Measuring disease activity to predict therapeutic outcome in Graves’ ophthalmopathy

Terwee, Caroline B.; Prummel, Mark F.; Gerding, M.N.; Kahaly, George J.; Dekker, Friedo W.; Wiersinga, Wilmar M.

doi:10.1111/j.1365-2265.2005.02186.x

Cited by 69 publications

(53 citation statements)

References 32 publications

(61 reference statements)

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“…Disease duration is perhaps the most useful parameter for the differential diagnosis of these two particular subgroups of GO patients; as previously reported by Terwee and colleagues, GO duration >16 months was a significant predictor of no change and no response to therapy (27). A very recent study has shown that the increase of fibroadipose tissue is observed in untreated patients with a longer duration of disease (28), resulting in increasing proptosis and orbital fat volume mimicking disease progression.…”

Section: Chronic Congestive Gomentioning

confidence: 59%

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

Campi

Vannucchi

Salvi

2016

European Journal of Endocrinology

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Management of Graves' orbitopathy (GO) must be based on the correct assessment of activity and severity of the disease. Activity is usually assessed with the Clinical Activity Score, whereas severity is classified according to a European Group On Graves' Orbitopathy (EUGOGO) consensus statement as mild, moderate-to-severe, and sight-threatening. Myopathic and chronic congestive forms are uncommon clinical presentations of GO. Restoration and maintenance of stable euthyroidism are recommended in the presence of GO. In moderate-to-severe disease, steroids have been widely employed and have shown to possess an anti-inflammatory activity, but about 20 -30% of patients are not responsive and present recurrence. Some novel immunosuppressors have already been employed in clinical studies and have shown interesting results, although the lack of randomized and controlled trials suggests caution for their use in clinical practice. Potential targets for therapy in GO are the thyroid-stimulating hormone and the insulin-like growth factor 1 receptor on the fibroblasts, inflammatory cytokines, B and T cells, and the PIK3/mTORC1 signaling cascades for adipogenesis. A recent open study has shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent reports on the efficacy of rituximab have recently been challenged by randomized controlled trials. As the main goal of treatment is the well-being of the patient, the therapeutic strategy should be addressed to better suit the patient needs, more than improving one or more biological parameters. The increasing availability of new therapies will expand the therapeutic options for GO patients and allow the clinician to really personalize the treatment to better suit the patients' personal needs.

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Section: Chronic Congestive Gomentioning

confidence: 59%

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

Campi

Vannucchi

Salvi

2016

European Journal of Endocrinology

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“…Thus, from this perspective, the population treated in the US trial had a lower likelihood of response to therapy. Another element that can predict response to therapy seems to be the duration of disease (24). Here again, the Italian trial recruited a population that had GO by an average of only 4.5 months by comparison with almost 3 times longer disease duration in the US trial.…”

Section: Analysis Of the Randomized Trials Characteristicsmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Rituximab therapy for Graves’ orbitopathy – lessons from randomized control trials

Stan

Salvi

2017

European Journal of Endocrinology

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Rituximab (RTX) use in open-label series has been associated with very encouraging responses in patients with active and moderate-to-severe Graves' orbitopathy (GO). Recently, randomized controlled trials of RTX have been performed in such patients to answer the question of clinical efficacy and the safety profile of this agent. That data, reported separately, focused on Clinical Activity Score (CAS) and indicated in one trial a strong benefit of RTX in comparison with IV glucocorticoids, whereas the other trial noted the absence of a benefit by comparison with placebo. The outcome was reanalyzed post hoc here, using EUGOGO criteria, and the results were not significantly different. The authors comment further on the differences between the two trials regarding populations treated, methodology, analysis of outcomes and the adverse effect profile of RTX. The populations treated appear different with younger patients, lower TRAb and shorter duration of disease prevalent in the Italian trial, all elements favoring a better response. Smoking, usually diminishing a response, was also more prevalent in some patients. The combined outcome proposed by EUGOGO revealed similar results with CAS regarding RTX efficacy; yet, it might be a more comprehensive outcome. The adverse events of concern relate mainly to the risk of DON, which seems to be increased by the use of RTX in a certain subset of patients. Based on available data, a multicenter trial using the EUGOGO-proposed outcomes might be the next best step to define the role of RTX in GO therapy.

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“…As there is still no specific treatment available to date (Heufelder 1995), one can only try to avoid these sequelae by early administration of non-specific anti-inflammatory agents such as systemic corticosteroids or orbital ionizing irradiation. Although useful classifications for the assessment of disease activity have been introduced (Mourits et al 1989(Mourits et al , 1997Terwee et al 2005), it is yet not easy to clinically estimate the further course of inflammatory activity at a certain stage of disease. Thus, the purpose of our study is to find a technique that could not only detect but also quantify early inflammatory activity.…”

Section: Introductionmentioning

confidence: 99%

Changes of saccadic eye movements in thyroid‐associated ophthalmopathy

Schworm¹,

Bolzani²,

Benassi³

et al. 2011

Acta Ophthalmologica

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ABSTRACT.Purpose: To establish whether or not the dynamics of saccadic eye movements are significantly changed in patients with different stages of thyroid-associated ophthalmopathy (TAO) and, subsequently, if analysis of saccades could serve as an additional diagnostic tool for early detection of inflammatory activity in TAO. Methods: Thirty-seven patients with TAO and 10 age-and gender-matched control subjects were investigated. The patients were divided into four groups according to the stage of the disease: (i) early mild disease (n = 10), (ii) early severe disease (n = 11), (iii) long-standing restrictive disease (n = 10) and (iv) proven auto-immune hyperthyroidism without any signs of TAO (n = 6). Horizontal and vertical saccades with amplitudes of 10°, 20°, 30°and 40°were recorded binocularly using the induction scleral search coil technique. The two main sequence constants V max and C were calculated for each eye. Repeated measurement analysis of variance was carried out to test for differences between different gaze directions, eyes and groups. Results: In horizontal saccades, significant differences were found between groups but not between abduction and adduction. In vertical saccades, differences between groups and the interaction between groups and up-and down-gaze saccades were significant. Compared with the control group, analysis of the main sequence curves revealed larger differences in patients of group 3 and 4 than in those of group 1 and 2. Whereas in the control group down-gaze saccades were faster than up-gaze saccades, the opposite behaviour was found in all patient groups. The largest differences were detected among those patients who had no signs of TAO (group 4). Conclusions: In this study, significant saccade differences were detected in all patients with TAO. In contrast to our earlier studies where evaluation of multiple individual saccade parameters did not reveal significant differences, analysis of the main sequence constants and mathematical reconstruction of the main sequence curves turned out to be a sensitive technique for reliable detection of subtle ocular motility changes. Significant differences were detected even in patients with auto-immune thyroiditis where no clinical signs of TAO were apparent.

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Measuring disease activity to predict therapeutic outcome in Graves’ ophthalmopathy

Cited by 69 publications

References 32 publications

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

THERAPY OF ENDOCRINE DISEASE: Endocrine dilemma: management of Graves’ orbitopathy

MANAGEMENT OF ENDOCRINE DISEASE: Rituximab therapy for Graves’ orbitopathy – lessons from randomized control trials

Changes of saccadic eye movements in thyroid‐associated ophthalmopathy

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