Pegaptanib Therapy in Uveitis

According to a recent estimate more than 280,000 people in the United States are affected by
uveitis each year. This report, also estimated that uveitis is the reason for 30,000 new
cases of blindness/year and up to 10 percent of all cases of blindness.

1. Cystoid macular edema is a common complication of uveitic intraocular inflammatory
diseases and is characterized by intraretinal edema involving the outer plexiform
layer. Intraocular inflammation or uveitis may be associated with non infectious or
infectious etiologies. The early symptoms of CME include a decrease or blurry central
vision. With long standing CME there is a substantial risk of photoreceptor
degeneration and ensuing long term decrease in the quality and level of visual acuity
(VA). Furthermore it has been shown that in patients with uveitis, the morphologic
features of macular edema and macular thickness correlated with final VA. Current
therapeutic interventions have had at best modest results in patients with CME who have
had decreased VA. This may the case with systemic interventions also.

2. Vascular endothelial growth factor is a very strong inducer of blood vessel
permeability and has been linked to the ocular manifestations of uveitis including CME
by experienced researchers both in experimental and clinical settings. In animal tests,
VEGF has been shown to be 50,000 times more potent than histamine, the molecule
commonly associated with blood vessel leakage related to allergies. Also in animal
tests, it has been shown that VEGF is required for the blood vessel permeability
associated with neovascular AMD and diabetic retinopathy that have been shown to have
an inflammatory component. In addition to its anti-angiogenic property of inhibiting
abnormal blood vessel growth, pegaptanib has been shown in animal tests to inhibit
blood vessels from leaking into the retina. Uveitis has been shown to be associated
with ocular neovascularization both clinically and well as in the clinical studies.
Thus, by preventing blood vessel leakage as well as abnormal blood vessel growth
pegaptanib may be a viable approach for the treatment of CME. Although pegaptanib use
has been associated with mild transient anterior segment inflammation CME itself has
not been linked to its use. Besides, pegaptanib has been demonstrated to effect a
sustainable decrease the macular edema in maculopathies, both age related and diabetic.

3. There is currently a need for considering alternative forms of local (ocular) therapy
for CME to triamcinolone (sub tenon and intraocular). The serious adverse effects with
intraocular corticosteroid use are well documented and include cataracts (nuclear and
subcapsular), glaucoma, endophthalmitis (may be significantly higher than pegaptanib in
patients who are treated exactly as per protocol) as well as sterile inflammatory
reactions.