profiles in pivotal randomized controlled trials. It remains to be established, however, whether their use in treating DR and DME, manifestations of a complex systemic disease, will also prove to be safe. With respect to bevacizumab, its safety as an intravitreous agent has yet to be examined in a controlled trial.

CONCLUSIONS

Since the initial proposal of Powell and Field (1) that DR is an inflammatory disease, both and preclinical clinical investigations have supported the importance of the influx of inflammatory cells, as well as the role of proinflammatory cytokines, in mediating both vascular damage and ischemia-induced neovascularization. These data support the concept that DR is a low-grade inflammatory disease. There is now strong evidence that VEGF, originally characterized as a promoter of angiogenesis, is itself a promoter of inflammatory processes, with the VEGF165 isoform being especially potent in this respect. The perspective of DR as an inflammatory disease has already provided the basis for several therapeutic approaches, including VEGF-targeted agents, corticosteroids, and NSAIDs. There is every reason for optimism that additional studies of the roles played by VEGF and other inflammatory cytokines will lead to further advances, including the rational design of combinatorial approaches employing more than one therapeutic agent in the treatment of DR.

ACKNOWLEDGMENT

The development of this chapter was supported by (OSI) Eyetech and Pfizer Inc.

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