Forty-four eyes of 23 patients with non-infectious uveitis, 13 (56.5%) women and 10 (43.5%) men, were included in the study. One eye of one patient was excluded from the study because of neovascular glaucoma and another patient because of phthisis bulbi.Behçet uveitis was diagnosedin 14 (60.9%) patients, sarcoidosis in two (8.7%), and idiopathic uveitis in seven (30.4%) patients. All patients were classified anatomically based on International Uveitis Study Group criteria. Panuveitis was present in 10 (43.5%) cases, posterior uveitis in four (17.4%), intermediate uveitis in five (21.7%), and posterior and uveitis in four (17.4%). The mean duration of uveitis was 5.26 ± 5.16 years. Etiologies and locationsof uveitis, and drug therapies prior to adalimumab are shown in Table 1.
Table 1
Distribution of diagnoses, involvements, durations of disease, and medications used
Patient/Gender/Age
|
Diagnosis
|
Site of involvement
|
Duration of disease
|
Medications used
|
1/M/51
|
BEHÇET
|
PANUVEITIS
|
20 YEARS
|
Prednol, azathioprine, interferon
|
2/M/26
|
BEHÇET
|
PANUVEITIS
|
2 YEARS
|
Prednol, azathioprine, interferon
|
3/F/34
|
BEHÇET
|
POSTERIOR
|
2 YEARS
|
Prednol, azathioprine, interferon
|
4/M/45
|
BEHÇET
|
POSTERIOR
|
2 YEARS
|
Prednol, azathioprine, cyclosporine, interferon
|
5/M/46
|
BEHÇET
|
PANUVEITIS
|
5 YEARS
|
Prednol, cyclosporine, infliximab
|
6/M/39
|
BEHÇET
|
PANUVEITIS
|
1 YEAR
|
Prednol, azathioprine, interferon
|
7/M/42
|
BEHÇET
|
POSTERIOR
|
16 YEARS
|
Prednol, azathioprine, interferon
|
8/F/19
|
BEHÇET
|
POSTERIOR + INTERMEDIATE
|
2 YEARS
|
Prednol, methotrexate, infliximab
|
9/F/62
|
IDIOPATHIC
|
POSTERIOR + INTERMEDIATE
|
2 YEARS
|
Prednol, azathioprine
|
10/F/48
|
IDIOPATHIC
|
PANUVEITIS
|
2 YEARS
|
Prednol, azathioprine
|
11/M/70
|
IDIOPATHIC
|
INTERMEDIATE
|
11 YEARS
|
Prednol, azathioprine
|
12/F/36
|
SARCOIDOSIS
|
INTERMEDIATE
|
6 YEARS
|
Prednol, azathioprine
|
13/M/28
|
BEHÇET
|
PANUVEITIS
|
2 YEARS
|
Prednol, azathioprine, interferon
|
14/57/M
|
IDIOPATHIC
|
INTERMEDIATE
|
2 YEARS
|
Prednol, azathioprine
|
15/F/20
|
BEHÇET
|
PANUVEITIS
|
2 YEARS
|
Prednol, azathioprine, interferon
|
16/F/23
|
BEHÇET
|
POSTERIOR
|
2 YEARS
|
Prednol, azathioprine
|
17/F/44
|
BEHÇET
|
PANUVEITIS
|
17 YEARS
|
Prednol, azathioprine, cyclosporine
|
18/F/23
|
IDIOPATHIC
|
INTERMEDIATE
|
4 YEARS
|
Prednol, methotrexate
|
19/M/47
|
IDIOPATHIC
|
INTERMEDIATE
|
4 YEARS
|
Prednol, azathioprine
|
20/F/28
|
BEHÇET
|
PANUVEITIS
|
3 YEARS
|
Prednol, azathioprine, sulfasalazine
|
21/F/49
|
SARCOIDOSIS
|
INTERMEDIATE
|
1 YEAR
|
Prednol, azathioprine
|
22/M/38
|
BEHÇET
|
PANUVEITIS
|
8 YEARS
|
Prednol, azathioprine, cyclosporine, interferon
|
23/F/56
|
IDIOPATHIC
|
PANUVEITIS
|
8 YEARS
|
Prednol, azathioprine
|
M: Male F: Female |
All patients had bilateral involvement. Active inflammation was observed in 19 (43.18%) eyes, while 25 (56.8%) eyes were clinically inactive. Active inflammation was present in both eyes in seven patients, and in one eye of five patients, while 11 patients were clinically inactive. The mean anterior chamber cell grade was 0.72 ± 1.29 at baseline, 0.22 ± 0.41 at thirdmonth, and 0.15 ± 0.41 at sixth month (p < 0.001). Vitreous cell grade was a mean of 1.13 ± 1.46 at baseline, 0.26 ± 0.44 at thirdmonth, and 0.17 ± 0.43 at sixth month (p < 0.001). Both anterior chamber reaction and vitreous reaction compared to initial values decreased significantly (p < 0.001).
