tacrolimus and Optic-Nerve-Diseases

Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss.. Case series and review of the literature.. We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy.. Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.

Topics: Aged; Bone Marrow Transplantation; Cerebrospinal Fluid; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukocytosis; Lymphocytes; Magnetic Resonance Imaging; Male; Middle Aged; Optic Disk; Optic Nerve Diseases; Tacrolimus; Visual Acuity; Visual Field Tests; Visual Fields

Topics: Humans; Optic Nerve; Optic Nerve Diseases; Tacrolimus

Tacrolimus is associated with optic neuropathy. The clinical features of tacrolimus-induced optic neuropathy (TION) are unclear. The purpose of this article is to explore the clinical features of TION.. TION-related case reports were collected and analysed by searching Chinese and English databases from 1989 to 31 December 2021.. Twelve males and 7 females were included, with a median age of 54 years (range 23-66). TION onset time ranged from 2 months to 16 years after administration, and the main clinical features were blurred vision (4 cases), decreased visual acuity (7 cases), decreased visual acuity (5 cases), grey films (3 cases), visual field damage (3 cases) and headache (2 cases). Fifteen patients developed bilateral optic neuropathy. Ophthalmological examination showed visual acuity ranging from 20/25 to blindness, pupillary examination revealed relative afferent pupillary defect in 9 patients and marked decrease in colour vision in 15 eyes. The optic disc showed pallor (10 cases), oedema (8 cases), atrophy (4 cases) and haemorrhage (2 cases). After discontinuation or dose reduction of tacrolimus, symptoms improved in 10 patients, 1 patient recovered completely, and 4 patients did not recover.. TION presents diverse clinical manifestations. TION should be promptly identified and treated to prevent severe and permanent vision loss.

Topics: Adult; Aged; Blindness; Female; Humans; Male; Middle Aged; Optic Nerve Diseases; Tacrolimus; Visual Acuity; Visual Fields; Young Adult

Tacrolimus is an immunosuppressant agent utilized for solid organ transplantations. It has been associated with rare neurotoxic effects. This case highlights one possible delayed neurotoxic effect. A 52-year-old lady on tacrolimus (3mg daily) among her immunosuppressive regimen for her kidney transplant 16 year ago. She presented with unilateral left paracentral black dots progressing over a week, associated with periorbital and temporal pain. The patient was diagnosed with left papillitis. Tacrolimus was tapered and then changed to cyclosporine. However, patient did not show any improvement of any parameter. Reports have indicated such neurotoxic effects with Tacrolimus use. Here, the report emphasizes on the unilateral optic neuropathic effect of tacrolimus even after one decade.

Topics: Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Optic Nerve Diseases; Tacrolimus

Tacrolimus, a calcineurin (CaN) inhibitor, has been used for treatment of refractory allergic ocular disease, although its role in optic nerve degeneration remains to be elucidated. In this study, we investigated whether tacrolimus modulates tumor necrosis factor (TNF)-mediated axonal degeneration and whether it alters nuclear factor of activated T cells (NFATc), a downstream effector of CaN signaling. Immunoblot analysis showed no significant difference in CaNAα protein levels in optic nerve on day 3, 7, or 14 after TNF injection compared with PBS injection. However, a significant increase in NFATc1 protein level was observed in optic nerve 7 days after TNF injection. This increase was negated by simultaneous administration of tacrolimus. Administration of tacrolimus alone did not change the NFATc1 protein level in comparison to that observed after PBS injection. A significant increase in TNF protein level was observed in optic nerve 14 days after TNF injection and this increase was prevented by tacrolimus. Immunohistochemical analysis showed the immunoreactivity of NFATc1 to be increased in optic nerve after TNF injection. This increased immunoreactivity was colocalized with glial fibrillary acidic protein and was suppressed by tacrolimus. Treatment of tacrolimus significantly ameliorated the TNF-mediated axonal loss. These results suggest that tacrolimus is neuroprotective against axon loss in TNF-induced optic neuropathy and that the effect arises from suppression of the CaN/NFATc1 pathway.

Topics: Animals; Axons; Calcineurin Inhibitors; Male; Nerve Degeneration; Neuroprotective Agents; Optic Nerve; Optic Nerve Diseases; Rats, Wistar; Signal Transduction; Tacrolimus; Transcription Factors; Tumor Necrosis Factor-alpha

Tacrolimus has been associated with several ocular adverse effects, such as optic neuropathy.. A 56-year-old woman noted sudden, severe, painless visual loss in her left eye. She had undergone liver transplantation for alcoholic related cirrhosis 6 months before. Her chronic immunosuppressive regimen consisted of prednisone and tacrolimus at dosage of 1.5 mg orally once daily. Consequently, the patient developed a left optic neuropathy.. We report the first case of unilateral optic neuropathy associated with oral tacrolimus medication. Surgeons and ophthalmologists must evaluate ocular symptoms in the post-transplantation period, and suspicion should be maintained even if unilaterality or asymmetry of symptoms against a toxic etiology.

