Short-term variability of systemic blood pressure and submacular choroidal blood flow in eyes of patients with primary open-angle glaucoma

Purpose: To analyse short-term variability of systemic blood pressure and choroidal blood flow in glaucoma patients, and compare them with ocular hypertensive patients and controls. Subjects and methods: Thirty untreated patients with primary open-angle glaucoma (POAG), 25untreated patients with ocular hypertension (OHT) and 50healthy controls without local therapy were included in the study. Continuous 5-minute measurements of arterial systemic blood pressure (SBP) by Finometer and choroidal blood flow (CBF) by laser Doppler flowmetry were obtained. Variability of SBP and CBF was analysed by means of coefficient of variation and analyzed in ANOVA model. Linear regression analysis was performed on parameters of morphological (nerve fiber layer thickness) and functional glaucomatous damage (visual field) on one side, and between SBP and CBF on the other side. Results: ANOVA model demonstrated significant differences in variability between the groups (p = 0.003); post-hoc analysis specified a significantly higher short-term variability of both the blood pressure and choroidal blood flow in POAG patients (coefficients of variation: 3.33% ± 1.05% and 3.90% ± 2.17% respectively) than in healthy controls (coefficient of variation: 2.57% ± 0.80% and 2.94% ± 1.52% respectively). No significant differences were found for OHT patients. Conclusions: POAG patients without local therapy demonstrate an increased short-term BP and CBF variabilit

How latanoprost changed glaucoma management

Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first-choice treatment for primary open-angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes

Retinal neurovascular coupling in patients with glaucoma and ocular hypertension and its association with the level of glaucomatous damage

Purpose: To analyze neurovascular coupling in the retina of untreated primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. Patients and methods: Maximal vessel dilation in response to flicker light was analyzed with Retinal Vessel Analyzer (RVA) in temporal superior/inferior arterioles and veins in 51 POAG patients, 46 OHT and 59 control subjects. RVA parameters were compared between groups, between contralateral POAG eyes, and correlated to intraocular pressure, visual field mean defect and retinal nerve fiber layer thickness. Results: POAG eyes demonstrated generally smaller response of all vessels to flicker light than the other two groups (ANOVA p = 0.026; mean arterial flicker response in percent of baseline, averaged superior and inferior was 3.48 ± 2.22% for controls , 2.35 ± 2.06 % for POAG patients , and 2.97 ± 2.35 % for OHT patients; corresponding values for venules were 3.88 ± 1.98%, 2.89 ± 1.72%, 3.45 ± 2.77%). There was no difference in flicker response between the eye with more and less advanced damage in each patient of the POAG group (ANOVA p = 0.79). Correlation of flicker response to intraocular pressure (IOP) was borderline at best, correlations to the level of glaucomatous damage were not significant. Correlation of flicker response of superior and inferior vessels of the same eye was significant for the arteries (Pearson r = 0.23, p = 0.004), as well as venules (r = 0.52, p < 0.001). Conclusion: General vessel response to flicker light was decreased in POAG patients, compared to normal controls and OHT patients. In contrast to significant correlation between the two contralateral eyes of the flicker response itself, only its borderline correlation to IOP was seen. There was no correlation to the level of damage, altogether indicating a systemic dysregulation phenomenon. Grants: Swiss National Foundation Grant 3200B0-113685, Velux Stiftung Grant, Freie Akademische Gesellschaft (FAG) Grant, Pfizer Inc. Grant Clinical trial registration reference number: ClinicalTrials.gov NCT0043020

Dynamics of retinal vessel response to flicker light in glaucoma patients and ocular hypertensives

