Investigative Ophthalmology & Visual Science Cover Image for Volume 52, Issue 7
June 2011
Volume 52, Issue 7
Free
Clinical Trials  |   June 2011
Effect of Latanoprost on Choroidal Blood Flow Regulation in Healthy Subjects
Author Affiliations & Notes
  • Agnes Boltz
    From the Departments of Clinical Pharmacology and
    the Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
  • Doreen Schmidl
    From the Departments of Clinical Pharmacology and
  • Günther Weigert
    From the Departments of Clinical Pharmacology and
    Ophthalmology and
  • Michael Lasta
    From the Departments of Clinical Pharmacology and
  • Berthold Pemp
    From the Departments of Clinical Pharmacology and
    Ophthalmology and
  • Hemma Resch
    From the Departments of Clinical Pharmacology and
    Ophthalmology and
  • Gerhard Garhöfer
    From the Departments of Clinical Pharmacology and
  • Gabriele Fuchsjäger-Mayrl
    From the Departments of Clinical Pharmacology and
    Ophthalmology and
  • Leopold Schmetterer
    From the Departments of Clinical Pharmacology and
    the Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
  • Corresponding author: Leopold Schmetterer, Department of Clinical Pharmacology, Währinger Gürtel 18-20, A-1090 Vienna, Austria, [email protected]
Investigative Ophthalmology & Visual Science June 2011, Vol.52, 4410-4415. doi:https://doi.org/10.1167/iovs.11-7263
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Agnes Boltz, Doreen Schmidl, Günther Weigert, Michael Lasta, Berthold Pemp, Hemma Resch, Gerhard Garhöfer, Gabriele Fuchsjäger-Mayrl, Leopold Schmetterer; Effect of Latanoprost on Choroidal Blood Flow Regulation in Healthy Subjects. Invest. Ophthalmol. Vis. Sci. 2011;52(7):4410-4415. https://doi.org/10.1167/iovs.11-7263.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose.: The present study tested the hypothesis that human choroidal blood flow (ChBF) regulation in the face of changes in ocular perfusion pressure (OPP) may be modified by a drug-induced decrease in intraocular pressure (IOP).

Methods.: This hypothesis was tested in a double-masked, randomized, placebo-controlled, parallel-group trial in 24 healthy volunteers. OPP was manipulated by 6 minutes of squatting and a subsequent period of artificial increase in IOP induced with a suction cup. These interventions were repeated after 14 days of treatment with either latanoprost or placebo. ChBF was measured continuously with a portable laser Doppler flowmeter.

Results.: As expected, latanoprost significantly reduced IOP compared with placebo (P = 0.008). The relative increases in OPP during squatting (P = 0.97) and an artificial IOP increase (P = 0.75), however, were comparable after placebo and latanoprost. The response of ChBF was, in contrast, different between the two treatment groups. During the squatting-induced elevation of OPP, ChBF increased less after latanoprost than after placebo treatment (P = 0.049). During the suction cup–induced increase in IOP, the decrease in ChBF was less pronounced after latanoprost than after placebo (P = 0.026). Latanoprost, however, did not modify baseline ChBF at rest (P = 0.30).

Conclusions.: The data indicate that latanoprost improves ChBF regulation during both an increase and a decrease in OPP. Since latanoprost did not affect baseline ChBF, the authors assume that this effect is related to the decrease in IOP. This finding has important implications for understanding the relation between IOP and vascular factors in glaucoma, because it indicates that a reduction in IOP itself improves ChBF regulation. (ClinicalTrials.gov number, NCT00712400.)

