The results of the CavNav Trial, where the combination of Initial ranibizumab and deferred navigated retinal laser was compared to ranibizumab monotherapy in DME showed clearly that it is possible to achive comparable good visual and morphological results, but in the combined Treatment Group significant less injections were needed.

Additional therapy in DVE in my experience include Azopt 1% topical twice a day up to 6 mo.

Thats an interesting approach! Do you recommend that in all cases of DME or how you select the patients for topical brinzolamide?

I would prefer the use of Brimonidine, even before there is a clinical or significant macular edema.

Invest Ophthalmol Vis Sci. 2011 Dec 16;52(13):9527-33. Print 2011.

Role of β-Adrenergic Receptor Regulation of TNF-α and Insulin Signaling in Retinal Muller Cells.

Walker RJ, Anderson NM, Jiang Y, Bahouth S, Steinle JJ.

This is an interesting approach, I don’t use it but is seems to make sense to consider combining anti-VEGF and brimonidine for CNV and DME. Potential excitotoxic metabolites and their implications in neuronal damage can be treated with brimonidine to protect neurons. However, further research is needed to understand the exact molecular mechanism of neurodegeneration so that effective neuroprotection strategies can be developed. Nevertheless, these 2 studies are interesting:

Brimonidine (BRI) treatment prevents the hyperglycemia-induced increase in vitreoretinal vascular endothelial growth factor (VEGF) expression and breakdown of the blood–retinal barrier (BRB) in streptozotocin (STZ)-induced diabetic rats.BRI produced marked decreases in vitreoretinal VEGF and inhibition of BRB breakdown in diabetic rats (Kusari et al. Invest. Ophthalmol. Vis. Sci. February 2010 vol. 51 no. 2 1044-1051). The mechanism for these effects may involve attenuation of retinal NMDA receptor activity by BRI. The results suggest that BRI would be useful for treatment of ocular diseases associated with BRB leakage, such as diabetic macular edema and retinopathy.

Same authors (Kusari et al. Invest Ophthalmol Vis Sci. 2011 July; 52(8): 5424–5431) determined whether chronic treatment with brimonidine (BRI) attenuates retinal vascular leakage and neovascularization in neonatal mice after exposure to high oxygen in a mouse model of retinopathy of prematurity (ROP), and choroidal neovascularization (CNV) in rats after laser treatment. BRI treatment significantly attenuated vitreoretinal VEGF concentrations, retinal vascular leakage, and retinal and choroidal neovascularization in animal models of ROP and CNV. BRI may inhibit underlying event(s) of ischemia responsible for upregulation of vitreoretinal VEGF and thus reduce vascular leakage and retinal-choroidal neovascularization.

My understanding is that currently there are clinical trials (ClinicalTrials.gov) combining anti-VEGF and topical brimonidine for DME and in AMD but only looking at IOP results.

Marcus Kernt · 35.82 · 177.68 · Ludwig-Maximilian-University of Munich

Thats an interesting approach! Do you recommend that in all cases of DME or how you select the patients for topical brinzolamide?

Dear Prof. Kent,

I recommend brinzolamide for all patients since it works in macular edema.