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Aetna Aetna
Clinical Policy Bulletin:
Graves' Ophthalmopathy Treatments
Number: 0419


Policy

  1. Aetna considers orbital decompression surgery, eye muscle surgery and/or eyelid surgery medically necessary for members with severe Graves' ophthalmopathy (especially individuals with marked proptosis and optic neuropathy) when both of the following measures have not been successful:

    1. A trial of conservative measures, such as elevating the head at night, cool compresses, sunglasses, lubricating eyedrops, and if the member has strabismus, prisms for glasses; and
    2. A trial of medications, such as diuretics, methimazole, prednisone, and propylthiouracil.

      Note: According to available literature, surgical treatment should not be undertaken until stability of the thyroid-related orbitopathy (TRO) has been demonstrated.  One of the advantages of waiting for stability of TRO is that some cosmetic problems may resolve or improve without intervention.  Fat pad removal is commonly requested with surgery for exophthalmos and is generally cosmetic in nature, and therefore, is considered not medically necessary.

  2. Aetna considers orbital radiotherapy medically necessary for the treatment of members with severe Graves' ophthalmopathy when both of the afore-mentioned criteria are met.

  3. Aetna considers the use of banked human tissue graft (e.g., Alloderm) to elevate the lower eyelids in members with lower eyelid retraction associated with Graves ophthalmopathy experimental and investigational because there is insufficient evidence to support this approach.

  4. Aetna considers the following interventions experimental and investigational for the treatment of Graves' ophthalmopathy because their effectiveness for this indication has not been established.

  • Intravenous immunoglobulins
  • Rituximab
  • Somatostatin analogs (e.g., lanreotide and octreotide)
  • Tumor necrosis factor-alpha inhibitors (e.g., etanercept and infliximab).


Background

Graves' disease (also known as Parry's or Basedow's disease) is a complex disease whose pathogenesis is believed to be autoimmune.  It is a disorder that affects mainly females, and although it may occur at any age, has a peak incidence in the 3rd and 4th decades.  Graves' disease has 3 principal manifestations: (i) hyperthyroidism with diffuse goiter, (ii) ophthalmopathy, and (iii) dermopathy; however, they do not necessarily appear simultaneously.

Graves' ophthalmopathy, also known as thyroid-associated ophthalmopathy (TAO), occurs in 2 to 7 % of patients with Graves' disease with the major manifestations being proptosis, ophthalmoplegia, optic neuropathy, and/or eyelid retraction.  Thyroid-associated ophthalmopathy is the commonest cause of proptosis in adults.  The term exophthalmos is used exclusively to describe the proptosis of TAO; exophthalmos may be unilateral early but usually becomes bilateral with time.  The term exophthalmic ophthalmoplegia refers to the ocular muscle weakness that results in impaired upward gaze and convergence and strabismus with varying degree of diplopia.

Physicians recommend treatment of Graves' ophthalmopathy according to each patient's symptoms.  Sometimes combinations of the following procedures are used:

  • Elevating the head at night, cool compresses, sunglasses, lubricating eyedrops, or prisms for glasses;
  • Eye muscle surgery, eyelid surgery, or both;
  • Medications or radiation to shrink tissue;
  • Orbital decompression surgery.

An assessment by the National Institute for Health and Clinical Excellence (2005) found that retrobulbar irradiation to be an effective procedure in patients for whom other treatments are inadequate or are associated with significant side effects.

Orbital Decompression Surgery

In orbital decompression surgery, the bone between the orbit and the sinuses is removed.  A successful procedure improves vision and provides room for the eye to slip back into the orbit's protection.  Orbital decompression is indicated in patients with severe ophthalmopathy refractory to medications and radiotherapy, especially in the presence of marked proptosis and optic neuropathy.

Eye Muscle Surgery

Diplopia often occurs because the eyes are misaligned.  Usually, mis-alignment is caused by 1 or more eye muscles that are too short or “tight” due to scar tissue from Graves' ophthalmopathy.  This scar tissue results from changes surrounding the eye because of swelling.  The goal of eye muscle surgery is to attain single vision when looking straight ahead and looking down when reading.  During eye muscle surgery, the muscle is cut from its attachment to the eyeball and re-attached further back on the eye.  Usually eye muscle surgery does not require an over-night stay in the hospital.  The physician evaluates the final results about 2 months later.  More than 1 operation is sometimes required.

