has an effective and tolerable treatment such as PRP. Nevertheless, cases of regression of PDR following intraocular triamcinolone establish that this treatment can be effective in select cases (128–130), and may be used adjunctively with PRP.

The relationship between intraocular NV and intraocular VEGF has been well demonstrated (74, 75, 131). By specifically blocking VEGF activity, therapies with bevacizumab, ranibizumab, and pegaptanib have been reported to temporarily ameliorate neovascular lesions in PDR (132–134), and have been considered as adjunctive therapies for eyes requiring vitrectomy (135) and also as adjunctive for PRP. Owing to the invasiveness of intravitreal injection and apparent temporary effects of the above-men- tioned drugs, it appears that the use of current agents in the management of PDR is reserved for occasional difficult cases, where there is considerable potential for benefit.

Protein Kinase C beta (PKCβ) is a regulatory intracellular protein that is activated by hyperglycemia and angiogenic growth factors such as VEGF (136, 137). A phase 3 trial demonstrated a modest effect of a specific inhibitor on preservation of vision and reduction in progression of DME, but no effect on the progression of moderate-to-severe NPDR to more severe levels or to PDR (138).

Although eyes with severe vitreous hemorrhage from PDR often proceed to vitrectomy surgery if there is delayed clearing, particularly if there has been no preceding PRP treatment, there has been interest in treatments to promote clearing of vitreous hemorrhage to avoid the risks of surgery and to allow PRP in those cases requiring more laser. Intravitreal hyaluronidase injection has been demonstrated to have modest efficacy with a good safety profile (139, 140). However, the clinical trials failed to achieve their primary endpoint, and hyaluronidase has not been approved by the FDA for this indication.

Pharmacologic management of PDR, either as primary therapy or as adjunctive therapy, has not yet become commonplace. With the intense level of interest in ocular antiangiogenic therapy for treatment of macular degeneration, undoubtedly new treatments will be introduced and tested in the near future. While laser photocoagulation treatment is well tolerated, with relatively rare serious adverse effects, and has excellent efficacy when applied appropriately, there is still opportunity to improve upon this great success.

ACKNOWLEDGMENT

Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., and by a Research to Prevent Blindness Senior Scientific Investigator Award (M.D.D.).

This chapter was based on and reprinted from Retina, 4th edition, Vol. 2 (eds Ryan SJ, Schachat AP), Davis MD, Blodi BA, “Proliferative Diabetic Retinopathy”, pp 1285–1322, 2006, with permission from Elsevier.

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