Comparison of Intraocular Pressure, Blood Pressure, Ocular Perfusion Pressure and Blood Flow Fluctuations During Dorzolamide Versus Timolol Add-On Therapy in Prostaglandin Analogue Treated Glaucoma Subjects

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.

Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis

“…[5][6][7] Since a lower BP in the context of higher IOP may result in poor optic nerve perfusion, glaucoma drugs are frequently scrutinized for their effects on both IOP and OPP. 8,9 Finally, post hoc analysis of two RCTs found that lower OPP was associated with glaucoma progression. 10,11 Several common gene variants have been identified for IOP 12 and BP.…”

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on 24-hour blood and ocular perfusion pressures: the results of a randomized trial

“…A recent 24-hour study found that timolol (both solution and gel formulations) had no relevant effect on BP and PP in patients with POAG [ 25 ]. In another clinical trial where the timolol add-on therapy in prostaglandin treated glaucoma patients was evaluated, larger PP fluctuations were recorded after timolol [ 26 ]. In another recent prospective cross-over study, timolol was found to cause retinal vascular dysregulation in response to posture change in 30% of the trial sample after 6 weeks of treatment [ 27 ].…”

Influence of Latanoprost on Retinal Microcirculation in Glaucoma

“…Januleviciene and coworkers compared dorzolamide and timolol as add-on therapy to latanoprost in glaucoma patients and found in both an additional IOP lowering effect but dorzolamide showed lower fluctuations in IOP, systolic perfusion pressure and blood pressure. They observed that higher variability of ocular perfusion pressure led to impaired retrobulbar blood flow [ 25 ].…”

“…Long-time follow-up studies have to show if glaucoma patients have a greater benefit from an intraocular pressure lowering therapy by surgery or laser which leads to an improved dilation of retinal vessels on metabolic demand [ 14 , 15 ] but which carries with it the danger of reperfusion damage or whether a topical treatment with drugs like latanoprost that does not alter vessel reaction in a statistical significant way is to be preferred. An alternative may be topical IOP lowering drugs with dual effect – IOP lowering and improvement of ocular blood supply [ 24 , 25 , 29 , 30 ].…”