Archived Policies - Other

Transpupillary Thermotherapy (TTT)


Effective Date:07-15-2014

End Date:09-30-2015


Transpupillary thermotherapy (TTT) may be considered medically necessary for treatment of:

  • Retinoblastoma involving less than half (50%) of the retina, without associated vitreal or subretinal seeds at the time of thermotherapy;
  • Treatment of small (2 to 4 mm) choroidal melanomas located posterior in the globe.

Transpupillary thermotherapy (TTT) is considered experimental, investigational and/or unproven as a treatment for choroidal neovascularization (CNV) secondary to ocular conditions, including but not limited to age-related macular degeneration (AMD).


Transpupillary thermotherapy (TTT) is a technique in which low level heat is delivered through the pupil using a modified diode laser. TTT is designed to gently heat subfoveal choroidal lesions while limiting damage to the overlying retinal pigment epithelium.


Retinoblastoma is a childhood cancer that accounts for about 3% of the cancers in children under the age of 15; arising from immature retinal cells in one or both eyes and can strike from the time a child is in the womb up to five years of age. Sixty percent of the cases involve only one eye; the rest affect both eyes (bilateral). Ninety percent of retinoblastoma patients have no family history of the disease and only 10% of newly diagnosed patients have other family members with retinoblastoma. This cancer is curable if caught early enough. However, 87% of the children stricken with this disease worldwide die, mostly in developing countries. In developed countries, 97% of those who do live have moderate to severe visual impairment.

Choroidal Melanoma

Choroidal melanoma is the most common primary intraocular tumor in adults. Initially appearing as a small freckle beneath the retina, choroidal melanoma can grow in height and diameter, and may eventually spread to other organs of the body, causing death. Because choroidal melanoma is intraocular and not usually visible, patients with this disease may not recognize its presence until the tumor grows to a size that impairs vision by obstruction, retinal detachment, hemorrhage, or other complication. Periodic dilated retinal examination is the best means of early detection

Choroidal neovascularization (CNV)

CNV is a common cause of adult-onset blindness, most commonly associated with age-related macular degeneration (AMD). In its earliest stages, AMD 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, 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 choroidal neovascularization (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 composed of only occult CNV, suggesting that the proliferative response that obscures new vessels may also favorably alter the clinical course of AMD.

There is ongoing research interest in the use of transpupillary thermotherapy to treat subfoveal choroidal neovascularization with an “occult” angiographic pattern. 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 laser used in standard photocoagulation therapy in that 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.

Laser photocoagulation has been used to treat CNV; however, 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.

Other Treatments for AMD

Other available therapeutic options for AMD not addressed in this policy include photodynamic therapy and vascular endothelial growth factor (VEGF) antagonists or angiostatics. These may be administered alone or in combination. Angiostatic agents target various points in the pathway leading to new blood vessel formation (angiogenesis): messenger RNA, vascular endothelial growth factors (VEGFs), and endothelial cell proliferation, migration, and proteolysis. Pegaptanib (Macugen®, Eyetech and Pfizer) and ranibizumab (Lucentis™, Genentech) are presently the only angiostatic drugs approved by the U.S. Food and Drug Administration (FDA) for use in AMD. Pegaptanib and ranibizumab bind extracellular VEGF to inhibit the angiogenesis pathway and are administered by intravitreous injections every 4–6 weeks.

Bevacizumab (Avastin, Genentech) has been used off label to treat AMD. It is derived from the same murine monoclonal antibody precursor as ranibizumab and is approved by the FDA for the treatment of metastatic cancer of the colon or rectum. Photodynamic therapy (PDT) has also 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. Photodynamic therapy as a treatment of CNV uses a nonthermal laser designed to activate verteporfin, the photosensitizing agent.


This policy was originally developed in 2003 and has been updated with searches of scientific literature through March 2014. This section of the current policy has been substantially revised. The following is a summary of the key literature to date.

The use of transpupillary thermotherapy (TTT) as a treatment for retinoblastoma and small choroidal melanomas has been demonstrated in multiple case series studies to have a significant positive impact on the health outcomes of patients with these conditions. In a study of TTT for retinoblastoma in children, tumor regression was achieved in 96.1% of patients. In this same study 97% of affected eyes were successfully preserved. In a case series study with 256 patients with small choroidal melanomas, TTT resulted in a tumor control rate of 92% (Shields, 2002). In patients who had relapse, 54% also gained tumor control.