If orbital decompression and eye muscle surgery are to be performed, the orbital decompression surgery generally is carried out first.

Eyelid Surgery

Graves' ophthalmopathy generally causes the eyelids to open more widely.  The front surface of the eyeball becomes exposed beyond the eyelid and causes excessive tearing and discomfort.  Lid retraction may be improved by orbital decompression, especially the lower lid.  However, the backward and downward movement of the globe following decompression may accentuate upper lid retraction.  Surgical re-positioning (recession) of the upper lid retractors may have to be performed as an adjunct.

If orbital decompression, eye muscle, and eyelid surgery are required, the eyelid procedure is generally performed as the final operation in a series.

Acellular human dermis is being investigated for elevating the lower eyelids in lower eyelid retraction associated with Graves ophthalmopathy.  However, current evidence in the peer-reviewed medical literature is limited to case reports and small, retrospective case series.

Orbital Radiation

Zoumalan and colleagues (2007) noted that thyroid eye disease (TED, Graves' ophthalmopathy, thyroid ophthalmopathy) is the most common cause of orbital inflammation and proptosis in adults.  There is no agreement on its management although corticosteroids and external beam orbital radiation have traditionally been believed to provide benefit in active inflammation.  A review of the published literature in English disclosed an overall corticosteroid-mediated treatment response of 66.9 % in a total of 834 treated patients who had moderate or severe TED.  Intravenous corticosteroids used in repeated weekly pulses were more effective (overall favorable response = 74.6 %, n = 177) and had fewer side effects than daily oral corticosteroids (overall favorable response = 55.5 %, n = 265).  A combination of corticosteroid and radiation therapy seemed to be more effective than corticosteroids alone.  However, the authors stated that these conclusions are tempered by a notable lack of standardization within and between study designs, treatment protocols, and outcome measures.  Accordingly, the North American Neuro-Ophthalmology Society, American Society of Ophthalmic Plastic and Reconstructive Surgery and the Orbital Society, in conjunction with Neuro-Ophthalmology Research and Development Consortium, will investigate the design and funding of a multi-center controlled trial.

A technology assessment on orbital radiation for Graves ophthalmopathy by the American Academy of Ophthalmology (Bradley et al, 2008) examined if orbital radiation offers effective and safe treatment for Graves ophthalmopathy.  Medical literature databases were searched to identify all published reports relating to orbital radiation treatment for Graves ophthalmopathy.  To be included in the technology assessment, reports had to provide original data, to report on a case series or uncontrolled trial of at least 100 subjects or a randomized clinical trial (RCT) of any size, to focus on orbital radiation for the treatment of Graves ophthalmopathy, and to follow-up patients for at least 3 months.  Abstracted data included study characteristics, patient characteristics, treatment response, and safety information.  A total of 14 studies were included in the technology assessment: 5 observational studies and 9 RCTs.  Three of the observational studies reported on treatment response, with overall favorable outcomes for 40 % to 97 % of patients.  Three of the observational studies provided intermediate-term safety data.  The risk of definite radiation retinopathy is 1 % to 2 % within 10 years after treatment.  Patients treated with orbital radiation did not have an increased risk of secondary malignancy or premature death.  The 9 RCTs were qualitatively heterogeneous.  Patients with optic neuropathy generally were excluded from participating in the RCTs.  Three of the RCTs were sham-controlled.  None of these studies showed that orbital radiation was more effective than sham irradiation for improving proptosis, lid fissure, or soft tissue changes such as eyelid swelling.  Two of the 3 sham-controlled RCTs demonstrated improved vertical range of motion in radiation-treated subjects compared with controls.  The authors concluded that systematic review of the effect of orbital radiation on Graves ophthalmopathy is limited by the lack of standardization and variable quality of published reports.  Extra-ocular motility impairment may improve with radiotherapy, although the evidence of a treatment effect is mixed in clinical trials.  Future studies are needed to determine if a potentially beneficial motility effect results in improved patient function and quality of life.  Level I evidence indicates that proptosis, eyelid retraction, and soft tissue changes do not improve with radiation treatment.  The effectiveness of orbital radiation for compressive optic neuropathy resulting from Graves ophthalmopathy has not been investigated in clinical trials and merits further study.  Radiation retinopathy, although rare, is a risk of orbital radiation, even in patients without diabetes who receive appropriate radiation dose and delivery.

