Photodynamic Therapy for Choroidal Neovascularization

POLICY NUMBER

A.9.03.08

DESCRIPTION

Verteporfin photodynamic therapy is a treatment modality designed to selectively occlude ocular choroidal neovascular tissue. The therapy is a 2-step process, consisting of an injection of the photosensitizer verteporfin, followed 15 minutes later by laser treatment to the targeted sites of retinal neovascularization. The laser treatment selectively damages the vascular endothelium, thereby occluding choroidal neovascularization tissue. Individuals may be retreated if leakage from choroidal neovascularization persists.

Vision Loss

Severe vision loss can occur with ocular neovascularization, the growth of abnormal blood vessels in the retina or choroid. Neovascularization occurs in a number of ocular diseases, including age-related macular degeneration.

Age-Related Macular Degeneration

Age-related macular degeneration is a degenerative disease of the retina that results in loss of central vision. Two distinctive forms, known as dry and wet degeneration, may be observed. The dry form (also known as atrophic or areolar) is more common and is often a precursor of the wet form (also known as exudative neovascular or disciform). The wet form is more devastating and characterized by serous or hemorrhagic detachment of the retinal pigment epithelium and development of choroidal neovascularization, which greatly increases the risk of developing severe irreversible loss of vision. Choroidal neovascularization is categorized as classic or occult. Classic choroidal neovascularization appears as an initial lacy pattern of hyperfluorescence followed by more irregular patterns as the dye leaks into the subretinal space. Occult choroidal neovascularization lacks the characteristic angiographic pattern. Classic choroidal neovascularization carries a worse prognosis for vision than occult choroidal neovascularization, suggesting that the proliferative response that obscures new vessels may also favorably alter the clinical course of age-related macular degeneration.

Pathologic Myopia

Pathologic myopia refers to an abnormal elongation of the eye associated with severe near-sightedness. It generally occurs among people older than 30 years of age and can result in a progressive, severe loss of vision, frequently related to the development of choroidal neovascularization. Verteporfin photodynamic therapy has also been investigated in patients with choroidal neovascularization related to pathologic myopia. Antivascular endothelial growth factor therapy is now considered a first-line intervention in patients with myopic choroidal neovascularization.

Presumed Ocular Histoplasmosis

Presumed ocular histoplasmosis may be the second most common cause of blindness in patients younger than 50 years of age in certain endemic areas (Ohio and Mississippi River Valleys in the United States). This condition is characterized by a positive skin test for histoplasmosis, military opacities of the lungs, tiny choroidal scars, peripapillary disruption of the choriocapillaris, and exudation or hemorrhage from choroidal lesions in or near the macula. The condition is asymptomatic and benign, unless the choroidal neovascularization lesions, which may develop many years after chorioretinal scarring has taken place, affect the macula.

Central Serous Chorioretinopathy

Central serous chorioretinopathy refers to an idiopathic disease in which there is a serous detachment of the macula due to leakage of fluid from the choriocapillaris through the retinal pigment epithelium. This condition is avascular; however, neovascularization can occur as a secondary complication. In most cases, central serous chorioretinopathy resolves spontaneously in 3 to 4 months. However, in a few cases, chronic progression or recurrence can lead to the progressive decline of visual acuity. Central serous chorioretinopathy has been treated with medication and laser photocoagulation, but these treatments have limited efficacy. Multiple definitions have been used in the literature to classify central serous chorioretinopathy as acute or chronic based cutoff time points (eg, persistent fluid for <3, 4 or 6 months) or less frequently based on the timing of treatment. For example, acute central serous chorioretinopathy defined as the first attempted treatment to improve visual acuity, and chronic central serous chorioretinopathy is defined as being refractory to treatment. Further, multiple verteporfin photodynamic therapy strategies that use either reduced-dose or half-fluency have been evaluated for the treatment of central serous chorioretinopathy because full-dose verteporfin photodynamic therapy used in age-related macular degeneration has shown a potentially higher risk of developing choroidal ischemia and retinal atrophic changes.

Polypoidal Choroidal Vasculopathy

Polypoidal choroidal vasculopathy arises primarily from abnormal choroidal circulation, resulting in characteristic lesions comprising well-defined vascular networks of vessels ending in polyp-like structures. A less common subtype is polypoidal choroidal neovascularization, and it may be considered a subtype of age-related macular degeneration. Eyes that develop a cluster of grape-like polypoidal dilations are at high risk for severe vision loss.

Chorioidal Hemangioma

Choroidal hemangioma is an uncommon, benign vascular tumor, manifesting as an orange-red mass in the posterior pole of the eye. Visual loss may be progressive and irreversible because of chronic foveal detachment.

Angioid Streaks

Angioid streaks result from crack-like breaks in the Bruch membrane (the innermost layer of the choroid) and occur in individuals spontaneously or due to blunt trauma or associated with some systemic diseases such as pseudoxanthoma elasticum, Paget disease of bone, or sickle hemoglobinopathy. Vision loss in eyes with angioid streaks occurs most frequently as a result of choroidal neovascularization.

