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Toscano DA, et al. observed excellent reproducibility of retinal thickness measurements with mean difference among measurements of about 1 µm (6) . Other SDOCT were also analyzed as RTVue which the RNFL thickness reproducibility showed the ICC ranged between 0.91 and 0.97 for the healthy group (60 eyes) and 0.86 and 0.97 for the glaucomatous group (76 eyes) (7) . Using the SD SLO/OCT OTI the lowest ICC was 0.961 at 3 o’clock in the normal group (98 eyes) and 0.951 at 4 o’clock in the glaucoma group (79 eyes) (9) . Bendschneider et al., analyzed the RNFL thickness in 170 healthy patients using the SDOCT Spectralis ® and observed that the RNFL thickness was significantly associated with age (1.9 µm decline in mean total RNFL thickness per age decade), axial length (total RNFL decrease of -4.79 mm per every increasing 1-mm-axial length) and optic disc area (with a total RNFL increase of 6.28 mm for every 1-mm 2 -increase in disc area). The total RNFL thickness in the study population was 97.2 ± 9.7 µm, which is comparable to our study (96.25 µm ± 10.28) (10) . Recently, Wu et al., reported the reproducibility of Spectralis in 45 normal patients and 33 glaucoma patients. Their ICCs ranged from 0.977 (temporal) to 0.990 (global and inferior-nasal sector) in normal eyes, and from 0.983 (temporal) to 0.997 (inferior quadrant) in glaucomatous eyes. CVs ranged from 1.45% (overall global) to 2.59% (temporal quadrant) for normal participants and ranged from 1.74% (overall global) to 3.22% (temporal quadrant) for glaucoma patients (16) . There were some differences between this study and the present study: they analyzed the RNFL thickness using more than four quadrants (overall global - 360 degrees), for 4 quadrants (superior, inferior, nasal, and temporal), and then for 4 additional sectors: superior-temporal (TS, 45 to 90 degrees), superior-nasal (NS, 90 to 135 degrees), inferior-nasal (NI, 225 to 270 degrees), and inferior- -temporal (TI, 270 to 315 degrees); the number of participants was smaller than ours; the subjects had different types of glaucoma, in cluding pseudoexfoliation glaucoma; and they used the TruTrack image alignment software (i.e., the eye tracking system). Probably because of all these facts theirs ICC and COV were better than the present study, especially because of the tracking system. Evaluating the impact of Spectralis ® self-acting eye tracking system and retest software on the reproducibility of RNFL thickness measurements in glaucomatous and healthy eyes it was observed that the reproducibility can be improved by using the eye tracker, and this gain was significantly higher in glaucomatous than in healthy eyes. In healthy subjects, COVs for RNFL thickness measurements without using the system ranged from 3.5% to 7.4% and with the eye tracker and retest protocol ranged from 1.0% to 2.5%. In glaucoma patients measurements without the eye tracker ranged from 5.8% to 10.5% and with the system ranged from 1.6% to 3.8%. The improvement in reproducibility was significantly higher in glaucomatous than in healthy eyes (17) . Our study showed COV ranged from 4.65% to 11.44% in the glaucomatous group similar to the previous study without using the eye tracker system. Despite not using the eye tracking system, our study showed an excellent reproducibility of RNFL thickness in normal and glaucomatous eyes. It is necessary to emphasize that the patients included in the present study had moderate to advanced glaucoma with difficult to fixation on one or both eyes and it may have contributed to the high COV. CONCLUSION The Spectralis ® spectral domain OCT equipped showed excellent reproducibility with regards to RNFL thickness measurements in normal and in moderate to advanced glaucoma patients. REFERENCES 1. Sehi M, Grewal DS, Sheets CW, Greenfield DS. Diagnostic ability of Fourier-domain vs time-domain optical coherence tomography for glaucoma detection. Am J Ophthalmol. 2009;148(4):597-605. 2. Sommer A, Miller NR, Pollack I, Maumenee AE, George T. The nerve fiber layer in the diagnosis of glaucoma. Arch Ophthalmol. 1977;95(12):2149-56. 3. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical coherence tomography. Science. 1991;254(5035):1178-81. 