Intravitreal sustained-release dexamethasone device in the treatment of experimental uveitis.
OBJECTIVE
Uveitis often runs a chronic course requiring long-term therapy. Topical treatment results in poor intravitreal penetration, and systemic therapy is associated with significant side effects. The authors investigated whether an intravitreal sustained-release dexamethasone device was effective in the treatment of severe panuveitis in a rabbit model.


METHODS
Twenty New Zealand white rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, sustained-release dexamethasone devices were implanted into the vitreous of the right eye of 10 rabbits. Ten control rabbits received a sham device. One day later, rabbits were challenged with an intravitreal injection of 33 micrograms of antigen. Three animals in each group were sacrificed on post-challenge days 7 and 13 for aqueous white blood cell (WBC) count, protein determination, and histologic examination. To simulate chronic inflammation with exacerbations, the eight remaining eyes were rechallenged with intravitreal antigen on day 15 and were observed for 3 1/2 months. Inflammation was graded clinically by two masked observers. Retinal function was evaluated by electroretinography (ERG). Light microscopy was used to evaluate the eyes histopathologically. The amount of residual drug in the devices was measured on day 13 and at the end of the experiment.


RESULTS
By all clinical criteria measured--anterior chamber cells, flare, and vitreous opacity--treated eyes had significantly less inflammation than untreated eyes (P < 0.05). Clinical examination correlated well with objective data. Both protein concentration (P < 0.05) and aqueous WBCs (P < 0.02) were approximately 10-fold higher, and ERGs were significantly depressed (P < 0.05) in untreated eyes compared to treated eyes. Histopathologic examination showed marked inflammation and tissue disorganization in the untreated compared to the treated eyes. After antigen rechallenge, inflammation in experimental eyes was still less than in control eyes. Late complications such as corneal neovascularization, cataract, and hypotony were also less in the treated eyes than in the untreated eyes. At the end of the experiment (99 days after device implantation), approximately 30% of drug remained in the devices.


CONCLUSIONS
The intravitreal sustained-release dexamethasone device is highly effective in suppressing inflammation and preventing complications after two episodes of experimental uveitis in a rabbit model for at least 3 1/2 months. This device may be useful in the management of patients with severe chronic posterior uveitis who cannot tolerate systemic or periocular therapy.
Department of Ophthalmology, Duke University Medical Center, North Carolina 27710.
C K
CK
Cheng
A S
AS
Berger
P A
PA
Pearson
P
P
Ashton
G J
GJ
Jaffe
D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D002924:Ciliary Body / Q000473:pathology; D003315:Cornea / Q000473:pathology; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004596:Electroretinography; D009169:Mycobacterium tuberculosis / Q000276:immunology; D015864:Panuveitis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011183:Postoperative Complications / Q000517:prevention & control; D011817:Rabbits; D012160:Retina / Q000473:pathology / Q000502:physiology; D014822:Vitreous Body
D000942:Antigens, Bacterial; D003692:Delayed-Action Preparations; D003907:Dexamethasone