Cummings and Cunha-Vaz Therefore, it may be concluded from both literature and clinical experience that diabetes may offer some degree of protection from the development of neovascular AMD. Current opinion in neovascular AMD treatment Although laser photocoagulation was the only treatment avail- able for many years, it is now only accepted for treatment of patients with well deﬁned, extrafoveally located CNV. Photo- dynamic therapy (PDT), which was approved in 2000 predomi- nantly for the treatment of CNV, has been shown to prevent progression of vision loss when compared with controls, but the main result is temporary stabilization of visual acuity loss. Combining PDT with anti-inﬂammatory drugs (such as triamcinolone or other steroids) has offered improved visual outcomes through a reduction of the inﬂammation caused by PDT. However, the use of steroids can induce several complications. In an attempt to deal with these problems, a variety of sustained-release devices have been introduced to modulate drug delivery to the eye. Although the current evidence base is inconclusive, it is expected that the inﬂammatory repair responses present in both diabetic retinopathy and neovascular AMD may be cumulative and may be compounded when wet AMD is pres- ent in eyes of patients with diabetic retinal disease. Vascular endothelial growth factor (VEGF) inhibitors are now being used for the treatment of eyes with neovascular AMD, and have shown a signiﬁcant degree of success. Treat- ment with these anti-VEGF agents has even demonstrated that a degree of recovery of visual function, followed by stabilization of such recovery, is possible. Pegaptanib sodium (Macugen®, [OSI] Eyetech Pharmaceuticals Inc, New York NY, USA), a selective inhibitor of VEGF, has shown efﬁ- cacy in trials including all angiographic types of neovascular AMD (Gragoudas et al 2004). The series of trials, together termed VISION, were speciﬁcally designed not to differenti- ate patients on angiographic indications, but rather with the intention of validating the hypothesis that selective inhibition of VEGF could provide a safe and effective treatment for patients of all subtypes of neovascular AMD. Ranibizumab (Lucentis®, Genentech Inc, South San Francisco, CA, USA) is a non-selective anti-VEGF agent and approaches inhibition of VEGF in more general terms. In clin- ical trials (Brown et al 2006; Rosenfeld et al 2006), the agent has demonstrated that it not only stabilizes the progression of neovascular AMD, but can also lead to an improvement in vision in patients with speciﬁc subtypes of the disease. A series of anecdotal reports have conﬁrmed these ﬁndings with 374 bevacizumab (Avastin®, Genentech Inc, South San Francisco, CA, USA), a drug of the same class, but which is indicated for colorectal cancer and has no license for use in the eye, and has not been submitted for clinical trial evaluation. Addressing CNV with a non-selective VEGF inhibition, as is the approach of ranibizumab, has demonstrated better visual outcomes. These data may suggest that selective inhi- bition of VEGF is an important component of combating the disease process, but that there are also other factors present that require treatment. This argument favors combination approaches for treatment of neovascular AMD. Treatment of neovascular AMD in patients with diabetes There are at least two important factors to consider when treating neovascular AMD in patients with diabetes: the role of retinal edema in the modulation of treatment and the relevance of associated side effects of the treatment. Evaluation of treatment and re-treatment timing is now very much associated with the degree and evolution of retinal edema detected by OCT. Retinal edema is the most frequent alteration in the diabetic retina and its presence may delay recovery and drying of the retina immediately after treatment for neovascular AMD. Also of note is the consideration of potential side effects that may be induced by repeated treatments with less selective anti-VEGF agents. Any such side effects may be particularly relevant in patients with diabetes, in light of their associated micro- and macrovascular complications. Conclusions Current evidence demonstrates that the coexistence of diabetic retinopathy and neovascular AMD is uncommon, potentially suggesting that diabetes may offer a protective role against the development of neovascular AMD. This interesting hypoth- esis may be explained by the fact that each disease is initiated by selective involvement of one of the two components of the BRB. The early stages of diabetic retinopathy begin with alterations of the inner BRB, whereas AMD involves the outer BRB. There is some evidence in the literature indicating that, in the case of diabetic retinal edema, there is signaling from the damaged inner BRB that induces up-regulation of the transport function of the RPE (outer BRB) (Sander et al 2001). As a result, diabetic retinal disease may help delay development of the AMD alterations that lead to wet AMD. In patients with diabetes who require treatment for neo- vascular AMD, the choice of therapy and timing of treatments and re-treatments (based on degree of retinal edema measured Clinical Ophthalmology 2008:2(2)