The relationship between various kinds of optic neuropathy and drugs including amiodarone, ethambutol, linezolid, sildenafil, and interferon is reported in the literature (1). Tacrolimus (FK506, Prograf; Fujisawa USA, Inc., Deerfield, IL)-induced optic neuropathy was reported in three case reports; however, the mechanism of neurotoxicity is unclear (2–4). We report a case of bilateral ischemic optic neuropathy in the patient using tacrolimus and suggest the mechanism of tacrolimus neurotoxicity. A 54-year-old male patient was referred with a 10-day history of painless decreased vision in the left eye. The patient had liver cirrhosis associated with hepatitis B virus infection and had undergone liver transplantation 6 months before. The patient did not have any vascular risk factors. At the presentation, he was receiving mycophenolate 250 mg two times per day, prednisolone 2 mg four times per day, and tacrolimus 2.5 mg two times per day orally to maintain immunosuppression for 5 months. The best corrected visual acuity at the first examination was 20/20 OD and 20/400 OS. Relative afferent pupillary defect was noted in the left eye. The anterior segment and the fundus examination were normal. Cecocentral scotoma with an inferior predilection was revealed in Goldmann visual field (GVF) test, and delayed P100 latency was revealed in visual-evoked potential in the left eye. Laboratory study results including coagulation test were normal, whereas the results of blood studies for cytomegalovirus and mycobacteria were negative. At this time, tacrolimus and mycophenolate plasmatic levels were 6.2 and 1.3 mg/L, respectively. Brain magnetic resonance imaging was normal. Initially, we suspected an idiopathic ischemic optic neuropathy and planned regular follow-up. Three months later, his visual acuity of the right eye was also decreased to counting fingers and relative afferent pupillary defect was noted in the left eye. Visual acuity was counting fingers OS. Fundus examination was normal in the right eye; however, temporal pallor of optic disc was noted in the left eye (Fig. 1A). GVF test revealed cecocentral scotoma with an inferior predilection in both the eyes. Fluorescein angiography (FA) demonstrated no fluorescence filling in the optic disc in both the eyes, from the early phase to the late phase (Fig. 1B).FIGURE 1.: (A) Optic disc photograph at presentation of the right and the left eye shows normal appearance in the right eye and temporal pallor in the left eye. (B) Late-phase fluorescein angiography of the right and the left eye when the visual acuity in the right eye was decreased. There was no fluorescence filling in the optic disc in both eyes.We suspected ischemic optic neuropathy associated with tacrolimus and recommended to the general surgery department to discontinue tacrolimus medication. At this time, there was a mild increase in liver enzymes, and chronic rejection was suspected. Tacrolimus was immediately discontinued, instead cyclosporine was started for immunosuppression. Two weeks later, visual acuity had improved to 20/60 in the right eye but was still limited to counting fingers in the left eye. One month after discontinuing the medication, visual acuity was improved to 20/50 OD and stationary OS. GVF test revealed improved visual field in the right eye and stationary in the left eye, but FA revealed no fluorescence filling in the optic disc in both the eyes. At this time, cyclosporine plasmatic level was 100.9 ng/mL. Optic neuropathy associated with tacrolimus has been reported in three literatures (2–4). Two cases were bilateral (2, 4) and the other case was not clear in bilaterality, because the left eye was already blind secondary to retinopathy (3). There was an improvement in the visual acuity after discontinuing tacrolimus in two patients (2, 3). Optic disc edema was demonstrated in one patient (2). In these previous reports, mechanism of the optic neuropathy was unclear and suggested to be ischemia or direct neurotoxic effect and corroborative evidence was not provided. In this study, absolutely no blood flow to the optic disc was evident according to the FA results, suggesting that tacrolimus-induced ischemia might be one of the mechanisms of optic neuropathy. In the previous case reports, tacrolimus was believed to cause vasoconstriction and tissue ischemia through direct neurotoxic effect and vascular mechanism, similar to cyclosporine (2). In this case, tacrolimus was discontinued, but instead of tacrolimus, cyclosporine was started because of suspected chronic rejection. Later, the visual acuity of the patient was improved even using cyclosporine. Therefore, pathogenesis of tacrolimus-induced optic neuropathy may be different from cyclosporine-induced optic neuropathy. Different individual sensitivity to the neurotoxic and ischemic effect of tacrolimus and cyclosproine on optic nerve is another possibility. Tacrolimus is used in patients who undergo liver transplantation. In the case of decreased vision in patients receiving tacrolimus, the possibility of tacrolimus-induced optic neuropathy should be considered. Jaeha Yun Kyung-Ah Park Sei Yeul Oh Department of Ophthalmology Samsung Medical Center Sungkyunkwan University Seoul, Korea
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Aug 5, 2010
Vinit B Mahajan + 1
Open Access
