Diabetic Macular Edema Clinical Trial
Official title:
Effect of Macugen (Pegaptanib) on Surgical Outcomes and Growth Factors Including Vascular Endothelial Growth Factor (VEGF) Levels in Patients With Proliferative Diabetic Retinopathy (PDR) and Clinically Significant Diabetic Macular Edema (CSDME)
Patients with proliferative diabetic retinopathy or clinically significant diabetic macular edema requiring surgical intervention will receive a pre-operative injection of Macugen. An initial, pre-injection vitreous tap will be done in order to provide baseline VRGF 165 and cytokine levels. At the onset of the vitrectomy, a second vitreous sample will be taken to obtain intra-operative levels of Macugen, VEGF 165 and cytokines.
Diabetes is one of the leading causes of blindness in North America. Diabetic retinopathy
(PDR) is characterized by disruption of the normal microvascular circulation in the retina
and results in the production of neovascularization and increased microvascular
permeability. Similarly, clinically significant diabetic macular edema CSDME) results in
loss of central visual acuity.
Many patients with these conditions, despite treatment, will go on to develop vitreous
hemorrhage or tractional changes that require surgical intervention (such)as vitrectomy
and/or vitrectomy with membrane peeling in the attempt to both restore vision and prevent
further visual loss or re-establish the normal macular anatomy and improve patient visual
acuity.
Although multiple etiologic factors are involved in the early changes seen in diabetic
retinopathy and maculopathy, it has been shown that VEGF is the primary angiogenic growth
factor implicated in the development of neovascularization in PRD and in increased vascular
permeability, resulting in CSDME. VEGF levels have been found to correlate tightly with the
extent of diabetic retinopathy and introduction of VEGF into normal primate eyes can induce
diabetic retinopathy. Although several isoforms of VEGF exist, isoform 165 (VEGF 165) is the
most pathogenic form of VEGF and therefore inhibition of VEGF 165 may play a significant
role in modulating diabetic retinopathy and maculopathy.
Macugen is a VEGF antagonist (anti-VEGF pegylated aptamer) which binds to VEGF 165 with high
specificity and affinity. In vitro pharmacology studies have shown that Macugen binds to the
amino acid isoform VEGF 165 and inhibits it from binding to its cellular receptors. As a
consequence, Macugen blocks signalling events and disrupts the cascade of proliferative and
vascular permeability responses associated with the binding of VEGF 165 to endothelial
cells. This effect has been clearly proven in Phase 3 trials for patients with age-related
macular degeneration (AMD), resulting in inhibition of vascular development and decrease in
vascular leakage.
Although diabetic retinopathy represents a different challenge than AMD, the underlying
pathogenic factors are similar in the role and effects of VEGF. Regression of retinal
neovascularization after Macugen therapy in diabetic individuals has been shown. Phase 2
studies have been completed and Phase 3 studies are currently underway in patients with
diabetic macular edema to evaluate the efficacy of Macugen to restore vision in patients
with CSDME. These studies are ongoing but exclude patients in whom vitrectomy has been
performed or is planned in the near future due to tractional effects on the macula from
epiretinal membranes or vitreomacular traction syndrome. No studies have been done to date
in patients with PDR or CSDME to quantify the reduction of intravitreal VEGF 165 levels in
these patients following intravitreal Macugen injection or to evaluate the effects of VEGF
165 blockade on the neovascular regression and surgical outcome in patients with extensive
diabetic proliferative neovascularization.
The goal of this study is to quantify the reduction of intravitreal VEGF 165 levels in
patients following intravitreal Macugen injection pre-operatively and determine the level of
Macugen in the vitreous cavity after variable time intervals (2,4, 6 or 8 weeks).
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Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
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