BlueCross and BlueShield of Montana Medical Policy/Codes
Transpupillary Thermotherapy (TTT)
Chapter: Vision
Current Effective Date: November 26, 2013
Original Effective Date: November 01, 2012
Publish Date: November 26, 2013
Revised Dates: October 30, 2013
Description

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.

Choroidal neovascularization (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 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.

Policy

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.

Coverage

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 unproven including but not limited to:

  • Treatment of choroidal neovascularization associated with age related macular degeneration.

Rationale

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.

Retinoblastoma

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

There are minimal published data regarding TTT.  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.  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.  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.  The mean follow-up was six months.  The mean change in vision in those with classic and occult CNV was –0.75 and –0.66 Snellen lines, respectively.  Further data were needed to confirm these preliminary results.

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.  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.  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.  Nagpal and colleagues concluded that there was effectiveness with TTT in Indian eyes, which responded to lower energy levels than did Caucasian eyes in their experience. In a study by Thach and colleagues, 69 eyes with occult CNV were treated with TTT.  After a minimum of six months’ follow-up, 71% of patients improved or stabilized.  Finally, in the Algvere study of TTT in predominately occult CNV, 8% improved, 40.7% stabilized, and 51.3% deteriorated after 12 months’ follow-up.  Algvere and colleagues reported minimally classic CNV responded poorly to TTT.  While there appears to be some improvement or stabilization in occult CNV in these studies, 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.

In a presentation at the American Academy of Ophthalmology meeting in October 2004, in New Orleans, Iridex Corporation announced preliminary results of the TTT4 CNV study.  The TTT4 CNV study is a nationwide study involving 22 centers that was started in March 2000 (available online at:  http://www.eyesight.org .  A total of 336 patients with symptomatic occult CNV that shows signs of exudation are being recruited.  Two-thirds of eyes will be treated and one-third will receive sham treatment.  Patients will be followed up for two years.  Iridex reported preliminary results did not show TTT for CNV resulted in significant benefit over sham treatment.  Only 47% of 303 patients who received TTT for CNV had modest or severe visual loss after two years, compared with 43% in those who received sham treatment.  Further analysis of the data will be performed, according to Iridex Chief Executive Theodore Boutacoff.

An October 2005 Blue Cross Blue Shield Association (BCBSA) Technical Evaluation Center (TEC) Special Report on the treatment of ARMD supports the conclusions given above noting TTT, when used alone, has not been efficacious.

In a retrospective, non-randomized study, Tsai et al assessed the therapeutic outcome and the recurrence of CNV secondary to ARMD after TTT in light-brown retinas (n = 58 eyes in 55 patients).  Power settings were set about half the value for Caucasian eyes.  The outcome was assessed with best-corrected visual acuity, fluorescein angiography, indocyanine green angiography, and funduscopic examination.  Forty-four membranes were occult, six classic, and eight mixed.  Mean follow-up was 16.6 +/- 10.7 months (range of 6 to 48 months).  Membranes closed in 46 eyes.  Iatrogenic complications included three subretinal hemorrhages, two retinal pigment epithelium tears, and two macular area cystic changes.  In eyes with occult CNV, visual acuity improved in six (13.6%), 14 (31.8%) remained unchanged, and 24 (54.6%) deteriorated. For various CNV, average logMAR changes from baseline at last follow-up were 0.30 in occult, -0.08 in classic, and 0.59 in mixed (p < 0.01).  Thirty eyes experienced recurrence within 9.2 +/- 6.2 months (range of 2 to 22 months).  Cumulative recurrence rate was 45% at 12 months and 71% at 22 months, with no significant difference between occult and non-occult type CNV.  The authors concluded that TTT does not cure CNV secondary to AMD.  High recurrence was found independent of CNV type.  Most improved vision was found mostly in classic CNV. Complications associated with high energy level should be considered in light-brown retinas.

Ozdek et al. examined the effect of TTT on CNV secondary to angioid streaks.  A total of six eyes of five patients with an average age of 61 years were diagnosed to have subfoveal CNV secondary to angioid streaks.  Four of the CNVs were predominantly classic and two were occult with no classic.  Visual acuity (VA) measurement, ophthalmoscopic and fluorescein angiographic examination, and optic coherence tomography (OCT) were carried out before TTT treatment and at each follow-up visit.  Activity scores (AS) based on and OCT findings were also recorded.  The mean follow-up was 12 months.  The VA initially ranged from counting fingers to 20/100 and remained stable in all patients.  The mean greatest lesion diameter increased significantly from 2221 microm to 3109 microm at last follow-up (p = 0.046).  The mean AS decreased significantly from 6.5 to 4.8 at the third month (p = 0.039), but tended to increase thereafter.  Re-treatment with TTT was applied to five eyes after a mean of 7.8 months but did not decrease CNV activity as effectively as the first treatments.  A fibrotic scar developed in one eye after the first treatment.  The authors concluded that TTT may decrease the activity of CNVs secondary to angioid streaks in the short-term, but re-treatment may be necessary with unfavorable results.  Transpupillary thermal therapy appears to stabilize VA but not lesion size in this group of patients, which may be the natural history rather than a treatment effect. 