TreatmentAvailable therapeutic options for choroidal neovascularization include anti-vascular endothelial growth factor inhibitors, verteporfin photodynamic therapy, antioxidants, thermal laser photocoagulation, and corticosteroids. The safety and efficacy of each treatment depends on the form and location of the neovascularization.

Verteporfin photodynamic therapy is a treatment modality designed to selectively occlude ocular choroidal neovascular tissue. The therapy is a 2-step process, consisting of an injection of the photosensitizer verteporfin, followed 15 minutes later by laser treatment to the targeted sites of retinal neovascularization. The laser treatment selectively damages the vascular endothelium and occludes the neovacularized tissue. Patients may be retreated if leakage from choroidal neovascularization persists.

Monotherapy with vascular endothelial growth factor inhibitors is now standard treatment of choroidal neovascularization due to age-related macular degeneration and pathologic myopia. Combining verteporfin photodynamic therapy with antivascular endothelial growth factor inhibitors, concurrently or sequentially, has a biologic basis and has been investigated in multiple trials particularly in the treatment of choroidal neovascularization due to age-related macular degeneration and pathologic myopia.

The use of verteporfin photodynamic therapy in choroidal neovascularization has decreased substantially with the availability of antivascular endothelial growth factor therapy. Subsequent to U.S. Food and Drug Administration (FDA) approval of verteporfin photodynamic therapy in 2000, the FDA approved pegaptanib in 2004 and ranibizumab in 2006 for treatment of age-related macular degeneration related choroidal neovascularization. The approval of pegaptanib was based on a sham-controlled, RCT while ranibizumab was approved based on a head-to-head comparison with verteporfin photodynamic therapy in the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) trial. Intravitreal injections of antivascular endothelial growth factor drugs such as ranibizumab and bevacizumab have shown superior efficacy compared with verteporfin photodynamic therapy in multiple head-to-head trials. Currently, verteporfin photodynamic therapy is used for patients in whom vascular endothelial growth factor inhibitors are contraindicated or for those who fail to benefit from vascular endothelial growth factor inhibitors.

In 2000,verteporfin (Visudyne®, Novartis [now Bausch & Lomb]), an intravenous photodynamic therapy agent, was approved by the FDA for the treatment of age-related macular degeneration in individuals with predominantly classic subfoveal choroidal neovascularization. Subsequently, in 2001, the indication was expanded to include presumed ocular histoplasmosis and pathologic myopia.

POLICY

Verteporfin photodynamic therapy as monotherapy may be considered medically necessary as a treatment of choroidal neovascularization associated with age-related macular degeneration, pathologic myopia, presumed ocular histoplasmosis, chronic central serous chorioretinopathy, or choroidal hemangioma.

Verteporfin photodynamic therapy is considered investigational as monotherapy for other ophthalmologic disorders.

Verteporfin photodynamic therapy is considered investigational when used in combination with one or more of the anti-vascular endothelial growth factor therapies (anti-VEGF): ranibizumab (Lucentis®), bevacizumab (Avastin®), aflibercept (Eylea®), brolucizumab-dbll (Beovu®), or faricimab-svoa (Vabysmo®) as a treatment of choroidal neovascularization associated with age-related macular degeneration, pathologic myopia, presumed ocular histoplasmosis, central serous chorioretinopathy, choroidal hemangioma, or for other ophthalmologic disorders.

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

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

A single payment will be made for OPT with verteporfin performed on both eyes on the same day, as a single infusion is adequate for treatment of both eyes.

FDA labeling for verteporfin indicates that the physician should re-evaluate the individual every 3 months and, if choroidal neovascularization leakage is detected on fluorescein angiography, therapy should be repeated. However, the total number of treatments is not addressed by the FDA. Evidence defining when treatment should stop is not available, but experts have suggested stopping “when the situation is judged to be ‘futile’." FDA labeling states that the “safety and efficacy of Visudyne beyond 2 years have not been demonstrated.”

Acute central serous chorioretinopathy refers to self-limiting disease that resolves spontaneously over a few months without any treatment. Chronic central serous chorioretinopathy has been defined as a serous macular elevation, visible biomicroscopically or detected by optical coherence tomography, that is associated with retinal pigment epithelial atrophic areas and subtle leaks or ill-defined staining by fluorescein angiography; it does not resolve spontaneously within a few months.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

11/2000: Approved by Medical Policy Advisory Committee (MPAC), CPT 67299, 92235, 92250 added, ICD-9 diagnosis 362.52 added, HCPCS J3490 added

1/17/2001: Code Reference section updated, CPT 67221 added

7/3/2001: Code Reference section updated; ICD-9 procedure code 14.24 deleted, HCPCS G0184 deleted, ICD-9 procedure code 14.29 added, HCPCS G0183 added

9/5/2001: Pathologic myopia and presumed ocular histoplasmosis added as covered indications

3/12/2002: New 2002 codes added, CPT 67225 added, HCPCS J3395, J7308, Q3013 added

5/2/2002: Type of Service and Place of Service deleted

9/2/2004: Code Reference section updated, CPT 67225 description revised, ICD-9 diagnosis code 115.92, 360.21 added, ICD-9 diagnosis code 362.52 description revised, CPT 67299, 92235, 92250 deleted, HCPCS G0183, J3490, J7308, Q3013 deleted

2/18/2005: HCPCS J3395 deletion date added, HCPCS J3396 added with a Note: "Indicate the number of units the patient receives. A unit is defined as 0.1 milligrams by this code."

