Archived Policies - Other


Photodynamic Therapy for Subfoveal Choroidal Neovascularization

Number:OTH903.015

Effective Date:01-15-2010

End Date:10-31-2010

Coverage:

Photodynamic therapy (PDT) as monotherapy may be considered medically necessary as a treatment of choroidal neovascularization (CNV) associated with the following conditions including but not limited to:

  • age-related macular degeneration (AMD),
  • myopic degeneration, 
  • presumed ocular histoplasmosis.

Photodynamic therapy is considered experimental, investigational and unproven, as monotherapy for other ophthalmologic disorders, including but not limited to CNV secondary to central serous chorioretinopathy.

Photodynamic therapy is considered experimental, investigational and unproven when used in combination with one or more anti-vascular endothelial growth factor (anti-VEGF) agents (including pegaptanib [Macugen®], ranibizumab [Lucentis®] and bevacizumab [Avastin®]) to treat the conditions considered medically necessary for treatment with photodynamic therapy alone.

Description:

Photodynamic therapy is a treatment modality designed to selectively occlude ocular choroidal neovascular tissue.  The therapy is a two-step process, consisting initially of an injection of the photosensitizer verteporfin, followed 15 minutes later by laser treatment to the targeted sites of neovascularization in the retina.  The laser treatment selectively damages the vascular endothelium.  Patients may be re-treated if leakage from CNV persists.

There is currently one intravenous photodynamic therapy agent that has received approval by the U.S. Food and Drug Administration (FDA): verteporfin (Visudyne®).  Indications include the treatment of predominantly classic subfoveal CNV due to AMD, pathologic myopia, and presumed ocular histoplasmosis.  The label notes that there is insufficient evidence for verteporfin use in predominately occult subfoveal CNV, and it is contraindicated in patients with porphyria.

Prior to the availability of photodynamic therapy, CNV was treated with photocoagulation using either argon, green, or infrared lasers.  This conventional photocoagulation was limited to extrafoveal lesions due to the risk of retinal burns.  However, recently, infrared lasers used at a low-power setting have been investigational as a technique to photocoagulate subfoveal lesions.

AMD is a painless, insidious process.  In its earliest stages, it is characterized by minimal visual impairment and the presence of large drusen and other pigmentary abnormalities on ophthalmoscopic examination.  As AMD progresses, two distinctively different forms of degeneration may be observed.  The first, called the atrophic or areolar or dry form, evolves slowly.  Atrophic AMD is the most common form of degeneration and is often a precursor of the second form, the more devastating exudative neovascular form, also referred to as disciform or wet degeneration.  The wet form is distinguished from the atrophic form by serous or hemorrhagic detachment of the retinal pigment epithelium and the development of CNV, sometimes called neovascular membranes.  Risk of developing severe irreversible loss of vision is greatly increased by the presence of CNV.  The pattern of CNV, as revealed by fluorescein or indocyanine angiography, is further categorized as classic or occult.  For example, classic CNV appears as an initial lacy pattern of hyperfluorescence followed by more irregular patterns as the dye leaks into the subretinal space.  Occult CNV lacks the characteristic angiographic pattern, either due to the opacity of coexisting subretinal hemorrhage or, especially in CNV associated with AMD, by a tendency for epithelial cells to proliferate and partially or completely surround the new vessels.   Interestingly, lesions consisting only of classic CNV carry a worse visual prognosis than those made up of only occult CNV, suggesting that the proliferative response that obscures new vessels may also favorably alter the clinical course of AMD.

Presumed ocular histoplasmosis may be the second most common cause of blindness in patients younger than 50 years of age in certain endemic areas (the Ohio and Mississippi River valleys in the United States).  It is a condition characterized by a positive skin test for histoplasmosis, miliary 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 neovascular lesions, which may develop many years after chorioretinal scarring has taken place, affect the macula.

Pathologic myopia refers to an abnormal elongation of the eye associated with severe near-sightedness.  It generally occurs among people over 30 years of age and can result in a progressive, severe loss of vision, frequently related to the development of CNV.

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.  Central serous chorioretinopathy may resolve spontaneously or can be treated with medication and laser photocoagulation.

