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DOI: 10.3341/kjo.2011.25.1.1
Original Article
Purpose: To compare the clinical manifestations between patients with ocular myasthenia gravis and those with
generalized myasthenia gravis (MG).
Methods: The medical records of 71 patients diagnosed with MG between January 1995 and December 2007 were
reviewed. Demographics, sensitivities of diagnostic methods, the presence of systemic autoimmune diseases,
ophthalmic complications caused by MG, and treatments were evaluated and compared.
Results: Fourteen patients (20%) were diagnosed with ocular MG and 57 patients (80%) with generalized MG.
Sensitivities of anti-acetylcholine receptor antibody and repetitive nerve stimulation tests were significantly higher
in the generalized MG group (84%, 89%) compared to those in the ocular MG group (50%, 54%) (p = 0.011, p =
0.008). The sensitivity of the neostigmine test was the highest in both groups (98% of generalized MG, 79% of ocular MG), and the difference between the two groups was borderline significant (p = 0.058). The most common
symptoms were ptosis and diplopia, and both groups presented with pain, blurred vision, and tearing. Systemic
autoimmune disease was more prominent in the generalized MG group (21%) than in the ocular MG group (14%),
and steroid therapy was used more frequently in the generalized MG group (82%) than in the ocular MG group
(57%). Ophthalmic complications associated with long-term steroid treatment were more profound in the generalized MG (30%) compared to those of the ocular MG (21%).
Conclusions: The generalized MG group was associated with higher sensitivities to diagnostic tests, more systemic
steroid use, higher ophthalmic complications caused by systemic autoimmune disease, and long-term steroid
treatment compared to those of the ocular MG group.
Key Words: Clinical features, Myasthenia gravis, Ophthalmic complications, Sensitivity and specificity, Systemic
autoimmune disease
Myasthenia gravis (MG) is an autoimmune disease characterized by muscular fatigue due to defective neuromuscular
transmission, with the levator palpebralis and extraocular
muscles preferentially affected [1]. More than three-quarters
of MG patients present with visual complaints such as droopy eyelids or double vision, and about half of patients who
present with ocular manifestations develop generalized
weakness within six months. Approximately 80% of MG patients will generalize within two years and approximately
90% within three years [2-5]. The first and sometimes only
Received: January 29, 2010 Accepted: August 31, 2010
Corresponding Author: Jin Sook Yoon, MD. Department of Ophthalmology,
Yonsei University College of Medicine, #134 Sinchon-dong, Seodaemun-gu,
Seoul 120-752, Korea. Tel: 82-2-2228-3586, Fax: 82-2-312-0541, E-mail:
yoonjs@yuhs.ac
manifestations of MG are ocular including fluctuating diplopia and/or ptosis worsened by exertion. Several retrospective studies have suggested that early treatment with oral
prednisolone can delay the onset and possibly decrease the
frequency of progression from ocular MG to generalized
MG. High-dose oral prednisolone over a period of two to
three months is generally required to induce remission
[6-12].
MG patients are more likely to develop other immune-related disorders including type I diabetes mellitus, Graves disease, Hashimoto disease, systemic lupus erythematosus,
rheumatoid arthritis, Sjogren syndrome or multiple sclerosis
[11,12]. These autoimmune diseases may be associated with
ophthalmic symptoms including blurry vision, tearing, pain,
photophobia, foreign body sensation, and ophthalmic signs
including reduced visual acuity, decreased tear film, inflammatory soft tissue, exophthalmos, and lid retraction that
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n = 43
Results
Gender (male)
Age (yr)
Age at onset of symptom (yr)
Thymectomy
Abnormal AchR antibody
Abnormal RNST
Patients
Total MG
28 (38)
48.5 16.1
41.2 16.9
40 (56)
55/71 (78)
63/67 (94)
56/68 (82)
71
MG patients
Ocular MG
Generalized MG
7 (50)
21 (37)
50.4 20.6
48.1 14.9
41.4 25.1
41.1 14.6
3 (21)
37 (65)
7/14 (50)
48/57 (84)
11/14 (79)
52/53 (98)
7/13 (54)
49/55 (89)
14
57
p-value
0.367*
0.430
0.490
0.003*
0.011
0.058
0.008
Symptom
Pain
Blurred vision
Tearing
Ptosis
Diplopia
Sign
*
Dry eye
Exposure keratitis
Lid retraction
Eyelid swelling or erythema
Cataract
Open angle glaucoma
Central serous chorioretinopathy
Total
MG patients
Generalized MG
Total MG
Ocular MG
p-value
29 (41)
17 (24)
23 (32)
62 (87)
66 (93)
6 (43)
4 (28)
5 (36)
13 (93)
13 (93)
23 (40)
13 (23)
18 (32)
49 (86)
53 (93)
0.864
0.730
0.759
0.677
1.000
19 (27)
1 (1)
2 (3)
3 (4)
12 (17)
5 (7)
3 (4)
71
3 (21)
0
0
1 (7)
1 (7)
1 (7)
1 (7)
14
16 (28)
1 (2)
2 (4)
2 (4)
11 (19)
4 (7)
2 (4)
57
0.745
NA
NA
0.488
0.437
1.000
0.488
1.56:1. The mean age at disease onset was 41.8 years (SD,
16.9 years; range, 3 to 71 years), and initial symptoms developed before the age of 50 in 65% (46/71) of MG patients.
