Intravitreal Bevacizumab (Avastin®) for Diabetic Retinopathy at 24-months: The 2008 Juan Verdaguer-Planas Lecture

Abstract

Diabetic retinopathy (DR) remains the major threat to sight in the working age population. Diabetic macular edema (DME) is a manifestation of DR that produces loss of central vision. Proliferative diabetic retinopathy (PDR) is a major cause of visual loss in diabetic patients. In PDR, the growth of new vessels is thought to occur as a result of vascular endothelial growth factor (VEGF) release into the vitreous cavity as a response to ischemia. Furthermore, VEGF increases vessel permeability leading to deposition of proteins in the interstitium that facilitate the process of angiogenesis and macular edema. This review demonstrates multiple benefits of intravitreal bevacizumab (IVB) on DR including DME and PDR at 24 months of follow up. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse diabetic macular edema. Therefore, in the future this new therapy could replace or complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to pan-retina photocoagulation so that more selective therapy may be applied. In addition, we report a series of patients in which tractional retinal detachment developed or progressed after adjuvant preoperative IVB in severe PDR.

Inhibitory Activity of Bevacizumab to Differentiation of Retinoblastoma Cells

“…Based on that the differentiated retinoblastoma cells are mostly photoreceptors [32], our result provides that anti-VEGF therapies would affect to the maintenance or function of photoreceptors in mature retina, which is supported by a recent report that the neutralization of endogenous VEGF leads to unexpected neural toxicity [29]. Therefore, regardless of recent reports to demonstrate few clinically relevant ocular side effect [27], [28], pros and cons of anti-VEGF treatment should be carefully scrutinized.…”

“…Therefore, regardless of empirical evidence in clinics, anti-VEGF treatment using bevacizumab has been extensively applied in variable vaso-proliferative retinopathies [12]–[14]. Some clinical reports have demonstrated that intravitreal bevacizumab would be most effective against angiogenic and edematous ocular diseases [27], [28]. However, because VEGF could play as a neurotrophic and neuroprotective factor in nervous system as well as critical roles in vessels, VEGF inhibition could lead to serious neuroretinal damages [3]–[7].…”

Inflammation and diabetic retinal microvascular complications

“…These studies have led to the recognition of hyperglycemia, hypertension and dyslipidemia as major risk factors for DR. Consequently, tight glycemic control, blood pressure control and lipid-lowering therapy have shown proven benefits in reducing the incidence and progression of DR.[5] In clinic, laser photocoagulation and vitrectomy remain the two conventional approaches to treat sight-threatening conditions such as macular edema and proliferative DR.[6] Vascular endothelial growth factor (VEGF) blockers (Pegaptanib, Ranibizumab and Bevacizumab) in combination with laser photocoagulation represents an emerging novel therapy to reduce macular edema and induce neovascular regression. [5–7] In spite of this progress, DR remains a major clinical challenge, and the number of patients keeps growing due to difficulty in achieving tight glycemic control, metabolic memory, unresponsive to the current therapeutic approaches and significant side-effects from therapies. [568–10] There is a great need to develop new therapeutic approaches for this devastating disease.…”

Diabetic macular edema: Current and emerging therapies

“…Results of another large randomized control trial demonstrated similar results for ranibizumab in the treatment of DME 4647. Promising results for the treatment of DME have also been reported for the use of bevacizumab in a large retrospective and one smaller prospective study48–50 and for pegaptanib in a randomized control trial 51…”