Use of Rituximab After Orbital Decompression Surgery in Two Grave’s Ophthalmopathy Patients Progressing to Optic Neuropathy

Abstract

Background: While orbital decompression can alleviate optic nerve compression and prevent further vision loss in dysthyroid optic neuropathy (DON), it cannot relieve inflammatory symptoms. Very high doses of intravenous glucocorticoids (GCs) are the first-line therapy for DON; however, the effective rate is only 40% and might be much lower in patients who fail high-dose GC pulse therapy and progressed to DON. The results of two case series studies indicated that rituximab treatment had a much better curative effect compared to very high doses of intravenous GCs, but some patients required urgent orbital decompression after rituximab injection because rituximab might lead to the release of cytokines, aggravated intraorbital edema, and further vision loss. Methods: We retrospectively studied the therapeutic process of two Grave's ophthalmopathy (GO) patients complicated with DON who failed high-dose GC pulse therapy and underwent orbital decompression. Both patients received single-dose (500 mg) rituximab treatment. Results: During more than 2 years of follow-up, rituximab treatment exhibited significant improvement in inflammatory symptoms, as manifested by a substantial decrease in Clinical Activity Score (CAS); meanwhile, the vision of both patients improved significantly and their diplopia was relieved. Conclusions: The results of this study were consistent with those of two previous case series studies indicating the significant and lasting effect of rituximab treatment on DON, especially for patients with GC resistance or recurrence after GC therapy. Orbital decompression before rituximab treatment might reduce the incidence of rapid vision loss and urgent orbital decompression surgery caused by aggravated orbital edema after rituximab injection; however, the necessity for preventive decompression surgery requires further study.

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

“…1 shows that 76 articles of the 954 screened records were included in the review. 25–101 The literature on the use of Mabs for treating GO has been centered on blockage of IL-6 (Tocilizumab), 34,39,41,49,50,53,56,58–60,63,64,68–72,79,80,84,87,90,96–98 anti-CD20 lymphocytes (Rituximab), 26–33,35,37,38,40,42–48,51,54,55,61,62,65,67,73,89 and IGF1R (Teprotumumab). 52,66,74–78,82,85,86,88,91,92,94,95,99–101 Three articles have described Mabs that block TNF-α, 25,36,83 and one article has described Mabs that block the B-lymphocyte stimulator (BLyS) protein (Belimumab).…”

“…34,39,41,49,58,59,63,68,69,71,72,79,80,84 The same trend is true for Rituximab (64.3% articles from Europe). 26,27,30,33,35,37,[42][43][44][46][47][48]54,55,61,62,65,67,73,89 In contrast, Teprotumab has only been tested in the USA. [74][75][76][77][78]82,85,86,88,91,92,94,95,99,100,102 Most articles on the three most tested Mabs consist of case reports and case series (Tables 2-4).…”

“…In several case reports and case series, there was no collateral effects 31,32,38,39,45,46,48,51,53,60,64,87,88 or they were not stated. 27,40,50,56,[69][70][71]73,76,78,86,90,95,100,102 Some collateral effects depended on the drug that was being used (Table 6). For instance, hyperlipidemia and neutropenia were common with Tocilizumab, 80,84,97 and infusion-related reactions (rash, cytokines release syndrome, bronchospasm, and erythroderma) and hypotension were the main concern with Rituximab.…”

“…34,39,41,49,58,59,63,68,69,71,72,79,80,84 The same trend is true for Rituximab (64.3% articles from Europe). 26,27,30,33,35,37,42–44,46–48,54,55,61,62,65,67,73,89 In contrast, Teprotumab has only been tested in the USA. 74–78,82,85,86,88,91,92,94,95,99,100,102…”

Diagnosis and Management of Dysthyroid Optic Neuropathy

“…Moreover, DON developed in 2 of 13 patients who underwent rituximab treatment, 56 which may be caused by an excess release of cytokines by this drug. 48 Although previous review and case reports showed favorable results of rituximab treatment for DON, 54,57,58 EUGOGO guidelines recommend avoidance of its use in patients with a risk of developing DON. 1 Teprotumumab is a human monoclonal antibody inhibitor of insulingrowth factor-1 receptor.…”