Anton Hommer

Endothelial dysfunction in glaucoma

Glaucoma is a group of ocular diseases characterized by optic neuropathy associated with loss of the retinal nerve fibre layer and re‐modelling of the optic nerve head, and a subsequent particular pattern of visual field loss. Increased intraocular pressure is the most important risk factor for the disease, but the pathogenesis of glaucoma is not monofactorial. Among other factors, ischaemia and vascular dysregulation have been implicated in the mechanisms underlying glaucoma. The vascular endothelium plays an important role in the regulation of ocular blood flow and pathological alterations of vascular endothelial cells may induce ischaemia and dysregulation. The present review summarizes our current evidence of endothelial dysfunction in glaucoma. This is of interest because endothelial dysfunction is a good prognostic factor for progression in several diseases. Although such data are lacking for glaucoma, endothelial dysfunction may provide an attractive target for therapeutic intervention in open‐angle glaucoma and other vascular disorders of the eye.

Estimation of Ocular Rigidity Based on Measurement of Pulse Amplitude Using Pneumotonometry and Fundus Pulse Using Laser Interferometry in Glaucoma

PURPOSE There is evidence from theoretical models and animal studies that the biomechanical properties of the optic nerve head and the sclera play a role in the pathophysiology of glaucoma. There are, however, only a few data available that demonstrate such biomechanical alterations in vivo. In this study, the hypothesis was that patients with primary open-angle glaucoma (POAG) have an abnormal ocular structural stiffness based on measurements of intraocular pressure amplitude and ocular fundus pulsation amplitude (FPA). METHODS Seventy patients with POAG and 70 healthy control subjects matched for age, sex, intraocular pressure and systemic blood pressure were included. The ocular PA and pulsatile ocular blood flow were assessed with pneumotonometry. The FPA was measured by using laser interferometry. Based on the Friedenwald equation, a coefficient of ocular rigidity (E1) was calculated relating PA to FPA. RESULTS There was no difference in systemic blood pressure, intraocular pressure, and ocular perfusion pressure (OPP) between the patients with glaucoma and the healthy control subjects. Both, FPA and PA were lower in the patients with glaucoma than in the control subjects. The calculated factor E1 was significantly higher in the patients with POAG (0.0454 +/- 0.0085 AU) than in the control subjects (0.0427 +/- 0.0058 AU, P = 0.03). Multiple regression analysis revealed that E1 was independent of age and sex, and correlated only slightly with OPP. CONCLUSIONS The present study indicates increased ocular rigidity in patients with POAG. This is compatible with a number of previous animal experiments and supports the concepts that the biomechanical properties of ocular tissues play a role in the diseases process.

Effect of Dual Endothelin Receptor Blockade on Ocular Blood Flow in Patients with Glaucoma and Healthy Subjects

PURPOSE Several lines of evidence indicate that altered blood flow regulation may contribute to the pathogenesis of glaucomatous optic neuropathy. Recent data support the hypothesis that the endothelin system is involved in the processes that lead to vascular dysregulation in glaucoma. This study was conducted to test the hypothesis that bosentan, a dual endothelin receptor antagonist, increases ocular blood flow in patients with glaucoma. METHODS Fourteen patients with primary open-angle glaucoma and 14 sex- and age-matched healthy volunteers were included. Both groups received bosentan 500 mg daily for 8 days. Ocular hemodynamics were assessed at baseline and on the last study day. Retinal vessel diameters and retinal red blood cell velocity were recorded with a retinal vessel analyser and laser Doppler velocimetry, respectively. Choroidal and optic nerve head blood flow were measured with laser Doppler flowmetry. RESULTS Retinal arteries and veins showed a significant dilatation after administration of bosentan in both groups (+5%-8%). Retinal blood velocity and retinal blood flow increased up to +45% after administration of bosentan in both patients and healthy subjects. Administration of bosentan increased choroidal (+12%-17%) and optic nerve head blood flow (+11%-24%) in both groups. The effect of bosentan on ocular blood flow parameters was comparable between the two groups. CONCLUSIONS The data from the present study indicate that dual inhibition of endothelin receptors increases ocular blood flow in patients with glaucoma and healthy subjects. Further studies are needed to study the dose-response relationship of this effect and to characterize the role of endothelin receptor subtypes.

