Abstract
Objective: To compare the effects of dorzolamide and timolol add-on therapy in open-angle glaucoma (OAG) patients previously treated with prostaglandin analogue (Pg), by evaluating fluctuations in the intraocular (IOP), blood (BP), ocular perfusion pressures (OPP) and retrobulbar blood flow (RBF) parameters. Methods: 35 OAG patients (35 eyes), 31 women (88.6%) age 63.3 (8.9) years were evaluated in a 3 month randomized, cross-over, single-masked study. During the experiments BP, heart rate, IOP and OPP were assessed 4 times per day (8–12–16–20 h). RBF was measured twice per day (8–20 h) using Color Doppler imaging in the ophthalmic (OA), central retinal (CRA), nasal (nSPCA) and temporal (tSPCA) posterior ciliary arteries. In each vessel, peak systolic velocity (PSV) and end-diastolic velocity (EDV) were assessed and vascular resistance (RI) calculated. Results: Both add-on therapies lowered IOP in a statistically significant manner from 15.7 ± 2.4 mmHg at latanoprost baseline to 14.9 ± 2.2 mmHg using dorzolamide (p < 0.001) and 14.2 ± 1.9 mmHg using timolol (p < 0.001). The IOP lowering effect was statistically significant at 20 h, favoring timolol as compared to dorzolamide (1.4 ± 2.4 vs. 0.2 ± 2.1 mmHg), (p < 0.05). Dorzolamide add-on therapy showed smaller IOP (2.0 ± 1.4), SPP (13.3 ± 7.9), systolic BP (13.5 ± 8.7) and diastolic BP (8.4 ± 5.4) fluctuations as compared to both latanoprost baseline or timolol add-on therapies. Higher difference between morning and evening BP was correlated to decreased evening CRA EDV in the timolol group (c = −0.41; p = 0.01). With increased MAP in the morning or evening hours, we found increased evening OA RI in timolol add-on group (c = 0.400, p = 0.02; c = 0.513, p = 0.002 accordingly). Higher MAP fluctuations were related to impaired RBF parameters during evening hours-decreased CRA EDV (c = −0.408; p = 0.01), increased CRA RI (c = 0.576; p < 0.001) and tSPCA RI (c = 0.356; p = 0.04) in the dorzolamide group and increased nSPCA RI (c = 0.351; p = 0.04) in the timolol add-on group. OPP fluctuations correlated with increased nSPCA RI (c = 0.453; p = 0.006) in the timolol group. OPP fluctuations were not related to IOP fluctuations in both add-on therapies (p < 0.05). Conclusions: Both dorzolamide and timolol add-on therapies lowered IOP in a statistically significant fashion dorzolamide add-on therapy showed lower fluctuations in IOP, SPP and BP. Higher variability of daytime OPP led to impaired RBF parameters in the evening.
Highlights
Several large, multicenter, randomized clinical trials have shown that in many cases glaucoma continues to progress, despite maintaining target intraocular pressure (IOP) [1,2] The contribution of vascular deficits in glaucomatous optic neuropathy (GON) is based upon a recent increase in clinical data on vascular dysregulation involved in glaucoma pathology and was reflected by the WorldGlaucoma Association consensus on ocular blood flow (OBF) in glaucoma [3].Non-IOP factors such as lower systolic ocular perfusion pressure (OPP), reduced OBF, cardiovascular disease, low systolic blood pressure (BP) have been identified as risk factors for primary GON
Higher variability of daytime OPP led to impaired retrobulbar blood flow (RBF) parameters in the evening
Higher MAP fluctuations were related to impaired RBF parameters during evening hours-decreased central retinal (CRA) end-diastolic velocity (EDV) (c = −0.408; p = 0.01), increased
Summary
Glaucoma Association consensus on ocular blood flow (OBF) in glaucoma [3]. Non-IOP factors such as lower systolic ocular perfusion pressure (OPP), reduced OBF, cardiovascular disease, low systolic blood pressure (BP) have been identified as risk factors for primary GON. Evidence suggest that subjects with glaucoma fail to adapt to changes either in IOP or BP that cause fluctuations in OPP, resulting in unstable blood flow to the retina and optic nerve head [5,6]. The day-night variations of IOP have been previously analyzed in healthy subjects and in primary glaucoma patients [7]. Asrani and colleagues pointed the risk associated with diurnal IOP variations in patients with open-angle glaucoma and showed the importance of controlling IOP throughout the day [8]
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