There has been a long-standing discussion on the regulatory capacity of the choroidal circulation. 1 18 We have recently shown that the regulatory capacity of the human choroid in face of changes in ocular perfusion pressure (OPP) may differ if either arterial blood pressure or intraocular pressure (IOP) is modified. 17 More specifically, we have shown that, during a combined-exercise–induced increase in mean arterial pressure (MAP) and a suction cup–induced increase in IOP, choroidal blood flow (ChBF) is regulated better during the former than during the latter. We have speculated that this behavior is related to either sympathetic vasoconstriction in response to isometric exercise on the arterial side of the vascular system or to a myogenic response. 17  
In a clinical trial in patients with primary open-angle glaucoma or ocular hypertension, the association between OPP and ocular blood flow parameters was compared before and after pressure reduction with either dorzolamide or timolol. 19 21 With both drugs, the correlation line between OPP and ocular blood flow parameters became less steep, indicating better blood flow regulation. Since only dorzolamide, not timolol, increased blood flow at baseline, we concluded that the change in the pressure-flow characteristics was due to the ocular hypotensive effects of the drug. 
In the present study we wanted to get further insight into ChBF regulation and the complex interaction between OPP, MAP, IOP, and choroidal perfusion. We hypothesized that a reduction in IOP may alter ChBF regulation in the face of changes in OPP. To test this hypothesis, we performed a randomized, double-masked, parallel-group study in healthy subjects. The participants received either latanoprost, a prostaglandin analogue, to lower IOP, or a placebo for 14 days, and the regulation of ChBF was tested before and after this period. The regulation during an increase in OPP was studied when MAP was increased by isometric exercise. The regulation during a decrease in OPP was studied when IOP was increased with a suction cup. 
Materials and Methods
The present study was performed in compliance with the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines. The study protocol was approved by the Ethics Committee of the Medical University of Vienna. A total of 24 healthy male subjects aged between 19 and 35 years participated. The nature of the study was explained to all subjects, and they gave written consent to participate. Each subject passed a screening examination including medical history and physical examination; 12-lead electrocardiogram; complete blood count; activated partial thromboplastin time; thrombin time; fibrinogen; clinical chemistry (sodium, potassium, creatinine, uric acid, glucose, cholesterol, triglycerides, alanine amino-transferase, aspartate transcarbamylase, γ-glutamyltransferase, alkaline phosphatase, total bilirubin, and total protein); hepatitis A, B, and C and HIV serology; urine analysis; and a urine drug-screening. Subjects were excluded if any abnormality was found as part of the pretreatment screening, unless the investigators considered the abnormality to be clinically irrelevant. Moreover, an ophthalmic examination, including slit lamp biomicroscopy and indirect funduscopy, was performed. Inclusion criteria were normal ophthalmic findings, ametropia of less than 3 D, and anisometropia of less than 1 D. 
Experimental Design
The study was performed in a randomized, double-masked, placebo-controlled design in two parallel groups. One group received latanoprost (Xalatan 0.005%; Pfizer, New York, NY) once daily for 14 days. The other group received a placebo (physiologic saline solution), which was identical in appearance. All subjects were asked to refrain from alcohol and caffeine for at least 12 hours before trial day. In addition, the subjects were instructed to have 7 to 8 hours of sleep and a light breakfast before arriving at the Department of Clinical Pharmacology on the trial day. On the first study day (day 1), after a resting period of at least 20 minutes in a sitting position, the participants underwent baseline measurements of ocular and systemic hemodynamics and IOP. Thereafter, the isometric exercise stimulation period was started. First, a 3-minute continuous baseline recording of ChBF was scheduled. After this baseline recording, each subject engaged in 6 minutes of isometric exercise. This period of isometric exercise consisted of squatting in a position where the upper and the lower legs formed approximately a right angle, to increase mean arterial blood pressure. During this squatting period, continuous measurement of ChBF was performed. At the end of the squatting period, IOP was measured again. Blood pressure and pulse rate were assessed every minute throughout these experiments. 
Thereafter, another resting period of 30 minutes was scheduled to allow for normalization of blood pressure and pulse rates. Afterward, ChBF was measured continuously for three minutes at baseline. Then, the suction cup was applied using a suction force of 50 mm Hg. The suction force was then increased in three consecutive steps to 75, 100, and 125 mm Hg. Each suction level was maintained for 2 minutes during which ChBF was continuously measured. After another resting period, a final suction cup period was scheduled that followed exactly the time course of the first suction cup period. During this period, IOP was measured at each suction cup level by applanation tonometry. 
After 14 days of eye drop instillation with either latanoprost or placebo a second study day was scheduled for each subject. The time course of this study day (day 2) was identical with that for study day 1. All IOP measurements were performed by investigators who were not involved in any other parts of the study including ChBF data collection, to allow for double-masked conditions. 
Measurements
Systemic Hemodynamics.
Brachial artery blood pressures: systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP were monitored on the upper arm by an automated oscillometric device. The pulse rate (PR) was automatically recorded from a finger pulse oximeter (HP-CMS; Hewlett Packard, Palo Alto, CA). 
Laser Doppler Flowmetry.
Continuous measurements of subfoveal ChBF were performed by laser Doppler flowmetry (LDF), as described in principle previously. 22 With this technique, the vascularized tissue is illuminated by coherent laser light. Light scattered by the moving red blood cells undergoes a frequency shift. In contrast, static tissue scatterers do not change the light frequency, but lead to randomization of light directions impinging on red blood cells. Hence, red blood cells receive light from numerous random directions. As the frequency shift is dependent, not only on the velocity of the moving red blood cells, but also on the angle between the incident and the scattered light, scattering of the light in tissue broadens the Doppler shift power spectrum. From this spectrum, hemodynamic parameters can be determined based on a theory of light scattering in tissue. In the present study, a compact laser Doppler flowmeter, which has been described in detail previously, was used. 23,24 All measurements were performed in the fovea by asking the subject to directly fixate at the beam. The fovea was chosen, because the retina is avascular in this region. The following blood flow parameters were obtained: ChBF, velocity (VEL), and volume (VOL). VEL is the mean velocity of the red blood cells moving in the sampled tissue proportional to the mean Doppler frequency shift. VOL is the number of moving red blood cells in the sampled tissue. ChBF was calculated as the product of VEL and VOL. 
Intraocular Pressure.
A slit lamp–mounted Goldmann applanation tonometer was used to measure IOP. Before each measurement, one drop of 0.4% benoxinate hydrochloride combined with 0.25% sodium fluorescein was used for local anesthesia of the cornea. 
Suction Cup Method.
The IOP was raised applying a method described by Ulrich and Ulrich. 25 In the present study, we used an automatic suction pump that is connected by plastic tubing to a rigid plastic suction cup. After topically applied local anesthesia, a standardized 11-mm diameter suction cup was placed on the temporal sclera with the anterior edge at least 1 mm from the limbus. The vacuum was increased in increments from 50 to 125 mm Hg. 
Data Analysis
OPP was calculated as ⅔MAP − IOP. 26 All blood flow values measured at OPP below 10 mm Hg were excluded from statistical analysis because of problems in LDF signal analysis at very low flow rates, as discussed in detail by Riva et al. 27  
A repeated-measures ANOVA model was used to analyze data. Data during the IOP increase and the squatting periods were analyzed separately. For both analyses the pretreatment and posttreatment data were included in one model. Accordingly the repeated-measures ANOVA model during IOP increase included 10 values for each dependent variable, and the model during squatting included 14 values for each dependent variable. Differences between latanoprost and placebo were calculated based on the interaction between time and treatment. Post hoc analyses were performed using planned comparisons. For this purpose, the time effect was used to characterize the effect of IOP increase and squatting on the outcome parameters. The treatment effect was used to characterize the effect of latanoprost on resting values. For data description, the percentage of change over baseline was calculated. P < 0.05 was considered the level of significance (CSS Statistica for Windows; StatSoft Inc., Tulsa, OK). 
Results
The baseline characteristics of the subjects are presented in Table 1. There were no significant differences between the group of subjects receiving placebo and the group receiving latanoprost. All participating subjects finished the study as scheduled, and no adverse reactions were noted except mild localized conjunctival hyperemia after suction cup application. 
Table 1.
 
