Ciclosporin A in bilateral auto-immune chronic posterior uveitis associated with macular oedema: a Long-term Observational Safety and Efficacy Study

Abstract

Objective: A non-interventional, longitudinal, retrospective follow-up study to assess CsA-induced nephrotoxicity (IN) and its reversibility after withdrawal in patients exhibiting a bilateral chronic posterior uveitis (CPU) associated with cystoid macular oedema (CMO) in at least one eye. Data from medical records between 1986 and 2013.

Methods: Primary outcome was the renal tolerance during and after CsA treatment assessed by plasma creatinine concentration and glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology (CKD-Epi) formula. Secondary outcomes were CsA through concentration, occurrence of cancers and ophthalmologic efficacy assessed by three parameters including CMO, vitreous inflammation, and best-corrected visual acuity BVCA changes.

Results: One hundred forty-three patients were followed for renal tolerance. Underlying diseases were Birdshot retinochoroiditis (n = 67), Behçet disease (n = 9), probable sarcoidosis (n = 23), sympathetic ophthalmia (n = 3), idiopathic (n = 41). After CsA discontinuation in 115 patients (mean treatment duration of 5.9 ± 3.8 years) mean plasma creatinine concentration was 82.2 ± 14.2 µmol/L versus 82.1 ± 14.1 µmol/L at baseline, mean GFR was 79.4 ± 13.9 mL/min versus 82.5 ± 14.3 mL/min at baseline, with no significant difference (respectively p = 0.91 and p = 0.09). Blood pressure did not significantly change during follow-up. CMO was completely resorbed in at least one eye, in 70.8% patients (n = 72) at 6 months, in 71.4% patients (n = 49) at 10 years and in 54.2% patients (n = 24) at 20 years. BCVA did not statistically change over time.

Conclusion: Early and long-term monitoring of renal tolerance and dual adjustment of CsA doses in inflammatory stages of CPU were associated with reversible CsA IN. CsA could be effective in the treatment of CMO in CPU patients.

Fig. 1. Multidiscplinary protocol of Ciclosporin A treatment, followup and longterm monitoring of plasma creatinine concentration.

a Flow chart. b Multidisciplinary protocol of treatment and follow-up of renal tolerance and ophthalmologic efficacy. c Long-term monitoring of plasma creatinine concentration in patients who discontinued CsA (n = 115). ***p value <0.001. 1: Baseline: (corresponding to a GFR level mean CKD-Epi of 80(±14.6) mL/min). 2: Zenith of plasma creatinine concentration: (CKD-Epi 55 ± 19.2) mL/min. 3: Nadir of plasma creatinine concentration: (CKD-Epi mean 80 ± 18.4). 4: End of the follow-up. 5: CsA discontinuation. d Long-term monitoring of plasma creatinine concentration in patients who continued CsA (n = 28). ***p value <0.001, NS not significant. 1: Baseline. 2: Zenith of plasma creatinine concentration. 3: Nadir of plasma creatinine concentration. 4: End of the follow-up.