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Editor,—We read with great interest the excellent editorial by Ciulla,1 which describes pathophysiological paradigms for age related macular degeneration (ARMD) and the development of choroidal neovascular membranes (CNVM). We were particularly pleased to note that Ciulla considered that “whatever the initial stimulus for CNVM formation, it is clear that angiogenic growth factors are ultimately involved.” Furthermore, he observed that primary vascular changes in the choroid may also be responsible.
In light of these observations, we had hypothesised a relation between abnormal vascularisation (angiogenesis), haemorheological factors, and endothelial dysfunction in patients with ARMD. We felt that abnormalities in the systemic and choroidal vasculature, may relate to the release of angiogenic factors and subsequent proliferation of choriocapillaris through a defect in Bruch's membrane in susceptible individuals. To investigate this hypothesis further, we recently reported a cross sectional study2 of patients presenting with ARMD and measured plasma levels of VEGF (an index of angiogenesis), haemorheological factors (fibrinogen, plasma viscosity), and von Willebrand factor (an index of endothelial damage/dysfunction) from these patients. Median plasma VEGF (225v 195 pg/ml, p = 0.019) and mean von Willebrand factor (124 v 99 IU/dl, p = 0.0004) levels were higher in ARMD patients compared with healthy controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the patients (both p <0.0001). Our observations would therefore suggest further pathophysiological insights into ARMD, with an association between this disorder and markers of angiogenesis (VEGF), haemorheological factors, haemostasis, endothelial damage/dysfunction.
Rather than the existence of individual pathogenic processes,1 perhaps a close interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may contribute to the pathogenesis of ARMD and the development of CNVM. Indeed, the availability of a blood marker for ARMD could have potential value, as measurement of such a marker can be a non-invasive way of perhaps predicting individuals at high risk of developing ARMD. We have recently applied such a concept (that is, a blood marker to monitor the progression of eye disease) in a study of plasma VEGF in diabetic proliferative retinopathy, where the high plasma levels were normalised at the 4 month follow up, after treatment with panretinal laser photocoagulation.3