121/4/2009

Pegaptanib Sodium (MACUGEN) for Macular

Edema Secondary to Central Retinal Vein

OcclusionMahmood J Showail

CRVO is a common retinal vascular disorder.

Clinically, CRVO presents with variable visual loss; the fundus may show retinal hemorrhages,

dilated tortuous retinal veins, cotton-wool spots, macular edema, and optic disc edema

Central retinal vein occlusion (CRVO)

Broadly, CRVO can be divided into 2 clinical types, ischemic and nonischemic

Non-ischemic CRVO is the milder form of the diseaseIt may present with good vision, few retinal

hemorrhages and cotton-wool spots no RAPD and good perfusion to the retina. It may resolve fully with good visual outcome or may

progress to the ischemic type.

classifications

Ischemic CRVO is the severe form of the disease. ischemic CRVO presents with severe visual

loss, extensive retinal hemorrhages and cotton-wool spots,

presence of RAPD, poor perfusion to retina, presence of severe electroretinographic

changes. patients may end up with neovascular

glaucoma and a painful blind eye

The exact pathogenesis of the thrombotic occlusion of the central retinal vein is not known.

Thrombotic occlusion of the central retinal vein can occur as a result of various pathologic insults, including

compression of the vein (mechanical pressure due to structural changes in lamina cribrosa, eg, glaucomatous cupping, inflammatory swelling in optic nerve,

orbital disorders);vessel wall changes (eg, vasculitis);changes in the blood (eg, deficiency of thrombolytic

factors, increase in clotting factors).

Pathophysiology

Macular edema following central retinal vein occlusion (CRVO) is the major cause of vision loss.

No United States Food and Drug Administration–approved pharmacologic treatments exist for macular edema in the setting of CRVO.1

Grid photocoagulation does not improve visual acuity when compared with controls 2

1. Central Vein Occlusion Study Group. A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion: the Central Vein Occlusion Study Group N report. Ophthalmology. 1995;102(10):1434-1444.

2. Central Vein Occlusion Study Group. Evaluation of grid pattern photocoagulation for

macular edema in central vein occlusion: the Central Vein Occlusion Study Group M report. Ophthalmology. 1995;102(10):1425-1433.

Pegaptanib, a 40-kDa RNA aptamer, binds to VEGF165, the predominant pathological isoform in ischemia mediated ocular neovascularization and in diseases such as diabetic macular edema.

Pegaptanib sodium is represented by the following structural formula:

and n is approximately 450.

MACUGEN® (pegaptanib sodium injection)

Pegaptanib is a selective vascular endothelial growth factor (VEGF) antagonist.

VEGF is a secreted protein that selectively binds and activates its receptors located primarily on the surface of vascular endothelial cells.

VEGF induces angiogenesis, and increases vascular permeability and inflammation, all of which are thought to contribute to the progression of the neovascularization.

MACUGEN® Mechanism of Action

Clinical trials have suggested that intravitreous injection of pegaptanib sodium can be effective in the treatment of diabetic macular edema (1) proliferative diabetic retinopathy(2) neovascular age-related macular

degeneration (3(1. Ng EW, Shima DT, Calias P, Cunningham ET Jr, Guyer DR, Adamis AP.

Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov. 2006;5(2):123-132.

2. Cunningham ET Jr, Adamis AP, Altaweel M, et al; Macugen Diabetic Retinopathy Study Group. A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology. 2005;112(10):1747-1757.

3. Adamis AP, Altaweel M, Bressler NM, et al; Macugen Diabetic Retinopathy Study Group. Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology. 2006;113(1):23-28.

So, does it work for

macular edema due to

CRVO!?

Pegaptanib Sodium for Macular Edema

Secondary to Central Retinal Vein Occlusion

John J. Wroblewski, MD; John A. Wells III, MD; Anthony P. Adamis, MD; Ronald R. Buggage, MD; Emmett T. Cunningham Jr, MD, PhD; Mauro Goldbaum, MD; David R. Guyer, MD; Barrett Katz, MD, MBA; Michael M. Altaweel, MD; for the Pegaptanib in Central Retinal Vein Occlusion Study Group

Arch Ophthalmol. 2009;127(4):374-380

To assess the safety and efficacy of intravitreous pegaptanib sodium for the treatment of macular edema following central retinal vein occlusion (CRVO).

Objectives

This was a randomized, dose-ranging, double masked, sham-controlled clinical trial.

The study was conducted between August 2004 and September 2006.

It was conducted within multiple centers all over the world ( Australia, France, Germany, Israel, Spain, and the United States).

Methods

It includes patients with CRVO for 6 months or less duration who will receive pegaptanib sodium or sham injection every 6 weeks for 24 weeks.

A total of 98 patients entered the study, with 33 patients in both the 0.3-mg and 1-mg pegaptanib sodium groups and 32 in the sham group.

Main Outcome Measure: Visual acuity at week 30

Eligible patients were allocated equally (1:1:1) to 1 of 3 treatment arms

0.3 mg of pegaptanib

sodium 1 mg of pegaptanib

sodium

Sham injectons

At baseline, subject characteristics were comparable and visual acuity was well balanced across study arms

Patients treated with pegaptanib sodium were less likely to lose 15 or more letters 9% and 0.3-mg pegaptanib sodium group

( P=.03 ) 6% 1-mg pegaptanib sodium groups (P=.01) 31% sham-treated eyes

Results

Figure 2. Distributions of changes in visual acuity from baseline at 6 and 30 weeks.

Patients treated with pegaptanib sodium showed greater improvement in mean visual acuity • 7.1 letters 0.3-mg pegaptanib sodium group ( P=.09 )• 9.9 letters , 1-mg pegaptanib sodium groups (P=.02)• −3.2 letters with sham

By week 1, the mean central retinal thickness decreased by

269 μm in 0.3-mg group (P=.001).210 μm in 1-mg pegaptanib sodium groups 5 μm with sham

Cont. Results

Figure 3. Mean change from baseline in center point thickness. Last observation carried forward. *P.001.

Based on this 30-week study, intravitreous pegaptanib sodium appears to provide visual and anatomical benefits in the treatment of macular edema following CRVO.

Improvement with intravitreous pegaptanib sodium treatment of macular edema following CRVO suggest a role for vascular endothelial growth factor in the pathogenesis of this condition.

Conclusions:

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