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Adverse effects of low-dose systemic cyclosporine therapy in high-risk penetrating keratoplasty

  • Cornea
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Abstract

Purpose

The purpose of this study was to investigate the adverse effects of low-dose oral cyclosporine (CsA) therapy following high-risk corneal transplantation.

Methods

The medical records from 88 subjects who had undergone high-risk penetrating keratoplasties and had been administered oral CsA were retrospectively analyzed. High risk was defined as a history of graft rejection, three or more quadrants of vascularization, or the presence or history of intraocular inflammation. An initial CsA dose of 3–5 mg/kg per day was given for 3–7 days, followed by 2.5–3.5 mg/kg per day for approximately 1 month. The concentration of CsA was maintained at the target trough level of 120–150 ng/ml for at least 6 months or until serious complications developed. The relationship between the cumulative dose and duration of CsA administration and the adverse systemic effects, including the frequency of herpes keratitis, was evaluated. The incidence of herpes keratitis in the study subjects was compared with the incidence in 185 patients who had not received CsA therapy following penetrating keratoplasty.

Results

The mean survival time of the grafts was 33.6 months. Adverse effects occurred in 81.8 % of subjects. Hypertension, elevated liver enzyme levels, elevated serum creatinine level, and decreased absolute neutrophil count (ANC) were observed in 14.8, 6.8, 5.7, and 5.7 % of subjects, respectively. Simvastatin-induced rhabdomyolysis also developed in one case. Some patients exhibited minor complications, with gastrointestinal problems and hypertrichosis recorded in 5.7 and 3.4 % of subjects, respectively. Hypertension and hepatotoxicity most frequently occurred after 4 to 8 weeks of medication, while ANC decrease and nephrotoxicity generally developed after 24 weeks of treatment, with incidence related to the cumulative dose. Herpes keratitis occurred more frequently (31.8 %) in the CsA-treated subjects than in subjects that did not receive CsA therapy (p = 0.005). Most of the adverse effects were reversed after discontinuation of CsA therapy.

Conclusion

The results of this study suggest that low-dose oral CsA therapy may induce various adverse effects, the most common of which are herpes keratitis and hypertension.

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Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (including honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (including personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Authors and Affiliations

  1. Department of Ophthalmology, Chungnam National University College of Medicine, Daejeon, Korea

    Jong Joo Lee

  2. Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea

    Mee Kum Kim & Won Ryang Wee

  3. Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea

    Mee Kum Kim & Won Ryang Wee

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  1. Jong Joo Lee
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Correspondence to Mee Kum Kim.

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Lee, J.J., Kim, M.K. & Wee, W.R. Adverse effects of low-dose systemic cyclosporine therapy in high-risk penetrating keratoplasty. Graefes Arch Clin Exp Ophthalmol 253, 1111–1119 (2015). https://doi.org/10.1007/s00417-015-3008-0

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