Effects of topical clonidine versus brimonidine on choroidal blood flow and intraocular pressure during squatting

PURPOSE. Clonidine and brimonidine, two ␣-2 agonists, have been shown to reduce intraocular pressure (IOP) in patients with glaucoma. Little is known, however, about the exact role of ␣ receptors in the control of ocular blood flow in the posterior pole of the eye. Hence, the study was conducted to investigate the effects of topical clonidine versus topical brimonidine on choroidal blood flow and intraocular pressure during squatting. METHODS. This was a randomized, double-masked, controlled, two-way crossover study. Twelve healthy male nonsmoking volunteers, aged between 19 and 35 years were included in the study. Two drops of clonidine or brimonidine were administered in the subjects' study eyes. Continuous measurement using the compact laser Doppler flowmeter was performed during a 6-minute squatting period, to assess choroidal blood flow regulation during an increase in ocular perfusion pressure. RESULTS. Both substances induced a pronounced but comparable (P ϭ 0.8) decrease in IOP. Squatting increased mean arterial pressure (MAP) and ocular perfusion pressure (P Ͻ 0.01). This increase was comparable between the clonidine and the brimonidine study day (P ϭ 0.88). Squatting induced an increase in choroidal blood flow that was less pronounced than the increase in ocular perfusion pressure. Compared with baseline the ␣-2 agonists decreased choroidal blood flow during squatting (P ϭ 0.0026) to a comparable degree (P ϭ 0.86). Vascular resistance increased at baseline and during squatting after administration of the ␣-2 agonists (P Ͻ 0.01) in both groups to a comparable degree (P ϭ 0.56). CONCLUSIONS. Topical ␣-2 agonists may induce changes in choroidal blood flow, even after a single administration. Long-term studies are needed to study potential effects of brimonidine and clonidine in the clinical setting. (Invest Ophthalmol Vis Sci. 2007;48:4220 -4225

Effects of Pentoxifylline and Alprostadil on Ocular Hemodynamics in Healthy Humans

PURPOSE. Alprostadil, a prostaglandin (PG)E 1 analogue and pentoxifylline, an alkylxanthine derivate, have been shown to exert vasodilatory effects in several vascular beds. The purpose of the present study was to investigate the effect of PGE 1 and pentoxifylline on the ocular circulation. METHODS. A placebo-controlled, double-masked, three-way, crossover study was performed in 15 healthy male subjects. Subjects received pentoxifylline (300 mg), PGE 1 (alprostadil 60 g), or placebo intravenously over 2 hours on three trial days. Choroidal red blood cell flow was assessed with laser Doppler flowmetry and pulsatile choroidal blood flow with laser interferometric measurement of fundus pulsation amplitude (FPA). Retinal blood cell flow was calculated based on the measurements of maximum erythrocyte velocity in a retinal vein assessed with bidirectional laser Doppler velocimetry, and diameter measurements of retinal vessels were obtained with a retinal vessel analyzer. RESULTS. Pentoxifylline increased FPA by 15.4% Ϯ 1.1% (P Ͻ 0.001 versus placebo and baseline). Alprostadil tended to increase FPA, but this effect did not reach the level of significance (P ϭ 0.07 versus placebo). Choroidal blood flow as measured with laser Doppler flowmetry tended to increase during pentoxifylline and PGE 1 infusion by 8.9% Ϯ 2.9% (P ϭ 0.062) and 4.5% Ϯ 6.2% (P ϭ 0.29), respectively, but none of these effects was significant. The drugs under study had no effect on mean red blood cell velocity in retinal veins, on retinal vessel diameters, intraocular pressure, blood pressure, or pulse rate. CONCLUSIONS. PGE 1 did not alter the parameters of retinal or choroidal circulation in healthy subjects. Pentoxifylline increased FPA, but did not change choroidal blood flow as measured with laser Doppler flowmetry and did not affect retinal blood flow parameters. Accordingly, neither pentoxifylline nor PGE 1 appears to be suitable to improve ocular blood flow in healthy subjects. Whether long-term treatment with alprostadil would improve choroidal blood flow in patients with vascular disease remains to be established. (Invest Ophthalmol Vis Sci

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

PLOS One / Compensation for Retinal Vessel Density Reduces the Variation of Circumpapillary RNFL in Healthy Subjects

This work intends to assess circumpapillary retinal vessel density (RVD) at a 3.46 mm diameter circle and correlate it with circumpapillary retinal nerve fiber layer (RNFL) thickness measured with Fourier-Domain Optical Coherence Tomography. Furthermore, it aims to evaluate the reduction of intersubject variability of RNFL when considering RVD as a source of information for RNFL distribution. For that, 106 healthy subjects underwent circumpapillary RNFL measurement. Using the scanning laser ophthalmoscope fundus image, thickness and position of retinal vessels were assessed and integrated in a 256-sector RVD profile. The relationship between local RVD value and local RNFL thickness was modeled by linear regression. RNFL was then compensated for RVD variation by regression formulas. A strong statistically significant intrasubject correlation was found for all subjects between RVD and RNFL profiles (mean R = 0.769). In the intersubject regression analysis, 247 of 256 RNFL sectors showed a statistically significant positive correlation with RVD (mean R = 0.423). RVD compensation of RNFL resulted in a relative reduction of up to 20% of the intersubject variance. In conclusion, RVD in a 3.46mm circle has a clinically relevant influence on the RNFL distribution. RVD may be used to develop more individualized normative values for RNFL measurement, which might improve early diagnosis of glaucoma.(VLID)491218

A Functional Regression Model of the Retinal Nerve Fiber Layer Thickness in Healthy Subjects

Purpose: A new functional regression model is presented to explain the intersubject variability of the circumpapillary retinal nerve fiber layer (RNFL) thickness in healthy subjects. Methods: To evaluate the functional regression approach we used data from 202 healthy volunteers, divided equally into training samples (TS) and validation samples (VS). Covariates included RNFL, fovea distance, fovea angle, optic disk ratio, orientation and area provided by Fourier-domainoptical coherence tomography, age, and refractive error. Root mean square errors (RMSE) were calculated for each of the 256 sectors and for the 12 clock-hour sectors in the TS and VS and were compared to the RMSE of the previous model and the standard deviation of the raw data. Results: With the functional regression approach, we were able to explain on average 27.4% of the variation in the TS and 25.1% of the variation in the VS. The new model performed better compared to a multivariate linear regression model. It performed best in the superior-temporal and inferior-temporal clock-hour sectors where the percentage of RMSE reduction ranged between 26.3% and 44.1% for the TS and between 20.6% and 35.4% for the VS. Conclusions: The new functional regression approach improves on the multivariate linear regression model and allows an even larger reduction of the amount of intersubject variability, while at the same time using a substantially smaller number of parameters to be estimated. Translational Relevance: The demonstrated reduction of interindividual variation is expected to translate into an improved diagnostic separation between healthy and glaucomatous subjects, but this remains to be demonstrated in further studies.(VLID)467278