Demographic and Baseline Characteristics of the Participating Subjects.
Table 1.
 
Demographic and Baseline Characteristics of the Participating Subjects.
Placebo Group (n = 12) Latanoprost Group (n = 12) P
Age, y 25 ± 3 24 ± 4 0.12
MAP, mm Hg 79 ± 6 82 ± 8 0.35
PR, bpm 69 ± 9 71 ± 11 0.48
IOP, mm Hg 13.4 ± 2.0 12.9 ± 1.7 0.60
OPP, mm Hg 39 ± 3 41 ± 4 0.24
ChBF, arbitrary units 17.3 ± 4.4 16.4 ± 4.5 0.51
The effect of latanoprost and placebo on all outcome variables is shown in Table 2. Neither of the two treatments affected blood pressure or PR. As expected, latanoprost caused a decline in IOP that was significant versus placebo (P = 0.013). On average, IOP was reduced by 17.9% (−2.5 ± 2.8 mm Hg), resulting in an average increase in OPP of 6.3% (+4.2 ± 5.9 mm Hg; P = 0.004 versus placebo). ChBF, however, was unchanged at baseline. 
Table 2.
 
Effect of 14 Days Treatment with Either Latanoprost or Placebo on All Outcome Variables
Table 2.
 
Effect of 14 Days Treatment with Either Latanoprost or Placebo on All Outcome Variables
Placebo Group (n = 12) Latanoprost Group (n = 12) P
MAP, mm Hg −0.2 ± 5.0 −1.5 ± 8.9 0.65
PR, bpm 0.1 ± 14.4 5.3 ± 21.6 0.50
IOP, mm Hg −3.2 ± 8.0 −17.9 ± 14.4 0.008*
OPP, mm Hg −2.6 ± 6.7 6.3 ± 6.7 0.004*
ChBF, arbitrary units 4.5 ± 7.9 2.6 ± 10.3 0.30
The effect of squatting on OPP and ChBF is shown in Figure 1. During all squatting periods, there was a significant increase in OPP (each P < 0.001 versus baseline) and ChBF (each P < 0.001 versus baseline). The increase in ChBF was less pronounced in both groups than the increase in OPP, indicating some degree of blood flow regulation. 
Figure 1.
 
Effect of squatting on OPP and ChBF. Squatting periods were scheduled before and after treatment with either latanoprost (●) or placebo (□). Data are presented as percentage of change from baseline (mean ± SD). *Significant differences between groups.
Figure 1.
 
