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Show from 2011 (4). These guidelines are based on a strong body of evidence and should be cited as such. Second, in the flowchart included in the review, both oral and intravenous corticosteroids have been included as equal choices. As mentioned above, intravenous pulse methylprednisolone is more effective than oral predni-sone (success rate 74% vs 51%) and is better tolerated (adverse effects 56% vs 81%) (4). These treatment pro-tocols recommend a 12-week course of intravenous methylprednisolone (0.5 g as a single dose per week for 6 consecutive weeks followed by 0.25 g as single dose per week for 6 consecutive weeks, not to exceed a total of 8 g) for patients with moderate-to severe active GO. Finally, orbital radiotherapy without concomitant cortico-steroids is presented in the flowchart as an equally weighted arm for the management of active GO. This contrasts with the EUGOGO consensus guidelines, which do not include orbital radiotherapy as a treatment option for active GO (3) and with the findings of the meta-analysis (2), which found that the efficacy of orbital radiotherapy as single therapy remains un-clear, whereas the combination of radiotherapy with cortico-steroids has better efficacy than either radiotherapy or oral corticosteroids alone. The review by Bhatti and Dutton is a commendable effort, since suboptimal management of patients with GO is widespread (5). Familiarity with the current lit-erature is extremely important, as both oral and intra-venous corticosteroids are associated with severe adverse effects, including fatal cases (6). Hadas Stiebel-Kalish, MD Neuroophthalmology Unit, Department of Ophthalmology, Rabin Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel Eyal Robenshtok, MD Institute of Endocrinology and Metabolism, Rabin Medical Center, Beilinson Hospital and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel The authors report no conflicts of interest. REFERENCES 1. Bhatti TM, Dutton JJ. Thyroid eye disease: therapy in the active phase. J Neuroophthalmol. 2014;34:186-197. 2. Stiebel-Kalish H, Robenshtok E, Hasanreisogly M, Ezrachi D, Shimon I, Liebovici L. Treatment modalities for Graves' ophthalmopathy: systematic review and meta-analysis. J Clin Endocrinol Metab. 2009;94:2708-2716. 3. Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall- Taylor P, Marcocci C, Mouritis MP, Perros P, Boboridis K, Bosch A, Currö N, Daumerie C, Kahaly GJ, Krassas G, Lane CM, Lazarus JH, Marinö M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM. Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy. Thyroid. 2008;18:333-346. 4. Bahn-Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011;21:593-646. Erratum in: Thyroid. 2011;21:1169. Thyroid. 2012;22:1195. 5. Perros P, Baldeschi L, Boboridis K, Dickinson AJ, Hullo A, Kahaly GJ, Kendell-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marino M, Mouritis MP, Nardi M, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Wiersinga WM. A questionnaire survey on the management of Graves' orbitopathy in Europe. The European Group of Graves' Orbitopathy. Eur J Endocrinol. 2006;155:207-211. 6. Marcocci C, Watt T, Altea MA, Rasmussen AK, Feldt- Rasmussen U, Orgiazzi J, Bartalena L. Fatal and non-fatal adverse events of glucocorticoid therapy for Graves' orbitopathy: a questionnaire survey among members of the European Thyroid Association. Eur J Endocrinol. 2012;166:247-253. Thyroid Eye Disease: Therapy in the Active Phase: A Comment: Reply We thank Drs Stiebel-Kalish and Robenshtok for their interest in our State-of-the-Art review on the treat-ment of active thyroid eye disease (TED) (1). Here are our responses to their 3 major critiques. First, Drs Stiebel-Kalish and Robenshtok take issue with our statement: "Few randomized controlled studies have systematically evaluated these treatment strat-egies. . .." Based on their very impressive review and meta-analysis on the treatment modalities of TED pub-lished in 2009, there were 33 randomized controlled trials (RCTs) conducted on TED (2). In fairness, our complete sentence should have been included in their letter: "Few randomized controlled studies have systematically evalu-ated these treatment strategies, and of those trials that have been executed, they are difficult to compare and contrast because of inconsistencies in study design and outcome meas-ures." We did not intend to suggest that in total, there have not been a number of RCTs performed in TED but rather that for each treatment modality (corticosteroids, orbital ra-diotherapy [ORT], and orbital decompression), the number of RCTs has not been very robust and variable in terms of study design and outcome measures. That point was empha-sized in the 3 tables included as electronic digital supplement 426 Letters to the Editor: J Neuro-Ophthalmol 2014; 34: 422-428 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. in our review (See Supplemental Digital