Surgery Section - Transpupillary Thermotherapy for Treatment of Choroidal Neovascularization

IMPORTANT REMINDER

Regence Medical Policies are developed to provide guidance for members and providers regarding coverage in accordance with contract terms. Benefit determinations are based in all cases on the applicable contract language. To the extent there may be any conflict between the Medical Policy and contract language, the contract language takes precedence.

PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are considered investigational or cosmetic. Providers may bill members for services or procedures that are considered investigational or cosmetic. Providers are encouraged to inform members before rendering such services that the members are likely to be financially responsible for the cost of these services.

Description

Transpupillary thermotherapy (TTT) is a technique in which heat is delivered to the choroid and retinal pigment epithelium through the pupil using a modified diode laser. This laser technique contrasts with the nonthermal laser used in standard photocoagulation therapy which is designed to activate verteporfin, a photosensitizing agent.  TTT uses a lower power laser for more prolonged periods of time and is designed to gently heat the choroidal lesion, thus limiting damage to the overlying retinal pigment epithelium.

Choroidal neovascularization (CNV) is a common cause of adult-onset blindness, most commonly associated with age-related macular degeneration (ARMD). While laser photocoagulation has been used to treat CNV, patients with subfoveal lesions are generally not candidates for this treatment due to the risk of an immediate reduction in central vision, outweighing any treatment advantage. Recently photodynamic therapy has been used with success in treating subfoveal CNV; the treatment has shown the greatest success in treating patients with classic CNV (as opposed to occult CNV), as defined angiographically. There is ongoing research interest in the use of transpupillary thermotherapy to treat subfoveal choroidal neovascularization with an "occult" angiographic pattern.

Policy/Criteria

Transpupillary thermotherapy is considered investigational as a treatment of choroidal neovascularization.

Scientific Background

Currently, the bulk of the published data regarding TTT consists of case series and small clinical trials with mixed results.  Reichel and colleagues reported on a case series of 16 eyes in 15 patients who presented with occult subfoveal choroidal neovascularization secondary to age related macular degeneration. (2) Three eyes showed a two or more line improvement in visual acuity over a period of 6 to 25 months. Visual acuity remained stable in nine treated eyes. The remaining four eyes showed a decline in visual acuity. Newson and colleagues reported on a case series of 44 eyes in 42 patients consisting of 12 eyes with classic CNV and 32 eyes with occult CNV. (3) The mean follow up was 6 months. The mean change in vision in those with classic and occult CNV was -0.75 and -0.66 Snellen lines, respectively.

One prospective nonrandomized study of 21 eyes with idiopathic CNV reported 81% of patients treated with TTT were improved or stabilized at a mean of 5.1 months follow-up.  (5) Three other nonrandomized studies of TTT in eyes with CNV related to ARMD were reported. Nagpal and colleagues reported on TTT for CNV in 160 eyes (99 classic and 61 occult) of patients of Indian descent. (6) The authors reported in classic CNV, 29.3% improved, 39.4% stabilized, and 31.3% deteriorated at 12 months’ follow-up. In occult CNV, 19.6% improved, 57.4% stabilized, and 22.9% deteriorated. The authors concluded that there was effectiveness with TTT in Indian eyes, which responded to lower energy levels than did Caucasian eyes in their experience.  Thach and colleagues reported on a study in which 69 eyes with occult CNV were treated with TTT. (7) After a minimum of six months follow-up, 71% of patients improved or stabilized.  Algvere and colleagues reported a study of TTT in predominately occult CNV, 8% improved, 40.7% stabilized, and 51.3% deteriorated after 12 months’ follow-up. (8) The authors concluded that minimally classic CNV responded poorly to TTT.  More recently, four additional randomized trials also reported no benefit from TTT compared with sham treatment. (8-11)  Two studies from Asia (one small controlled trial and 1 case series) were identified; both studies indicated that the rationale for using TTT was the lower cost of this treatment in comparison with photodynamic therapy (PDT) with verteporfin. (12,13) In the controlled trial, patients chose PDT or TTT after an explanation of the costs, benefits, and risks of each treatment. (12) Sixteen patients (16 eyes) selected PDT, and 14 patients (16 eyes) selected TTT; treatments were repeated if dye leakage was evident at follow-up. The average pre-treatment visual acuity was similar in the two groups. At six months’ follow-up, loss of visual acuity was 15 letters or less in 14 (87%) eyes treated with TTT and in 13 (81%) eyes treated with PDT; however, more patients with good initial visual acuity (20/63 or greater) had a loss of two or more lines following TTT (4 of 4), than following PDT (1 of 6). Although the authors concluded that patients with good initial visual acuity should be treated with PDT, the study was limited by selection bias and small subject number. Larger prospective studies are needed to evaluate whether TTT may be an acceptable option in comparison with photodynamic therapy.  An October 2005 TEC Special Report on the treatment of AMD supports this noting that TTT, when used alone, has not been efficacious. (14) Preferred Practice Patterns (practice guidelines) on photodynamic therapy from the American Academy of Ophthalmology (AAO) indicated that there is insufficient evidence to guide treatment recommendations for transpupillary thermal therapy. (15)

An updated search of the MEDLINE database through April 2008 failed to return any clinical trials for TTT for the treatment of CNV that alter the conclusions reached above.  Further study is needed to demonstrate that improvements in health outcomes occur with acceptable levels of adverse effects with TTT over the natural course of the disease.

