Bevacizumab Versus Ranibizumab for Diabetic Retinopathy
Status:
Completed
Trial end date:
2013-04-01
Target enrollment:
Participant gender:
Summary
Treatment of diabetic macular edema with perifoveal focal/grid laser coagulation was found to
be effective saving the visual acuity only in 50% of patients and only 3-14% of treated
patients had an improved visual acuity postoperatively. The decent results of
lasercoagulation are associated with potential side effects, as focal scotomas, change of
color discrimination and development of epiretinal gliosis. The frequency of perifoveal laser
treatments is anatomically limited in case of diabetic macular edema: after application of
about 350 coagulates there is no possibility to repeat the laser treatment perifoveolar
without creating confluent lasercoagulates and causing significant scotomas. In case of
persistence of edema in spite of complete perifoveal grid coagulation, no standard therapy
exists. Some previous studies investigated the effect of steroids in patients with diabetic
macular edema unresponsive to grid laser photocoagulation, but the benefit on the visual
acuity was only temporary and the intravitreal application was associated with significant
side effects as cataract progression (up to 50%) and ocular hypertension (up to 20%).
In the Diabetic Retinopathy Study the 4-years rate for severe vision loss in patients with
high-risk retinopathy was 20.4 %. In cases of proliferative retinopathy, panretinal (scatter)
photocoagulation can reduce the risk for development of high-risk retinopathy by 50% over 6
years. When panretinal lasercoagulation is initiated, about 2000 laser spots are equally
distributed in all four quadrants. Since panretinal photocoagulation bares risks like loss of
field of vision, central vision reduction and loss of colour vision, this treatment can not
be continued unlimited.
In cases of persisting neovascularisations in spite of panretinal photocoagulation, no
evidence based therapy exists. There is a high risk for intravitreal bleeding, rubeosis,
secondary glaucoma with severe vision loss. When fibrovascular proliferation leads to retinal
detachment, vitreo-retinal surgery might be indicated.
Now we know that vascular endothelial growth factor (VEGF) is the major angiogenic stimulus
responsible for increase of vasopermeability, cellproliferation and angiogenesis in diabetic
retinopathy (DRP). Several studies, evaluating VEGF levels in vitreous, have indicated a role
for VEGF in diabetic macular edema: vitreous samples of patients with diabetic macular edema
contain elevated VEGF concentration and VEGF injected in experimental studies results in
breakdown of the blood-retina barrier.
There is increasing evidence for a therapeutic role of anti-VEGF drugs not only in
age-related macular degeneration but also in other diseases as in diabetic macular edema.
Intravitreal injections have become the most favored treatment procedure for administering
anti-VEGF drugs.
The side effects and the decent results of laser treatment on the visual acuity in diabetic
macular edema led to studies using anti-VEGF therapy. Unpublished study results on the
aptamer pegaptanib (Macugen™) are promising. A study using the antibody fragment Ranibizumab
(Lucentis™) in patiens with diabetic macula edema is in progress. Ranibizumab is now approved
to be used as an intravitreal injection.
Currently there is one additional anti-VEGF drug already on the market: Bevacizumab
(Avastin™), which has approved as intravenous infusion for the treatment of metastatic
colo-rectal cancer. Previous studies have shown that systemic use of Bevacizumab (Avastin™)
can obtain very promising results on patients with choroidal neovascularisation (CNV) by
age-related macular degenetration. This drug, a monoclonal full-length antibody, designed to
bind all isoforms of VEGF is a large molecule. But case reports in patients with CNV caused
by age-related macular degeneration and with macular edema from central retinal vein
occlusion indicate that intravitreally given Bevacizumab (Avastin™) is effective in diseases
originating from the choroids and the retina, too. These findings imply a sufficient
penetration of the retina by Bevacizumab (Avastin™).
Based on these new findings and the important role of VEGF in diabetic retinopathy, we
propose a pilot study for treatment of persistent diabetic macular edema or persisting active
neovascularistaions following lasercoagulation with intravitreally administered Bevacizumab
(Avastin™) or Ranibizumab (Lucentis™).