There is a CPT category III code for this procedure effective July 2008:
CPT code 0190T is to be used in conjunction with 67036.
CPT code 0190T differs from code 67218 because the radiation source is not implanted.
This policy was created in 2008 and has since been periodically updated with literature searches using the MEDLINE database. The most recent literature search covers the period of January 2011 through November 2011.
A search of the MEDLINE database when this policy was created did not identify any peer-reviewed publications on epiretinal radiation. The original search did identify some older randomized trials using external beam radiotherapy for age-related macular degeneration (AMD)-associated choroidal neovascularization (CNV). Little to no benefit in visual acuity was observed following repeated single treatments of 2 Gy to a total of 12–20 Gy. (1, 2) The absence of recent literature on external beam radiotherapy suggests that this treatment approach is not being pursued.
The potential use of proton beam focal epiretinal radiation for management of choroidal neovascularization was described in 2011 using choroidal endothelial cells for an in vitro dose-response study. (3) The investigators noted that, given the radiation complications reported in clinical trials (including radiation retinopathy), further study is needed to test the differential toxicity of proton beam therapy in choroidal endothelial, retinal ganglion, and pigment epithelial cells.
Three publications from 2 studies have been reported by Avila and colleagues on epiretinal radiation using the EPI-RAD90™ system. (4-6) These are case series that describe outcomes of treatment with EPI-RAD90™ alone or in conjunction with other treatments. No controlled trials of EPI-RAD90™ were identified.
One report described 12-month safety and visual acuity results of a feasibility study in 34 treatment-naïve patients from Turkey, Mexico, and Brazil recruited between February 2005 and February 2006. (4) Patients received a single treatment with either 15 Gy (n=8) or 24 Gy (n=26). Of the 21 patients (62%) who met inclusion criteria and were treated according to protocol, 50% (2 of 4) of the 15 Gy-treated patients and 76% (13 of 17) of the 24 Gy-treated patients improved or maintained their visual acuity at 12 months. In the 24-Gy group, 29% (5 of 17) gained 3 lines or more in visual acuity.
The second report described 12-month safety and visual acuity results from 24-Gy epiretinal radiation combined with bevacizumab in 34 treatment-naïve patients enrolled between June 2006 and April 2007. (5) A second intravitreal injection of bevacizumab was given 1 month after epimacular brachytherapy, and additional injections of bevacizumab could be given at any subsequent visits at the investigator’s discretion. During the first year of the study, a total of 4 additional injections were administered to 3 eyes. Although only 24 of the 34 patients enrolled met the protocol-specified eligibility criteria, all patients were included in the intent-to-treat (ITT) safety and efficacy analysis. Twelve-month follow-up showed an average gain in best-corrected visual acuity (BCVA) of 8.9 letters; 68% of patients had stable or improved vision; and approximately 40% of patients had a gain of 15 or more letters (3 lines). No radiation exposure-related adverse events were detected within the first 12 months, although these events may not be detected for several years. Adverse events related to the device or procedure included subretinal hemorrhage (n=1), retinal tear (n=1), subretinal fibrosis (n=2), epiretinal membrane (n=1), and cataract (6 of 24; 24 patients were phakic at baseline). All occurrences of cataracts were deemed to be related to the vitrectomy procedure.
Two- and 3-year results from this trial were published in 2012. (6) All 34 subjects were followed up for 24 months; 1 site that enrolled 19 patients agreed to re-consent and follow-up the patients for 3 years. In the second year of the study, a total of 10 bevacizumab injections were administered to 7 eyes; and in the third year, a total of 4 injections were administered to 4 eyes. On average, the cohort of subjects followed for 36 months received 3.0 bevacizumab injections.
At 24 months’ follow-up, 35% of patients had gained >1 letter and 15% had gained >15 letters. The mean change in visual acuity at 24 months was -5.6 letters. Twelve of the 24 phakic patients (50%) developed cataracts, and 4 had phacoemulsification with intraocular lens implantation. At 36 months, 53% of patients had gained >1 letter and 21% had gained >15 letters. The mean change in visual acuity at 36 months was +3.9 letters. Seven of 13 phakic patients (54%) developed cataracts, and 4 had phacoemulsification with intraocular lens implantation. One case of nonproliferative radiation retinopathy was observed at 36 months of follow-up.
These uncontrolled case series are not adequate evidence to determine the efficacy of EPI-RAD90™ compared to alternative treatments. Controlled studies are needed to evaluate whether epiretinal radiation therapy improves visual outcomes compared to available alternatives and/or reduces the need for anti-vascular endothelial growth factor (VEGF) therapy.
A search of online site www.clinicaltrials.gov in December 2011 identified the following studies:
NCT00809419 – This is a Phase I and II study of the NeoVista Ophthalmic System (EPI-RAD90™) for the treatment of subfoveal CNV associated with wet AMD in patients who require persistent anti-VEGF therapy to maintain an adequate response to treatment (MERITAGE). This study, which is being conducted at one site in the U.S., has closed recruiting with an estimated enrollment of 32 subjects. The expected study completion date is November 2012.
NCT00679445 – This is a Phase II feasibility study to evaluate the safety and tolerability of the EPI-RAD90™ system, combined with an injection of ranibizumab (Lucentis®), in patients with AMD who have failed primary anti-VEGF therapy. This study has closed recruiting (from 2 sites in the United States) with a projected enrollment of 20 subjects with AMD-related wet CNV. This study has been completed.
NCT00454389 – This Phase III, CNV secondary to AMD treated with beta radiation epiretinal therapy (CABERNET) trial is a multicenter, randomized, controlled study to evaluate the safety and efficacy of beta radiation epiretinal therapy combined with 2 injections of ranibizumab (Lucentis®) versus ranibizumab alone. This study has closed recruiting with a projected enrollment of 450 subjects with AMD-related wet CNV from international locations in addition to 30 sites in the U.S. Final data collection for the primary outcome measure was expected to be completed September 2011. The projected study completion date is August 2012.
NCT01006538 – This is a multicenter Phase IV randomized controlled trial of macular epiretinal brachytherapy (VIDION® system by NeoVista) versus Lucentis [ranibizumab]-only treatment (MERLOT). The trial is sponsored by King’s College Hospital National Health Service Trust in the United Kingdom (UK) and targets patients who are requiring frequent injections of ranibizumab to try to reduce or eliminate the need for ongoing, regular eye injections. The active control group will continue to receive intravitreal injections of ranibizumab on a monthly basis as required. Twenty-nine sites in the U.K. will be participating. The study has an estimated enrollment of 363 patients with study completion expected in 2014.
Epiretinal radiation describes the intraocular administration of radiation to the choroidal vascular bed of the retina to treat age-related macular degeneration (AMD). Evidence to date consists of 2 small case series. Controlled studies, which are ongoing, are needed to evaluate whether epiretinal radiation therapy improves health outcomes compared to alternative treatments. In addition, no devices have been approved by the FDA. As a result, this procedure is considered investigational.
Practice Guidelines and Position Statements
The 2011 guidance from the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) states that current evidence on the efficacy of epiretinal brachytherapy for wet age-related macular degeneration (AMD) is inadequate and limited to small numbers of patients. With regard to safety, vitrectomy has well-recognized complications and there is a possibility of subsequent radiation retinopathy. Therefore this procedure should only be used in the context of research. (7)