TTT4CNV Clinical Trial

The TTT4CNV Study was a prospective, sham-controlled, randomized nationwide study involving 22 centers and conducted on 305 eyes of 305 patients with occult AMD.  Two-thirds of eyes were treated and one-third received sham treatment.  This study was physician initiated and supported by Iridex, the manufacturer of the 810 nm IRIS Medical® OcuLight® SLx photocoagulator used in the study.

In a presentation at the American Academy of Ophthalmology meeting in October 2004, in New Orleans, Iridex Corporation announced preliminary results of the TTT4CNV study.  These results did not show significant benefit of TTT for CNV over sham treatment. Of the patients who received TTT for CNV, 47% had modest or severe vision loss after two years, compared with 43% in those who received sham treatment. Final results of the TTT4CNV study were due to be presented to the Association for Research in Vision and Ophthalmology (ARVO) in May 2005.  However, those results have not been published in the peer-reviewed literature and information about this trial is no longer available in the Iridex, CinicalTrials.gov or ARVO web sites.

References

1. BlueCross and BlueShield Association Medical Policy Reference Manual, Policy No. 9.03.10
2. Reichel E, Berrocal AM, Ip M et al. Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration. Ophthalmology 1999;106:1908-14
3. Newson RS, McAlister JC, Saeed M, McHugh JD. Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularization. Br J Ophthalmol 2001;85:173-78
4. Kumar A, Prakash G, Singh RP. Transpupillary thermotherapy for idiopathic subfoveal choroidal neovascularization. Acta Ophthalmol Scand. 2004;82(2):205
5. Nagpal M, Nagpal K, Sharma S, et al. Transpupillary thermotherapy for treatment of choroidal neovascularization secondary to age -related macular degeneration in Indian eyes. Indian J Ophthalmol  2003;51(3):243-50
6. Thach AB, Sipperley JO, Dugel PU, et al. Large -spot size transpupillary thermotherapy for the treatment of occult choroidal neovascularization associated with age-related macular degeneration.  Arch Ophthalmol 2003;121(6):817-20
7. Algvere PV, Libert C, Lindgarde G, Seregard S. Transpupillary thermotherapy of predominantly occult choroidal neovascularization in age-related macular degeneration with 12 months follow-up. Acta Ophthalmol Scand 2003;81(2):110-7
8. Myint K, Armbrecht AM, Mon S, et al. Transpupillary thermotherapy for the treatment of occult CNV in age-related macular degeneration: a prospective randomized controlled pilot study. Acta Ophthalmol Scand 2006;84(3):328-32
9. Gustavsson C, Agardh E. Transpupillary thermotherapy for occult subfoveal choroidal neovascularization: a 1-year, prospective randomized pilot study. Acta Ophthalmol Scand 2005; 83(2):148-53
10. Rougier MB, Francois L, Fourmaux E et al. Complications and lack of benefit after transpupillary thermotherapy for occult choroidal neovascularization: 1-year results. Retina 2005; 25(6):784-8
11. Agurto-Rivera R, Diaz-Rubio J, Torres-Bernal L et al. Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal neovascularization in age related macular degeneration. A randomized controlled pilot study [ISRCTN74123635]. BMC Ophthalmol 2005;5:27
12. Tewari HK, Prakash G, Azad RV et al. A pilot trial for comparison of photodynamic therapy and transpupillary thermotherapy for the management of classic subfoveal choroidal neovascularization secondary to age-related macular degeneration. Indian J Ophthalmol 2007;55(4):277-81
13. Zhang X, Zhu X, Wang D et al. Low-power transpupillary thermotherapy combined with intravitreal triamcinolone acetonide for subfoveal choroidal neovascularization. Ophthalmic Res 2007;39(4):241-2
14. TEC Special Report: Current and evolving strategies in the treatment of age-related macular degeneration. BlueCross BlueShield Association Technology Evaluation Center. October 2005
15. American Academy of Ophthalmology. Age-Related Macular Degeneration, Preferred Practice Pattern. San Francisco: American Academy of Ophthalmology, 2006. Available at www.aao.org/ppp

Cross References

Photocoagulation of Macular Drusen, Regence Medical Policy Manual, Surgery, Policy No. 116

Epiretinal Radiation Therapy for Age-Related Macular Degeneration, Regence Medical Policy Manual, Medicine, Policy No. 134

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