Effect of dorzolamide and timolol on ocular pressure: blood flow relationship in patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE The authors have reported previously that a study population, consisting of patients with glaucoma and ocular hypertension, is characterized by an impaired association between ocular blood flow parameters and systemic blood pressure, indicative of abnormal autoregulation. Here they report on the effects of dorzolamide and timolol on ocular pressure/flow relationships to test the hypothesis that these drugs improve autoregulation. METHODS One hundred forty patients with primary open-angle glaucoma or ocular hypertension were included in a clinical trial in a controlled, randomized double-masked study in two parallel groups. Seventy patients were randomly assigned to receive timolol, and 70 patients were randomly assigned to receive dorzolamide for a 6-month period. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. The association between blood flow parameters and systemic blood pressure was compared before and after the 6-month treatment period. RESULTS Before treatment a significant association was observed between ocular blood flow parameters and systemic blood pressure in both parallel groups (r = 0.23-0.42). All regression lines between ocular hemodynamic parameters and systemic blood pressure were less steep after treatment with either dorzolamide or timolol (r = 0.03-0.24). CONCLUSIONS The present study indicates that intraocular pressure reduction with timolol or dorzolamide is associated with normalization of the ocular pressure/flow relationship. Whether this is related to the beneficial effects of IOP-lowering therapy in glaucoma remains to be established. (ClinicalTrials.gov number, NCT00991822.).

Retrobulbar blood flow velocities in open angle glaucoma and their association with mean arterial blood pressure.

PURPOSE A number of previous studies have shown that blood velocities in retrobulbar arteries, as assessed with color Doppler imaging (CDI), are reduced in primary open angle glaucoma (POAG) patients, indicative of reduced blood flow to the eye. In the present study, the authors hypothesized that patients with POAG show an abnormal association between retrobulbar blood flow velocities as assessed with CDI and blood pressure, indicative of vascular dysregulation. METHODS A total of 252 POAG patients and 198 healthy age-matched control subjects were included. Mean flow velocity (MFV) in the ophthalmic artery (OA), posterior ciliary artery (PCA), and central retinal artery (CRA) were measured with CDI. Mean arterial blood pressure was measured noninvasively using automated oscillometry, and intraocular pressure was measured using Goldmann applanation tonometry. RESULTS Intraocular pressure was increased in POAG patients compared with healthy controls (P < 0.01). Mean arterial blood pressure was not different between groups. All blood flow velocities were significantly reduced in POAG patients compared with healthy control subjects (P < 0.01 each). The correlation between MFV and mean arterial blood pressure in the CRA was stronger in POAG subjects than in healthy control subjects. CONCLUSIONS These data indicate that blood flow velocities in retrobulbar vessels are reduced in POAG patients compared with healthy control subjects. In addition, an abnormal correlation between blood velocities and mean arterial blood pressure was found in POAG. This suggests vascular dysregulation and supports the concept that reduced ocular blood flow in glaucoma is not solely a consequence of the disease.

Comparison of Travoprost and Bimatoprost plus Timolol Fixed Combinations in Open-Angle Glaucoma Patients Previously Treated with Latanoprost plus Timolol Fixed Combination

PURPOSE To compare the ocular hypotensive effect of bimatoprost plus timolol and travoprost plus timolol fixed combinations in glaucoma patients whose disease was controlled but had not reached their target intraocular pressure (IOP) with the fixed combination of latanoprost plus timolol. DESIGN A 2 × 3-month, multicenter, prospective, randomized, double-masked, cross-over clinical trial. METHODS Eighty-nine open-angle glaucoma (OAG) patients were included. After a 6-week run-in period with latanoprost plus timolol, patients were randomized to either travoprost plus timolol or bimatoprost plus timolol for 3 months. Patients then switched to the opposite therapy for 3 additional months. The primary end point was the comparison of mean daily IOP after 3 months of each treatment. RESULTS At baseline, mean IOP was 16.5 mm Hg (95% confidence interval, 16.0 to 17.0 mm Hg) with treatment with latanoprost plus timolol. Both bimatoprost plus timolol and travoprost plus timolol statistically significantly reduced the mean IOP from baseline (P < .0001). Mean IOP at month 3 was statistically significantly lower in the bimatoprost plus timolol group compared with the travoprost plus timolol group (14.7 mm Hg [95% confidence interval, 14.3 to 15.3 mm Hg] vs 15.4 mm Hg [95% confidence interval, 15.0 to 15.9 mm Hg]; P = .0041). IOP was lower during bimatoprost plus timolol treatment at all time points and statistical significance was reached at 8 am, 11 am, and 5 pm, but not at 2 pm and 8 pm. Both treatments showed similar tolerability profile. CONCLUSIONS Bimatoprost plus timolol and travoprost plus timolol can provide additional IOP-lowering effect in patients not fully controlled with latanoprost plus timolol. The observed additional IOP reduction was greater with bimatoprost plus timolol with a similar tolerability profile.