Purpose: To analyze dynamics of retinal vessel dilation response to flicker light in patients with glaucoma and ocular hypertension. Patients and methods: Response to flicker light was measured in retinal vessels by means of Retinal Vessel Analyzer. After the baseline 50seconds long diameter recording of inferior and superior temporal artery and vein, three flicker stimulations of 20seconds duration was applied, with a 80seconds break in between. Area under the curve of the vessel diameter (AUC) was compared during 3 flicker periods in the open angle glaucoma patients group (POAG, n = 47) and ocular hypertensives (OHT, n = 46) and age-matched healthy controls (n = 56) Results: POAG eyes demonstrated smaller response of all vessels to flicker light in general than the other two groups (p = 0.0008), but the response dynamics was significantly different between the groups (p = 0.038), showing in three flicker periods a delayed increasing response in the POAG and OHT groups, and remaining stable in healthy subjects. Conclusion: General vessel response to flicker light was decreased in POAG patients despite the slow improvement in repeated flicker stimulation, indicating an altered response patter

Circulatory response to blood gas pertubations

PURPOSE. To investigate the response of the optic nerve head and the choroidal circulation to blood gas perturbations in otherwise healthy subjects with a history of cold hands. METHODS. Thirty-five healthy subjects were selected and grouped according to the related history of cold hands. All 12 selected male subjects, aged 21 to 38 years (mean Ϯ SD ϭ 28 Ϯ 5.2 years) had a negative history of cold hands. Female subjects were almost equally divided between the groups with a negative (11 subjects, aged 18 -36 years; mean, 25.7 Ϯ 5.5) or positive (12 subjects, aged 19 -45 years; mean, 25 Ϯ 6.8) history of cold hands. Blood gas perturbations were created by having subjects breath a gas mixture consisting of 21% O 2 , 74% N 2 , and 5% CO 2 . The partial pressures pCO 2 and pO 2 were continuously monitored transcutaneously. Choroidal and optic nerve head blood flow response was evaluated by means of laser Doppler flowmetry. RESULTS. Systolic and diastolic blood pressure (SBP/DBP at baseline, three-group average: 111.2/71.9 mm Hg), heart rate (HR; 70.3 bpm), and intraocular pressure (IOP; 14.7 mm Hg) increased during the blood gas perturbation phase (123.1/77.7 mm Hg, 78.5 bpm, and 15.6 mm Hg, respectively) and returned to baseline in the recovery phase (109.9/73.4 mm Hg, 69.5 bpm, and 13.5 mm Hg, respectively). There was no difference between groups (one-way ANOVA of the percentage change from baseline for SBP, P ϭ 0.75; DBP, P ϭ 0.36; HR, P ϭ 0.95; and IOP, P ϭ 0.72). pCO 2 increased from 5.52 to 6.59 kPa and returned to 5.50 kPa. pO 2 increased from 10.64 to 13.12 kPa and returned to 10.73 kPa. Again, there was no difference between groups (one-way ANOVA for the percentage change: pCO 2 , P ϭ 0.17; pO 2 , P ϭ 0.78). In the women with vasospasm, optic nerve head blood flow increased 17.1% and the choroidal blood flow decreased Ϫ3.6%, whereas in the women and men without vasospasm the optic nerve head blood flow decreased Ϫ5.8% and -4.8%, and the choroidal blood flow increased 13.3% and 18.3%, respectively (two-way ANOVA interaction; P ϭ 0.001). CONCLUSIONS. The pCO 2 increase was accompanied by a pO 2 increase. Blood pressure and HR increased comparably in all groups, indicating sympathetic arousal. The women with vasospasm demonstrated an inverse response pattern of choroidal and optic nerve head circulation to blood gas perturbation compared with the women without vasospasm and compared with the men. (Invest Ophthalmol Vis Sci. 2005;46:3288 -3294

Short-term high-intensity interval training improves micro- but not macrovascular function in hypertensive patients