Effect of squatting on OPP and ChBF. Squatting periods were scheduled before and after treatment with either latanoprost (●) or placebo (□). Data are presented as percentage of change from baseline (mean ± SD). *Significant differences between groups.
The response of OPP to squatting was not significantly different between the pretreatment periods and the posttreatment periods with either latanoprost or placebo (P = 0.97). Posttreatment mean OPP (SD) increased on average by 46.5% (±17.5%) in the placebo group and 51.2% (±19.8%) in the latanoprost group compared with baseline. By contrast, there was a significant difference between the response of ChBF to squatting after latanoprost treatment and that after placebo treatment. Whereas the response after placebo was not different compared with that in the pretreatment period, the increase in mean ChBF after latanoprost treatment was less pronounced (10.9% ± 5.9%; P = 0.049 between groups) compared to both the pretreatment (19.8% ± 9.9%) and placebo (19.0% ± 7.5%) responses. 
The effect of the suction cup application on IOP, OPP, and ChBF is show in Figure 2. Although subjects receiving latanoprost started at lower IOPs, the increase during suction cup application was parallel. As expected, this result was associated with a decrease in OPP and ChBF (each P < 0.001 versus baseline). The relative change in ChBF was less pronounced than the decrease in OPP (73.7% ± 12.3%), indicating some regulatory capacity of the choroid under these circumstances. The response of OPP was not different between the pre- and posttreatment periods (P = 0.75). The response of ChBF to the artificial increase in IOP was not altered during placebo administration. By contrast, the reduction in ChBF after administration of latanoprost was significantly less pronounced (26.8% ± 15.3%) compared with the pretreatment response (40.0% ± 11.5%) and the placebo response (41.0% ± 12.4%; P = 0.024 between groups). 
Figure 2.
 
Effect of an artificial increase in intraocular pressure using a suction cup on OPP, ChBF, and IOP. Periods of artificial increase in intraocular pressure were scheduled before and after treatment with either latanoprost (●) or placebo (□). IOP data are presented as absolute values, OPP and ChBF data are presented as percentage change from baseline (mean ± SD). *Significant differences between groups.
Figure 2.
 
