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We read with great interest the excellent Editorial by Ciulla  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.' Furtherm...
We read with great interest the excellent Editorial by Ciulla  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 relationship 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 study  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 [225 vs 195pg/ml, p=0.019] and mean von Willebrand factor [124 vs 99 IU/dL, p=0.0004] levels were higher in ARMD patients compared to healthy controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the patients [both p<_0.0001. our="our" observations="observations" would="would" therefore="therefore" suggest="suggest" further="further" pathophysiological="pathophysiological" insights="insights" into="into" armd="armd" with="with" an="an" association="association" between="between" this="this" disorder="disorder" and="and" markers="markers" of="of" angiogenesis="angiogenesis" vegf="vegf" haemorheological="haemorheological" factors="factors" haemostasis="haemostasis" endothelial="endothelial" damage="damage" dysfunction.p="dysfunction.p"/>
Rather than the existence of individual pathogenic processes , 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 4 months follow-up, following treatment with pan-retinal laser photocoagulation .
Peck-Lin Lip (1,2)
Gregory YH Lip (2)
(1) The Birmingham and Midland Eye Centre, City Hospital, Birmingham, England;
(2) Haemostasis Thrombosis and Vascular Biology Unit,
University Department of Medicine, City Hospital, Birmingham;
(1) Ciulla TA. Evolving pathophysiological paradigms for age related macular degeneration. BJO 2001; 85: 510-12.
(2) Lip PL, Blann AD, Hope-Ross MW, Gibson J. Lip GYH. Age-Related Macular Degeneration Is Associated With Increased Vascular Endothelial Growth Factor, Hemorheology and Endothelial Dysfunction. Ophthalmology 2001;108:705-10
(3) Lip PL, Belgore F, Blann AD, Hope-Ross MW, Gibson JM, Lip GYH. "Plasma VEGF and Soluble VEGF Receptor Flt-1 in Proliferative Retinopathy: Relationship to Endothelial Dysfunction and Laser Treatment." Investigative Ophthalmology & Visual Science 2000; 41: 2115-19.