In a pilot study, Tewari et al. compared the visual outcomes of photodynamic therapy (PDT) with verteporfin and TTT for classic subfoveal choroidal neovascularization (CNVM) secondary to AMD.  Patients with subfoveal classic CNVM caused by AMD attending vitreo-retinal services at a tertiary care setup were included in this non-randomized, open label, prospective, clinical, comparative pilot trial.  Standardized refraction, VA testing, evaluation of fundus and serial color photography and fundus fluorescein angiography were carried out to evaluate the effects of treatment in 32 eyes each undergoing either PDT or TTT.  Follow-up was carried out at four weeks, 12 weeks and six months.  Re-treatment, if indicated, was carried out three months post-treatment.  Stabilization or improvement occurred in 69 % of patients undergoing PDT and 50 % patients undergoing TTT at six-month follow-up.  Among patients with a pre-treatment VA greater than or equal to 20/63, only one out of six patients who underwent PDT had a drop of VA greater than two lines as compared to four patients (100 %) who underwent TTT (p = 0.0476, two-tailed Fisher's exact test).  The authors concluded that for short-term preservation of vision in patients of classic CNVM due to AMD, PDT seems to be better than TTT if the pre-laser best corrected visual acuity is greater than 20/63 but both are equally effective if pre-laser best corrected visual acuity is less than 20/63.

In a prospective study, Kuo et al. carried out a safety and effectiveness study of TTT in Chinese patients with CNV secondary to AMD.  A total of 26 patients (27 eyes) completed greater than or equal to six months of follow-up and were included in this report.  Fourteen eyes (52 %) had improved or stable VA (loss of less than three lines) and 13 eyes (48 %) had vision loss of greater than or equal to three lines.  The serial mean VA initially decreased during follow-up, and then stabilized by six months.  In the subgroup of occult or minimally classic CNV (20 eyes), 13 eyes (65%) had improved or stable vision.  The major complication of TTT included laser-related retinal pigment epithelium (RPE) atrophy in 10 eyes (37%).  Six eyes had mild RPE atrophy; four eyes had severe RPE-choroid atrophy (macular burn).  Analysis of possible risk factors for macular burn showed that three eyes had to have the power amplified due to nuclear sclerosis, and one pseudophakic eye had regular power.  The authors concluded that TTT in AMD patients with occult or minimally classic CNV prevented severe vision loss in the majority of patients, but power amplification due to medium lens opacity induced RPE atrophy or burn in some patients.

2011 Update

A search of peer reviewed literature through July 2011 identified no new clinical trial publications or any additional information that would change the coverage position of this medical policy.

Two small randomized trials (28 and 25 patients) reported no benefit of TTT in preventing further visual loss in patients with occult CNV, while a case series reported macular burn as a complication of TTT in 8.6% of 35 patients available for follow-up.  One randomized, non- blinded study of 26 patients did not find a statistically significant improvement for combination treatment with triamcinolone and TTT in comparison with TTT alone.

Two small studies from Asia indicated that the rationale for using TTT was the lower cost of this treatment in comparison with photodynamic therapy (PDT) with verteporfin.  In the controlled trial, patients chose PDT or TTT after an explanation of the costs, benefits, and risks of each treatment.  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 is limited by selection bias and small subject number.

A European trial with 98 patients reported similar outcomes between TTT (136 mW/mm) and PDT.  Patients with occult CNV were randomly assigned to either TTT with sham PDT (n=52), or to PDT with sham TTT (n=46); 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 non-significant 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%).

In a publication on patient-reported visual function from the randomized trial described above,  outcomes on the National Eye Institute Visual Function Questionnaire 25 were similar in patients treated with TTT (change of +1.2) or PDT (change of +0.7) at 12 months.  It was reported that the study was underpowered and unable detect differences in outcome measures.

Coding

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. 