Other available therapeutic options for AMD not addressed in this policy include antioxidants, thermal laser photocoagulation and VEGF antagonists or angiostatics.  The role for each varies according to location and AMD subclassification.  For those whose visual losses impair their ability to perform daily tasks, low-vision rehabilitative services offer resources to compensate for deficits.

Angiostatic agents block some stage in the pathway leading to new blood vessel formation (angiogenesis):  In contrast to palliative treatments for CNV (e.g., thermal photocoagulation and photodynamic therapy), they are potentially disease modifying.  Drugs currently under study target various parts of the angiogenic pathway: messenger RNA; Anti-Vascular Endothelial Growth Factor (VEGF); endothelial cell proliferation, migration, and proteolysis. Refer to Medical Policy OTH903.020 for other VEGF indications.

Rationale:

This policy is based in part on a 2000 Blue Cross Blue Shield Technology Evaluation Center Assessment (TEC) that offered the following observations and conclusions:

  • Two multicenter, double-masked, randomized placebo-controlled trials including 402 patients reported that, at one year of follow-up, fewer patients treated with photodynamic therapy experienced a clinically significant loss of visual acuity compared to those treated with placebo: 38.8% compared to 53.6% (p<0.001).
  • Subgroup analysis suggests that the treatment effect is predominantly experienced by patients with AMD characterized by at least 50% classic CNV.
  • There were inadequate data to permit scientific conclusions regarding other etiologies of CNV.

The TEC Assessment did not specifically address the issue of frequency of treatment or treatment extending beyond one year.  Since the completion of the TEC Assessment, the two-year results of the pivotal Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) randomized trial of patients with AMD were published.  Beneficial outcomes regarding visual acuity and contrast sensitivity noted after 12 months were sustained through 24 months.  At the end of two years, 53% of the treatment group, as compared to 38% of the placebo group, lost fewer than 15 letters.  The average number of applications of verteporfin treatment in the second year (2.2) was lower than that required during the first year.  A subgroup analysis was reported, comparing results between those patients with predominantly classic CNV (>50% of lesional area) compared to minimally classic CNV (<50%).  For patients with minimally classic disease, no statistically significant differences in visual acuity were noted.

The verteporfin in photodynamic therapy (VIP) trial is another randomized study that primarily focused on efficacy of photodynamic therapy in patients with occult but no classic lesions that were presumed to have progressive disease due to visual or anatomic deterioration within the previous three months.  Of the 339 patients enrolled in the trial, 76% had occult disease; the remainder had early classic CNV with good visual acuity.  Similar to other randomized trials, the primary outcome was the proportion of eyes with fewer than 15 letters of visual acuity loss. While there was no significant difference between the treatment and placebo groups at 12 months, by 24 months, a significantly lower percentage of those with occult CNV had lost vision (55% vs. 68%, p=0.032).  These results contrast with those of the TAP trial, although the patient populations are slightly different.  The TAP trial required all patients to have some percentage of classic CNV, while the VIP trial recruited patients with occult disease without evidence of classic CNV.  In addition, the VIP trial required patients with occult disease to have experienced recent deterioration in vision. Results for the subgroup of patients with classic CNV but good visual acuity were not reported separately.

Photodynamic therapy has also been investigated in patients with CNV related to pathologic myopia and presumed ocular histoplasmosis.  A second arm of the VIP trial focused on 120 patients with pathologic myopia and CNV, either classic, occult, or mixed (although 90% of patients had classic CNV) who were randomized to receive photodynamic therapy or placebo.  At month 12, photodynamic therapy stabilized or improved vision (as defined by a loss of fewer than eight letters on a standard eye chart) in 72% of patients versus 44% on placebo.  The authors concluded that verteporfin therapy increases the chance of stabilizing or improving vision compared to placebo treatment for at least one year. Results were not reported separately for those with predominantly classic CNV versus occult CNV.

There are minimal published data regarding the use of photodynamic therapy in patients with CNV related to ocular histoplasmosis.  The FDA approval was based on an open-label safety study involving 26 patients with ocular histoplasmosis.  Visual acuity improved by an average of more than one line on a standard eye chart at 12 months (6.7 letters on a standard eye chart) with 28% of patients experiencing a visual acuity improvement of three lines (15 letters) or more. Visual acuity decreased by less than three lines of vision in 88% of patients during the same time period.

