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Topical Cyclosporine A Inhibits Subepithelial Immune Infiltrates but Also Promotes Viral Shedding in Experimental Adenovirus Models

Romanowski, Eric G MS; Pless, Patricia MD; Yates, Kathleen A BS; Gordon, Y Jerold MD

doi: 10.1097/01.ico.0000127481.23714.b6
Basic Investigations

Purpose: To determine the effects of topical cyclosporine A (CsA), an immunomodulating T-cell inhibitor, on the formation of subepithelial immune corneal infiltrates (SEIs) and acute adenovirus replication in the NZW Rabbit Ad5 SEI and Ad5 replication models.

Methods: In the Ad5 SEI model, eyes were treated topically with either 2% CsA in corn oil, 0.5% CsA in artificial tears, or their respective control vehicles 4 times daily for 14 days and then twice daily for 4 days. SEIs were graded on day 23 by masked slit-lamp examination. Using the same treatment protocol in the Ad5 replication model, rabbit eyes were cultured on days 0, 1, 3, 4, 5, 7, 9, 11, 14, 16, 18, and 21 postinoculation, and their tear film viral titers were determined on A549 cells.

Results: The formation of SEIs was significantly reduced following treatment with either 2.0% or 0.5% CsA. However, 2% and 0.5% CsA significantly increased viral titers on several days, prolonged the duration of Ad5 shedding, and increased the number of Ad5-positive cultures per total during the late phase of infection (days 7–21) compared with their respective controls. The 0.5% CsA was equipotent to 2% CsA for most outcome parameters tested.

Conclusions: A role for topical CsA in the treatment of adenovirus ocular infections remains to be defined in large, randomized controlled clinical trials. During acute infection, reducing SEI formation is highly desirable, but enhancing viral replication may inadvertently serve to promote local epidemics. Future trials should address the important issues of optimized formulation and dose regimen and the possibility of prolonging virus shedding.

From The Charles T. Campbell Laboratory, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Received for publication October 17, 2003; revision received February 26, 2004; accepted March 3, 2004.

This study was supported by NIH Grant EY08227, NIH Core Grant for Vision Research EY08098, and The Eye and Ear Foundation of Pittsburgh, Pittsburgh, PA.

The authors have no financial interest in any of the products mentioned in this manuscript.

Reprints: Eric G. Romanowski, MS, Department of Ophthalmology, University of Pittsburgh School of Medicine, The Eye & Ear Institute, Room 1020, 203 Lothrop Street, Pittsburgh, PA 15213 (e-mail:

© 2005 Lippincott Williams & Wilkins, Inc.