Using the modified Osserman score, patients were classified as I (20%), IIa (16%), IIb (39%), III (21%), and IV (4%).
Fourteen patients presented with ocular MG and 57 patients
with generalized MG. In patients with generalized MG, the
mean time interval from the onset of ocular MG to generalization was 3.5 years. Table 1 presents the comparative demographic and clinical characteristics. Age, gender, and age of
disease onset were not significantly different between the ocular MG and generalized MG groups. Thymoma was radiologically diagnosed and surgically resected in 40 patients
(56%, 27 women and 13 men), with 22 cases of histologically confirmed thymoma postoperatively (ocular MG, 3 patients; generalized MG, 19 patients). Thymectomy was performed significantly more in the generalized MG group
(65%) than in the ocular MG group (21%) (p = 0.003, Fishers
exact test). The remaining 18 patients with generalized MG
had hyperplastic thymus (n = 14) or normal histology (n = 4).
Fig. 1 presents the distribution for age of disease onset according to gender. The criteria in Fig. 1 are based on the report by Beekman et al. [14]. Mean age of disease onset was
40.1 years (SD, 13.6 years; range, 3 to 67 years) in male MG
patients and 42.8 years (SD, 13.9 years; range, 3 to 69 years)
in female MG patients. The ages of disease onset were not
significantly different between female and male MG groups
(p = 0.693, Wilcoxon rank sum test).
The anti-acetylcholine receptor antibody test was performed in 71 patients, repetitive nerve stimulation test in 68
patients and neostigmine test in 67 patients (Table 1). The
sensitivities of the anti-acetylcholine receptor antibody and
Symptom
Rheumatoid arthritis
Systemic lupus erythematosus
Hyperthyroidism
Hypothyroidism
Multiple sclerosis
Behcets disease
Sjogrens syndrome
Total
Discussion
This is the first study comparing the ophthalmic manifestations and complications associated with MG, systemic autoimmune disease and long-term steroid treatment. As MG is
a rare disease, it is often difficult to analyze a large patient
population. We evaluated 71 patients that were followed for
at least one year and analyzed and compared the demo-
Acetylcholinesterase inhibitors
Prednisone
Steroid pulse therapy
Combined with non-steroidal immunosuppressant
Plasmapheresis
No treatment
Patients
Values are presented as number (%).
NA = not available.
*
According to Fishers exact test.
Total MG
16 (20)
55 (77)
23 (31)
24 (34)
2 (3)
0 (0)
71
MG patients
Ocular MG
Generalized MG
6 (44)
10 (20)
8 (57)
47 (82)
3 (21)
20 (35)
2 (14)
22 (39)
2 (4)
14
57
p-value
0.070*
0.070*
0.525*
0.118*
NA
-
immune diseases and steroid treatment. As a result, MG patients with ophthalmic signs and symptoms may not receive
immediate proper ophthalmic management. We evaluated
ophthalmic complications in addition to ptosis and diplopia
in relation to the presence of autoimmune diseases and long
term steroid treatment. It is important that patients with ocular MG or generalized MG with ophthalmic symptoms
should undergo regular eye examinations. In cases of MG,
the neurologist should recommend an eye specialist who is
well aware of the ophthalmic complications of the disease
and its prognosis. Most importantly, careful attention must be
given to generalized MG patients because they have a higher
risk of ophthalmic and other problems associated with systemic autoimmune disease and long-term treatment of MG
than do ocular MG patients.
Selection bias, which is commonly found in retrospective
studies, was a potential problem in the current study as our
analysis was limited to information available from medical
records. It was impossible to quantitatively compare the
treatment efficacies of anticholinesterase inhibitors and steroids or to objectively evaluate the severity of ptosis and diplopia due to fluctuations in disease status and treatment
response.
In conclusion, MG patients may experience less common
eye problems including dry eye symptoms, pain, blurry vision, and tearing in addition to more well-known symptoms
such as ptosis and diplopia. These less common eye problems can impair quality of life and should not be neglected.
In addition, common autoimmune diseases such as thyroid
associated ophthalmopathy, Sjogrens disease, multiple sclerosis and Behcets disease may develop in MG patients, further supporting ophthalmic complications. In generalized
MG, the incidence of autoimmune disease is higher and more
variable than that in ocular MG patients; therefore, generalized MG patients should be screened for ophthalmic complications on a regular basis. In MG patients with long-term steroid use, glaucoma may develop due to optic nerve damage
and can lead to irreversible visual field defects. Since loss of
vision is often only recognized when the disease is advanced,
early detection of glaucoma is very important in a background of MG. Long term steroid treatment in MG patients
may also cause complications of posterior polar cataract and
central serous chorioretinopathy, effects which must be taken
into careful consideration.
Conflict of Interest
No potential conflict of interest relevant to this article was
reported.
References
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2. Grob D, Arsura EL, Brunner NG, Namba T. The course of