Effect of an artificial increase in intraocular pressure using a suction cup on OPP, ChBF, and IOP. Periods of artificial increase in intraocular pressure were scheduled before and after treatment with either latanoprost (●) or placebo (□). IOP data are presented as absolute values, OPP and ChBF data are presented as percentage change from baseline (mean ± SD). *Significant differences between groups.
Discussion
In keeping with results from previous studies performed by our group as well as other investigators, ChBF showed some regulatory capacity in response to OPP changes induced by isometric exercise 10,12 15 or an artificial IOP increase. 8,17 In the present study we hypothesized that the counterregulatory capacity of the choroidal vasculature may be altered by a lower IOP after a 14-day treatment period with latanoprost. The response of ChBF to both interventions was significantly different with the prostaglandin analogue compared with placebo, although the relative change in OPP was comparable. During isometric exercise, the increase in ChBF was less pronounced after latanoprost than after placebo administration. This result indicates that the increase in vascular resistance was more pronounced after latanoprost due to more distinctive vasoconstriction in the face of the OPP increase. During the artificial increase in IOP, the decrease in ChBF was less pronounced after latanoprost than after placebo. Considering that this decrease was observed at a comparable OPP decrease, it indicates more counterregulatory vasodilatation after a latanoprost-induced decrease in IOP compared with placebo. 
How can these results be interpreted? After topical administration of antiglaucoma drugs, two distinct mechanisms have to be distinguished. 28,29 On the one hand, the drug itself may induce direct vasomotor effects if it reaches the posterior pole of the eye at a sufficient concentration. In the present study we deem it unlikely that this is the case, because latanoprost did not affect baseline ChBF. Hence, the different behavior of the choroidal vasculature in face of the changes in OPP after latanoprost is unlikely to be related to a direct vasomotor effect, because the drug did not alter baseline vascular tone. On the other hand, any topical glaucoma drug alters OPP, because of the ocular hypotensive action. Since choroidal venous pressure is very close to IOP over a wide range of pressures, 30 any decrease in IOP directly transfers into an increase in OPP. The observation that ChBF reacts differently to changes in OPP at comparable ChBF levels at baseline may well be related to the increase of OPP induced by latanoprost. 
We have shown in two studies that ChBF may be regulated better at lower levels of IOP than at higher levels of IOP. In a study in healthy subjects, we investigated the effects of combined increase in IOP using a suction cup and an increase in MAP with isometric exercise. In that study, the regulatory mechanisms of choroidal circulation compensated better for an increase in blood pressure than for an increase in IOP. 17,31 The mechanism that may be responsible for this behavior was first formulated for the choroid by Kiel 4 7 based on his results in the rabbit. This method assumes that the choroid shows at least to some degree a myogenic response. Hence, changes in transmural pressure are responsible for smooth muscle constriction in response to an OPP increase due to the IOP-lowering effect of latanoprost. Consequently, the system is at a stage of relative vasoconstriction after latanoprost, compared with placebo or baseline conditions. When IOP is then artificially increased by use of a suction cup, the vasodilator reserve will be higher after latanoprost than under placebo, resulting in better counterregulation, as observed in the present study. In case of the isometric exercise period, however, the arteriovenous pressure difference is larger after latanoprost than after placebo. In this case, a more pronounced myogenic response will be initiated because of the increase in transmural pressure in the arterial system supplying the choroid resulting in vasoconstriction and a better regulatory capacity. 
Several limitations need to be considered when discussing the results of our experiments. Choroidal vessels show a rich innervation, 32 35 and stimulation of the sympathetic system induced pronounced vasoconstriction. 36 38 Obviously, the neural input into the system cannot be eliminated in a human experiment, and it is likely that this influenced the response of the choroidal vasculature in our studies. As such, one should not refer to the regulatory behavior of the choroid in the present study as autoregulation. The fact that latanoprost altered the regulatory behavior in response to both an increase and a decrease in OPP indicates, however, that the mechanism underlying blood flow regulation in the present study is not entirely neural. 
In addition, we cannot entirely exclude that small amounts of the prostaglandin analogue reached the posterior pole of the eye, influencing vascular tone to a small degree. In this context, the sample size of the present study allowed only for detection of changes in ChBF at baseline in the order of 12%. 39 Previous studies on the effect of latanoprost on ocular blood flow are equivocal. 40 49 Most studies that indicate increased blood flow after latanoprost treatment, however, were based on pneumotonometric studies, in which the effect on the IOP on the ocular pressure pulse was not adequately taken into account. 50,51 On the basis of the results of our studies with β-receptor antagonists and carbonic anhydrase inhibitors, 21 we deem it unlikely, however, that a direct vasomotor effect contributes to the altered blood flow response in the face of the OPP changes. On the other hand, one needs to consider that the effects of latanoprost on IOP (−2.5 mm Hg) and OPP (+4.2 mm Hg) were small. It is striking that such small changes in IOP can cause pronounced changes in ChBF regulation. Further studies with alternative methods to modify IOP and OPP are needed, to gain more insight into this topic. 