Guidance on retrobulbar irradiation for thyroid eye disease from the National Institute for Health and Clincial Excellence (NICE, 2005) concluded: "Current evidence on the safety and efficacy of retrobulbar irradiation for thyroid eye disease appears adequate to support the use of this procedure in patients for whom other treatments are inadequate or associated with significant side effects."

Other Treatments

Bartalena and Tanda (2009) noted that RCT have not shown a benefit of somatostatin analogs (e.g., lanreotide and octreotide) for Graves' ophthalmopathy.  They stated that there are also few data to support the use of intravenous immune globulin for this condition.  This is in agreement with the consensus statement of the European Group on Graves' orbitopathy on the management of Graves' orbitopathy (Bartalena et al, 2008), which stated that treatments of marginal or unproven value include somatostatin analogs and intravenous immunoglobulins.

In a retrospective, interventional case series, Khanna and colleagues (2010) examined the effectiveness of rituximab in patients with severe, corticosteroid (CS)-resistant TAO.  Responses to rituximab therapy were graded using standard clinical assessment and flow cytometric analysis of peripheral lymphocytes.  Main outcome measures were clinical activity score (CAS), proptosis, strabismus, treatment side effects, and quantification of regulatory T cells; 6 patients were studied.  Systemic CS failed to alter clinical activity in all patients (mean CAS +/- standard deviation, 5.3 +/- 1.0 before versus 5.5 +/- 0.8 during therapy for 7.5 +/- 6.4 months; p = 1.0).  However, after rituximab therapy, CAS improved from 5.5 +/ -0.8 to 1.3 +/- 0.5 at 2 months after treatment (p < 0.03) and remained quiescent in all patients (CAS, 0.7 +/- 0.8; p < 0.0001) at a mean follow-up of 6.2 +/- 4.5 months.  Vision improved bilaterally in all 4 patients with dysthyroid optic neuropathy (DON).  None of the 6 patients experienced disease relapse after rituximab infusion, and proptosis remained stable (Hertel measurement, 24 +/- 3.7 mm before therapy and 23.6 +/- 3.7 mm after therapy; p = 0.17).  The abundance of T regulatory cells, assessed in 1 patient, increased within 1 week of rituximab and remained elevated at 18 months of follow-up.  The authors concluded that in progressive, CS-resistant TAO, rapid and sustained resolution of orbital inflammation and DON followed treatment with rituximab.

In a systematic review and meta-analysis on treatment modalities for Graves' ophthalmopathy, Stiebel-Kalish et al (2009) concluded that current evidence demonstrates the effectiveness of intravenous corticosteroids in decreasing CAS in patients with moderate-to-severe Graves' ophthalmopathy.  Intravenous pulse corticosteroids therapy has a small but statistically significant advantage oral therapy and causes significantly fewer adverse events.  Somatostatin analogs have marginal clinical efficacy.  The efficacy of orbital radiotherapy as single therapy remains unclear, whereas the combination of radiotherapy with corticosteroids has better efficacy than either radiotherapy or oral corticosteroids alone.  Rituximab is not listed as a therapeutic option.  Furthermore, Hegedus (2009) stated that no data as yet support the routine use of biological therapies (e.g., rituximab).  The author stated that prospective, randomized trials comparing available and any novel therapeutic options for Graves' disease are needed.

