A review of the medical literature did not reveal any reports about the local used of medication in the treatment of OMG. Whether uveitis is caused by systemic disease or thyroid-related ophthalmopathy, local inflammation is a contributing factor. Local inflammation may respond to anti-inflammatory medication. Notably, myasthenia is not the direct result of inflammation but, rather, an antibody-mediated weakness. The symptoms associated with myasthenia are caused by antibody production that is not necessarily localized, so local injections of corticosteroid are not expected to reduce the production of circulating antibodies to the acetylcholine receptor. This may be the main reason why few studies published to date have investigated the administration of local treatment for MG. However, Agius maintain that OMG may be associated with ocular muscle antigen structure and/or reduced susceptibility to risk factors[16]. Soltys et al.[17] reported that, in autoimmune MG, the neuromuscular junctions in extraocular muscles are more susceptible to complement-mediated injury than are those of other muscles. Local factors thus appear to be a major cause of OMG. Although numerous issues remain to be elucidated, the local injection of dexamethasone appears to be an effective treatment option. The local use of dexamethasone is simple, convenient, and almost risk free.
More importantly, local injections of dexamethasone have achieved good outcomes in clinical practice. In our prospective small-scale case study, which included 14 cases, 11 cases achieved drug-independent remission; 1 case achieved drug-dependent remission, 1 case improved; 1 case failed to improve. The overall cure rate was 85.7%. Although the mechanism of local hormone therapy for OMG remain unclear, the clinical effect cannot be denied.
Among numerous studies have investigated oral drug therapy for OMG, few have examined strabismus, ptosis, or quantified measurements of the range of eye movement as outcomes [6, 18, 19]. Kupersmith et al.[18]reported on the use of prednisone and pyridostigmine for the treatment of patients with OMG. One month later after treatment, the degree of strabismus had not changed significantly in the pyridostigmine group and had decreased from 12.2 PD to 5.5 PD in the prednisone group. Among 51 patients who responded to prednisone treatment, 26 experienced symptom recurrence as the dose of prednisone was decreased. At 2 years of follow-up, only 12 of 55 patients in the prednisone group reported that symptoms were completely relieved. No patient in the pyridostigmine group was completely relieved. Park et al.[19] followed 20 patients with MG who had obvious paralytic strabismus as the initial symptom for 45.4 ± 39.7 months. After systemic drug therapy (hormone and cholinesterase inhibitor), only 6 patients (21.4 ± 11.1) had responded well to treatment and reported the disappearance of diplopia. Four patients (14.3%) had partial reactions, and 18 cases (64.3%) had slight or no response to treatment; 10 cases (35.7%) continued to suffer from strabismus of > 15 PD. Six cases underwent strabismus surgery. Vanikieti et al. [6]performed a retrospective study of the effect of oral prednisone and/or pyridostigmine for OMG in children. Only 13 (21.67%) of 60 children with blepharoptosis achieved drug-independent remission, and only 3 (7.9%) of 38 patients with ophthalmoplegia achieved drug-independent remission. About 50% of patients responded slightly or not at all to oral medication. We summary of the results of this study and previous reports of oral hormonal therapy for OMG in table3.In contrast to those previous reports on the use of oral drugs, our study show that local injection of dexamethasone has better treatment result for OMG.
In our study, we preferred directly inject the drug into the affected extraocular muscles, typically the medial rectus, and investigated the duration of remission for various symptoms. We believe that this approach may help to identify the optimal therapeutic approach with which to accelerate recovery from extraocular paralysis. Among the patients who ultimately recovered from ptosis, the time to recovery time was ≤ 1 week. The average time to recovery from diplopia was 1.75 ± 0.62 weeks; the average time to recovery of ocular duction was 4.55 ±2.44 weeks. The recovery of extraocular paralysis is still the most difficult, which may take several months. We found that the recovery of extraocular paralysis is the most difficult, which may take several months,and the recovery time is related to the degree of muscle paralysis. The recovery time is related to the degree of muscle paralysis. Compared with systemic steroids, local dexamethasone injections have a faster onset in OMG patients. Oral steroid-induced clinical improvement usually begins within 2 to 4 weeks, with marked improvement requiring 6–8 weeks[20].
Notably, although the direct injection of extraocular muscles was chosen, the sequence of symptom recovery observed in patients of our study was similar to that observed in patients who received oral drug therapy[6, 18, 19, 21].we also noted the neck muscle farthest from the injection point recovered fastest. We sought to identify the reason for this phenomenon. Nan et al.[6, 18, 19, 21] reported that a single sub-Tenon injection of triamcinolone acetonide (TA) was able to diffuse throughout the globe, including the aqueous, iris-ciliary body, vitreous, neuroretina, retinal pigment epithelium, and choroid, with therapeutic concentrations maintained for at least 30 days. Roesel et al.[23] observed similar results for the use of periocular corticosteroid injections, administered via the sub-Tenon route or as an orbital floor injection, for the treatment of uveitis. Based on the above research, we speculate that periocular corticosteroid injections could easily diffuse into adjacent muscle tissues and thus reach therapeutic concentrations. Recent studies have reported that high-dose intravenous methylprednisolone therapy in patients with OMG[24] or mild GMG[25] achieves faster improvement with better efficacy than oral prednisone. Dexamethasone injection into the periocular or extraocular muscles can also reach other parts of the body through circulating blood. This capacity for diffusion may explain the rapid relief of neck-related symptoms observed in this study. Sub-Tenon injections may achieve the same treatment effects as extraocular muscle injections while reducing risk for muscle hemorrhage and local injury.
Although most of the patients had good results, we noticed that two elderly patients with severe blepharoptosis had poor results (Patients 7 and 13). In addition to the fact that some patients are not sensitive to hormones, we also note that the results of systemic oral medication therapy show that the treatment of OMG in children seems to be better than that in older people[6]. Whether the same problem exists in local therapy remains to be seen further.
For OMG that is treated with systemic medication, continued corticosteroid therapy is typically necessary to prevent recurrence and conversion to GMG. Considering the side effects of hormones, we did not administer continuous injection therapy to patients whose symptoms had resolved. In this study, 10 of 14 patients (71.3%) remained stable during the follow-up period after the treatment was stopped. Some studies suggest that patients who receive immune interval therapy during the early stage of OMG are less likely to develop systemic disease.[18, 26-29] Agius[16] reported that GMG may be due to increased antibody production and the expansion of antigenic molecular targets. The duration of the initial phase of immune attack on the neuromuscular junction may be an important determinant of disease severity. We speculate that the effectiveness of topical corticosteroids in alleviating OMG symptoms may reduce the possibility of recurrence and aggravation. The dramatic results of this study may also reflect a statistical error caused by the short observation time and the small number of cases. In conclusion, the long-term effects of local hormone therapy on OMG require further study.
This study had some limitations. Firstly, the mechanism of local hormone injection in the treatment of OMG is not clear. Secondly, there is no clinical comparison with systemic drugs. In addition, the number of cases included in this study is small. As a systemic immune disease, MG commonly persist over time, despite temporary remission. Therefore, further studies will be necessary to determine the optimal site to be used for injection, the optimal time interval between injections and the optimal course of treatment. The stability of the curative effect achieved, the recurrence rate, and the rate of conversion will need to investigated on a larger scale and for a longer period of time.