TAP trial reports demonstrated positive outcomes with the use of photodynamic therapy for subfoveal choroidal neovascularization, and further supported the findings of the earlier TAP trial reports.  A Cochrane review was published during this time period that concluded that photodynamic therapy is effective in preventing visual loss in classic and occult CNV due to age-related macular degeneration. 

Ergun and colleagues reported on a case series of photodynamic therapy for CNV secondary to central serous chorioretinopathy on 26 eyes in 24 patients.  Results demonstrated a mean increase in 2.2 lines of visual improvement at two years and no adverse outcomes.  While promising, larger and comparative studies are warranted for photodynamic therapy for this indication.

The Visudyne in Minimally Classic Choroidal Neovascularization (VIM) Study Group randomized 117 patients to verteporfin or placebo infusion with standard or reduced light fluence rates.  The authors concluded after 24 months of follow-up that verteporfin therapy was safe and reduced the risks of disease progression to predominantly classic CNV and visual acuity loss of at least 15 letters.  In a meta-analysis of the safety of photodynamic therapy, Azab and colleagues analyzed data from the 24-month TAP A and B and VIP trials totaling 948 patients with age-related macular degeneration.  The authors concluded the safety profile of verteporfin therapy was not statistically different from placebo.  An October 2005 TEC Special Report on the treatment of age-related macular degeneration also supports the conclusions given here and notes that the pathway leading to choroidal neovascularization is complex. 

An October 2005 BCBSA TEC Special Report noted that therapies are available for AMD to potentially modify (angiostatic agents) and palliate photodynamic therapy (PDT) the disease.  Combining these modalities concurrently or sequentially has a biological basis.  The 2005 TEC Special Report found that a host of trials are in progress combining an angiostatic agent with PDT.  The angiostatic agents being studied in trials include pegaptanib, ranibizumab, anecortave acetate, squalamine, vitalinib, and triamcinolone.  For example, in the pegaptanib trial, PDT was administered at physician discretion but an analysis was not provided that examined possible synergistic effects.

Efficacy for pegaptanib was demonstrated at one year.  However, superiority over PDT has not been shown (i.e., head-to-head comparison).  There is an absence of evidence to guide the use of combination therapy.  Until trials in progress combining angiostatic agents with PDT are completed, it is impossible to assess potential benefit or harm.  Furthermore, it may ultimately be difficult to compare effects of combination therapies unless such studies allow comparison, albeit indirectly, to existing trials.  Of concern is that as therapies become approved, combination therapy without supportive evidence could become commonplace—particularly for those not responding to initial monotherapy.

Kaiser reported results of a three-year, open-label extension of the TAP study.  Out of 402 verteporfin-treated patients who completed the 24-month randomized study, 320 (80%) enrolled in the extension protocol.  Patients who chose not to participate in the TAP extension were more likely to be older, have a poorer level of visual acuity, and have evidence of fluorescein leakage, or evidence of progression, at the 24-month examination.  Of the 320 enrolled, 193 (60%) completed the 60-month examination and 122 (38%) discontinued prematurely, three (1%) were noncompliant.  Yearly treatment rates declined from 3.5 treatments in the first year to 0.1 in the fifth year; subjects who remained in the study lost an additional 2.3 lines of letters over the three-year extension.

The FOCUS study group reported first year results of a blinded phase I/II multicenter, randomized controlled trial of ranibuzumab (0.5 mg) combined with photodynamic therapy.  Patients with choroidal neovascularization secondary to age-related macular degeneration were randomized in a 2:1 ratio to ranibizumab (n=106) or sham (n=56) injection (initially seven days) following verteporfin photodynamic therapy.  A higher than expected rate of serious intraocular inflammation occurred in the first patients, and the two treatments were subsequently scheduled no closer than 21 days apart.  Intent-to-treat analysis (93% retention) showed an average improvement in acuity of 4.9 letters, compared with a decrease of 8.2 letters in the verteporfin group alone.  The percentage of subjects who gained more than 15 letters was 24% for the combined treatment in comparison with 5% for photodynamic therapy alone.  Interpretation of this study is limited, since there was no control group treated with ranibizumab without photodynamic therapy.  Thus, one can not determine whether combined treatment is more effective than intravitreal injection of ranibizumab alone.

