Misaki Ishioka

FK506 Treatment of Noninfectious Uveitis

PURPOSE We studied the clinical effects of the immunosuppressive agent FK506 in patients with noninfectious uveitis. METHODS This study was designed as a multicenter open clinical trial in Japan. Sixteen patients with noninfectious uveitis who had visited the Uveitis Survey Clinic of the Yokohama City University Hospital were given FK506. Eight had Behçets disease; five, Vogt-Koyanagi-Harada syndrome; one, sympathetic ophthalmia; one, retinal vasculitis; and one, sarcoidosis. In patients with Behçets disease, ocular attack score before and after therapy was compared to judge clinical status. For the other diseases, the ocular inflammatory symptoms were observed after the initiation of FK506 treatment. All patients underwent blood and urine examinations, electrocardiography, and chest x-rays before and after FK506 treatment. RESULTS Of the patients with Behçets disease, five improved, one remained unchanged, one deteriorated, and the status of one could not be determined. Of the patients with Vogt-Koyanagi-Harada syndrome, four improved, and one remained unchanged. The patient with sympathetic ophthalmia improved, the patient with retinal vasculitis remained unchanged, and the status of the patient with sarcoidosis could not be determined. Major adverse effects were sensations of warmth, hypomagnesemia, renal dysfunction, glucose intolerance, nausea, vomiting, and disorders of the central nervous system. All adverse effects disappeared or improved when FK506 was stopped or when the dosage was decreased. Renal dysfunction and glucose intolerance appeared when the blood level of FK506 was high. CONCLUSIONS FK506 was effective in patients with uveitis, but it is important to monitor the occurrence of adverse effects.

Bilateral herpes simplex keratitis in a patient with chronic graft-versus-host disease

Purpose To describe a case of bilateral herpes simplex keratitis accompanying chronic graft-versus-host disease (GVHD). Design Observational case report. Case report An 11-year-old boy with myelocytic leukemia underwent allogeneic bone marrow transplantation. He developed symptoms of the skin, eyes, and mouth, and lip biopsy indicated chronic GVHD. Persistent keratitis with corneal filaments and neovascularization was noted in both eyes. Sodium hyaluronate, autoserum, and 0.1% fluorometholone eyedrops were instilled for approximately 2 years to treat this keratitis, and there were no other ocular changes. Bilateral herpes simplex keratitis developed with geographic ulcers after topical betamethasone therapy, but responded to acyclovir ointment. Conclusions Herpes keratitis should be considered in the differential diagnosis of bilateral keratitis in patients with reduced immunocompetence. During the course of chronic GVHD, corneal herpes may occur, so ocular treatment with topical corticosteroids should be managed by an ophthalmologist to monitor sight-threatening conditions such as corneal herpes.

Suppression of actively induced experimental autoimmune uveoretinitis by CD4+ T cells

Abstract• Background: Helper/inducer T cells that exert an inhibitory effect on disease induction have been recently found in many experimental models. In order to clarify the mechanisms of spontaneous remission of experimental autoimmune uveoretinitis (EAU), we investigated the inhibitory effect and the phenotype of the post-recovery suppressor cells. • Methods: In a series of experiments, we separated spleen cells of rats that had recovered from EAU. Three groups of spleen cells, CD4+ T, CD8+ T and B cells, were each adoptively transferred into naive syngeneic rats before active immunization with retinal soluble antigen (S-Ag) and Freunds complete adjuvant or passive immunization with uveitogenic T cells from donor rats. Inflammation was examined clinically and histologically. • Results: The development of EAU could be significantly prevented by adoptive transfer of CD4+ T cells, whereas CD8+ T cells could not suppress the onset. However, post-recovery CD4+ T cells failed to inhibit EAU induced by passive immunization with uveitogenic T cells. • Conclusion: These findings indicate that CD4+ post-recovery (suppressor) T cells may play an important role in the remission of EAU.

Prevalence of HTLV-1-associated uveitis in the Kanto Plain, Japan

Abstract• Background: Seroprevalence of antibody to human T-lymphotropic virus type I (HTLV-I) is high in the island of Kyushu, Japan. Reports on the etiological analysis of HTLV-I in patients with uveitis primarily document cases in this island. We studied the seroprevalence of HTLV-I at the Department of Ophthalmology in Yokohama City University Hospital and in Odawara Municipal Hospital, which are in the Kanto Plain on the island of Honshu, Japan. • Methods: The subjects were 741 patients who visited the two hospitals. The presence of serum antibodies against HTLV-I was assessed using the method of particle agglutination. • Results: Of 454 patients with nonuveitic ocular diseases, 9 (1.98%) were seropositive. Of 143 patients with definite diagnosis of uveitis, 1 (0.70%) was seropositive. Of 144 patients with non-specific uveitis (etiology undefined), 8 (5.56%) were seropositive. Thus, the prevalence of serum antibodies to HTLV-I was higher in patients with non-specific uveitis than in patients with specific uveitis or nonuveitic ocular diseases. Common ocular symptoms of 8 HTLV-I-infected patients with non-specific uveitis were compatible with the clinical features of uveitis described as HTLV-I-associated uveitis (HAU). • Conclusion: It is important to suspect HAU in patients with uveitis of unknown etiology, even outside known areas of prevalence.