While the mean initial drug burden was 9.91 ± 3.78, it was 7.3 ± 4.25 at third month, and 8.0 ± 4.71 at sixth month after adalimumab therapy. The drug burden decreasedsignificantly compared to baseline (p = 0.022). No significant relationship was determined between drug burden and uveitis etiologies (p = 0.23). Twenty of the 23 patients were receiving oral Prednisolone prior to adalimumab therapy. The mean baseline prednisolone dose was 17.5 mg/day (4–64 mg), which decreased to 5.56 mg/day by the third month. The mean oral prednisolone dose at six months was 8.34 mg. Prednisolone doses were lowered significantly ineach consecutive visit compared to baseline (p < 0.001). Recurrence developed in only one patient receiving adalimumab therapy duringsix months and prednisolone at 1 mg/kg was again started on. With this exception, no patients developed attacks during receiving adalimumab therapy.
The mean visual acuity was 0.58 ± 0.96 logMAR at baseline, 0.47 ± 0.96 logMAR at thirdmonth, and 0.54 ± 1.05 logMAR at sixth month. There was no significant difference in visual acuity between the visits (p = 0.07). The mean central retinal thickness was 182.38 ± 43.89 µm, compared to 177.24 ± 49.37 µm at third month and 180.73 ± 50.17 µm at sixth month. There was no significant difference in retinal thickness between the visits (p > 0.05). The mean choroidal thickness was 256.65 ± 43.63 µm at baseline, 240.49 ± 36.73 µm at third month, and 224.81 ± 34.91 µm at sixth month. The changes in choroidal thickness values between the examinationswere significant (p = 0.005).
Retinal vascular leakage was observedin 16 eyes at fundus fluorescein angiography performed before adalimumab therapy (in two eyes of six patients, and in one eye of four patients). Leakages in peripheral were in 11 (68.75%) eyes and diffuse in five eyes (31.25%). Leakage was present in a mean of 2.95 ± 4.55 clock hour quadrants at baseline, in 2.41 ± 3.91 at third month, and in 1.76 ± 3.44 at sixth month. Statistically significant difference was observed in leakageextend between the visits (p < 0.001). However, the grade of leakage decreased significantly during the study (p < 0.001). The changes in leakage extentand grades are shown in Table 2.