Bartalena et al (2010) stated that non-surgical treatments for moderate to severe and active Graves' orbitopathy (systemic glucocorticoids with or without orbital radiotherapy) have limited effects on the underlying autoimmune process causing the disease.  Although the clinical responses to treatment are often good, at least one-third of patients with Graves' orbitopathy are eventually dissatisfied with the treatment outcome.  Advent in the understanding of the autoimmune basis of Graves' orbitopathy (although still incomplete) made it possible, similar to other autoimmune disorders, to envision the use of novel immunomodulating drugs.  Among the currently available biologic agents, the CD20+ B cell-depleting agent, rituximab, and tumor necrosis factor-alpha inhibitors (e.g., etanercept and infliximab) are presently the drugs that have the best chance of being employed in the future for the treatment of Graves' orbitopathy.  However, the authors noted that RCTs to support their use are needed.

Viani et al (2012) evaluated the effectiveness of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy.  A systematic review and meta-analysis of RCTs was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy.  The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched.  Relevant reports were reviewed by 2 reviewers.  Response to radiotherapy was defined as clinical success according to each trial.  These investigators also evaluated the quality of life and whether RT to produce fewer side effects than other treatments.  A total of 8 RCTs (439 patients) were identified.  In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid versus glucocorticoids alone, OR = 17.5 (95 % CI: 1.85 to 250, p = 0.04), RT 20 Gy versus sham RT, OR = 3.15 (95 % CI: 1.59 to 6.23, p = 0.003) and RT 20Gy plus intravenous glucocorticoid versus RT 20Gy plus oral glucocorticoid, OR = 4.15(95 % CI: 1.34 to 12.87, p = 0.01).  There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone.  Radiotherapy 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility.  No difference was seen for costs, intra-ocular pressure and quality of life.  The authors concluded that these findings showed that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate-to-severe ophthalmopathy.  The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids.  Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intra-ocular pressure, without any difference in quality of life and costs.

Tanda and Bartalena (2012) examined the safety and effectiveness of orbital radiotherapy (OR) for graves' orbitopathy (GO).   The major source of data acquisition included PubMed strategies.  Original articles, systemic reviews and meta-analyses, and other relevant citations were screened.  Randomized clinical trials evaluating the effectiveness of OR are limited.  However, available data suggest that OR is a safe treatment, which seems to be effective particularly on ocular motility impairment, especially if it is of recent onset.  Orbital radiotherapy seems to be effective also on soft tissue changes, whereas exophthalmos and long-standing extra-ocular muscle dysfunction are poorly affected. The effectiveness of OR on dysthyroid optic neuropathy is uncertain.  The combination of OR and oral glucocorticoids (GCs) is more effective than either treatment alone, suggesting a synergistic effect of the 2 treatments.  There is no available evidence that the addition of OR to intravenous GCs provides an advantage over intravenous GCs alone.  The authors concluded that OR can be considered a safe second-line treatment for patients with moderate-to-severe and active GO but less effective than GCs.  A possible strategy may include its use in combination with intravenous GCs in patients whose GO has only partially responded to a first-course of intravenous GCs alone and is still active.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
CPT codes covered if selection criteria are met:
15820
15822
61330
67414
67445
67909
67911
77789
CPT codes not covered for indications listed in the CPB:
15821
15823
90281
90283
90284
Other CPT codes related to the CPB:
67311 - 67343
67901 - 67908
HCPCS codes covered if selection criteria are met:
V2710 Slab off prism, glass or plastic, per lens [for members with strabismus]
V2715 Prism, per lens [for members with strabismus]
V2718 Press-on lens, Fresnel prism, per lens [for members with strabismus]
HCPCS codes not covered for indications listed in the CPB:
J0135 Injection, adalimumab, 20 mg
J0717 Injection, certolizumab pegol, 1 mg (code may be used for medicare when drug administered under the direct supervision of a physician, not for use when drug is self administered)
J1438 Injection, etanercept, 25 mg
J1459 Injection, immune globulin (Privigen), intravenous, nonlyophilized (e.g., liquid), 500 mg
J1561 Injection, immune globulin, (Gamunex/Gamunex-C/Gammaked), nonlyophilized (e.g., liquid), 500 mg
J1566 Injection, immune globulin, intravenous, lyophilized (e.g., powder), not otherwise specified, 500 mg
J1568 Injection, immune globulin, (Octagam), intravenous, nonlyophilized (e.g., liquid), 500 mg
J1569 Injection, immune globulin, (Gammagard liquid), nonlyophilized, (e.g., liquid), 500 mg
J1572 Injection, immune globulin, (Flebogamma / Flebogamma Dif), intravenous, nonlyophilized (e.g., liquid), 500 mg
J1745 Injection, infliximab, 10 mg
J1930 Injection, lanreotide, 1 mg
J2353 Injection, octreotide, depot form for intramuscular injection, 1 mg
J2354 Injection, octreotide, nondepot form for subcutaneous or intravenous injection, 25 mcg
J2792 Injection, Rho D immune globulin, intravenous, human, solvent detergent, 100 IU
J7342 Dermal (substitute) tissue of human origin, with or without other bioengineered or processed elements, with metabolically active elements, per square centimeter
J7344 Dermal (substitute) tissue of human origin, with or without other bioengineered or processed elements, without metabolically active elements, per square centimeter
J9310 Injection, rituximab, 100 mg
Other HCPCS codes related to the CPB:
S9338 Home infusion therapy, immunotherapy, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9359 Home infusion therapy, anti-tumor necrosis factor intravenous therapy, (e.g., Infliximab); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
ICD-9 codes covered if selection criteria are met:
242.00 - 242.01 Toxic diffuse goiter
376.21 Thyrotoxic exophtalmos
376.22 Exophthalmic ophthalmoplegia
Other ICD-9 codes related to the CPB:
367.52 Total or complete internal ophthalmoplegia
368.15 Other visual distortions and entoptic phenomena
368.16 Psychophysical visual disturbances
368.2 Diplopia
374.41 Lid retraction or lag
376.30 - 376.36 Other exophthalmic conditions
377.30 - 377.39 Optic neuritis
377.41 - 377.49 Other disorders of optic nerve
378.00 - 378.9 Strabismus and other disorders of binocular eye movements