Finally, assessment of OPP may have limitations, particularly in connection with the suction cup technique. OPP is calculated as ⅔MAP − IOP, but this equation may not be appropriate at high IOP levels because of the compression of larger vessels entering the sclera. There is, however, no equation that accounts for this problem. The limitation applies to both the latanoprost and the placebo groups and therefore does not affect the primary hypothesis of the study. 
Our results may have implications for the understanding of current glaucoma therapy. It has been suggested that vascular factors play a role in the pathogenesis of the disease, particularly vascular dysregulation and low OPP. 52,53 Part of the vascular dysregulation may result from systemic disease and endothelial dysfunction. 54 57 There is, however, accumulating evidence from our previous studies and the present study that the level of IOP is a major determinant of the regulatory capacity of the choroid. Whether this concept is also true for optic nerve head blood flow is currently under investigation in our laboratory. Most studies focused on the effect of antiglaucoma drugs on baseline ocular blood flow, and only one study is available indicating that an increase in blood flow is indeed beneficial in terms of visual field preservation. 58 Our data indicate that future studies should particularly focus on blood flow regulation and the relation to progression of glaucoma. Moreover, the present results suggest that any reduction in IOP is by itself associated with an improvement in ocular blood flow regulation. 
In conclusion, the present study indicates that administration of latanoprost improves ChBF regulation during both an increase and a decrease in OPP. Since latanoprost did not affect baseline blood flow we assume that the ocular hypotensive effect of latanoprost is responsible for this improvement in regulation compatible with a myogenic mechanism. These results may improve our understanding of ocular blood flow regulation and glaucoma, because any reduction in IOP, proven to be beneficial for slowing down the progression of the disease, appears to be associated with improved ChBF regulation. 
Footnotes
 Supported by the Austrian National Bank, project number 11309.
Footnotes
 Disclosure: A. Boltz, None; D. Schmidl, None; G. Weigert, None; M. Lasta, None; B. Pemp, None; H. Resch, None; G. Garhöfer, None; G. Fuchsjäger-Mayrl, None; L. Schmetterer, None
References
Friedman E . Choroidal blood flow: pressure-flow relationships. Arch Ophthalmol. 1970;83:95–99. [CrossRef] [PubMed]
Alm A Bill A . Blood flow and oxygen extraction in the cat uvea at normal and high intraocular pressures. Acta Physiol Scand. 1970;80:19–28. [CrossRef] [PubMed]
Alm A Bill A . Ocular and optic nerve blood flow at normal and increased intraocular pressures in monkeys (Macaca irus): a study with radioactively labelled microspheres including flow determinations in brain and some other tissues. Exp Eye Res. 1973;15:15–29. [CrossRef] [PubMed]
Kiel JW Shepherd AP . Autoregulation of choroidal blood flow in the rabbit. Invest Ophthalmol Vis Sci. 1992;33:2399–2410. [PubMed]
Kiel JW . Choroidal myogenic autoregulation and intraocular pressure. Exp Eye Res. 1994;58:529–543. [CrossRef] [PubMed]
Kiel JW van Heuven WA . Ocular perfusion pressure and choroidal blood flow in the rabbit. Invest Ophthalmol Vis Sci. 1995;36:579–585. [PubMed]
Kiel JW . Modulation of choroidal autoregulation in the rabbit. Exp Eye Res. 1999;69:413–429. [CrossRef] [PubMed]
Riva CE Titze P Hero M Petrig BL . Effect of acute decreases of perfusion pressure on choroidal blood flow in humans. Invest Ophthalmol Vis Sci. 1997;38:1752–1760. [PubMed]
Findl O Strenn K Wolzt M . Effects of changes in intraocular pressure on human ocular haemodynamics. Curr Eye Res. 1997;16:1024–1029. [CrossRef] [PubMed]
Riva CE Titze P Hero M Movaffaghy A Petrig BL . Choroidal blood flow during isometric exercises. Invest Ophthalmol Vis Sci. 1997;38:2338–2343. [PubMed]
Reitsamer HA Kiel JW . A rabbit model to study orbital venous pressure, intraocular pressure, and ocular hemodynamics simultaneously. Invest Ophthalmol Vis Sci. 2002;43:3728–3734. [PubMed]
Luksch A Polska E Imhof A . Role of NO in choroidal blood flow regulation during isometric exercise in healthy humans. Invest Ophthalmol Vis Sci. 2003;44:734–739. [CrossRef] [PubMed]
Fuchsjager-Mayrl G Luksch A Malec M Polska E Wolzt M Schmetterer L . Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans. Invest Ophthalmol Vis Sci. 2003;44:728–733. [CrossRef] [PubMed]
Polska E Luksch A Schering J . Propranolol and atropine do not alter choroidal blood flow regulation during isometric exercise in healthy humans. Microvasc Res. 2003;65:39–44. [CrossRef] [PubMed]
Kiss B Dallinger S Polak K Findl O Eichler HG Schmetterer L . Ocular hemodynamics during isometric exercise. Microvasc Res. 2001;61:1–13. [CrossRef] [PubMed]
Reiner A Zagvazdin Y Fitzgerald ME . Choroidal blood flow in pigeons compensates for decreases in arterial blood pressure. Exp Eye Res. 2003;76:273–282. [CrossRef] [PubMed]
Polska E Simader C Weigert G . Regulation of choroidal blood flow during combined changes in intraocular pressure and arterial blood pressure. Invest Ophthalmol Vis Sci. 2007;48:3768–3774. [CrossRef] [PubMed]
Simader C Lung S Weigert G . Role of NO in the control of choroidal blood flow during a decrease in ocular perfusion pressure. Invest Ophthalmol Vis Sci. 2009;50:372–377. [CrossRef] [PubMed]
Fuchsjager-Mayrl G Wally B Georgopoulos M . Ocular blood flow and systemic blood pressure in patients with primary open-angle glaucoma and ocular hypertension. Invest Ophthalmol Vis Sci. 2004;45:834–839. [CrossRef] [PubMed]
Fuchsjager-Mayrl G Wally B Rainer G . Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension. Br J Ophthalmol. 2005;89:1293–1297. [CrossRef] [PubMed]
Fuchsjager-Mayrl G Georgopoulos M Hommer A . Effect of dorzolamide and timolol on ocular pressure: blood flow relationship in patients with primary open-angle glaucoma and ocular hypertension. Invest Ophthalmol Vis Sci. 2010;51:1289–1296. [CrossRef] [PubMed]
Riva CE Cranstoun SD Grunwald JE Petrig BL . Choroidal blood flow in the foveal region of the human ocular fundus. Invest Ophthalmol Vis Sci. 1994;35:4273–4281. [PubMed]
Geiser MH Riva CE Dorner GT Diermann U Luksch A Schmetterer L . Response of choroidal blood flow in the foveal region to hyperoxia and hyperoxia-hypercapnia. Curr Eye Res. 2000;21:669–676. [CrossRef] [PubMed]
