Significance of Acetylcholine Receptor Antibody Titers in Acetylcholine Receptor Antibody-Positive Ocular Myasthenia Gravis: Generalization and Presence of Thyroid Autoimmune Antibodies and Thymoma

Figures & data

Table 1 Detailed Demographic Data, Clinical Characteristics, Serology Tests, Presence of Thymoma, Treatment, and Conversion to GMG of the Study Subjects

Variables	Values
Number of subjects	118
Age at onset, mean ± SD, years	56.1 ± 16.9
Sex, n of subjects (%)
Female	73 (61.86)
Male	45 (38.14)
Underlying diseases, n of subjects (%)
Hypertension	39 (33.05)
Diabetes mellitus	23 (19.49)
Others	6 (5.08)
Initial ocular signs, n of subjects (%)
Moderate-to-severe ptosis	90 (76.27)
Lid fatigability	74 (62.71)
Cogan lid twitch	50 (42.37)
Orbicularis oculi weakness	70 (59.32)
Duction limitation	38 (32.20)
Positive ice-pack test, n of subjects/n of subjects with available data (%)	64/105 (60.95)
AChR antibody titers, median (range), nmol/L	3.33 (0.46–141.09)
Thyroid serology tests, n of subjects/n of subjects with available data (%)
Abnormal thyroid function tests	6/115 (5.22)
Presence of thyroid autoimmune antibodies	26/79 (32.91)
Presence of thymoma, n of subjects/n of subjects with available data (%)	9/106 (8.49)
Treatment, n of subjects (%)
Pyridostigmine alone	69 (58.47)
Immunosuppressive treatment	49 (41.53)
Conversion to GMG, n of subjects (%)	19 (16.10)
Time to conversion, median (range), months	30 (3–96)
Follow-up period, median (range), months	14.5 (3–113)

Abbreviations: GMG, generalized myasthenia gravis; SD, standard deviation; n, number; AChR, acetylcholine receptor.

Table 2 Factors Associated with Conversion to GMG

Variables	Pure OMG	GMG Conversion	Univariate Analysis		Multivariate Analysis
			OR (95% CI)	p-value	OR (95% CI)	p-value
n of subjects (%)	99 (83.90)	19 (16.10)
AChR antibody titer, n of subjects (%)
≥ 8.11 nmol/L	30 (30.30)	13 (68.42)	4.36 (1.47, 12.91)	0.008*	3.66 (1.19, 11.26)	0.023*
< 8.11 nmol/L	69 (69.70)	6 (31.58)	1
Demographic data
Age at onset, mean (SD), years	55.7 (16.6)	57.7 (18.8)	1.01 (0.98, 1.04)	0.636
Sex, female, n of subjects (%)	60 (60.61)	13 (68.42)	1.41 (0.49, 4.02)	0.522
Hypertension, n of subjects (%)	30 (30.30)	9 (47.37)	2.07 (0.76, 5.61)	0.153
Diabetes mellitus, n of subjects (%)	18 (18.18)	5 (26.32)	1.61 (0.51, 5.03)	0.415
Initial ocular signs, n of subjects (%)
Moderate-to-severe ptosis	72 (72.73)	18 (94.74)	6.75 (0.86, 53.05)	0.069
Lid fatigability	59 (59.60)	15 (78.95)	2.54 (0.79, 8.22)	0.119
Cogan lid twitch	38 (38.38)	12 (63.16)	2.75 (1.00, 7.60)	0.051
Orbicularis oculi weakness	55 (55.56)	15 (78.95)	3.00 (0.93, 9.69)	0.066
Duction limitation	31 (31.31)	7 (36.84)	1.27 (0.46, 3.56)	0.637
Positive ice-pack test, n of subjects/n of subjects with available data (%)	49/88 (55.68)	15/17 (88.24)	6.00 (1.29, 27.68)	0.022*	3.37 (0.60, 18.86)	0.167
Thyroid serology tests, n of subjects/n of subjects with available data (%)
Abnormal thyroid function tests	3/96 (3.13)	3/19 (15.79)	5.81 (1.07, 31.37)	0.041*	6.09 (1.00, 36.86)	0.051
Presence of thyroid autoimmune antibodies	22/68 (32.35)	4/11 (36.36)	1.19 (0.32, 4.51)	0.793
Presence of thymoma, n of subjects/n of subjects with available data (%)	7/87 (8.05)	2/19 (10.53)	1.34 (0.26, 7.05)	0.726
Treatment, n of subjects (%)
Pyridostigmine alone	63 (63.64)	6 (31.58)	0.26 (0.09, 0.75)	0.013*	0.40 (0.12, 1.37)	0.145
Immunosuppressive treatment	36 (36.36)	13 (68.42)	1
Follow-up period, median (range), months	14 (3–113)	30 (3–84)	1.00 (0.98, 1.02)	0.796

Note: *Statistically significant (p < 0.05).

Abbreviations: GMG, generalized myasthenia gravis; OMG, ocular myasthenia gravis; OR, odds ratio; CI, confidence interval; n, number; AChR, acetylcholine receptor; SD, standard deviation.