Based on numerous case reports and case series, that photodynamic therapy is being used in an attempt to decrease choroidal neovascularization of many different etiologies.  For example, photodynamic therapy has been reported to slow down, but not prevent or reverse, the progression of disease of choroidal neovascularization associated with angioid streaks (n=15) and inflammatory chorioretinal disease (n=5).  Controlled studies are lacking, and photodynamic therapy is considered investigational for ophthalmologic disorders other than age-related macular degeneration, pathologic myopia, or presumed ocular histoplasmosis.

An open-label assessor-blinded trial (n=165) from Croatia with short-term (three-month) follow-up reported similar results with bevacizumab and PDT.  The frequency of treatment was described only as “standard procedures.”  Twenty-two of 52 (42%) patients improved by >0.2 (logarithm of the minimum angle of resolution) following combined treatment, compared with one (2%) patient treated with bevacizumab alone and none treated with PDT alone.  Adverse events (21%) in the bevacizumab groups (alone or combined) were frequent, and included three pigment epithelial tears, 12 posterior vitreous detachments, and seven cataract progressions.

Preferred Practice Patterns (practice guidelines) on photodynamic therapy from the American Academy of Ophthalmology (AAO) are based on the TAP and VIP reports described here.  The AAO recommends PDT with verteporfin for subfoveal CNV where the classic component is greater than 50% of the lesion and the entire lesion is 5400 microns or less in diameter.  Occult subfoveal CNV may be considered for PDT under specified conditions.  While PDT was recommended for recurrent juxtafoveal CNV, evidence was considered insufficient to guide treatment recommendations for the primary use of PDT for juxtafoveal CNV. Combination therapy with VEGF inhibitors and PDT was not discussed.

2009 Update

A search of the MEDLINE database was performed for the period through August 2009.  The literature search identified four publications based on clinical trials, one retrospective registry analysis and two technology assessments.

Brown et al. evaluated the two-year results of the phase III trial designated Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR).  This multicenter, manufacturer-funded study compared ranibizumab with verteporfin photodynamic therapy (PDT) in treating predominantly classic CNV.  Patients with subfoveal choroidal neovascularization and a predominantly classic lesion (n=423) were randomized in a 1:1:1 ratio to receive 0.3mg (n = 137) or 0.5 mg (n = 139) of intravitreal ranibizumab plus sham verteporfin or sham injections plus active verteporfin (n = 142) monthly.  Patients were to receive monthly injections for two years in the study eye.  Only one eye per patient was chosen as the study eye, and only the study eye received ranibizumab with sham PDT or sham injection with active PDT.  The primary, intent-to-treat efficacy analysis was at 12 months, with continued measurements to month 24.  Key measures included the following: the percentage losing <15 letters from baseline visual acuity (VA) score (month 12 primary efficacy outcome measure); percentage gaining >or=15 letters from baseline; and mean change over time in VA score and fluorescein angiography (FA) assessed lesion characteristics. Adverse events were monitored.  Of 423 patients, at least 77% in each group completed the two-year study.  Consistent with results at month 12, at month 24, the VA benefit from ranibizumab was statistically significant and felt to be clinically meaningful; 89.9% to 90.0% of ranibizumab-treated patients had lost <15 letters from baseline vs. 65.7% of PDT patients; and 34% to 41.0% had gained 15 or more letters vs. 6.3% of PDT group.  Changes in lesion anatomic characteristics on FA also favored ranibizumab.  There was a trend for an increased incidence of cataract in the ranibizumab groups compared with the PDT group, which was statistically significant at the 0.5mg dose.  There were no statistically significant differences among the three treatments in the rates of serious nonocular adverse events.  The authors concluded “… In this two-year study, ranibizumab provided greater clinical benefit than verteporfin PDT in patients with age-related macular degeneration with new-onset, predominantly classic CNV.  Rates of serious adverse events were low.”

Bressler et al. conducted a multi-center, manufacturer-funded trial to compare patient-reported visual function in those with neovascular age-related macular degeneration treated with ranibizumab or verteporfin photodynamic therapy (PDT).  This study is a sub-analysis of the patient-reported outcomes from the ANCHOR trial.  The National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) was administered at baseline and 1, 2, 3, 6, 9, 12, 18, and 24 months.  The primary outcome measure was mean change from baseline in NEI VFQ-25 scores at 12 months.  At 12 months, patients treated with ranibizumab had mean improvements in National Eye Institute (NEI) VFQ-25 composite scores of 5.9 (range: 3.6 to 8.3) for 0.3mg dose group and 8.1 (range: 5.3 to 10.8) points for the 0.5mg dose group; patients treated with PDT had a mean improvement of 2.2 points (range: -0.3 to 4.7).  At each dose through 24 months, patients treated with ranibizumab were more likely to improve in most subscales, including the pre-specified subscales (near activities, distance activities, and vision-specific dependency).  The authors concluded that “… patients treated with ranibizumab were more likely to report clinically meaningful improvements in visual function through 24 months compared with those treated with verteporfin PDT.”