Contents, Tables 2-4, http://links.lww.com/WNO/A101; http://links.lww. com/WNO/A102; http://links.lww.com/WNO/A103). We agree with the 2009 Stiebel-Kalish et al meta-analysis that states "Current evidence demonstrates the efficacy of in-travenous (IV) corticosteroids in decreasing CAS in patients with moderate-to-severe Graves' Ophthalmop-athy. Intravenous pulse corticosteroids therapy has a small but statistically significant advantage (over) oral therapy and causes significantly fewer adverse events." (2). In fact, in our review article, we state something very similar: "The response rate with PO corticosteroids is less than IV cor-ticosteroids (60% vs 80%, respectively). Pooled data have shown that patients who received IV corticosteroids com-pared with PO corticosteroids fared better in terms of double vision, ocular motility, and proptosis, with fewer side effects." Second, the intention of our flowchart was to provide the reader with a treatment paradigm for active TED based on our clinical experience and published data. We provided the option of both oral (1 mg/kg prednisone) and intravenous (12-week course of methylprednisolone) corticosteroids because we would be remiss if we excluded one of these options. We believe that tailoring treatment to an individual patient is an important part of clinical practice in any proposed treatment flowchart unless there is overwhelming and indisputable evidence to suggest one treatment is far superior or significantly less harmful than another. Finally, our flowchart does indeed provide the reader with the option of corticosteroids or ORT (with or without concomitant corticosteroids) in the management of patients with moderate-to-severe TED. However, we do not believe this is contrary in any significant way with the EUGOGO consensus guidelines.We re-reviewed the EUGOGO consensus statement published by Bartalena et al (3). In that publication, figure 1 indicates in parentheses with a 6 symbol the option of ORT with the use of IV corticosteroids in a patient with active moderate-to-severe TED. The first entry of Box 9, titled "treatment of moderate to severe Graves' orbitopathy that is active" in the article states: "The treatment of choice for moderate to severe and active (CAS . 3/7) Graves' orbit-opathy is pulses of IV glucocorticoids." Additional entries in the box state "orbital irradiation should be considered in patients with active disease who have diplopia or restricted motility. The combination of oral glucocorticosteroids with orbital irradiation is more effective than either treatment alone, but randomized clinical trials indicating that combi-nation of intravenous glucocorticosteroids with orbital irra-diation is better than intravenous glucocorticosteroids alone are lacking." One of the conclusions of the meta-analysis by Stiebel-Kalish et al (2) was that the efficacy of ORT as a single treatment for active TED remains "unclear"; in other words, it has yet to be determined if ORT alone is or is not an effective treatment modality (2). To illustrate this point, the results of one of the RCT comparing ORT alone with placebo (4), which did not show a beneficial effect of ORT, was met with caution in generalizing the findings to all patients with TED (5). Therefore, we believe our flowchart as presented provides the necessary options for the clinician when faced with a very challenging case of active moderate-to-severe TED to determine the best course of action for that particular patient. M. Tariq Bhatti, MD Departments of Ophthalmology and Neurology, Duke Eye Center and Duke University Medical Center, Durham, North Carolina Jonathan J. Dutton, MD, PhD, FACS Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (www.jneuro-ophthalmology.com). REFERENCES 1. Bhatti MT, Dutton JJ. Thyroid eye disease: therapy in the active phase. J Neuroophthalmol. 2014;34:186-197. 2. Stiebel-Kalish H, Robenshtok E, Hasanreisoglu M, Ezrachi D, Shimon I, Leibovici L. Treatment modalities for Graves' ophthalmopathy: systematic review and meta analysis. J Clin Endocrinol Metab. 2009;94:2708-2716. 3. Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall- Taylor P, Marcocci C, Mourits MP, Perros P, Boboridis K, Boschi A, Curro N, Daumerie C, Kahaly GJ, Krassas G, Lane CM, Lazarus JH, Marino M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM. Consensus statement of the European Group on Graves' Orbitopathy (EUGOGO) on management of Graves' orbitopathy. Thyroid. 2008;18:333-346. 4. Gorman CA, Garrity JA, Fatourechi V, Bahn RS, Petersen IA, Stafford SL, Earle JD, Forbes GS, Kline RW, Bergstralh EJ, Offord KP, Rademacher DM, Stanley NM, Bartley GB. A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy. Ophthalmology. 2001;108:1523-1534. 5. Feldon SE. Radiation therapy for Graves' ophthalmopathy: trick or treat? Ophthalmology. 2001;108:1521-1522. Letters to the Editor: J Neuro-Ophthalmol 2014; 34: 422-428 427 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