The above policy is based on the following references:
  1. Bartalena L, Pinchera A, Marcocci C. Management of Graves' ophthalmopathy: Reality and perspectives. Endocr Rev. 2000;21(2):168-199.
  2. Pliego-Maldonado A, Miranda-Ruiz R, Vargas-Aguayo A, et al. Orbit decompression surgery in patients with exophthalmos caused by Graves-Basedow disease. Gac Med Mex. 2000;136(1):11-15.
  3. Ulualp SO, Massaro BM, Toohill RJ. Course of proptosis in patients with Graves' disease after endoscopic orbital decompression. Laryngoscope. 1999;109(8):1217-1222.
  4. Kalmann R, Mourits MP. Prevalence and management of elevated intraocular pressure in patients with Graves' orbitopathy. Br J Ophthalmol. 1998;82(7):754-757.
  5. Adenis JP, Robert PY, Lasudry JG, Dalloul Z. Treatment of proptosis with fat removal orbital decompression in Graves' ophthalmopathy. Eur J Ophthalmol. 1998;8(4):246-252.
  6. Weetman AP, Harrison BJ. Ablative or non-ablative therapy for Graves' hyperthyroidism in patients with ophthalmopathy? J Endocrinol Invest. 1998;21(7):472-475.
  7. Tallstedt L. Surgical treatment of thyroid eye disease. Thyroid. 1998;8(5):447-452.
  8. Bartalena L, Marcocci C, Pinchera A. Treating severe Graves' ophthalmopathy. Baillieres Clin Endocrinol Metab. 1997;11(3):521-536.
  9. Tremolada C, Tremolada MA. The 'triple technique' for treating stable Graves' ophthalmopathy. Plast Reconstr Surg. 1997;100(1):40-48.
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  14. Gorman CA. Radiotherapy for Graves' ophthalmopathy: Results at one year. Thyroid. 2002;12(3):251-255.
  15. Gorman CA, Garrity JA, Fatourechi V, et al. A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy. Ophthalmology. 2001;108(9):1523-1534.
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  20. Soares-Welch CV, Fatourechi V, Bartley GB, et al. Optic neuropathy of Graves disease: Results of transantral orbital decompression and long-term follow-up in 215 patients. Am J Ophthalmol. 2003;136(3):433-441.
  21. Cruz AA, Leme VR. Orbital decompression: A comparison between trans-fornix/transcaruncular inferomedial and coronal inferomedial plus lateral approaches. Ophthal Plast Reconstr Surg. 2003;19(6):440-445; discussion 445.
  22. Kalpadakis P, Rudolph G, Mueller A, Boergen KP. Muscle surgery in patients with Graves' disease using topical anesthesia. Ophthalmology. 2004;111(8):1563-1568.
  23. Hintschich C, Haritoglou C. Full thickness eyelid transsection (blepharotomy) for upper eyelid lengthening in lid retraction associated with Graves' disease. Br J Ophthalmol. 2005;89(4):413-416.
  24. Taban M, Douglas R, Li T, et al. Efficacy of 'thick' acellular human dermis (AlloDerm) for lower eyelid reconstruction: Comparison with hard palate and thin AlloDerm grafts. Arch Facial Plast Surg. 2005;7(1):38-44.
  25. Wakelkamp IM, Baldeschi L, Saeed P, et al. Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves' ophthalmopathy? A randomized controlled trial. Clin Endocrinol (Oxf). 2005;63(3):323-328.