Preservative-free treatment in glaucoma: who, when, and why?

Purpose To review and summarize the available literature on the effect of preservatives on the eye, to provide practical guidance for the clinical assessment of the ocular surface in glaucoma patients, and to define patient populations that might benefit from preservative-free topical intraocular pressure (IOP)–lowering agents. Methods This manuscript is based on a combination of a literature review on preservatives and the eye and expert opinion from glaucoma specialists with an interest in ocular surface disease. Results There is an increasingly recognized association between eyedrop preservatives and ocular surface disease. Preservative-free therapy is now available for a wide range of active compounds, although there are still some misconceptions regarding their appropriate use. For patients treated topically for glaucoma or ocular hypertension, a rough estimate could be that 20% may need treatment with topical IOP-reducing agents that are free from preservatives. Conclusions This review provides an up-to-date account of the literature regarding preservatives and the eye, as well as suggestions and recommendations on to when to use preservative-free antiglaucoma treatment.

Correlation of optic disc morphology and ocular perfusion parameters in patients with primary open angle glaucoma

Purpose:  Little information is available about the relationship between glaucomatous visual field defects, morphological changes of the optic disc and ocular blood flow. In this study, ocular blood flow parameters were correlated with parameters of optic nerve head (ONH) morphology and visual field performance in a cross‐sectional study.

Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation during Isometric Exercise in Healthy Humans

PURPOSE We determined whether administration of a nitric oxide synthase (NOS) inhibitor alters optic nerve head blood flow (ONHBF) regulation during isometric exercise in healthy subjects. METHODS Our study was done in a randomized, placebo-controlled, double-masked, three-way crossover design. A total of 18 healthy subjects was randomized to receive either placebo, phenylephrine, or an inhibitor of NOS (L-NMMA) on three different study days. ONHBF was measured with laser Doppler flowmetry while the study participants performed isometric exercise (squatting). This was done before drug administration and during infusion of the study drugs. Mean arterial pressure (MAP) and IOP were measured noninvasively, and ocular perfusion pressure (OPP) was calculated as 2/3 MAP - IOP. RESULTS The response in ONHBF to isometric exercise was less pronounced than the response in OPP, indicating for some autoregulatory capacity in the ONH. Administration of L-NMMA significantly decreased ONHBF at rest (P < 0.01). In contrast, inhibition of NOS did not alter the pressure-flow relationship in the ONH during an experimental increase in OPP compared to phenylephrine and placebo (P = 0.37 between groups). CONCLUSIONS The data of our study support previous findings that ONHBF is autoregulated during an experimental increase in OPP. Nitric oxide has an important role in basal ONHBF regulation, but seems not to be involved in the autoregulatory response during an increase in OPP induced by isometric exercise. (ClinicalTrials.gov number, NCT00806741.).

Scanning Laser Polarimetry (SLP) for Optic Nerve Head Drusen

Optic nerve head drusen (ONHD) are either clinically invisible or clearly protruding from the disc, in the later case leading to the condition of an irregular, indistinct disc margin or a swollen disc on biomicroscopy. They also may cause visual field defects, even with slow progression. Scanning laser polarimetry (SLP) has been proposed as a rapid, objective and reproducible technology for retinal nerve fiber layer (RNFL) assessment and clinical studies have demonstrated that SLP can help to distinguish between normal andglaucomatous eyes, identify glaucoma suspects and correlates well with visual field defects.The purpose of this study was to evaluate the potential applicabilityof SLP in 20 consecutive patients with optic nerve head drusen (18 bilateral) thatwere clinically visible (22 eyes) and invisible (16 eyes). RNFL thickness was studied in patients with and without visual field defects.Patients with visual field defects and ONHD were significantly olderand had a small, but significant reduction of visual acuity. Some global SLP parameters (average thickness, ellipse average) were significantly different between subjects with normal and abnormal visual fields. The comparison of the groups with visible and invisible drusen showed that there was no difference in demographic or perimetric data. RNFL thickness measurements were also very similar in both groups.Clinical visibility of drusen was not correlated with RNFL thinningas measured with the GDxTM. SLP assessment, however, was well correlated with functional loss. This objective, non-invasive technology may be an additional option for RNFL evaluation in this condition and an especially useful tool for long-term follow-up.