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Background: To investigate the levels of nitric oxide (NO) markers in plasma and aqueous humour of patients with primary open angle glaucoma (POAG) and their relation to ocular perfusion pressure. Methods: Cyclic guanosine monophosphate (cGMP) and nitrite (NO2-) were determined in plasma and aqueous humour of 38 patients with POAG and 46 controls. Blood pressure and IOP were measured to calculate ocular perfusion pressure (PP). Results: cGMP and NO2- plasma levels were significantly decreased in glaucoma patients compared with controls (p=0.001 v p=0.004). In the aqueous humour of subjects with POAG, cGMP and NO2- concentrations were also lower than in normal eyes (p=0.0001 v p=0.001). There was a linear association between cGMP in plasma and aqueous humour in glaucomas and controls (r=0.514, p= 0.029 and r= 0.558, p = 0.004) and this relation differed in the two groups (p = 0.003). Considering glaucoma patients with controls, a positive correlation was found between cGMP and PP (r=0.379, p=0.01) and between NO2- and PP (r=0.339, p=0.040). The cGMP/PP correlation was of borderline statistical significance in controls (p = 0.050), whereas it did not attain statistical significance in POAG, as well as the association between NO2- and PP when glaucomas and controls were considered separately. Conclusions: The authors found alterations of NO markers in the plasma and aqueous humour of glaucoma patients. Primary or secondary impaired NO balance could alter ocular perfusion pressure. [ABSTRACT FROM AUTHOR]