3/17/2006: Policy reviewed, no changes

4/21/2006: Policy revised

5/21/2007: Policy reviewed, no changes

6/24/2008: Policy reviewed, no changes

12/30/2010: Policy description updated to add information regarding Bevacizumab. Added link to related medical policy. Policy statement revised to add "monotherapy" to the first investigational policy statement. Added the following investigational policy statement: Photodynamic therapy is considered investigational when used in combination with one or more of the anti-vascular endothelial growth factor therapies (anti-VEGF), i.e., pegatanib (Macugen®), ranibizumab (Lucentis®), bevacizumab (Avastin®), as a treatment of CNV associated with age-related macular degeneration, pathologic myopia, presumed ocular histoplasmosis, or for other ophthalmologic disorders, including CNV secondary to central serous chorioretinopathy. FEP verbiage added to the Policy Exceptions section.

06/22/2011: Policy description and statement unchanged. Deleted "Subfoveal" from the title. Removed outdated references from the Sources section.

07/12/2012: Added aflibercept (Eylea™) as investigational when used in combination with photodynamic therapy.

09/25/2012: Policy description updated regarding treated conditions. Added "as monotherapy" to the medically necessary policy statement for clarity purposes. Added chronic central serous chorioretinopathy, choroidal hemangioma to the medically necessary policy statement. Added ICD-9 codes 228.09 and 362.41 to the Covered Codes table.

10/23/2013: Policy reviewed; no changes to policy statement. Removed deleted HCPCS code J3395 from the Code Reference section.

08/12/2014: Policy reviewed; description updated. First investigational statement revised to remove "including choroidal neovascularization secondary to central serous chorioretinopathy." It previously stated: Photodynamic therapy is considered investigational, as monotherapy for other ophthalmologic disorders, including choroidal neovascularization secondary to central serous chorioretinopathy. Second investigational statement revised to add "chronic central serous chorioretinopathy, choroidal hemangioma" and remove "including CNV secondary to central serous chorioretinopathy." It previously stated: Photodynamic therapy is considered investigational when used in combination with one or more of the anti-vascular endothelial growth factor therapies (anti-VEGF), i.e., pegatanib (Macugen®), ranibizumab (Lucentis®), bevacizumab (Avastin®), and aflibercept (Eylea™) as a treatment of CNV associated with age-related macular degeneration, pathologic myopia, presumed ocular histoplasmosis, or for other ophthalmologic disorders, including CNV secondary to central serous chorioretinopathy. Policy guidelines updated to add FDA labeling information for verteporfin and to define acute and chronic central serous chorioretinopathy.

08/27/2015: Code Reference section updated for ICD-10.

10/28/2015: Policy reviewed. Policy statements unchanged. Policy guidelines updated to add medically necessary and investigative definitions.

04/22/2016: Policy description updated. Policy statements unchanged.

05/27/2016: Policy number A.9.03.08 added.

09/30/2016: Code Reference section updated to add the following new ICD-10 diagnosis codes: H35.3210 - H35.3293.

03/31/2017: Policy description updated regarding monotherapy and age-related macular degeneration. Policy statements updated to change "Photodynamic therapy" to "Verteporfin photodynamic therapy."

09/29/2017: Code Reference section updated to add ICD-10 diagnosis codes H44.2A3, H44.2A9, H44.2B1, H44.2B2, H44.2B3, H44.2B9, H44.2C1, H44.2C2, H44.2C3, H44.2C9, H44.2D1, H44.2D2, H44.2D3, H44.2D9, H44.2E1, H44.2E2, H44.2E3, and H44.2E9, effective 10/01/2017. Removed deleted ICD-10 diagnosis code H35.32.

04/11/2018: Policy description updated to add information regarding pathologic myopia, presumed ocular histoplasmosis, central serous chorioretinopathy, choroidal hemangioma, angioid streaks, and treatment for CNV. Policy statements unchanged.

04/09/2019: Policy description updated regarding polypoidal choroidal vasculopathy. Policy statements unchanged.

04/17/2020: Policy reviewed. Second investigational statement updated to change "chronic central serous chorioretinopathy" to "central serous chorioretinopathy."

05/28/2021: Policy description updated regarding the use of verteporfin photodynamic therapy. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

05/20/2022: Policy reviewed; no changes.

04/18/2023: Policy description and Policy Guidelines updated to change "patients" to "individuals." Policy statements unchanged.

04/24/2024: Policy description updated to change "patients" to "individuals." Policy statements unchanged.

04/22/2025: Policy description updated. Policy statement regarding combination therapy revised to remove pegaptanib (Macugen®) and add brolucizumab-dbll (Beovu®) and faricimab-svoa (Vabysmo®) as investigational.

SOURCE(S)

Blue Cross Blue Shield policy #9.03.08

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

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

Covered Codes

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.