Kaiser et al. conducted a retrospective case series database (registry) analysis to assess outcomes for patients with CNV due to AMD treated with combination therapy of verteporfin PDT and bevacizumab.  Patients (n=1196) with CNV due to AMD who received one or more combination treatment of 1.25 mg intravitreal bevacizumab within 14 days of verteporfin PDT were included in the analysis.  Physicians from 45 clinical centers entered patient data at baseline and follow-up examinations, including subsequent treatments.  The primary outcome measure was change from baseline in VA and retreatment rates of any therapy after the initial combination treatment.  The authors concluded that combination therapy with PDT and bevacizumab led to vision benefit for most patients, particularly those who were treatment naïve at baseline.  However, given that these data are from a registry, randomized clinical trials are needed to confirm these findings.

Schmidt et al. conducted a multicenter clinical trial to compare efficacy and safety of a more intense regimen versus a standard one for retreatment of neovascular age-related macular degeneration (AMD) during the early period of verteporfin therapy (VT).  Patients (n=231) with predominantly classic CNV secondary to AMD were included.  During the first six months of VT, patients were randomly assigned 1:1 to retreatment every two months (group A) or three months (group B).  After six months, both groups underwent retreatment every three months for as long as CNV activity was documented.  The primary outcome measures were: best-corrected visual acuity (BCVA) measured every six months; mean number of treatments per patient during 24 months' follow-up; proportions of patients in each group losing at least three lines of vision or gaining at least one line; greatest linear dimension (GLD) of the lesion as documented by fluorescein angiography every six months, and relationship between initial lesion size and BCVA.  At all follow-up, mean BCVAs were similar for groups A and B; mean numbers of photodynamic therapy treatments were similar for both groups (4.07 vs. 4.36); a lower proportion (51.9% vs. 56.7%) of patients in group A had lost at least three lines of vision at 24 months; and groups A and B had similar increases in mean lesion size from baseline to 24 months.  The authors concluded that overall outcomes regarding visual benefit, lesion anatomic features, and number of retreatments after six months, were similar for patients receiving more intense or standard early therapy.

Piermarocchi et al. conducted a prospective randomized study in Italy to evaluate the long-term effect of intravitreal triamcinolone acetonide (IVT) treatment combined with photodynamic therapy (PDT) vs. PDT alone for neovascular age-related macular degeneration.  Eighty-four patients were enrolled to receive PDT (n = 41) or IVT treatment followed by PDT (n = 43) within approximately a 7- to 15-day interval.  All patients were naive to treatment.  At baseline and each follow-up visit at 3, 6, 12, and 24 months, measurement of best-corrected visual acuity (VA), fluorescein angiography, indocyanine green angiography, and optical coherence tomography were performed.  Mean changes in VA and retreatment rate were considered as primary outcome indicators.  Mean VA increased at one month of follow-up but decreased progressively by the 24-month point in both groups (P =.74).  The retreatment rate was significantly lower in the combined therapy group.  Choroidal hypoperfusion/nonperfusion and areas with decreased/absent fundus autofluorescence within the PDT spot area were significantly greater with combined therapy.  The authors concluded that “… combination IVT treatment with PDT seemed to be more effective for managing neovascular age-related macular degeneration, but long-term analysis failed to demonstrate functional benefits.”

The available published literature supports the use of PDT as monotherapy for the treatment CNV associated with AMD, pathologic myopia, or presumed ocular histoplasmosis.  There is insufficient evidence to support the use of PDT in combination with anti-VEGF therapies for the treatment CNV associated with AMD, pathologic myopia, or presumed ocular histoplasmosis or as monotherapy or in combination therapy for other ophthalmologic disorders, including CNV secondary to central serous chorioretinopathy.  The policy statement has been clarified with the addition of PDT use as monotherapy and a new statement has been added that PDT in combination with anti-VEGF therapies is investigational for all ophthalmic disorders.