Shields et al. published a large study of retinoblastoma treated by TTT in 188 retinoblastomas in 80 eyes of 58 patients. Small tumors were managed by TTT alone, and larger tumors were managed by chemo-reduction, followed by tumor consolidation with thermotherapy. Complete tumor regression was achieved in 161 tumors (85.6%), 27 tumors (14.4%) developed recurrence. Complications of thermotherapy included focal iris atrophy in 29 eyes (36%), peripheral focal lens opacity in 19 eyes (24%), retinal traction in four eyes (5%), and retinal vascular obstruction in two eyes (2%). There were no cases of corneal scarring, central lens opacity, iris or retinal neovascularization, or rhegmatogenous retinal detachment. All eyes with focal lens opacity demonstrated adjacent focal iris atrophy. The investigators found that larger tumors require more intense treatment than smaller tumors and are at greatest risk for ocular complications such as focal iris atrophy and focal paraxial lens opacity.

The authors explained that there is little or no role for thermotherapy alone for retinoblastomas that have produced significant vitreal or subretinal tumor seeds. Such tumors are generally best managed by chemo-reduction, followed by plaque brachytherapy or external beam irradiation.

However, supplemental thermotherapy can often be employed in such cases if vitreal or subretinal seeds have resolved following irradiation.

Choroidal Melanoma

The evidence supporting the use of transpupillary thermotherapy for choroidal melanoma is based on the results of short-term uncontrolled case series. Transpupillary thermotherapy has been reported to cause tumor necrosis in choroidal melanomas up to 4 mm in thickness. Shields et al. (1998) reported the results of the largest published case series of transpupillary thermotherapy for choroidal melanoma at that time. After a mean of three treatment sessions and 14 months of follow-up, tumor control was successful in 94% of patients. The six eyes (6%) classified as treatment failures included four eyes with tumors that showed partial or no response to thermotherapy, thus requiring plaque radiotherapy or enucleation, and two eyes with recurrence, subsequently controlled with additional thermotherapy. In more than half (58%) of patients, visual acuity was the same (within one line) or better than before treatment, depending primarily on tumor location. Complications are generally limited to the site of treatment. The most common complications of transpupillary thermotherapy for choroidal melanoma were retinal vascular obstruction (5%), retinal traction (10%), and optic disc edema (1%). Tumors located temporal to the fovea demonstrated a statistically higher risk for retinal traction than those located in other quadrants.

In a study by Shields et al. in 2002 the authors concluded that transpupillary thermotherapy is an effective treatment for certain small choroidal melanomas. Appropriate tumor selection is critical to successful treatment. Patients with tumors abutting or overhanging the optic disc or those requiring more than three sessions for tumor control are more likely to develop ultimate tumor recurrence to the retina, leading to visual loss shortly after treatment.

Choroidal Neovascularization (CNV)

Transpupillary Thermotherapy versus Sham

In a presentation at the American Academy of Ophthalmology meeting in October 2004, in New Orleans, Iridex Corporation announced preliminary results of the TTT4 choroidal neovascularization (CNV) study. The TTT4 CNV study is a nationwide study involving 22 centers that began in March 2000. A total of 336 patients with symptomatic occult CNV that show signs of exudation were to be recruited. Two-thirds of eyes would be treated and one third would receive sham treatment. Patients would be followed up for 2 years. Iridex-reported preliminary results did not show TTT for CNV resulted in significant benefit over sham treatment. Forty-seven percent of 303 patients who received TTT for CNV had modest or severe visual loss after 2 years, compared with 43% in those who received sham treatment. To date, results of this trial have not been published.

Two small randomized trials (28 and 25 patients) from 2005 and 2006 reported no benefit of TTT in preventing further visual loss in patients with occult CNV who were not candidates for photodynamic therapy (PDT). (4, 5)

TTT versus PDT

The largest published controlled trial randomly assigned 98 patients with occult CNV to TTT (136 mW/mm) with sham PDT (n=52), or to PDT with sham TTT (n=46). (6) Retreatment was given if leakage was documented by fluorescein angiography (follow-up of 6, 12, 18, 24, 36, and 48 weeks). With a mean of 3.0 treatments in the TTT group and 2.3 treatments in the PDT group, a similar percentage of patients had lost fewer than 15 letters at 12 months (75% for TTT and 74% for PDT). There were nonsignificant trends for a larger percentage of patients to have preserved or improved best corrected visual acuity in the TTT group (37%) than in the PDT group (24%) and to have less of a decrease in foveal thickness (15% vs 24%). Patient-reported visual function from this trial was reported in 2010.(7) Outcomes on the National Eye Institute Visual Function Questionnaire 25 were similar in patients treated with TTT (change, +1.2) or PDT (change, +0.7) at 12 months, but the study was underpowered to detect differences in this outcome measure.