4. Chen TC, Cense B, Pierce MC, Nassif N, Park BH, Yun SH, et al. Spectral domain optical coherence tomography: ultra-high speed, ultra-high resolution ophthalmic imaging. Arch Ophthalmol. 2005;123(12): 1715-20. 5. Nassif N, Cense B, Park B, Pierce M, Yun S, Bouma B, et al. In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve. Opt Express. 2004;12(3):367-76. 6. Menke MN, Dabov S, Knecht P, Sturm V. Reproducibility of retinal thickness measurements in healthy subjects using spectralis optical coherence tomography. Am J Oph thalmol. 2009;147(3):467-72. 7. Gonzalez-Garcia AO, Vizzeri G, Bowd C, Medeiros FA, Zangwill LM, Weinreb RN. Reproducibility of RTVue retinal nerve fiber layer thickness and optic disc measurements and agreement with Stratus optical coherence tomography measurements. Am J Ophthalmol. 2009;147(6):1067-74, 1074 e1. 8. Leung CK, Ye C, Weinreb RN, Cheung CY, Qiu Q, Liu S, et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography a study on diagnostic agreement with Heidelberg Retinal Tomograph. Ophthalmology. 2010;117(2):267-74. 9. Lee SH, Kim SH, Kim TW, Park KH, Kim DM. Reproducibility of retinal nerve fiber thickness measurements using the test-retest function of spectral OCT/SLO in normal and glaucomatous eyes. J Glaucoma. 2010;19(9):637-42. 10. Bendschneider D, Tornow RP, Horn FK, Laemmer R, Roessler CW, Juenemann AG, et al. Retinal Nerve Fiber Layer Thickness in Normals Measured by Spectral Domain OCT. J Glaucoma. 2010;19(7):475-82. 11. Tan BB, Natividad M, Chua KC. Comparison of retinal nerve fiber layer measurement between 2 spectral domain OCT instruments. J Glaucoma. 2012;21(4):266-73. 12. Blumenthal EZ, Williams JM, Weinreb RN, Girkin CA, Berry CC, Zangwill LM. Reproducibility of nerve fiber layer thickness measurements by use of optical coherence to mography. Ophthalmology. 2000;107(12):2278-82. 13. Budenz DL, Fredette MJ, Feuer WJ, Anderson DR. Reproducibility of peripapillary retinal nerve fiber thickness measurements with stratus OCT in glaucomatous eyes. Ophthalmology. 2008;115(4):661-6. e4. 14. Budenz DL, Chang RT, Huang X, Knighton RW, Tielsch JM. Reproducibility of retinal nerve fiber thickness measurements using the stratus OCT in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci. 2005;46(7):2440-3. 15. Paunescu LA, Schuman JS, Price LL, Stark PC, Beaton S, Ishikawa H, et al. Reproducibility of nerve fiber thickness, macular thickness, and optic nerve head measurements using StratusOCT. Invest Ophthalmol Vis Sci. 2004;45(6):1716-24. 16. Wu H, de Boer JF, Chen TC. Reproducibility of retinal nerve fiber layer thickness mea surements using spectral domain optical coherence tomography. J Glaucoma. 2011;20(8):470-6. 17. Langenegger SJ, Funk J, Toteberg-Harms M. Reproducibility of retinal nerve fiber layer thickness measurements using the eye tracker and the retest function of Spectralis SD-OCT in glaucomatous and healthy control eyes. Invest Ophthalmol Vis Sci. 2011;52(6):3338-44. Arq Bras Oftalmol. 2012;75(5):320-3 323
Artigo Original | Original Article Radiation therapy for Graves’ ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials Radioterapia para oftalmopatia de Graves: uma revisão sistemática e meta-análise de ensaios clínicos randomizados e controlados Gustavo Arruda Viani 1 , André Campiolo Boin 2 , Ligia Issa De Fendi 3 , Ellen Carrara Fonseca 3 , Eduardo Jose Stefano 1 , Jayter Silva de Paula 4 ABSTRACT Purpose: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves’ ophthalmopathy. Methods: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to cli nical treatments for Graves’ ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. Results: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 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, intraocular pressure and quality of life. Conclusion: Our data have shown that RT 20 Gy should be offered as a valid the - rapeutic 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 intraocular pressure, without any difference in quality of life and costs. Keywords: Graves ophthalmopathy; Exophthalmos; Radiotherapy; Meta-analysis, Review RESUMO Objetivo: Avaliar a eficácia da radioterapia (RT) com dose total de 20 Gy (RT 20 Gy) no tratamento da oftalmopatia de Graves. Métodos: Uma revisão sistemática e meta-análise de ensaios clínicos randomizados foram realizadas comparando RT 20 