Long-term effects of tocilizumab on retinal and choroidal inflammation in Birdshot uveitis

Abstract

Background: Tocilizumab (TCZ), an interleukin-6 receptor antagonist, is approved for treating rheumatic diseases and has demonstrated efficacy in managing refractory non-infectious uveitis (NIU). This retrospective study aimed to investigate the long-term effects of TCZ on inflammation in the retinal and choroidal compartments in Birdshot NIU.

Methods: Eight patients (16 eyes) received TCZ and were included in the analysis. The primary outcomes measured were inflammatory activity in the retina and choroid, assessed by fluorescein angiography (FA) and indocyanine green angiography (ICGA) using the Angiography Scoring for Uveitis Working Group at baseline, 6, 12, 24, and 36 months.

Results: The mean follow-up time with TCZ treatment was 33 months. At baseline, the median FA score was 14 (quartiles: 10.25, 15.25), which significantly decreased over time (at 36 months: 8 (5.5, 11); p = 0.004). In contrast, the ICGA score significantly increased within the first year (median at baseline: 5 (4.75, 7.25); at 6 months: 7 (6, 9.25); at 12 months: 7 (6.5, 9.25); p = 0.002), but returned to baseline levels after two years (at 24 months: 5 (5, 6.5); at 36 months: 5.5 (4, 7.5)). Central retinal thickness (CRT) improved significantly after 6 months (median at baseline: 295 µm (275, 322); at 6 months: 275 µm (251, 308); p = 0.01).

Conclusion: TCZ is effective in reducing retinal vasculitis and CRT in refractory Birdshot uveitis over time, but might be less effective in managing choroidal inflammation. Further studies are needed to determine the optimal treatment strategies for TCZ therapy in NIU.

Keywords: Angiography; Birdshot uveitis; Choroidal inflammation; Indocyanine green; Interleukin-6; Tocilizumab; Uveitis; Vasculitis.

Fig. 1

Example of a fluorescein angiography image showing the division into quadrants regarding the allocation of points in the angiography scores. The white circle illustrates the defined posterior pole [17]

Fig. 2

Fluorescein angiography score. For the complete calculation of the score, the points of the posterior pole, and of each quadrant were added together [17]

Fig. 3

Indocyanine green angiography score. For the complete calculation of the score, the points of the posterior pole, and of each quadrant were added together [17]

Fig. 4

Graphical representation of fluorescein angiography (FA) scores. Individual patient data for FA scores are depicted over a 36-month observation period. At baseline, the recorded median FA score was 14 (quartiles: 10.25, 15.25), and it significantly decreased to 10 (5.75, 12) at 6-month. The FA score showed a diminished effect throughout the observation period. The scores for the right eyes are represented by solid lines, while the scores for the left eyes are represented by dashed lines. The bold line on the graph indicates the mean value of the scores, providing an overview of the central trend of the data over time

Fig. 5

Graphical representation of indocyanine green angiography (ICGA) scores. Individual patient data for ICGA scores are depicted over a 36-month observation period. At baseline, the median ICGA score was recorded as 5 (quartiles: 4.75, 7.25). Over the first year of treatment, there was a significant increase in the mean ICGA score, reaching 7 (6, 9.25) at 6 months and 7 (6.5, 9.25) at 12 months. Following two years, the mean ICGA score returned to 5.5 (4, 7.5). The scores for the right eyes are represented by solid lines, while the scores for the left eyes are represented by dashed lines. The bold line on the graph indicates the mean value of the scores, providing an overview of the central trend of the data over time

Fig. 6

This figure illustrated the changes in Vitreous haze (VH) observed in individual eyes over a 36-month observation period. VH exhibited a significant decrease during the course of therapy (p = 0.02). At baseline, 9 out of 16 eyes had VH > 0.5. After 12 months of therapy, 2 out of 16 eyes had VH > 0.5, and at 36 months, 0 out of 14 eyes had VH > 0.5

Fig. 7

The figure presents the changes in Visual acuity (VA) measured in logarithm of minimum angle of resolution [logMAR] for individual patients over a 36-month observation period. VA exhibited slight improvement during the therapy (p = 0.31). The maximum improvement in VA was noted after 12 months of therapy. The VA for the right eyes is represented by solid lines, while the left eyes VA is represented by dashed lines. The graph’s bold line represents the mean value of VA

Fig. 8

Changes in central retinal thickness (CRT) over the 36-month observation period. The figure illustrates the variation in CRT measured in micrometers [µm] for individual patients during 36-month observation period. At baseline, the mean CRT was 295 µm (quartiles: 275, 322), and it significantly declined over time (b = −0.58, p < 0.001). The lowest CRT level was reached after 36 months at 258 µm (243, 290). Solid lines represent data from right eyes, dashed lines from left eyes, and the bold line on the graph represents the mean CRT