Arterial hypertension is a global health burden that affects vascular structure and function. Assessment of endothelial function can improve cardiovascular (CV) risk stratification. Exercise treatment reduces over all CV risk and improves vascular health. However, it is still not clear which part of the vascular bed is most sensitive to exercise treatment in patients with CV risk. This study aimed to investigate the effects of an 8-week walking based and supervised high-intensity interval training (HIIT) on macro- and microvascular endothelial function as add-on therapy in patients with arterial hypertension.; Forty patients (mean age 58 ± 7 years) treated for arterial hypertension were randomized in the HIIT (3×/week) or control group (CG) receiving standard physical activity recommendations. Arteriolar (aFID) and venular (vFID) flicker light-induced dilatation for retinal microvascular and flow-mediated dilatation (FMD) for macrovascular endothelial function were assessed. In addition, standardized assessments of patients' characteristics were performed before and after 8 weeks.; Both groups reduced weight and body mass index but only the HIIT group reduced body fat, visceral fat, and increased peak oxygen uptake after 8 weeks. The control group reduced diastolic blood pressure. No blood pressure changes were found in the HIIT group. Arteriolar FID increased in the HIIT group independently of confounders (pre: 2.40 ± 0.98%, post: 3.19 ± 1.31%, p < 0.001) but not in the control group (pre: 3.06 ± 1.50%, post: 2.90 ± 1.46%, p = 0.280). No changes were found for FMD in either group.; Arteriolar FID was found to be a sensitive vascular biomarker to assess exercise-induced microvascular improvements even in a short time setting of an 8-week exercise therapy with HIIT. Short-term exercise training affects microvascular endothelial function but not large artery endothelial function. Thus, retinal aFID appears to be a sensitive biomarker to detect short-term exercise efficacy on a vascular level. Dynamic retinal vessel analysis as a diagnostic approach may prove to be an ideal candidate vascular biomarker to monitor treatment effects of exercise in patients with hypertension on top of standard clinical care and may support clinical decision-making in the future

On Pulse-Wave Propagation in the Ocular Circulation

PURPOSE. To measure the oscillation phase delay between retinal arterioles and venules in order to analyze pulse wave propagation in the ocular circulation of vasospastic and nonvasospastic subjects and a change thereof during the cold pressor test in another group of healthy subjects. METHODS. Twenty-four young, healthy women, 12 vasospastic and 12 nonvasospastic, were analyzed. A retinal vessel analyzer was used to obtain 1-minute recordings of the ocular fundus. A phase delay between the arteriole and venule pulsations was assessed at three sites, one (proximal) in the close retinal vicinity of the disc, one (middle) 1 to 2 disc diameters away from the disc, and a third (distal) 3 to 4 disc diameters away from the disc; and, assuming that venules are counterphased to the choroidal circulation, a choroid-to-retina pulse delay was calculated. In addition, the change in these parameters was analyzed during the modified cold-pressor test in 10 healthy subjects (five women, five men). RESULTS. Pulse oscillations in arterioles led those in venules by 95.0°Ϯ 39.0°, 60.5°Ϯ 57.5°, and 47.5°Ϯ 64.0°in vasospastic subjects, and 76.0°Ϯ 58.0°, 31.5°Ϯ 60.0°, and 2.5°Ϯ 80.5°in nonvasospastic subjects in the proximal, middle, and distal measuring sites, respectively. Calculated choroid-to-retina pulse delays in vasospastic subjects were 0.20 Ϯ 0.10, 0.28 Ϯ 0.14, and 0.30 Ϯ 0.11 seconds and in nonvasospastic subjects 0.25 Ϯ 0.15, 0.35 Ϯ 0.11, and 0.43 Ϯ 0.2 seconds at the proximal, middle, and distal measuring sites, respectively. The difference was significant between vasospastic and nonvasospastic subjects (P ϭ 0.033) and among the measuring sites (P ϭ 0.0023). During exposure to cold, the choroid-to-retina pulse delays changed from 0.31 Ϯ 0.08, 0.40 Ϯ 0.16, and 0.51 Ϯ 0.26 seconds to 0.26 Ϯ 0.12, 0.30 Ϯ 0.10, and 0.33 Ϯ 0.14 seconds at the proximal, middle, and distal measuring sites, respectively (P ϭ 0.024 for the change from baseline to cold exposure, and P ϭ 0.022 for measuring sites). CONCLUSIONS. Retinal vessels in vasospastic subjects demonstrate an altered pattern of oscillation phase delay between arterioles and venules. Vessels in vasospastic subjects seem to conduct pulse waves faster and are thus stiffer than those in nonvasospastic subjects. The pattern of oscillation demonstrates changes during the cold pressor test in healthy subjects, indicating faster pulse-wave propagation. (Invest Ophthalmol Vis Sci. 2006;47:4019 -4025 10 Evaluation of vascular pulsations in the eye has been mostly limited to the choroidal circulation. 16,17 An actual pulse-wave propagation from the heart to the ophthalmic artery and choroidal circulation has been estimated at 4.08 m/s in a study of healthy subjects by Michelson et al. 11,20 The retinal vessel analyzer (Retinal Vessel Analyzer [RVA]; IMEDOS GmbH, Weimar, Germany) offers high spatial vessel width resolution 21 ; high reproducibility of measurements METHODS Subjects Forty healthy nonsmoking women were screened for the study. After approval by the ethics committee, we obtained informed consent from the subjects, in accordance with the guidelines of the Declaration of Helsinki. A notification in the University Eye Clinic of Basel informed potential volunteers (collaborators, students, parents, and friends of patients) of the opportunity to participate in a scientific research project. Subjects were screened for ocular and systemic diseases. A detailed medical and ophthalmic history was recorded, and all subjects completed an ophthalmic examination. Included were individuals with no history of ocular or systemic disease, no history of chronic or current systemic or topical medication, and no history of drug or alcohol abuse Further inclusion criteria were a normal systolic (100 -140 mm Hg) and diastolic (60 -90 mm Hg) blood pressure, a best corrected visual acuity 20/25 or better in both eyes, ametropia within Ϫ3.0 to ϩ3.0 D of spherical equivalent and less than a 1-D astigmatism in each eye, intraocular pressure (IOP) lower than 20 mm Hg in each eye by (Goldmann) applanation tonometry, and no pathologic findings in slit lamp examination and indirect funduscopy. Subjects were classified as having vasospasm if they related a clear history of frequently cold hands (answering &quot;yes&quot; to the questions: &quot;do you always have cold hands, even during the summer?&quot; and &quot;do other people tell you that you have cold hands?&quot;) and as healthy subjects if they reported n