  26. Goh MS, McNab AA. Orbital decompression in Graves' orbitopathy: Efficacy and safety. Intern Med J. 2005;35(10):586-591.
  27. National Institute for Health and Clinical Excellence (NICE). Retrobulbar irradiation for thyroid eye disease. Interventional Procedure Guidance 148. London, UK: NICE; 2005.
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  30. Wiersinga WM. Management of Graves' ophthalmopathy. Nat Clin Pract Endocrinol Metab. 2007;3(5):396-404. 
  31. Zoumalan CI, Cockerham KP, Turbin RE, et al. Efficacy of corticosteroids and external beam radiation in the management of moderate to severe thyroid eye disease. J Neuroophthalmol. 2007;27(3):205-214.
  32. Bradley EA, Gower EW, Bradley DJ, et al. Orbital radiation for graves ophthalmopathy: A report by the American Academy of Ophthalmology. Ophthalmology. 2008;115(2):398-409.
  33. Stålberg P, Svensson A, Hessman O, et al. Surgical treatment of Graves' disease: Evidence-based approach. World J Surg. 2008;32(7):1269-1277.
  34. Bartalena L, Baldeschi L, Dickinson A, et al; European Group on Graves' Orbitopathy (EUGOGO). Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol. 2008;158(3):273-285. Available at: http://www.eje-online.org/cgi/content/long/158/3/273. Accessed May 1, 2009.
  35. Bartalena L, Tanda ML. Clinical practice. Graves' ophthalmopathy. N Engl J Med. 2009;360(10):994-1001.
  36. Stiebel-Kalish H, Robenshtok E, Hasanreisoglu M, et al. Treatment modalities for Graves' ophthalmopathy: Systematic review and metaanalysis. J Clin Endocrinol Metab. 2009;94(8):2708-2716.
  37. European Group on Graves' Orbitopathy (EUGOGO), Mourits MP, Bijl H, Altea MA, et al. Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures. Br J Ophthalmol. 2009;93(11):1518-1523.
  38. Hegedüs L. Treatment of Graves' hyperthyroidism: Evidence-based and emerging modalities. Endocrinol Metab Clin North Am. 2009;38(2):355-371, ix.
  39. Leong SC, White PS. Outcomes following surgical decompression for dysthyroid orbitopathy (Graves' disease). Curr Opin Otolaryngol Head Neck Surg. 2010;18(1):37-43.
  40. Khanna D, Chong KK, Afifiyan NF, et al. Rituximab treatment of patients with severe, corticosteroid-resistant thyroid-associated ophthalmopathy. Ophthalmology. 2010;117(1):133-139.
  41. Abraham P, Avenell A, McGeoch SC, Clark LF, Bevan JS. Antithyroid drug regimen for treating Graves' hyperthyroidism Cochrane Database of Systematic Reviews: Reviews 2010;(1):CD003490.
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  45. Viani GA, Boin AC, De Fendi LI, et al. Radiation therapy for Graves' ophthalmopathy: A systematic review and meta-analysis of randomized controlled trials. Arq Bras Oftalmol. 2012;75(5):324-332.
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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
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