Topics: Blindness; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Middle Aged; Optic Nerve Diseases; Tacrolimus; Tomography, Optical Coherence

To report the first histopathologic description of optic nerve demyelination from tacrolimus (FK 506) toxicity in the absence of toxic levels of tacrolimus in a patient presenting with asymmetric bilateral visual loss after 5 years of tacrolimus therapy.. We report a patient status post cardiac and renal transplantation who developed severe, progressive and asynchronous bilateral visual loss after prolonged treatment with tacrolimus. Orbital MRI showed an enlarged left optic nerve that enhanced with gadolinium.. After extensive negative work up, biopsy of one optic nerve was performed. Microscopic analysis showed extensive demyelination in the absence of vasculitis, neoplastic or infectious etiologies. Our patient illustrates that demyelination of the optic nerve causing asynchronous vision loss can be associated with tacrolimus toxicity in the absence of toxic drug levels.

Topics: Biopsy; Demyelinating Diseases; Diabetes Complications; Disease Progression; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Optic Nerve; Optic Nerve Diseases; Postoperative Complications; Risk Factors; Tacrolimus; Visual Acuity

The transcriptional regulator, nuclear factor-kappa B (NF-κB)/Rel family are involved in neuronal cell death and survival. Previously, we reported that NF-κBp50-deficient (p50-deficient) mice exhibit many features resembling human normal tension glaucoma (NTG). The developmental mechanism of human NTG is not clearly understood, and a radical curative treatment has yet to be established. Our aim is to elucidate the signal cascade which mediates the spontaneous optic neuropathy in p50-deficient mice as a model of NTG.. To demonstrate the expression and activation of pro-apoptotic factors, which mediate the death of retinal ganglion cells (RGCs) in p50-deficient mice, western blot (WB) and luciferase reporter assays with retinas from p50-deficient and wild type mice, and cultured RGC-5 cells were performed. Furthermore, we tested the neuroprotective effects of chemical reagents (memantine, lomerizine, and tacrolimus) against N-methyl-D-aspartate (NMDA)-susceptible RGC damage according to in vitro experiments with RGC-5 cells. To elucidate the NF-κB-mediated death signaling, the effects of chemical reagents on spontaneous optic neuropathy were examined by histopathological studies.. WB experiments and luciferase reporter assays showed that NF-κB-inducible BCL2-associated X protein (Bax) and a pro-apoptotic factor, activated caspase 3 were expressed in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Further, the constitutively active cleaved forms of calcineurin (CaN), which have been reported to lead to apoptosis, were detected in the retina of p50-deficient mice as well as NMDA-treated RGC-5 cells. Pre-treatment with tacrolimus markedly protected RGC-5 cells from NMDA-induced neurotoxicity, and then both spontaneous RGC death and degenerative changes to the optic nerve in p50-deficient mice were significantly reduced by the chronic administration of tacrolimus. The experiments with cultured RGC-5 cells supported the results of histological examinations with p50-deficient mice, suggesting that CaN activation leads to NF-κB-induced Bax activation and caspase 3 activation, and mediates spontaneous optic neuropathy in p50-deficient mice.. Research findings show that the chronic administration of tacrolimus significantly reduces spontaneous optic neuropathy in p50-deficient mice. We demonstrated a potential CaN signal cascade, which spontaneously induces age-dependent RGC death and degenerative optic nerve changes in p50-deficient mice.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Calcineurin; Genes, Reporter; Humans; Intravitreal Injections; Luciferases; Memantine; Mice; Mice, Inbred C57BL; Mice, Knockout; N-Methylaspartate; Neuroprotective Agents; NF-kappa B p50 Subunit; Optic Nerve; Optic Nerve Diseases; Piperazines; Retinal Ganglion Cells; Signal Transduction; Tacrolimus

Topics: Evoked Potentials, Visual; Female; Humans; Immunosuppressive Agents; Middle Aged; Optic Nerve Diseases; Pancreas Transplantation; Sirolimus; Tacrolimus; Visual Acuity

Topics: Adult; Cystic Fibrosis; Electroretinography; Humans; Immunosuppressive Agents; Male; Optic Nerve Diseases; Tacrolimus; Visual Acuity

To report a case of bilateral optic neuropathy in a patient receiving tacrolimus (FK 506, Prograf; Fujisawa USA, Inc, Deerfield, Illinois) for immunosuppression after orthotropic liver transplantation.. Case report. In a 58-year-old man receiving tacrolimus after orthotropic liver transplantation, serial neuro-ophthalmologic examinations and laboratory studies were performed.. The patient had episodic deterioration of vision in both eyes, with clinical features resembling ischemic optic neuropathies. Deterioration of vision occurred despite discontinuation of the tacrolimus.. Tacrolimus and other immunosuppressive agents may be associated with optic nerve toxicity.

Topics: Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Optic Nerve Diseases; Tacrolimus; Visual Acuity; Visual Fields