Retinal vascular diameter in young subjects with a vasospastic propensity

Purpose: Retinal vascular diameters have recently been shown not to be related to an increased risk of open-angle glaucoma. Because vasospastic propensity has been suggested to represent a risk factor for various ocular diseases, especially glaucoma, the steady-state retinal vascular diameter in subjects with a propensity for systemic vascular dysregulation was compared with a group of age-matched gender-matched controls. Methods: Thirty healthy non-smoking individuals [female/male 26/4; mean±SD age 22.8±3.4 (range 18-31) years] were enrolled into the study. Subjects were classified as having vasospasm (15 subjects) if they related a clear history of frequently cold hands and as healthy subjects (15 subjects) if they denied such a history. Vasospastic propensity or the absence of it had to be confirmed by nail-fold capillaroscopy. Vascular diameter of retinal vessels was measured repeatedly on two days with the retinal vessel analyser and corrected for perfusion pressure, age, and refraction. Results: Neither retinal arteriole diameter (P=0.30) or retinal venule diameter (P=0.49), nor retinal arteriole-to-venule ratio (P=0.96), differed between the two experimental groups. Conclusions: Although vasospastic propensity has been suggested to represent a risk factor in various ocular diseases, the steady-state retinal vessel diameters are not altered in healthy vasospastic subjects. It is probable that the steady-state retinal vessel diameters are no adequate risk indicators for the haemodynamic risk in diseases such as glaucom

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 "yes" to the questions: "do you always have cold hands, even during the summer?" and "do other people tell you that you have cold hands?") 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

Intravenous administration of diphenhydramine reduces histamine-induced vasodilator effects in the retina and choroid. Invest Ophthalmol Vis Sci.

PURPOSE. Intravenous administration of histamine causes an increase in choroidal blood flow (ChBF) and retinal vessel diameters in healthy subjects. The receptor mediating this response has not yet been identified. The present study was undertaken to clarify whether H 1 receptor blockade with diphenhydramine affects the hemodynamic response of histamine in the choroid and the retina. METHODS. A randomized, double-masked, placebo-controlled, two-way crossover study was performed in 18 healthy, male, nonsmoking subjects. Histamine (0.32 g/kg per minute over 30 minutes) was infused intravenously in the absence (NaCl as placebo) or presence of the H 1 blocker diphenhydramine (1.0 mg/min over 50 minutes). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of diphenhydramine or placebo, and after co-infusion of histamine. Subfoveal ChBF and fundus pulsation amplitude (FPA) were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser Doppler velocimetry. RESULTS. Administration of histamine caused a decrease in mean arterial pressure by Ϫ4% Ϯ 9% (ANOVA P ϭ 0.01). This effect was blunted by coadministration of diphenhydramine (ANOVA, P ϭ 0.04). Histamine significantly increased FPA and subfoveal ChBF. Coadministration of diphenhydramine significantly reduced this effect (ANOVA; FPA P ϭ 0.001, ChBF P ϭ 0.049). Histamine significantly increased retinal arterial diameter by ϩ3.5% Ϯ 4.5% and retinal venous diameter by ϩ3.7% Ϯ 2.8%. Again, coadministration of diphenhydramine significantly reduced the vasodilative effect to ϩ0.3% Ϯ 5.5% in retinal arteries (ANOVA, P ϭ 0.00006) and to ϩ0.9% Ϯ 2.5% in retinal veins (ANOVA, P ϭ 0.004). CONCLUSIONS. The present data confirm that histamine increases ChBF and retinal vessel diameters in healthy subjects. Administration of the H 1 receptor blocker diphenhydramine significantly reduced histamine-induced changes in ocular perfusion parameters. These results strongly indicate that in the retina and choroid, H 1 receptors are involved in the histamine-mediated hemodynamic effects in vivo. (Invest Ophthalmol Vis Sci