Ocular microangiopathy syndrome in patients with AIDS is associated with increased plasma levels of the vasoconstrictor endothelin-1

Abstract

Ocular microangiopathic syndrome is the most frequent ophthalmic finding in patients suffering from the acquired immunodeficiency syndrome (AIDS). Ocular microvascular changes including cotton-wool spots are closely associated with neuroretinal and cognitive deficits in patients infected with the human immunodeficiency virus type 1 (HIV-1). Endothelin-1 is a recently identified cytokine with potent vasoconstrictor activity which is associated with various diseases involving vascular structures. We studied 29 patients with AIDS by indirect ophthalmoscopy and by slit lamp biomicroscopy, and endothelin-1 immunoreactivity (IR) was measured in plasma by radioimmunoassay. Cotton-wool spots were counted as indicator of retinal microvasculopathy. Conjunctival bloodflow sludging in conjunctival vessels was measured by a standardized rating scale as indicator of conjunctival microvasculopathy. Parameters of immunosystemic damage were determined as covariates. Endothelin-1 IR was closely associated with the number of cotton-wool spots (Spearman r = 0.53, p < 0.01) and with the extent of conjunctival blood-flow sludging (r = 0.61, p < 0.001). The level of significance became stronger applying analysis of covariance with Endothelin-1 IR as dependent variable and number of cotton-wool spots (p < 0.0001) or extent of conjunctival blood-flow sludging (p < 0.0001) as independent variables. Our data are consistent with the hypothesis that the vasoconstrictor endothelin-1 has an important role in the pathogenesis of HIV-1-related ocular microangiopathic syndrome. As HIV-1-related ocular microangiopathic syndrome is associated with neuroretinal and cognitive deficits in patients with HIV-1 disease the therapeutic use of endothelin antagonists currently under investigation should be discussed.