tacrolimus and Cataract

The ocular complications of Behçet's disease are considered one of the major criteria upon which the diagnosis is based. Its complications are frequently sight threatening and require constant attention. The ocular disease is characterized by repeated, explosive ocular inflammatory attacks which get better by themselves, so that in-between attacks there is little or no evidence of inflammatory disease in the eye. The anterior segment can be involved alone, most frequently presenting as a severe anterior uveitis, frequently with hypopyon. This is not associated with a poor visual outcome, and usually treated with topical medication to make the patient more comfortable. However, the anterior segment disease is usually accompanied by recurrent retinal vaso-occlusive disease which is sight threatening if repeated attacks occur. Treatment is with systemic medications, including corticosteroids, cyclosporine, FK506, anti-metabolites, and cytotoxic agents. Complications of the inflammation can include retinal and optic atrophy, vitreous hemorrhage, neovascular glaucoma, and retinal detachment.

Topics: Adrenal Cortex Hormones; Anterior Eye Segment; Behcet Syndrome; Cataract; Colchicine; Cyclosporine; Humans; Tacrolimus; Uveitis; Vitreous Body

The purpose of this study was to investigate ocular complications among a group of patients on long-term, high-dose immunosuppression and corticosteroids for the maintenance of orthotopic heart transplants. Additionally, we provided information pertinent for the early diagnosis and treatment of eye diseases. In this study, we retrospectively assessed the clinical data of 138 patients with orthotopic heart transplantations from May 2000 to October 2005, including assessment of ophthalmic symptoms and signs, as well as the general condition, treatment, and prognosis. Of 138 transplant recipients examined (276 eyes), 47 eyes (17.0%) showed ocular surface diseases. Sixty-four (23.2%) had a posterior subcapsular cataract, and 16 (5.8%) corticosteroid glaucoma. Fifteen (5.6%) had ocular fundus diseases. Various ocular complications related to immunosuppression and corticosteroids appear among heart transplant patients. Cardiac surgeons and ophthalmologists must closely evaluate ocular symptoms in the posttransplantation period.

Topics: Asian People; Cataract; China; Eye Diseases; Female; Follow-Up Studies; Glaucoma; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Retrospective Studies; Tacrolimus

FK506 (tacrolimus), a potent immunosuppressant, is used for inhibiting allograft rejection in the organ transplantation field. In a preclinical toxicity study in rats, FK506 induced various toxicities, including renal and pancreatic injuries. One of these toxic findings was cataract, and we have found that cataract appeared in rats dosed orally with FK506 for 13 weeks and more. Therefore, to better elucidate the onset mechanism of FK506-induced cataract, we measured biochemical parameters, such as sorbitol, Na,K-ATPase and glutathione in the lens of rats. Rats were dosed with FK506 in oral daily doses of 0.2, 1 or 5 mg/kg for 13 weeks, the lowest dose of which approximated the expected clinical dosage. Cataract developed in the 5-mg/kg/day group, with an incidence of 25%, whereas no cataract formation was observed in the 0.2- or 1-mg/kg/day groups. Five mg/kg/day led an increase of sorbitol and a decrease of reduced type glutathione, but did not affect Na,K-ATPase activity of the lens. FK506 is known to have diabetogenicity mediated through pancreatic injury, which appears as vacuolation of islet cell in rats. Five mg/kg/day of FK506 induced an elevation of blood glucose associated with glucose intolerance, and decrease of both basal insulin level and insulin content in the pancreas, and the changes were in parallel with the cataract development in the present study. On the other hand, diabetic parameters did not change in the 0.2- or 1-mg/kg/day groups. These observation suggest that diabetes developed in the rats dosed with 5 mg/kg/day of FK506. Coadministration of a novel aldose reductase inhibitor, Zenarestat, at an oral dose of 50 mg/kg/day resulted in a reduction of incidence of the FK506-induced cataract and a decrease of sorbitol levels in the lens when compared to that in the lens of rats dosed with 5 mg/kg/day of FK506. These results suggest that FK506-induced cataract in rats is due to an accumulation of sorbitol in the lens, secondary to the diabetogenic effect of FK506. FK506 treatment at the doses of 0.2 and 1 mg/kg/day neither affected parameters indicative of diabetes nor induced cataract in rats, suggesting that the cataract would not develop with FK506 if diabetic parameters were kept under control.

Topics: Administration, Oral; Aldehyde Reductase; Animals; Blood Glucose; Body Weight; Cataract; Diabetes Mellitus, Experimental; Enzyme Inhibitors; Glucose Tolerance Test; Glutathione; Immunosuppressive Agents; Insulin; Lens, Crystalline; Male; Quinazolines; Rats; Sodium-Potassium-Exchanging ATPase; Sorbitol; Tacrolimus