Treatment of neovascular age-related macular degeneration in patients with diabetes The accepted clinical hallmark of dry AMD is the appearance of drusen: localized deposits lying between the basement membrane of the retinal pigment epithelium (RPE) and Bruch’s membrane. Clinically, drusen are clas- siﬁed morphologically as either hard or soft. Soft drusen are generally larger and have indistinct edges, and have a tendency to become conﬂuent. Typically, drusen are clustered in the central macula, where the pathological abnormalities in AMD are most pronounced. At various stages, the RPE, photoreceptors and choroidal vasculature are involved. Geographic atrophy is characterized by the presence of conﬂuent areas of RPE cell damage accompanied by overlying photoreceptor atrophy. Geographic atrophy can develop following fading of drusen, in areas of RPE attenuation, following flattening of an RPE detachment, or after involution of choroidal neovascularization (CNV). The visible atrophy is usually accompanied by an atrophic underlying choriocapillaris. Both geographic atrophy and CNV tend to develop in patients with large drusen and pigmentary changes. Patients with bilateral atrophy can develop CNV at a rate of 2%–4% over a 2-year period. The development of CNV (ie the growth of new blood vessels from the choroids) is the hallmark of neovascular (or exudative/wet) AMD. In AMD, the new vessels can remain beneath the RPE, or may breach the RPE and enter the retina space. The earliest signs of CNV are retinal edema and visual distortions. The ﬂuorescein angiographic leakage patterns of CNV are classiﬁed as either classic or occult. The former refers to discrete areas that hyperﬂuoresce early in the examination and continue to exhibit progressive leakage with increasing intensity and extent. Occult CNV refers either to a ﬁbrovascular RPE detachment with irregular elevation of the RPE, with stippled hyperﬂuorescence and late leakage, or to late leakage of undetermined origin. Retinal edema is particularly well demonstrated by OCT examination, and is indicated by an increase in thickness of the retina. It is one of the most widely accepted criteria for treatment and re-treatment of neovascular AMD. There are two special subtypes of wet AMD that are better identiﬁed with indocyanine green angiography (ICG): chorioretinal anasto- moses and polypoidal-choroidal neovascularization (Slakter et al 2000; Yannuzzi et al 1990). The two exhibit different patterns of disease progression and have different prognoses. The Disciform Scar Represents End-Stage Disease. Diabetic retinopathy and neovascular AMD are the two most frequent retinal degenerative diseases and are Clinical Ophthalmology 2008:2(2) responsible for the majority of cases of blindness due to retinal disease. The two conditions predominantly affect the central macula; their development is associated with the presence of retinal edema and an aggressive inﬂammatory repair process that accelerates disease progression. Both the retinal edema and the inﬂammatory repair process are directly associated with breakdown of the BRB. However, the underlying alterations to the BRB are very different in these two diseases. Diabetic retinopathy is, initially, a disease of the inner layers of the retina, beginning with an alteration of the inner BRB, located in the retinal endothelial cells. Contrastingly, neovascular AMD initially affects the outer retinal layers and starts at the chorioretinal interface (with an alteration of the outer BRB), located in the retinal pigment epithelium, which then allows invasion of the retina by neovessels located in the choriocapillaries. Treatment of neovascular AMD in patients with diabetes The population-based Framingham Eye Study, in addition to a number of other case-controlled studies, failed to ﬁnd an association between macular degeneration and diabetes mellitus. Data from the Beaver Dam Study (Klein et al 1992) suggest that diabetes is not related to macular drusen or geographic atrophy. The only association demonstrated was that between exudative macular degeneration and diabetes in men aged 75 years or older. In a different study (Zylbermann et al 1997), the preva- lence of neovascular AMD in patients with diabetic reti- nopathy was only 0.86%, which is lower than the prevalence in the general population. Furthermore, the investigators reported that patients treated with laser photocoagulation for diabetic retinopathy are less prone to the development of neovascular AMD. More recently, data were reported from a 10-year follow- up study of newly diagnosed patients with type 2 diabetes in Finland (Voutilainen-Kaunisto et al 2000). The study dem- onstrated that the incidence of neovascular AMD over time was possibly lower in the patients with diabetes compared with control subjects. Furthermore, the diabetic retinopathy fundus photography screening program in progress in the central region of Portu- gal has detected an incidence of diabetic retinopathy in 2.6% of patients with type 2 diabetes, but an incidence of only 0.4% of all types of AMD (and 0.05% of neovascular AMD). These values are clearly lower than the values reported for the general population, even taking into consideration the age of the patients examined. 373