Geiser MH Diermann U Riva CE . Compact laser Doppler choroidal flowmeter. J Biomed Opt. 1999;4:459–464. [CrossRef] [PubMed]
Ulrich WD Ulrich C . Oculo-oscillo-dynamography: a diagnostic procedure for recording ocular pulses and measuring retinal and ciliary arterial blood pressures. Ophthalmic Res. 1985;17:308–317. [CrossRef] [PubMed]
Robinson F Riva CE Grunwald JE Petrig BL Sinclair SH . Retinal blood flow autoregulation in response to an acute increase in blood pressure. Invest Ophthalmol Vis Sci. 1986;27:722–726. [PubMed]
Riva CE Hero M Titze P Petrig B . Autoregulation of human optic nerve head blood flow in response to acute changes in ocular perfusion pressure. Graefes Arch Clin Exp Ophthalmol. 1997;235:618–626. [CrossRef] [PubMed]
Schmetterer L Strenn K Findl O . Effects of antiglaucoma drugs on ocular hemodynamics in healthy volunteers. Clin Pharmacol Ther. 1997;61:583–595. [CrossRef] [PubMed]
Costa VP Harris A Stefansson E . The effects of antiglaucoma and systemic medications on ocular blood flow. Prog Retin Eye Res. 2003;22:769–805. [CrossRef] [PubMed]
Maepea O . Pressures in the anterior ciliary arteries, choroidal veins and choriocapillaris. Exp Eye Res. 1992;54:731–736. [CrossRef] [PubMed]
Schmidl D Garhofer G Schmetterer L . The complex interaction between ocular perfusion pressure and ocular blood flow: relevance for glaucoma. Exp Eye Res. Published online September 22, 2010.
Lütjen-Drecoll E . Choroidal innervation in primate eyes. Exp Eye Res. 2006;82:357–361. [CrossRef] [PubMed]
Ehinger B . Ocular and orbital vegetative nerves. Acta Physiol Scand Suppl. 1966;268:1–35. [PubMed]
Stone RA . Neuropeptide Y and the innervation of the human eye. Exp Eye Res. 1986;42:349–355. [CrossRef] [PubMed]
Ruskell GL . Facial parasympathetic innervation of the choroidal blood vessels in monkeys. Exp Eye Res. 1971;12:166–172. [CrossRef] [PubMed]
Alm A . The effect of sympathetic stimulation on blood flow through the uvea, retina and optic nerve in monkeys (Macacca irus). Exp Eye Res. 1977;25:19–24. [CrossRef] [PubMed]
Kawarai M Koss MC . Sympathetic vasoconstriction in the rat anterior choroid is mediated by alpha1-adrenoceptors. Eur J Pharmacol. 1998;363:35–40. [CrossRef] [PubMed]
Steinle JJ Krizsan-Agbas D Smith PG . Regional regulation of choroidal blood flow by autonomic innervation in the rat. Am J Physiol Regul Integr Comp Physiol. 2000;279:R202–R209. [PubMed]
Polska E Polak K Luksch A . Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects. Br J Ophthalmol. 2004;88:533–537. [CrossRef] [PubMed]
Stjernschantz J Selen G Astin M Resul B . Microvascular effects of selective prostaglandin analogues in the eye with special reference to latanoprost and glaucoma treatment. Prog Retin Eye Res. 2000;19:459–496. [CrossRef] [PubMed]
Georgopoulos GT Diestelhorst M Fisher R Ruokonen P Krieglstein GK . The short-term effect of latanoprost on intraocular pressure and pulsatile ocular blood flow. Acta Ophthalmol Scand. 2002;80:54–58. [CrossRef] [PubMed]
Geyer O Man O Weintraub M Silver DM . Acute effect of latanoprost on pulsatile ocular blood flow in normal eyes. Am J Ophthalmol. 2001;131:198–202. [CrossRef] [PubMed]
Inan UU Ermis SS Yucel A Ozturk F . The effects of latanoprost and brimonidine on blood flow velocity of the retrobulbar vessels: a 3-month clinical trial. Acta Ophthalmol Scand. 2003;81:155–160. [CrossRef] [PubMed]
Arend O Harris A Wolter P Remky A . Evaluation of retinal haemodynamics and retinal function after application of dorzolamide, timolol and latanoprost in newly diagnosed open-angle glaucoma patients. Acta Ophthalmol Scand. 2003;81:474–479. [CrossRef] [PubMed]
Zeitz O Matthiessen ET Reuss J . Effects of glaucoma drugs on ocular hemodynamics in normal tension glaucoma: a randomized trial comparing bimatoprost and latanoprost with dorzolamide [ISRCTN18873428]. BMC Ophthalmol. 2005;5;6. [CrossRef] [PubMed]
Koz OG Ozsoy A Yarangumeli A Kose SK Kural G . Comparison of the effects of travoprost, latanoprost and bimatoprost on ocular circulation: a 6-month clinical trial. Acta Ophthalmol Scand. 2007;85:838–843. [CrossRef] [PubMed]
Gherghel D Hosking SL Cunliffe IA Armstrong RA . First-line therapy with latanoprost 0.005% results in improved ocular circulation in newly diagnosed primary open-angle glaucoma patients: a prospective, 6-month, open-label study. Eye (Lond). 2008;22:363–369. [CrossRef] [PubMed]
Sugiyama T Kojima S Ishida O Ikeda T . Changes in optic nerve head blood flow induced by the combined therapy of latanoprost and beta blockers. Acta Ophthalmol. 2009;87:797–800. [CrossRef] [PubMed]
Harris A Garzozi HJ McCranor L Rechtman E Yung CW Siesky B . The effect of latanoprost on ocular blood flow. Int Ophthalmol. 2009;29:19–26. [CrossRef] [PubMed]
Berisha F Findl O Lasta M Kiss B Schmetterer L . A study comparing ocular pressure pulse and ocular fundus pulse in dependence of axial eye length and ocular volume. Acta Ophthalmol. 2010;88:766–772. [CrossRef] [PubMed]
Dastiridou AI Ginis HS De Brouwere D Tsilimbaris MK Pallikaris IG . Ocular rigidity, ocular pulse amplitude, and pulsatile ocular blood flow: the effect of intraocular pressure. Invest Ophthalmol Vis Sci. 2009;50:5718–5722. [CrossRef] [PubMed]
Flammer J Orgul S Costa VP . The impact of ocular blood flow in glaucoma. Prog Retin Eye Res. 2002;21:359–393. [CrossRef] [PubMed]
Leske MC . Ocular perfusion pressure and glaucoma: clinical trial and epidemiologic findings. Curr Opin Ophthalmol. 2009;20:73–78. [CrossRef] [PubMed]
Gugleta K Orgul S Hasler PW Picornell T Gherghel D Flammer J . Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma. Invest Ophthalmol Vis Sci. 2003;44:1573–1580. [CrossRef] [PubMed]
Emre M Orgul S Gugleta K Flammer J . Ocular blood flow alteration in glaucoma is related to systemic vascular dysregulation. Br J Ophthalmol. 2004;88:662–666. [CrossRef] [PubMed]
Flammer J Pache M Resink T . Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye. Prog Retin Eye Res. 2001;20:319–349. [CrossRef] [PubMed]
Resch H Garhofer G Fuchsjager-Mayrl G Hommer A Schmetterer L . Endothelial dysfunction in glaucoma. Acta Ophthalmol. 2009;87:4–12. [CrossRef] [PubMed]
Martinez A Sanchez-Salorio M . Predictors for visual field progression and the effects of treatment with dorzolamide 2% or brinzolamide 1% each added to timolol 0.5% in primary open-angle glaucoma. Acta Ophthalmol. 2010;88:541–552. [CrossRef] [PubMed]
Figure 1.
 