In a controlled trial from Asia, patients chose PDT or TTT after an explanation of the costs, benefits, and risks of each treatment.(8) 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 pretreatment visual acuity was similar in the 2 groups. At 6-month 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 2 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 is limited by selection bias and small subject number. The authors of this study and another report from Asia indicated that the rationale for using TTT was the lower cost of this treatment in comparison with PDT. (8, 9)

In 2012, Nowak et al. reported on 222 eyes with AMD treated with TTT, 100 eyes treated with PDT, and 104 eyes treated with intravitreal bevacizumab.(10) Assignment into the 3 groups was based on the angiographic appearance of CNV, and patients who did not meet criteria for the randomized comparison of bevacizumab and PDT were treated with TTT. Following treatment with TTT, there was a mean decline of visual acuity 0.05 log MAR, compared with a decline of 0.12 log MAR following PDT and improvement of 0.03 logMAR following treatment with intravitreal bevacizumab. Out of the 222 eyes treated with TTT, visual acuity improved in 14.9%, remained unchanged in 64.4%, and was reduced in 20.7%. This study is limited by selection bias and differences in baseline visual acuity in the 3 groups.

TTT Combined with Intravitreal Ranibizumab

In a 2012 report, Soderberg et al. randomized 100 patients with neovascular AMD to low-dose TTT and intravitreal ranibizumab or to sham TTT and intravitreal ranibizumab. (11) At 24-month follow-up (78 patients), quarterly TTT was found to decrease the mean number of ranibizumab injections from 8.0 to 6.3 with no significant difference between the sham and active TTT groups in best corrected visual acuity (+4.0 vs +0.9, respectively). Thus, 7 quarterly treatments with TTT resulted in a mean reduction of 1.7 ranibizumab injections. It was not described whether the investigator who determined if the patient met retreatment criteria was masked to treatment allocation. Masked evaluation found no significant difference between the sham and active TTT groups in central retinal thickness (-49.9% vs -36.4%) or lesion area (-0.3% vs -10.6%, both respectively).


One randomized (not masked) study of 26 patients from 2005 did not find a statistically significant improvement for combination treatment with triamcinolone and TTT in comparison with TTT alone. (12)

Four nonrandomized studies of TTT in eyes with CNV related to AMD were identified from 2003 and 2004. (13-16) The largest series is from Nagpal et al., who reported on TTT for CNV in 160 eyes (99 classic and 61 occult) of patients of Indian descent.(13) The authors reported that in eyes with classic CNV, 29.3% improved, 39.4% stabilized, and 31.3% deteriorated at 12-month follow-up. In occult CNV, 19.6% improved, 57.4% stabilized, and 22.9% deteriorated. Nagpal et al. concluded that there was effectiveness with TTT in Indian eyes, which responded to lower energy levels than did Caucasian eyes in their experience.

In 2011, Peyman et al. reported treatment of a small series of patients (n=4) with peripapillary CNV that was recalcitrant to other treatments, including intravitreal angiostatic agents. (19) These investigators used a variation of TTT with indocyanine green dye as a thermal enhancing agent, which permitted use of a lower energy level (oscillatory thermotherapy). The photodynamic treatment was combined with bevacizumab and intravitreal dexamethasone, and visual acuity was found to remain stable (1 of 4 improved visual acuity) at a mean 12-month follow-up.

Small case series from Asia describe the use of TTT for central serous chorioretinopathy and choroidal hemangioma. (18, 19)

Adverse Events

A case series reported macular burn as a complication of TTT in 8.6% of 35 patients available for follow-up. (20)

Questions have been raised about the potential harms of this treatment if given at higher intensity, while Peyman et al. note that a major limitation of TTT is the inability to titrate the energy level and subsequently control both the rate and the total amount of temperature rise during the procedure. (17, 21). Evidence is insufficient to determine whether TTT is as beneficial as the established alternative for treatment of CNV therefor this procedure is considered experimental, investigational and/or unproven.

Practice Guidelines and Position Statements

Recent practice guidelines on treatment of age-related macular degeneration from the American academy of Ophthalmology (AAO) do not mention TTT. In the 2006 Preferred Practice Patterns the AAO indicated that there was insufficient evidence to guide treatment recommendations for TTT. Preferred Practice Patterns from 2008 and 2011 and the AAO’s 2013 Summary Benchmark do not describe TTT as a treatment option. (25)


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Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.


