Calcium channel antagonists are peripheral vasodilators and theoretically may increase optic nerve perfusion, a possible beneficial effect for NTG and OAG patients [26, 27]. However, reports indicate that patients taking systemic calcium channel antagonists have a significantly increased risk of developing OAG [28]. The Rotterdam Eye Study recently reported that participants taking calcium channel antagonists for systemic hypertension had a 1.8-fold higher risk of developing incident OAG [29] than those not taking these medications. These results are in contradiction to other small studies (n < 60 in each study) that support the use of calcium channel antagonists for the treatment of NTG [27, 30].

The Thessaloniki Eye Study [31] and a recent study by Jonas [32] showed that in persons without glaucoma, both lower diastolic blood pressure secondary to systemic antihypertensive and lower OPP were associated with increased optic nerve cupping and thinner neuroretinal rims, thus suggesting that hypotension or low OPP may predispose one to glaucoma. The Barbados Eye Study also recently reported that the lower the OPP the greater the risk to develop OAG, with the relative risk at least doubling in the lowest perfusion pressure categories [14]. These results are in line with a recent review by Pache and Flammer [7] who concluded that the evidence is stronger for a link between OAG and hypotension than between OAG and hypertension.

19.3.1.2  Patients with Vasospasm

Another potential source of glaucomatous optic nerve damage is a transient change in vascular perfusion due to vasospasm [11, 26]. Such vascular alterations may provoke reperfusion damage [33]. Vasospasm can be provoked by many factors, including exposure to cold, stress, emotional upset, and nicotine. These frequently encountered triggers may possibly promote daily episodes of hypoxia-reperfusion injury [7].

The data concerning an association between vasospasm and glaucoma is conflicting, however. Earlier reports suggested a link between vasospasm and NTG [34]. In NTG, migraine (a form of vasospasm) was reported to be an independent risk factor for progressive visual field loss [35]. These findings were not confirmed in high pressure POAG patients [36]. However, it has been suggested that POAG patients suffer from

systemic autonomic and ocular vascular dysregulation. Cold provocation elicits blood pressure and OBF changes in patients with POAG which are different from that seen in control subjects [37]. Clinical features of primary vascular dysregulation include low blood pressure, slower onset of sleep and sleep apnea [38, 39], decreased awareness of thirst [40] coupled with low daily fluid intake, and low body mass index [8]. People with vasospastic syndrome usually are otherwise healthy and require no special treatment. Buckley et al. hypothesized that a possible cause of vasospastic­ syndrome is vascular endotheliopathy [41].

19.3.1.3  Patients with Nocturnal Blood Pressure Dips

Nocturnal hypoperfusion of the eye in glaucoma has been described widely by Hayreh et al. [42], who reported lower systolic and diastolic nocturnal blood pressure in anterior ischemic optic neuropathy and in glaucomatous optic neuropathy. Other studies have also reported lower nocturnal blood pressure parameters in patients with progressive visual field defects compared to patients with stable visual fields [43] and in OAG patients with progression despite well controlled IOP [44].

The most devastating factor in these patients is a drop in diastolic blood pressure to levels of 40 mmHg in contrast to values of 70 mmHg in normal patients. [42]. The literature suggests that nocturnal hypotension in the presence of other vascular risk factors, may reduce optic nerve head blood perfusion below a critical level and thereby may play a role in the pathogenesis of glaucomatous optic neuropathy [45]. Ambulatory monitoring of blood pressure during a 24-h period is the method of choice to assess blood pressure dips.

19.3.1.4  Diabetes

The relationship between diabetes and OAG is also inconsistent. There was no association between diabetes, hypertension, and OAG in the prevalence papers from the Rotterdam Eye Study [19, 46]. Other studies have shown that diabetic patients are at significantly increased risk for developing POAG [47, 48].