In September 2003, the National Institute for Clinical Excellence (NICE) issued Technology Appraisal Guidance 68, “Guidance on the use of photodynamic therapy for age-related macular degeneration”.  The guidance states that “…Photodynamic therapy (PDT) is recommended for the treatment of wet age-related macular degeneration for individuals who have a confirmed diagnosis of classic with no occult subfoveal choroidal neovascularization (CNV) (that is, whose lesions are composed of classic CNV with no evidence of an occult component) and best- corrected visual acuity6/60 or better.  PDT should be carried out only by retinal specialists with expertise in the use of this technology.”

In April 2008, the Canadian Agency for Drugs and Technologies in Health (CADTH), released a Health Technology Assessment (HTA) titled Management of Neovascular Age-related Macular Degeneration: Systematic Drug Class Review and Economic Evaluation.  The authors concluded that “…overall, the efficacy of anti-vascular endothelial growth factor (anti-VEGF) therapies over verteporfin (V-PDT) is well supported by [randomized controlled trials (RCTs)]. What remains unclear is whether combination therapy (and which combinations) are superior or equal to monotherapy…”

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

None


Medicare Coverage:

The information contained in this section is for informational purposes only.  HCSC makes no representation as to the accuracy of this information.  It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been developed or changed since this medical policy document was written.  See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

Photodynamic Therapy for Subfoveal Choroidal Neovascularization.  Chicago, Illinois:  Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (2000 December) 15(18).

Bressler, N.M.  Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials. TAP Study Group. Archives of Ophthalmology (2001)119(2):198-207.

Verteporfin in Photodynamic Therapy (VIP) Study Group.  Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization—verteporfin in photodynamic therapy report 2.  American Journal of Ophthalmology (2001) 131(5):541-60.

Verteporfin in Photodynamic Therapy (VIP) Study Group.  Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial—VIP report no. 1.  Ophthalmology (2001) 108(5):841-52.

Bressler, N.M., Arnold, J., et al.  Verteporfin therapy of subfoveal choroidal neovascularization in patients with age-related macular degeneration: additional information regarding baseline lesion composition’s impact on vision outcomes – TAP report No. 3.  Archives of Ophthalmology (2002) 120(11):1443-54.

Rubin, G.S., and N.M. Bressler.  Effects of verteporfin therapy on contrast sensitivity: Results from the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) investigation – TAP report No. 4.  Retina (2002) 22(5):536-44.

Blumenkranz, M.S., Bressler, N.M., et al.  Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: three-year results of an open-label extension of 2 randomized clinical trials – TAP report No. 5. Archives of Ophthalmology (2002) 120(10):1307-14.

National Institute for Clinical Excellence (NICE).  Technology Appraisal Guidance 68.  Guidance on the use of photodynamic therapy for age-related macular degeneration. Issue date: (2003 September). <http://www.nice.org.uk>.  (accessed 2009 August).

Wormald, R., Evans, J., et al.  Photodynamic therapy for neovascular age-related macular degeneration (Cochrane Review).  In: The Cochrane Library, (2004) 1.  Chichester, U.K: John Wiley & Sons, Ltd.

Azab, M., Benchaboune, M., et al.  Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: meta-analysis of 2-year safety results in three randomized clinical trials: Treatment of Age-Related Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic Therapy Study Report no. 4.  Retina (2004) 24(1):1-12.

Gragoudas, E.S., Adamis, A.P., et al.  Pegaptanib for neovascular age-related macular degeneration.  New England Journal of Medicine (2004) 351(27):2805-16.

Ergun, E., Tittl, M., et al.  Photodynamic therapy with verteporfin in subfoveal choroidal neovascularization secondary to central serous chorioretinopathy.  Archives of Ophthalmology (2004)122(1):37-41.

Azab, M., Boyer, D.S., et al.  Verteporfin therapy of subfoveal minimally classic choroidal Neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial. Archives of Ophthalmology (2005) 123(4):448-57.

Heimann, H., Gelisken, F., et al.  Photodynamic therapy with verteporfin for choroidal neovascularization associated with angioid streaks.  Graefes Archives of Clinical Experimental Ophthalmology (2005) 243(11):1115-23.