Analysis of Retinal Vasodilation after Flicker Light Stimulation in Relation to Vasospastic Propensity

PURPOSE. To explore the maximum retinal vasodilation in response to repeated flicker light stimulation in relation to vasospastic propensity in healthy subjects. METHODS. Twenty-four young healthy women were grouped as vasospastic and nonvasospastic, based on their history of cold extremities and on the results of nailfold capillaroscopy. A retinal vessel analyzer was used to obtain recordings of the ocular fundus during still illumination and three flicker light stimulations. Retinal vessels were analyzed in the immediate vicinity of the optic nerve head and 2 to 3 disc diameters away from the disc. The maximum dilatory amplitudes were always the highest 1-second mean vessel diameter in response to each of the three flicker light stimuli. RESULTS. Maximum dilatory amplitude (in percent) was, in the proximal measurement site in the arterioles, 6.2 Ϯ 2.6, 4.8 Ϯ 2.1, and 6.6 Ϯ 3.9 in the vasospastic group, and 7.9 Ϯ 3.2, 8.6 Ϯ 4.1, and 9.1 Ϯ 4.7 in the nonvasospastic group in three repeated flicker stimulations. Corresponding values for distal measurement sites were 6.7 Ϯ 2.5, 4.8 Ϯ 3.4, and 4.7 Ϯ 4.4 and 9.0 Ϯ 3.7, 11.0 Ϯ 5.2, and 12.3 Ϯ 7.7. The maximum amplitude was significantly lower in the vasospastic group (P ϭ 0.001). The maximum venule dilation was also significantly lower in the vasospastic group (P ϭ 0.037). Vessel diameters failed to stabilize at the original baseline level during the 80-second recovery period, and this baseline offset had opposite signs in the arterioles in the vasospastic (remained below the original baseline) and nonvasospastic (remained above the original baseline) groups. CONCLUSIONS. The maximum dilatory amplitude was significantly lower in vessels in the vasospastic group. An augmentation of the maximum vasodilation was observed in the nonvasospastic group after repeated flicker stimulations, a phenomenon that was missing in arterioles of vasospastic subjects. It seems that such different behavior is due to the opposite baseline offsets in interflicker periods in the two groups. (Invest Ophthalmol Vis Sci. 2006;47:4034 -4041