Effect of squatting on OPP and ChBF. Squatting periods were scheduled before and after treatment with either latanoprost (●) or placebo (□). Data are presented as percentage of change from baseline (mean ± SD). *Significant differences between groups.
Figure 1.
 
Effect of squatting on OPP and ChBF. Squatting periods were scheduled before and after treatment with either latanoprost (●) or placebo (□). Data are presented as percentage of change from baseline (mean ± SD). *Significant differences between groups.
Figure 2.
 
Effect of an artificial increase in intraocular pressure using a suction cup on OPP, ChBF, and IOP. Periods of artificial increase in intraocular pressure were scheduled before and after treatment with either latanoprost (●) or placebo (□). IOP data are presented as absolute values, OPP and ChBF data are presented as percentage change from baseline (mean ± SD). *Significant differences between groups.
Figure 2.
 
Effect of an artificial increase in intraocular pressure using a suction cup on OPP, ChBF, and IOP. Periods of artificial increase in intraocular pressure were scheduled before and after treatment with either latanoprost (●) or placebo (□). IOP data are presented as absolute values, OPP and ChBF data are presented as percentage change from baseline (mean ± SD). *Significant differences between groups.
Table 1.
 
Demographic and Baseline Characteristics of the Participating Subjects.
Table 1.
 
Demographic and Baseline Characteristics of the Participating Subjects.
Placebo Group (n = 12) Latanoprost Group (n = 12) P
Age, y 25 ± 3 24 ± 4 0.12
MAP, mm Hg 79 ± 6 82 ± 8 0.35
PR, bpm 69 ± 9 71 ± 11 0.48
IOP, mm Hg 13.4 ± 2.0 12.9 ± 1.7 0.60
OPP, mm Hg 39 ± 3 41 ± 4 0.24
ChBF, arbitrary units 17.3 ± 4.4 16.4 ± 4.5 0.51
Table 2.
 
Effect of 14 Days Treatment with Either Latanoprost or Placebo on All Outcome Variables
Table 2.
 
Effect of 14 Days Treatment with Either Latanoprost or Placebo on All Outcome Variables
Placebo Group (n = 12) Latanoprost Group (n = 12) P
MAP, mm Hg −0.2 ± 5.0 −1.5 ± 8.9 0.65
PR, bpm 0.1 ± 14.4 5.3 ± 21.6 0.50
IOP, mm Hg −3.2 ± 8.0 −17.9 ± 14.4 0.008*
OPP, mm Hg −2.6 ± 6.7 6.3 ± 6.7 0.004*
ChBF, arbitrary units 4.5 ± 7.9 2.6 ± 10.3 0.30
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×