Rationale for Benefit Administration
 
ICD-9 Codes

190.0, 190.5, 190.6, 362.50-362.57

ICD-10 Codes
H35.30-H35.389, 085F3ZZ, 085E3ZZ 
Procedural Codes: 67299
References
  1. Shields, C.L., Shields, J.A., et al.  Transpupillary thermotherapy for choroidal melanoma:  Tumor control and visual results in 100 consecutive cases.  Ophthalmology (1998) 105(4):581-90.
  2. Shields, C.L., Shields, J.A., et al.  Transpupillary thermotherapy for choroidal melanoma.  Current Opinions in Ophthalmology (1999) 10(3):197-203.
  3. Reichel, E., Berrocal, A.M., et al.  Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration.  Ophthalmology (1999) 106(10):1908-14.
  4. Newson, R.S., McAlister, J.C., et al.  Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularization.  British Journal of Ophthalmology (2001) 85(2):173-8.
  5. Shields, C.L., Shields, J.A., et al.  Primary transpupillary thermotherapy for small choroidal melanoma in 256 consecutive cases: outcomes and limitations.  Ophthalmology (2002 February) 109(2):225-34.
  6. 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.
  7. Archives of Ophthalmology (2002 July) 120(7):933-40.
  8. Robertson, D.M.  TTT as rescue treatment for choroidal melanoma not controlled with iodine-125 brachytherapy.   Ocular Immunology and Inflammation (2002 December) 10(4):247-52.
  9. Lumbroso, L., Doz, F., et al.  Chemothermotherapy in the management of retinoblastoma.  Ophthalmology (2002 June) 109(6):1130-6.
  10. Schueler, A.O., Jurklies, C., et al.  Thermochemotherapy in hereditary retinoblastoma.  British Journal of Ophthalmology (2003 January) 87(1):90-5.
  11. Bartlema, Y.M., Oosterhuis, J.A., et al.  Combined plaque radiotherapy and transpupillary thermotherapy in choroidal melanoma: 5 years' experience.  British Journal of Ophthalmology (2003 November) 87(11):1370-3.
  12. Nagpal, M., Nagpal, K., et al.  Transpupillary thermotherapy for treatment of choroidal neovascularization secondary to age-related macular degeneration in Indian eyes.  Indian Journal of Ophthalmology (2003) 51(3):243-50.
  13. Thach, A.B., Sipperley, J.O., et al.  Large-spot size transpupillary thermotherapy for the treatment of occult choroidal neovascularization associated with age-related macular degeneration.  Archives of Ophthalmology (2003) 121(6):817-20.
  14. Algvere, P.V., Libert, C., et al.  Transpupillary thermotherapy of predominantly occult choroidal neovascularization in age-related macular degeneration with 12 months follow-up.  Acta Ophthalmologica Scandinavica (2003 April) 81(2):110-7.
  15. Lee, T.C., Lee, S.W., et al.  Chorioretinal scar growth after 810-nanometer laser treatment for retinoblastoma.  Ophthalmology. (2004 May) 111(5):992-6.   
  16. Kumar, A., and G. Prakash.  Transpupillary thermotherapy for idiopathic subfoveal choroidal neovascularization.  Acta Ophthalmologica Scandinavica (2004) 82(2):205-8.
  17. Abramson, D.H., and A.C. Schefler.  Transpupillary thermotherapy as initial treatment for small intraocular retinoblastoma:  technique and predictors of success.  Ophthalmology (2004 May) 111(5):984-91.
  18. 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) Tab 11.
  19. Gustavsson, C., and E. Agardh.  Transpupillary thermotherapy for occult subfoveal choroidal neovascularization: a 1-year, prospective randomized pilot study.  Acta Ophthalmologica Scandinavica (2005) 83(2):148-53.
  20. Hayes, Inc. Medical Technology Directory. Transpupillary Thermotherapy for Choroidal Tumors and Macular Degeneration. Lansdale, Pennsylvania: Hayes, Inc. (September 2002) (accessed on 2005, December 22).
  21. Agurto-Rivera, R., Diaz-Rubio, J., et al.  Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal neovascularization in age related macular degeneration.  A randomized controlled pilot study [ISRCTN74123635].  BMC Ophthalmology (2005) 5:27.
  22. Rougier, M.B., Francois, L., et al.  Complications and lack of benefit after transpupillary thermotherapy for occult choroidal neovascularization: 1-year results.  Retina (2005) 25(6):784-8.
  23. Stolba, U., Krebs, I., et al.  Long term results after transpupillary thermotherapy in eyes with occult choroidal neovascularization associated with age related macular degeneration:  a prospective trial.  British Journal of Ophthalmology (2006 February) 90(2):158-61.
