Intravitrealsubstained-releasecyclosporjne a (CsA) inthh treatment of experimental uveitis

Purpose. To investigate the efficacy of an intravitreal CsA sustained delivery device in the treatment ol experimental uveitis in the rabbit. Methods. New Zealand While rabbits were immunized subcutancously with Mycobacterium tuberculosis antigen. Two uccks later, sustained release CsA devices and sham devices were implanted into the vitreous cavities of experimental and control rabbits respectively. One week later, rabbits were challenged with an intravitreal injection of tuberculin antigen. Some rabbits were rcchallenged on day 21. The effects of CsA on ocular inflammation were evaluated by slit lamp biomicroseopy, ERG, histologie examination, aqueous while blood cell count and aqueous protein levels. How cytometry was used to measure the proliferating and CD4+ lymphocytes in aqueous and serum. HPLC was used to measure CsA levels. Results. By all clinical parameters, treated eyes had significantly less inflammation than untreated eyes (p < 0.05 ). The quantitative measurements of aqueous cells and protein paralleled clinical assessment of anterior chamber cells and flare. The total number of proliferating lymphocytes and the subset ol proliferating CD4 lymphocytes as well as the percentage of CD4+ lymphocyies were lower in the Ireatcd eyes than in the untreaied eyes. The ERG b-wave was significantly lower in untreated eyes compared to treated eyes (p < 0.02 ). Histologically, untreated eyes had marked inflammation and tissue disorganization, while CsA-treated eyes had preserved architecture and greatly reduce inflammatory cells. Vitreous CsA remained at therapeutic levels for at least 6 months after device implantation, whereas blood levels were low to non-detectable. Conclusions. The intravitreal CsA device effectively suppresses ocular inflammation in a rabbit model of uvciiis. This device may be useful in the management of patients with serve chronic uveitis who are intolerant to currently available therapies. Supported by NIH grants EYO9I06. None.

Duke Scholars

Author Scott William Cousins Ophthalmology, Vitreoretinal Diseases & Surgery