Intrinsic vasomotricity and adrenergic effects in a model of isolated rabbit eye

Título da Revista: Acta Ophthalmologica ScandinavicaPurpose: We aimed to investigate the responsiveness of the ocular arteries to adrenergic drugs in a model of perfused isolated rabbit eye. Methods: Rabbit external ophthalmic arteries (n = 15) in a head-mounted preparation were cannulated and the retinal and uveal vasculature perfused at a constant flow with warmed tyrode. The three-way polypropylene catheter was further connected to a pressure transducer and intraluminal pressure was taken as a measure of vascular resistance. Effects of intra-arterial injections of phenylephrine (group A, n = 5), prazosin (group B, n = 5) and phentolamine (group C, n = 5) on the recorded pressure were obtained. Student’s paired-t test and one-way analysis of variance were used for statistical analysis (p < 0.05). Results: Intrinsic vasomotricity was observed in all preparations prior to any drug administration. Phenylephrine produced an increase in total vascular resistance. Intrinsic vasomotricity became more evident, showing a lower frequency but higher amplitude of oscillations. Evoked vasomotor responses with phenylephrine (250 lg ⁄ ml) were inhibited by intra-arterial administration of the selective a1-adrenergic antagonist, prazosin (0.5 mg⁄ ml), as well as the non-selective a-adrenergic antagonist phentolamine (6 mg⁄ ml). Conclusions: Rabbit external ophthalmic arteries showed spontaneous contractions under constant perfusion. Phenylephrine elicited a vasoconstrictor response that was inhibited by adrenergic antagonists. In addition, the intrinsic vasomotricity was enhanced by phenylephrine and blocked by adrenergic antagonists. These results show that under in vitro perfusion the territory presents similar responses to adrenergic drugs to those observed in in vivo models and also provides evidence of myogenic autoregulatory properties in the rabbit ophthalmic artery and ⁄ or choroidCIISA (Centro de Investigação Interdisciplinar em Sanidade Animal

High-intensity interval training in patients with glaucoma (HIT-GLAUCOMA): protocol for a multicenter randomized controlled exercise trial

BackgroundGlaucoma stands as a prominent global cause of irreversible blindness and the primary treatment approach involves reducing intraocular pressure (IOP). However, around one-third of patients exhibit disease progression despite effective IOP reduction. Microvascular endothelial function, chronic inflammation, and oxidative stress are known to affect retinal neuronal networks and have been associated with disease severity and progression. Exercise training has the potential to counteract these mechanisms as add-on treatment to usual care.AimsThe HIT-GLAUCOMA study will investigate the effects of a 6-month high-intensity interval training (HIIT) on intermediate endpoints such as local retinal microvascular and systemic large artery function, inflammation, and oxidative stress as well as clinical endpoints such as visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology.MethodsThe study is a multi-center randomized controlled clinical trial in patients with both normal tension and high-tension primary open angle glaucoma. Across two study centers, 128 patients will be enrolled and randomized on a 1:1 basis into an exercise intervention group and a usual care control group. The primary microvascular endpoints are retinal arteriolar and venular flicker light-induced dilation at 6 months. The primary endpoint in the systemic circulation is brachial artery flow-mediated dilation at 6 months.Anticipated resultsWe hypothesize that exercise therapy will improve retinal microvascular function and thus ocular blood flow in patients with glaucoma. As clinical outcomes, we will investigate the effect of exercise on visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology.DiscussionHIT-GLAUCOMA is a blueprint trial design to study the effect of exercise training on neurodegenerative and cardiovascular diseases. Importantly, patients are also expected to benefit from improvements in general health and cardiovascular co-morbidities. If proven effective, exercise may offer a new add-on treatment strategy to slow glaucoma progression.Clinical Trial Registration NumberThe trial is registered at Clinicaltrials.gov under the identifier NCT06058598 and is currently in the recruitment stage