The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes




ICD-9 Diagnosis Codes

190.0, 190.5, 190.6, 362.50-362.57

ICD-9 Procedure Codes


ICD-10 Diagnosis Codes

C69.20 - C69.22, C69.30 - C69.32, C69.40 - C69.42, H35.00 - H35.00, H35.30-H35.389

ICD-10 Procedure Codes

085F3ZZ, 085E3ZZ

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 not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <


1. 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(10):1908-14.

2. Shields CL, Santos MC, Diniz W, et al. Thermotherapy for retinoblastoma. Arch Ophthalmol. 1999; 117(7):885-893.

3. Shields JA. Thermotherapy for retinoblastoma. In: Year Book of Ophthalmology 2000. R.P. Wilson, ed. St. Louis, MO: Mosby; 2000.

4. Newsom RS, McAlister JC, Saeed M et al. Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularisation. Br J Ophthalmol 2001; 85(2):173-8.

5. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). TEC Special Report: Current and evolving strategies in the treatment of age-related macular degeneration. TEC Assessments 2005; Volume 20, Tab 11.

6. 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.

7. 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.

8. Odergren A, Algvere PV, Seregard S et al. A prospective randomised study on low-dose transpupillary thermotherapy versus photodynamic therapy for neovascular age-related macular degeneration. Br J Ophthalmol 2008; 92(6):757-61.

9. Odergren A, Algvere PV, Seregard S et al. Vision-related function after low-dose transpupillary thermotherapy versus photodynamic therapy for neovascular age-related macular degeneration. Acta Ophthalmol 2010; 88(4):426-30.

10. 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.

11. 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.

12. Nowak MS, Jurowski P, Grzybowski A et al. A prospective study on different methods for the treatment of choroidal neovascularization. The efficacy of verteporfin photodynamic therapy, intravitreal bevacizumab and transpupillary thermotherapy in patients with neovascular age-related macular degeneration. Med Sci Monit 2012; 18(6):CR374-80.

13. Soderberg AC, Algvere PV, Hengstler JC et al. Combination therapy with low-dose transpupillary thermotherapy and intravitreal ranibizumab for neovascular age-related macular degeneration: a 24-month prospective randomised clinical study. Br J Ophthalmol 2012; 96(5):714-8.

14. 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.

15. 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.

16. Algvere PV, Libert C, Lindgarde G et al. 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.

17. 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.

18. Kumar A, Prakash G, Singh RP. Transpupillary thermotherapy for idiopathic subfoveal choroidal neovascularization. Acta Ophthalmol Scand 2004; 82(2):205-8.

19. Peyman G, Tsipursky M, Gohel P et al. Regression of peripapillary choroidal neovascularization after oscillatory transpupillary thermotherapy and anti-VEGF pharmacotherapy. Eur J Ophthalmol 2011; 21(2):162-72.

20. Kawamura R, Ideta H, Hori H et al. Transpupillary thermotherapy for atypical central serous chorioretinopathy. Clin Ophthalmol 2012; 6:175-9.

21. Kwon HJ, Kim M, Lee CS et al. Treatment of serous macular detachment associated with circumscribed choroidal hemangioma. Am J Ophthalmol 2012; 154(1):137-45 e1.

22. 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.

23. Mason JO, 3rd, Colagross CC, Feist RM et al. Risk factors for severe vision loss immediately after transpupillary thermotherapy for occult subfoveal choroidal neovascularization. Ophthalmic Surg Lasers Imaging 2008; 39(6):460-5.

24. Shields, C.L., Cater, J., et al. Combined plaque radiotherapy and transpupillary thermotherapy for choroidal melanoma: tumor control and treatment complications in 270 consecutive patients. Archives of Ophthalmology (2002 July) 120(7): 933-40.

25. American Academy of Ophthalmology. Age-Related Macular Degeneration. Available online at: Last accessed January, 2014.

26. Transpupillary Thermotherapy for Treatment of Choroidal Neovascularization. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2014 February) Vision 9.03.10.

Policy History:

Date                   Reason

7/15/2014            Document updated with literature review. Coverage unchanged.

11/1/2011            Document updated with literature review. Coverage unchanged.

12/1/2009            Review of policy with literature search, references added no coverage change.

11/15/2007          Revised/Updated Entire Document

12/1/2003            New medical document

Archived Document(s):

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