characterized by neovascularization and macular edema. The macula, with the fovea at its center, has the highest photoreceptor concentration and is where visual detail is discerned. The anti-VEGF agents ranibizumab (Lucentis™), bevacizumab (Avastin®), and pegaptanib (Macugen®) are used to treat choroidal neovascularization associated with age-related macular degeneration (AMD) and are being evaluated for the treatment of disorders of retinal circulation (e.g., diabetic retinopathy and retinal vein occlusion).

Diabetic Retinopathy

Diabetic retinopathy is a common microvascular complication of diabetes and a leading cause of blindness in adults. The two most serious complications for vision are diabetic macular edema and proliferative diabetic retinopathy. At its earliest stage (nonproliferative retinopathy), microaneurysms occur. With disruption of the blood-retinal barrier, macular retinal vessels become permeable, leading to exudation of serous fluid and lipids into the macula (macular edema). As the disease progresses, blood vessels that provide nourishment to the retina are blocked, triggering the growth of new and fragile blood vessels (proliferative retinopathy). Severe vision loss with proliferative retinopathy arises from vitreous hemorrhage. Moderate vision loss can also arise from macular edema (fluid accumulating in the center of the macula) during the proliferative or nonproliferative stages of the disease. Although proliferative disease is the main blinding complication of diabetic retinopathy, macular edema is more frequent and is the leading cause of moderate vision loss in people with diabetes.

Tight glycemic and blood pressure control is the first line of treatment to control diabetic retinopathy, followed by laser photocoagulation for patients whose retinopathy is approaching the high-risk stage. Although laser photocoagulation is effective at slowing the progression of retinopathy and reducing visual loss, it results in collateral damage to the retina and does not restore lost vision. Focal macular edema (characterized by leakage from discrete microaneurysms on fluorescein angiography) may be treated with focal laser photocoagulation, while diffuse macular edema (characterized by generalized macular edema on fluorescein angiography) may be treated with grid laser photocoagulation. Corticosteroids may reduce vascular permeability and inhibit vascular endothelial growth factor (VEGF) production but are associated with serious adverse effects including cataracts and glaucoma with damage to the optic nerve. Corticosteroids can also worsen diabetes control. VEGF inhibitors (e.g., ranibizumab, bevacizumab, and pegaptanib), which reduce permeability and block the pathway leading to new blood vessel formation (angiogenesis) are being evaluated for the treatment of diabetic macular edema and proliferative diabetic retinopathy. For diabetic macular edema, outcomes of interest are macular thickness and visual acuity. For proliferative diabetic retinopathy, outcomes of interest are operative and perioperative outcomes and visual acuity.

Central and Branch Retinal Vein Occlusions

Retinal vein occlusions are classified by whether there is a central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). CRVO is also categorized as ischemic or non-ischemic. Ischemic CRVO is associated with a poor visual prognosis, with macular edema and permanent macular dysfunction occurring in virtually all patients. Non-ischemic CRVO has a better visual prognosis, but many patients will have macular edema, and it may convert to the ischemic type within 3 years. Most of the vision loss associated with CRVO results from the main complications, macular edema and intraocular neovascularization. BRVO is a common retinal vascular disorder in adults between 60 and 70 years of age and occurs approximately 3 times more commonly than CRVOs. Macular edema is the most significant cause of central visual loss in BRVO.

Retinal vein occlusions are associated with increased venous and capillary pressure and diminished blood flow in the affected area, with a reduced supply of oxygen and nutrients. The increased pressure causes water flux into the tissue while the hypoxia stimulates the production of inflammatory mediators such as VEGF, which increases vessel permeability and induces new vessel growth. Intravitreal corticosteroid injections or implants have been used to treat the macular edema associated with retinal vein occlusions, with a modest beneficial effect on visual acuity. However, cataracts are a common side effect, and steroid-related pressure elevation occurs in about one-third of patients, with some requiring filtration surgery. Macular grid photocoagulation has also been used to improve vision in BRVO but is not recommended for CRVO. The serious adverse effects of available treatments have stimulated the evaluation of new treatments, including intravitreal injection of VEGF inhibitors. Outcomes of interest for retinal vein occlusions are macular thickness and visual acuity.