  24. Tranos, P., Peters, N.M., et al.  Visual function following transpupillary thermotherapy with adjusted laser parameters for the treatment of exudative age-related macular degeneration:  a pilot study.  Clinical Experiment Ophthalmology (2006 April) 34(3):226-32.
  25. Myint, K., Armbrecht, A.M., et al.  Transpupillary thermotherapy for the treatment of occult CNV in age-related macular degeneration: a prospective randomized controlled pilot study.  Acta Ophthalmologica Scandinavica (2006 June) 84(3):328-32.
  26. Win, P.H., Robertson, N.W., et al.  Extended follow-up of small melanocytic choroidal tumors treated with transpupillary thermotherapy.  Archives of Ophthalmology (2006 April) 124(4):503-6.
  27. Ozdek, S., Bozan, E., et al.  Transpupillary thermotherapy for the treatment of choroidal neovascularization secondary to angioid streaks. Can J Ophthalmol. (2007)42(1):95-100.
  28. Zhang, X., Zhu, X., et al.  Low-power transpupillary thermotherapy combined with intravitreal triamcinolone acetonide for subfoveal choroidal neovascularization.  Ophthalmic Res (2007) 39(4):241-2.
  29. Tsai, T.H., Yang, C.M., et al.  Transpupillary thermotherapy for the treatment of choroidal neovascularization in age-related macular degeneration in Taiwan. Eye. (2007)21(6):721-726.
  30. Tewari, H.K., Prakash, G., 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 Journal of Ophthalmology (2007 July – August) 55(4):277-81.
  31. Retinoblastoma International.  What is Retinoblastoma.  Los Angeles, Califormia:  Available at http://www.retinoblastoma.net (accessed – 2007 November 28).
  32. Mason, J.O. 3rd.  Colagross, C.C., 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.
  33. Kuo, H.K., Kao, M.T., et al.  Transpupillary thermotherapy in Chinese patients with choroidal neovascularization secondary to age-related macular degeneration: Emphasis on the influence of power setting. Ophthalmologica. (2008)222(2):117-122.
  34. American Academy of Ophthalmology (AAO) Preferred Practice Pattern™, Age-Related Macular Degeneration (2008 September 27) http://one.aao.org (accessed 2011 August 15).
  35. Odergren, A., Algvere, P.V., et al.  A prospective randomized study on low-dose Transpupillary thermotherapy versus photodynamic therapy for neovascular age-related macular degeneration.  British Journal of Ophthalmology (2008 January) 92(6):757-64.
  36. Pan, Y., Diddle, K., et al.  Primary Transpupillary thermotherapy for small choroidal melanomas. British Journal of Ophthalmology (2008 June) 92(6):747-50.
  37. Pilotto, E., Vujosevic, S., et al.  Long-term vascular changes after iodine brachytherapy versus Transpupillary thermotherapy for choroidal melanoma.  European Journal of Ophthalmology (2009 July/August) 19(4):646-53F.
  38. National Cancer Institute (NCI).  Retinoblastoma (PDQ®):  Treatment-health professional.  Updated 2010 July 10 Available at, http://www.cancer.gov. ( accessed on – 2001 August).
  39. Odergren, A., Algvere, P.V., et al.  Vision-related function after low-dose transpupillary thermotherapy versus photodynamic therapy for neovascular age-related macular degeneration. Acta Ophthalmology (2010) 88(4):426-30.
  40. Sagoo, M.S., Shields, C.L., et al.  Plaque radiotherapy for juxtapapillary choroidal melanoma tumor control in 650 consective cases.  Ophthalmology (2010 August 31).
  41. Stoffelns, B.M., Schoepfer, K., et al.  Tumor regression in malignant choroidal melanomas after transpupillary thermotherapy (TTT) versus ruthenium brachytherapy and sandwich therapy – a comparative analysis.  KlinMombi Augnenheilkd (2010) 227(4):262-8.
  42. Sharma, T., Parikh, S.D., et al.  Transpupillary Thermotherapy for Juxtafoveal Leak in Central Serous Chorioretinopathy.  Ophthalmic Surgical Lasers Imaging (2010 March 10) 9:1-3, E-published ahead of print.  Available at  www.ncbi.nih.gov  (Accessed 2011 August 24)
  43. Transpupillary Thermotherapy for Treatment of Choroidal Neovascularization.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2011 February) Vision 9.03.10.
History
July 2012 New Policy for BCBSMT: Literature review through December 2011; policy statement is investigational
November 2013 Policy formatting and languague revised.  Title changed from "Transpupillary Thermotherapy for Treatment of Choroidal Neovascularization" to "Transpupillary Thermotherapy (TTT)".  Policy statement revised from strictly investigational to "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".
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Transpupillary Thermotherapy (TTT)