Monoclonal Antibodies for the Treatment of Graves Orbitopathy: Precision Medicine?

PURPOSE: To summarize the development, nomenclature, and rationale of the reported use of monoclonal antibodies (Mabs) in Graves Orbitopathy (GO) and to undertake a systematic review of the management of GO with Mabs. METHODS: The Pubmed and Embase databases and the Federal Brazilian searching site (Periódicos-CAPES) were screened. The authors searched all the keywords "monoclonal antibodies," "adalimumab," "belimumab," "infliximab," "rituximab," "teprotumumab," and "tocilizumab" combined with the terms "Graves Orbitopathy," "Graves eye disease" and "thyroid eye disease." All the articles published in English, French, and Spanish from 2000 to May 2022 were screened. Only publications with quantitative data on the activity of orbitopathy, proptosis, or both were included. RESULTS: Seventy-six articles of the 954 screened records met the inclusion criteria. Seven Mabs were described for treating GO. The three most reported Mabs were Rituximab, Tocilizumab, and Teprotumumab. Only eight randomized clinical trials compared the effect of these three Mabs and Belimumab with the effect of steroids or placebos. Adalimumab, Infliximab, and K1-70 only appeared in a few case series and case reports. Frequent mild-to-moderate and few major side effects occurred with the three most used Mabs. Relapse rates ranged from 7.4% for Tocilizumab to at least 29.4% for Teprotumumab. No randomized clinical trials compared Mabs head-to-head. CONCLUSION: Considering the lack of head-to-head comparisons between Mabs, the relapse rate, the possibility of severe collateral effects, and the cost of Mabs, it is not clear which Mab is the safest and most useful to treat GO.

Fluência do laser e tempo de parada cirúrgica, por perda de fixação, como fatores relacionados à precisão refracional / Fluency of laser and surgical downtime, loss of fixation, as factors related to the precision refractive

OBJETIVO: Avaliar a correlação da fluência e o tempo de parada transoperatória por perda de fixação, como fatores de hiper ou hipocorreções das ametropias pós-Lasik. MÉTODOS: A idade variou entre 19 e 61 anos com média de 31,27 ± 9,99. O tempo mínimo de acompanhamento pós-operatório foi de 90 dias. Foram excluídos indivíduos com topografia corneana pré-operatória com ceratometria máxima maior que 46,5D ou presença de irregularidades; ceratometria média pós-operatória simulada menor que 36,0D; pupilas maiores que 6mm; paquimetria menor que 500 µm; miopia maior que -8,0DE, hipermetropia maior que +5,0DE e astigmatismo maior que -4,0DC. O laser utilizado foi o Esiris Schwind com Eye-Tracking de 350Hz e scanning spot de 0,8 mm. O microcerátomo utilizado foi o M2 da Moria com programação de 130µm de espessura. RESULTADOS: A acuidade visual logMAR pré-operatória com correção variou de 0,40 a 0 com média de 0,23 ± 0,69; a pós-operatória sem correção foi de 0,40 a 0 com média de 0,30 ± 0,68. A mediana foi de 0 logMAR para os dois momentos (p=0,424). No equivalente esférico pré e pós-operatório, notou-se uma óbvia diferença (p< 0,0001), no pré-operatório com média de -4,09 ± 2,83 e o pós com média de -0,04 ± 0,38. A mediana foi de -4,75 no pré e de 0 no pós-operatório. Sessenta e nove casos (78,3%) ficaram plano ± 0,25. A fluência mínima foi de 0,513 mJ/cm² e a máxima de 0,581 mJ/cm² com média de 0,545 ± 0,01, não se percebendo correlação (r= -0,03266; IC 95% -0,241 a 0,178; p= 0,762) entre a fluência e o equivalente esférico final (média= -0,04 ± 0,38) nos olhos operados. O tempo mínimo de parada transoperatória foi de dois segundos e o máximo de 12 segundos com média de 4,90 ± 3,47. Fazendo-se uma correlação (r= 0,08865; IC 95%= -0,123 a 0,293; p= 0,411) entre o equivalente esférico pós-operatório e o tempo de parada transoperatória, não se percebeu diferenças. CONCLUSÃO: Não houve correlação entre a fluência do laser e o tempo de parada transoperatória por perda de fixação, com hiper ou hipocorreções nas ametropias pós-Lasik.

OBJECTIVE: To evaluate the correlation of flow and stopping time intraoperative loss of attachment factors as hypertension or hipocorreções of refractive errors after Lasik. METHODS: The age ranged between 19 and 61 years (mean= 31.27 ± 9.99). The minimum follow-up period was 90 days. Individuals with: corneal topography preoperative maximum keratometry greater than 46.5D or presence of irregularities, corneal curvature postoperative simulated smaller 36.0D, pupils more 6mm; corneal thickness smaller 500 µm; Myopia more -8.0, hyperopia more +5.0DE and astigmatism more -4.0DC. The laser was used with Esir Schwind Eye-Tracking and 350Hz scanning spot of 0.8 mm. The microkeratome used was the Moria M2 with programming 130µm thick. RESULTS: The visual acuity logMAR preoperative correction ranged from 0.40 to 0 (mean= 0.23 ± 0.69) and postoperative uncorrected 0.40-0 (x= 0.30 ± 0, 68). The Median= 0 logMAR for both time points (p= 0.424). For spherical equivalent before and after surgery, we found an obvious difference, with the pre (mean= -4.09 ± 2.83) and post (mean= -0.04 ± 0.38). The Median was -4.75 in the pre and zero postoperatively (p <0.0001). Sixty-nine cases (78.3%) were plan ± 0.25. Fluency minimum= 0.513 mJ/cm2 and maximum= 0.581 mJ/cm2 (mean= 0.545 ± 0.01), no correlation (r = -0.03266, 95% CI -0.241 to 0.178, p = 0.762) between the flow and spherical equivalent (mean = -0.04 ± 0.38) in eyes operated. The minimal downtime during surgery was 02 seconds and maximum was 12 seconds (mean= 4.90 ± 3.47). Making a correlation (r = 0.08865, 95% CI = -0.123 to 0.293, p = 0.411) between the postoperative spherical equivalent and downtime during surgery, not perceived differences. CONCLUSION: There was no correlation between the fluency of the laser during surgery and downtime due to loss of fixation with hipocorreções in hyper-or post-Lasik ametropia.