IOI is considered to be the third most common orbit condition in adults [17, 18]. IOI may present in an acute, subacute, or chronic fashion. IOI often presents with different degrees eyelid swelling, orbital pain, restricted ocular motility, diplopia, visual loss, and minimal proptosis. Corticosteroids and immunomodulatory therapies are currently the main treatments for IOI. Systemic corticosteroids may be effective as the monotherapy in at least 40% of patients, and the combination therapy with other immunosuppressants can improve the effectiveness in approximately 60% of patients [2]. In our study, all patient received repeated systemic corticosteroids and other immunomodulatory therapies. However, these patients recurred repeatedly within 1 to 3 moths after drug withdrawal, and were lack of response to corticosteroids. In addition, two patients received radiotherapy, but the orbital pain was slightly improved, and the restrictive ocular motility and diplopia were not improved. Therefore, it was necessary and urgent to find other treatments for these patients.
Recently studies showed that cytokines play an important role in the pathogenesis of ocular inflammation, and the imbalance of inflammatory cytokines has also been documented in IOI [19]. The rationale for the use of TCZ in IOI is the depletion of interleukin 6 (IL-6), which is a proinflammatory cytokine produced by a variety of cells, such as T and B cells, lymphocytes, monocytes, and fibroblasts. TCZ is a humanized monoclonal antibody against the IL-6 receptor that has been widely used in both immune system dysregulation [20, 21], and a variety of ocular inflammatory diseases [22, 23], but rarely in IOI. June AA. and Tapias Elias reported the case of a 59-year-old woman who was diagnosed with a unilateral sclerosing IOI for 9 years. The patient showed poor response with previous oral steroids, peribulbar steroid injections, radiotherapy, immunosuppressants, and intravenous rituximab. After the initiation of intravenous TCZ, complete reductions in the pain and orbital inflammation signs were observed, and the patient’s condition remained stable in the following 6 years under a monthly dose of 4 mg/kg TCZ [15].
There was no clinical practice guidelines for the medical management of idiopathic orbital inflammation, therefore the TCZ was not part of the standard treatment to patients with glucocorticoid-refractory IOI. In this study, sixteen patients with corticosteroids-resistant IOI disease were received treatment with TCZ, and the results showed that TCZ treatment was effective and safe. The meaning finding was that the oppressive orbital pain, eyelid swelling and ptosis were significant improved after fist dose of TCZ and completely reduced after treatment with TCZ.
Orbital myositis is regarded as a subtype of IOI, which often affects young adults in the third to fourth decade of life, and involves single or multiple EOMs [24]. Ocular motility varies between patients and over the course of the disease. It was reported that medial rectu muscle was most involved in orbital myositis [25]. In our study, the medial rectu muscle was involved in 6 myositis patients. These results are similar to those previously reported by other researchers [3, 16]. The CT/MRI showed that the enlargement of EOMs in all patients were close to normal condition after last follow up. The diplopia had completely resolved in 8 patients after the treatment of with TCZ. In particular, the tenth patient (case 10) who had three EOMs involved completely returned to normal ocular motility after TCZ therapy.
Some studies reported that radiotherapy has shown a modest efficacy rate of 70% in treatment of IOI, but it can induce muscle fibrosis [26]. The biopsy of the avascular area indicated a replacement of the normal muscle tissue by dense fibrous tissue and restricted ocular motility due to EOM fibrosis in IOI patients after external beam radiotherapy [27]. In our study, because of adhesion and fibrosis of extraocular muscles caused by biopsy and external beam radiotherapy of EOMs, enlargement of EOMs had significantly reduced, but had diplopia in four patients with TCZ treatment. Therefore, we might assume that patients with recurrent and corticosteroids-resistant IOI disease should choose TCZ treatment to avoid EOM fibrosis caused by radiotherapy.
Dosing of TCZ and treatment cycles for IOI has not been established. Prior studies of TAO patients have been treated with 8mg/kg IV of TCZ every 4 weeks [28, 29]. Therefore, in this study, most patients were treated with 8mg/kg monthly for 4 times, except for one patient with 2 cycles and withdrawn due to low disease activity, two patients with 6 cycles due to EOM fibrosis after radiotherapy. To date, no recurrence was observed in all patients. No patient demonstrated adverse side effects such as neutropenia or infection, although longer follow up would be needed to fully investigate the safety of this therapy. Further study is required to determine the most efficacious dose and route for IOI patients.
In this study, due to the clear diagnosis of IOI and exclusion of similar diseases, no orbital biopsy was performed in all patients, except for two patients who had no response to corticosteroids before TCZ treatment.
The limitation of this study includes the small number of patients recruited and the relatively short follow-up time, and other types of IOI were not evaluated. In the future studies, we will be designed well clinical trials, strengthen the follow-up of patients and add additional types of IOI to confirm the effects of TCZ and to evaluate its safety profile in larger populations of IOI. More studies are needed to state clear indications, dosages, effectiveness, and side effects for this new therapeutic option.