TEC Special Report: Current and evolving strategies in the treatment of age-related macular degeneration.  Chicago, Illinois:  Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program Special Report (2005 December) 20(11).

Kaiser, P.K.  Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: 5-year results of two randomized clinical trials with anopen-label extension: TAP report no. 8. Graefes Archives of Clinical Experiments in Ophthalmology (2006) 244(9):1132-42.

American Academy of Ophthalmology.  Age-Related Macular Degeneration, Preferred Practice Pattern. San Francisco: American Academy of Ophthalmology (2006). <www.aao.org/ppp> (accessed 2009 August 27).

Heier, J.S., Boyer, D.S., et al.  FOCUS Study Group.  Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the FOCUS Study. Archives of Ophthalmology (2006) 124(11):1532-42.

Brown, D.M., Kaiser, P.K., et al.  ANCHOR Study Group.  Ranibizumab versus verteporfin for neovascular age-related macular degeneration.  New England Journal of Medicine (2006) 355(14):1432-44.

Lim, J.I., Flaxel, C.J., et al.  Photodynamic therapy for choroidal neovascularization secondary to inflammatory chorioretinal disease.  Annals of the Academy of Medicine in Singapore (2006) 35(3):198-202.

Lazic, R., and N. Gabric.  Verteporfin therapy and intravitreal bevacizumab combined and alone in choroidal neovascularization due to age-related macular degeneration.  Ophthalmology (2007) 114(6):1179-85.

Gilson, M.M., Bressler, N.M., et al.  Neovascular Age-Related Macular Degeneration, Periocular Corticosteroids, and Photodynamic Therapy.  (NAPP) Trial Research Group, Periocular triamcinolone and photodynamic therapy for subfoveal choroidal neovascularization in age-related macular degeneration. Ophthalmology (2007) 114(9):1713-21.

Wormald, R., Evans, J., et al.  Photodynamic therapy for neovascular age-related macular degeneration.  Cochrane Database System Review (2007) (3):CD002030.

Iriyama, A., Obata, R., et al.  Effect of posterior juxtascleral triamcinolone acetonide on the efficacy and choriocapillaris hypoperfusion of photodynamic therapy.  Graefes Arch Clin Exp Ophthalmology (2008) 246(3):339-44.

Schmidt-Erfurth, U., and S. Sacu.  Early Retreatment Study Group.  Randomized multicenter trial of more intense and standard early verteporfin treatment of neovascular age-related macular degeneration.  Ophthalmology (2008) 115(1):134-40.

Piermarocchi, S., Sartore, M., et al.  Combination of photodynamic therapy and intraocular triamcinolone for exudative age-related macular degeneration and long-term chorioretinal macular atrophy.  Archive of Ophthalmology (2008) 126(10):1367-74.

Antoszyk, A.N., Tuomi, L., et al.  FOCUS Study Group.  Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration (FOCUS): year 2 results.  American Journal of Ophthalmology (2008) 145(5):862-74.

Photodynamic Therapy for Subfoveal Choroidal Neovascularization.  Chicago, Illinois:  Blue Cross Blue Shield Association Medical Policy Reference Manual (2009 August) Other 9.03.08.

Canadian Agency for Drugs and Technologies in Health (CADTH).  Technology Overview. Management of Neovascular Age-related Macular Degeneration: Systematic Drug Class Review and Economic Evaluation. (2008 April): Issue 43. <http://www.cadth.ca>. (accessed 2009 August 27).

Brown, D.M., Michels, M., et al.  ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology (2009) 116(1):57-65.e5.

Bressler, N.M., Chang, T.S, et al.  Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) Research Group.  Improved vision-related function after ranibizumab vs. photodynamic therapy: a randomized clinical trial. Archive of Ophthalmology (2009) 127(1):13-21.

Boyer, D.S., Garcia, R., et al.   Registry of Visudyne AMD Therapy Writing Committee. Verteporfin photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration.  Ophthalmology (2009) 116(4):747-55, 755.e1.

Policy History:

1/15/2010        Revised/updated entire document with addition of Photodynamic therapy as experimental, investigational and unproven when used in combination with one or more of the anti-vascular endothelial growth factor therapies.

11/1/2007        Revised/updated entire document

12/1/2003        New medical document

Archived Document(s):

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