Table 3 Factors Associated with the Presence of Thyroid Autoimmune Antibodies

Variables	Absence of Thyroid Autoimmune Antibodies	Presence of Thyroid Autoimmune Antibodies	Univariate Analysis		Multivariate Analysis
			OR (95% CI)	p-value	OR (95% CI)	p-value
n of subjects (%)^†	53 (67.09)	26 (32.91)
AChR antibody titer, n of subjects (%)
≥ 2.81 nmol/L	23 (43.40)	19 (73.08)	3.54 (1.27, 9.85)	0.015*	6.16 (1.79, 21.22)	0.004*
< 2.81 nmol/L	30 (56.60)	7 (26.92)	1
Demographic data
Age at onset, mean (SD), years	53.5 (19.3)	61.7 (13.3)	1.03 (1.00, 1.06)	0.060
Sex, female, n of subjects (%)	29 (54.72)	17 (65.38)	1.56 (0.59, 4.13)	0.368	1.37 (0.45, 4.20)	0.583
Hypertension, n of subjects (%)	15 (28.30)	7 (26.92)	0.93 (0.33, 2.67)	0.898
Diabetes mellitus, n of subjects (%)	12 (22.64)	3 (11.54)	0.44 (0.11, 1.74)	0.246
Initial ocular signs, n of subjects (%)
Moderate-to-severe ptosis	37 (69.81)	25 (96.15)	10.81 (1.35, 86.80)	0.025*	8.75 (0.84, 71.73)	0.064
Lid fatigability	29 (54.72)	20 (76.92)	2.76 (0.96, 7.97)	0.061
Cogan lid twitch	21 (39.62)	10 (38.46)	0.95 (0.36, 2.49)	0.921
Orbicularis oculi weakness	28 (52.83)	18 (69.23)	2.01 (0.74, 5.42)	0.168
Duction limitation	18 (33.96)	6 (23.08)	0.58 (0.20, 1.71)	0.326
Positive ice-pack test, n of subjects/n of subjects with available data (%)	24/47 (51.06)	21/26 (80.77)	4.02 (1.30, 12.47)	0.016*	4.14 (0.51, 8.76)	0.080
Thyroid serology tests, n of subjects (%)
Abnormal thyroid function tests	1 (1.89)	2 (7.69)	4.33 (0.37, 50.15)	0.241
Presence of thymoma, n of subjects/n of subjects with available data (%)	4/47 (8.51)	1/26 (3.85)	0.43 (0.05, 4.06)	0.461	0.17 (0.01, 2.00)	0.160

Notes: ^†Percentages of 79 subjects with available thyroid autoimmune antibodies data. *Statistically significant (p < 0.05).

Abbreviations: OR, odds ratio; CI, confidence interval; n, number; AChR, acetylcholine receptor; SD, standard deviation.

Table 4 Factors Associated with the Presence of Thymoma

Variables	Absence of Thymoma	Presence of Thymoma	Univariate Analysis		Multivariate Analysis
			OR (95% CI)	p-value	OR (95% CI)	p-value
n of subjects (%)^†	97 (91.51)	9 (8.49)
AChR antibody titer, n of subjects (%)
≥ 15.12 nmol/L	15 (15.46)	4 (44.44)	1.44 (0.01, 2.86)	0.048*	4.97 (1.10, 22.48)	0.037*
< 15.12 nmol/L	82 (84.54)	5 (55.56)	1
Demographic data
Age at onset, mean (SD), years	55.5 (17.6)	56.2 (13.4)	1.00 (0.96, 1.04)	0.903	1.00 (0.96, 1.04)	0.867
Sex, female, n of subjects (%)	61 (62.89)	5 (55.56)	0.74 (0.19, 2.93)	0.665	0.55 (0.12, 2.44)	0.428
Hypertension, n of subjects (%)	29 (29.90)	5 (55.56)	2.93 (0.73, 11.71)	0.128
Diabetes mellitus, n of subjects (%)	19 (19.59)	2 (22.22)	1.17 (0.23, 6.10)	0.850
Initial ocular signs, n of subjects (%)
Moderate-to-severe ptosis	76 (78.35)	5 (55.56)	0.35 (0.09, 1.40)	0.137
Lid fatigability	63 (64.95)	5 (55.56)	0.67 (0.17, 2.68)	0.576
Cogan lid twitch	45 (46.39)	2 (22.22)	0.33 (0.07, 1.67)	0.180
Orbicularis oculi weakness	56 (57.73)	6 (66.67)	1.46 (0.35, 6.20)	0.605
Duction limitation	35 (36.08)	1 (11.11)	0.22 (0.03, 1.84)	0.163
Positive ice-pack test, n of subjects/n of subjects with available data (%)	53/87 (60.92)	7/8 (87.50)	4.49 (0.53, 38.13)	0.169
Thyroid serology tests
Abnormal thyroid function tests, n of subjects (%)	6 (6.19)	0 (0.00)	N/A	N/A
Presence of thyroid autoimmune antibodies, n of subjects/n of subjects with available data (%)	25/68 (36.76)	1/5 (20.00)	0.43 (0.05, 4.06)	0.461

Notes: ^†Percentages of 106 subjects with available thoracic CT data. *Statistically significant (p < 0.05).

Abbreviations: OR, odds ratio; CI, confidence interval; n, number; AChR, acetylcholine receptor; SD, standard deviation; N/A, not applicable.