Intravitreal Ranibizumab for VH Due to PDR (N)

In mild to moderate cases of vitreous hemorrhage, PRP is performed when possible to achieve
regression of new vessels or at least stabilization of the neovascularization with no
further growth in order to decrease the probability of subsequent vitreous hemorrhage while
spontaneous absorption of the hemorrhage occurs. In cases in which the hemorrhage is too
dense to apply PRP, vitrectomy is considered to remove the hemorrhage and provide a clear
media for application of PRP (often as endolaser photocoagulation) as well as eliminate
extensive neovascularization and relieve traction retinal detachments. Pars plana vitrectomy
was introduced in the 1970s as a surgical intervention in diabetes for non-clearing vitreous
hemorrhage, traction retinal detachment or very severe PDR. The goal of vitrectomy in such
eyes is to remove the hemorrhage and provide a clear media for application of PRP (often as
endolaser photocoagulation) as well as eliminate extensive neovascularization and relieve
traction retinal detachments. Many advances in instrumentation and technique have resulted
in a dramatic reduction in complications over the last few decades, but surgical
complications remain including the following: neovascular glaucoma, retinal detachment,
fibrinoid syndrome, endophthalmitis and hypotony with subsequent phthisis bulbi. Recovery
for the subject can take up to 6 weeks.

Increased VEGF levels have been demonstrated in the retina and vitreous of human eyes with
diabetic retinopathy, especially PDR. VEGF has been demonstrated to increase vessel
permeability by increasing the phosphorylation of tight junction proteins, and has been
shown to increase retinal vascular permeability in in vivo models. Anti-VEGF therapy,
therefore, may represent a useful therapeutic modality which targets the underlying
pathogenesis of PDR while vitreous hemorrhage clears to facilitate the placement of PRP,
potentially avoiding vitrectomy.

This study is designed to determine if intravitreal injections of ranibizumab will
facilitate clearing of vitreous hemorrhage and avoidance of vitrectomy and its potential
complications. Compared with a surgical intervention, use of an intravitreal agent
associated with fewer vitrectomies would be preferable because of the reduced costs, reduced
time to treatment, reduced intervention time, relatively low risk of side effects, and
reduced recovery time. An intravitreal agent also would be a useful alternative for patients
who are unwilling to undergo surgery. Furthermore, the study will determine the safety of
this medication in the setting of PDR.