Gy, com ou sem glicocorticoides a tratamentos clinicos para a oftalmopatia de Graves. O MEDLINE, EMBASE, bases de dados da Biblioteca Cochrane e recentes de revistas relevantes foram pesquisados. Relatórios relevantes foram revisados por dois revisores. A resposta à radioterapia foi definida através do sucesso clinico de acordo a cada ensaio clínico. Nós também avaliamos a qualidade de vida e se a radioterapia produzia menos efeitos colaterais comparados a outras intervenções. Resultados: Um total de 8 ensaios clínicos randomizados (439 pacientes) foram iden - tificados. Na análise de subgrupo, a resposta global para as taxas de tratamento foi melhor para: RT 20 Gy além de glicocorticoides vs glicocorticoides sozinhos, OR=17,5 (IC95% 1,85-250, p=0,04), RT 20 Gy vs sham RT, OR=3,15 (IC95% 1,59-6,23, p=0,003) e RT 20 Gy além de glicocorticoides por via intravenosa RT 20 Gy além de glicocorticoides orais, OR=4,15 (IC95% 1,34-12,87, p=0,01). Não houve diferenças entre RT 20 Gy contra outros fracionamentos e 20 Gy RT contra glicocorticoides sozinhos. RT 20 Gy, com ou sem glicocorticoides mostraram uma melhoria no grau de diplopia, acuidade visual, neuropatia óptica, abertura palpebral, proptose e da motilidade ocular. Não foi observada diferença para os custos, a pressão intraocular e a qualidade de vida. Conclusão: Nossos dados mostraram que 20 Gy RT deve ser oferecida como uma opção terapêutica válida para pacientes com moderada a severa oftalmopatia de Graves. A eficácia da radioterapia orbital pode ser aumentada pela interação sinérgica com os glicocorticoides. Além disso, RT 20 Gy é útil para melhorar vários sintomas oculares, excluindo a pressão intraocular, sem qualquer diferença de qualidade de vida. Descritores: Oftalmopatia de Graves; Exoftalmia; Radioterapia; Meta-análise, Revisão INTRODUCTION Graves’ ophthalmopathy is a debilitating disease impairing the quality of life of the affected individuals. Despite recent progress in the understanding of its pathogenesis, treatment is often not sa - tisfactory. In mild cases, local therapeutic measures (artificial tears and ointments, sunglasses, nocturnal eyes taping, prisms) can control symptoms and signs. In severe forms of the disease, aggressive measures are required. The management strategy for moderate tosevere Graves’ ophthalmopathy is controversial. Systemic steroids are often effective (1-4) , but relapse is common when they are tapered or withdrawn (5) . A number of retrospective studies have reported the efficacy of orbital irradiation (6,7) but prospective studies have shown conflicting results (8-10) . Some investigators have suggested that ste - roids provide excellent improvement in orbital inflammation in the short term, whereas the effects of orbital irradiation take longer to appear (11) . Studies that have compared combination therapy of or - bi tal irradiation and systemic steroids with steroids alone therapy have produced conflicting results (12-18) . The accomplishment of a sys tematic review is the best manner for describing the state of our knowledge, and hence becomes the best way of obtaining high qua lity scientific evidence. Consequently, this systematic review was proposed to analyze the results from clinical trials that compared ra - diotherapy to any other treatment. Submitted for publication: February 6, 2012 Accepted for publication: August 27, 2012 Study carried out at Faculty of Medicine of Marília, Department of Radiation Oncology. 1 Physician, Radiation Oncology Department, Escola de Medicina de Marília, Marília (SP), Brazil. 2 Medical Student, Escola de Medicina de Marília, Marília (SP), Brazil. 3 Department of Ophthalmology, Escola de Medicina de Marília, Marília (SP), Brazil. 4 Physician, Department of Ophthalmology, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo - USP - Ribeirão Preto (SP), Brazil. Funding: No specific financial support was available for this study. Disclosure of potential conflicts of interest: G.A.Viani, None; A.C.Boin, None; L.I.De Fendi, None; E.C.Fonseca, None; E.J.Stefano, None; J.S.de Paula, None. Correspondence address: Gustavo Arruda Viani. Rua Coronel José Brás, 205/72 - Marília (SP) - 17501-570 - Brazil - E-mail-gusviani@gmail.com 324 Arq Bras Oftalmol. 2012;75(5):324-32
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