Table 2
Changes in extents and grades of leakage before and after treatment in patients with leakage observed at fundus fluorescein angiography
|
Before adalimumab treatment
|
Third month after treatment
|
Sixth month after treatment
|
|
Clock hour quadrant right
|
Clock hour quadrant left
|
Leakage grade right
|
Leakage grade left
|
Clock hour quadrant right
|
Clock hour quadrant left
|
Leakage grade right
|
Leakage grade left
|
Clock hour quadrant right
|
Clock hour quadrant left
|
Leakage grade right
|
Leakage grade left
|
1
|
0
|
12
|
0
|
Grade2
|
0
|
10h
|
0
|
Grade1
|
0
|
6h
|
0
|
Grade1
|
2
|
8
|
6
|
Grade2
|
Grade1
|
8h
|
3h
|
Grade2
|
Grade1
|
8h
|
3h
|
Grade1
|
Grade1
|
3
|
5
|
5
|
Grade 1
|
Grade1
|
2h
|
5h
|
Grade1
|
Grade1
|
0
|
0
|
0
|
0
|
4
|
3
|
5
|
Grade2
|
Grade2
|
4h
|
5h
|
Grade2
|
Grade2
|
4h
|
3h
|
Grade2
|
Grade2
|
5
|
12
|
4
|
Grade2
|
Grade1
|
12h
|
2h
|
Grade1
|
Grade1
|
0
|
0
|
0
|
0
|
6
|
12
|
12
|
Grade3
|
Grade3
|
12h
|
12h
|
Grade2
|
Grade3
|
12h
|
12h
|
Grade2
|
Grade3
|
7
|
8
|
0
|
Grade2
|
0
|
8h
|
0
|
Grade1
|
0
|
4h
|
0
|
Grade1
|
0
|
8
|
12
|
8
|
Grade3
|
Grade2
|
6h
|
4h
|
Grade1
|
Grade1
|
9h
|
3h
|
Grade2
|
Grade1
|
9
|
12
|
0
|
Grade3
|
0
|
8h
|
0
|
Grade1
|
0
|
7h
|
0
|
Grade 2
|
0
|
10
|
0
|
12
|
0
|
Grade2
|
0
|
10h
|
0
|
Grade1
|
0
|
10h
|
0
|
Grade1
|
Statistically significant correlation was observed between extent and grade of leakage at baseline (r = 0.98, p < 0.001). The choroidal thickness exhibited significant correlation with extent and grade of leakage (r = 0.31, p = 0.04, and r = 0.37, p = 0.016, respectively). At the beginning of treatment, optic disk staining was observed in eight eyes, compared to four eyes at thirdmonth and five eyes at the sixth month. No significant difference was determined in terms of optic disc staining between the visits (Chi square, p = 0.074). However, significant correlation was observed between optic disc staining and extent and grade of leakage (r = 0.73, p < 0.001, and r = 0.68, p < 0.001, respectively). Significant correlation was also determined at the third month of treatment between extent of leakage and optic disc staining, and between extent of leakage and leakage grade (r = 0.537, p < 0.001, and r = 0.952, p < 0.001, respectively).
No statistically significant correlation was observed at the third month of treatment between choroidal thickness and extent or grade of leakage (r = 0.18, p = 0.24 and r = 0.23, p = 0.14, respectively). Significant correlation was observed between extent of leakage and optic discstaining atthe sixth month of treatment (r = 0.661, p < 0.001). Similarly, significant correlation was observed between extent and grade of leakage at the sixth month of treatment (r = 0.984, p < 0.001). No significant correlation was observed at the sixth month of treatment between choroidal thickness and extent or grade of leakage (r = 0.21, p = 0.19 and r = 0.24, p = 0.12, respectively). Macular leakage was observed at fluorescein angiography in five eyes (one eye in three patients and two eyes in one patient). No edema at OCT was observed in noneof these patients. Macular leakage resolved entirely at angiography in two eyes with adalimumab therapy, while decreasing from grade 2 to grade 1 in the other three eyes.
Adalimumab therapy was well-tolerated by patients, although local side-effects such as pain in the injection site, rash and itching were frequently seen. Pulmonary thromboembolism was observed in one patient. We think that this embolism is secondary to the vasculitis seen in Behçet's disease. These were regarded as the mild risk group and were started on anticoagulant therapy, while adalimumab therapy was maintained.
Figure 1. A, B, C image from a patient with grade 3, 12 clock hour quadrant peripheral leakage and optic disk staining in the right eye. D, At the third month of adalimumab therapy, the leakage decreased to grade 1, the extent of leakage improved to six quadrants, and the optic disk staining also decreased
Figure 2. A, B. Images from a patient with initial optic disk staining and grade 2, 12 clock hour quadrant ,peripheral leakage in the left eye, improving to grade 1 and 10 clock hour quadrants at the third month of treatment (C, D), and to grade 1 and six clock hour quadrant at the six month (E, F).