Use of any VEGF inhibitors for diabetic retinopathy would be considered off-label.

In 2010, Ranibizumab (Lucentis™, Genentech, 0.5 mg) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of macular edema following retinal vein occlusion. Labeling indicates that patients should be treated monthly. The FDA has required a postmarketing safety and efficacy study on at least 150 patients who have received at least 7 doses of Lucentis™ and have been followed for at least 15 months.

Pegaptanib (Macugen®, Eyetech and Pfizer) and ranibizumab (Lucentis™) are presently the only angiostatic drugs approved by the FDA for use in the eye. Pegaptanib was the first VEGF antagonist to be approved by the FDA for use in wet AMD. Ranibizumab is approved for the treatment of patients with neovascular AMD. Pegaptanib and ranibizumab bind extracellular VEGF to inhibit the angiogenesis pathway and are administered by intravitreous injections every 4–6 weeks. Pegaptanib binds to the VEGF-165 isomer of VEGF-A while ranibizumab is an antibody fragment directed at all isoforms of VEGF-A. Bevacizumab (Avastin®) is derived from the same murine monoclonal antibody precursor as ranibizumab, which binds to all isoforms of VEGF-A. Bevacizumab has been developed and approved for use in oncology but has not been licensed for use in the eye.

Aflibercept (previously called VEGF Trap-Eye) is a recombinant fusion protein consisting of the VEGF binding domains of human VEGF receptors 1 and 2 fused to the Fc domain of human immunoglobulin-G1. Aflibercept was approved by the FDA in 2011 for the treatment of wet (neovascular) age-related macular degeneration and is administered by intravitreous injections every 4 or 8 weeks. As of February 2012, a supplemental Biologics License Application (sBLA) was under review by the FDA for the treatment of patients with diabetic macular edema (DME).

Related medical policies are as follows:

 

POLICY

Intravitreal injection of bevacizumab (Avastin®) may be considered medically necessary for the treatment of the following retinal vascular conditions:
  • Diabetic macular edema
  • Proliferative diabetic retinopathy as an adjunctive treatment to vitrectomy or photocoagulation
  • Macular edema following central retinal vein occlusion*
  • Macular edema following branch retinal vein occlusion*

Intravitreal injection of bevacizumab (Avastin®) may be considered medically necessary for the treatment of stage 3+ retinopathy of prematurity.

Macugen® (pegaptanib sodium injection), Lucentis® (ranibizumab injection), Eylea® (aflibercept injection) are addressed in a separate policy.  

 

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

 

POLICY GUIDELINES

Investigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

 

POLICY HISTORY

03/22/2012: Approved by Medical Policy Advisory Committee.

04/26/2012: Policy description updated regarding FDA status of the drugs. Added the following policy statements:  1) Intravitreal injection of bevacizumab may be considered medically necessary for the treatment of stage 3+ retinopathy of prematurity. 2) Intravitreal injection of aflibercept may be considered medically necessary for treatment of diabetic macular edema.

08/03/2012:  Revised policy statement to note that Macugen® (pegaptanib sodium injection), Lucentis® (ranibizumab injection), Eylea® (aflibercept injection) are addressed in a separate policy. 

 

SOURCE(S)

Blue Cross Blue Shield Association policy # 9.03.27 

 

CODE REFERENCE

This is not intended to be a comprehensive list of codes. Some covered procedure codes have multiple descriptions.

The code(s) listed below are ONLY covered if the procedure is performed according to the "Policy" section of this document. 

Covered Codes

Code Number

Description

CPT-4

67028

Intravitreal injection of a pharmacologic agent (separate procedure)

ICD-9 Procedure

 

 

ICD-9 Diagnosis

250.50 – 250.53 

Diabetes with ophthalmic manifestations

362.02Proliferative diabetic retinopathy
362.07Diabetic macular edema
362.83Retinal edema

HCPCS

 

 

 

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