Effects of pranidipine, a new calcium antagonist, on circulation in the choroid, retina and optic nerve head.

PURPOSE. To study the effects of pranidipine, a newly developed Ca(2+)-antagonist, on tissue circulation in the optic nerve head (ONH), choroid, and retina in rabbits. METHODS. Pranidipine (5 microg/kg) or vehicle solution was injected intravenously in urethane-anesthetized rabbits and the normalized blur value (NB), a quantitative index of in vivo tissue blood velocity, was measured in the choroid and in an area of the ONH and retina free of visible surface vessels before and for 90 min after injection, using the laser speckle method. Measurements in the ONH and choroid were performed in the same albino rabbit eyes (pranidipine group, n = 10; control group, n = 10) and those in the retina in another group of Dutch rabbits (pranidipine group, n = 10; control group, n = 10). RESULTS. Between 30 and 90 min after injection, the NB in the pranidipine group increased by 24% in the ONH, 19% in the choroid, and 17% in the retina on an average compared to baseline, and was significantly different from that in the control group (P < 0.0001, ANOVA). There were no significant inter-group differences in the systemic parameters, except for a transient decrease in blood pressure in the pranidipine groups. CONCLUSIONS. Pranidipine increased blood velocity and probably blood flow in the ONH, choroid, and retina of rabbits.     

Effects of nilvadipine, a calcium antagonist, on rabbit ocular circulation and optic nerve head circulation in NTG subjects

PURPOSE: To study the effects of nilvadipine, a Ca2+ antagonist, on tissue circulation in the optic nerve head (ONH), choroid, and retina in rabbits and on the ONH circulation in normal tension glaucoma (NTG) patients. METHODS: Nilvadipine (3.2 microg/kg) or vehicle solution was injected intravenously into urethane-anesthetized rabbits, and the normalized blur value (NB), a quantitative index of in vivo tissue blood velocity, was measured in the choroid and in an area of the ONH and retina free of visible surface vessels before and for 90 minutes after injection, using the laser speckle method. The effects of nilvadipine on the ONH circulation was also studied using the H2 gas clearance method in separate groups of rabbits. Oral nilvadipine (4 mg/d) or placebo was administered to NTG patients in a double-masked manner, and NB in an area of the ONH rim free of visible surface vessels was measured by the same method before and 2, 4, 8, and 12 weeks after administration. RESULTS: The NB obtained from the ONH, choroid, or retina during the experimental period was increased by approximately 10% to 25% in the nilvadipine group compared with the NB in the control group (P < 0.0001, ANOVA), although systemic condition parameters and intraocular pressure (IOP) showed no significant intergroup difference except for a transient decrease in blood pressure in the nilvadipine groups. Blood flow rate in the ONH determined by the H2 gas clearance method also showed an approximately 25% increase in the nilvadipine group. The NB in the ONH of the oral nilvadipine-treated patients was significantly increased, by approximately 20% compared with the placebo-treated patients throughout the follow-up period. No significant intergroup difference was seen in blood pressure, pulse rate, or IOP. CONCLUSIONS: Nilvadipine increased blood velocity and, probably, blood flow in the ONH, choroid, and retina of rabbits. It also increased blood velocity in the ONH of NTG patients.     

Effect of topically applied iganidipine dihydrochloride, a novel calcium antagonist, on optic nerve head circulation in rabbits

PURPOSE: To study the effect of topically applied iganidipine dihydrochloride (iganidipine), a novel water-soluble calcium channel blocker, on blood flow in the optic nerve head (ONH), intraocular pressure, and systemic blood pressure in rabbits. METHODS: After 0.1% iganidipine (20 microL) was instilled into normal eyes, the change in ONH blood flow was measured using a hydrogen gas clearance flowmeter. Iganidipine (0.0001% to 0.1%) was instilled into eyes with impaired ocular circulation before or after the intravitreal injection of endothelin-1, and the change in ONH blood flow was measured. Changes in intraocular pressure and blood pressure after instillation of 0.1% iganidipine were measured. In all experiments, physiological saline was instilled into the contralateral eye as a control. RESULTS: Iganidipine significantly increased the ONH blood flow in normal eyes with the maximum increment of 31.7% at 45 minutes after instillation. Preinstillation of 0.01% and 0.1% iganidipine significantly inhibited the decrease in ONH blood flow in the eyes with impaired circulation. Moreover, ONH blood flow recovered with postinstillation of 0.1% iganidipine. These effects were persistent. Instillation of 0.1% iganidipine did not change either the intraocular pressure or the blood pressure. CONCLUSION: The instillation of iganidipine persistently increased and maintained the ONH blood flow in rabbit eyes with normal and impaired ocular circulation.     

Effects of lomerizine, a calcium channel antagonist, on retinal and optic nerve head circulation in rabbits and humans

PURPOSE: To investigate the effects of lomerizine, a Ca2+ antagonist, on the ocular tissue circulation in rabbits and on the circulation in the optic nerve head (ONH) and choroid in healthy volunteers. METHODS: Lomerizine (0.1 [n=10] or 0.3 [n=11] mg/kg) or vehicle solution (n=11) was injected intravenously in urethane-anesthetized rabbits, and blood flow in the retina, choroid, and iris-ciliary body was measured by the microsphere method and that in the ONH by the H2 gas-clearance method (0.1 [n=6] or 0.3 [n=9] mg/kg or vehicle, n=6). Oral 5 mg lomerizine or placebo was administered to volunteers (n=8) in a crossover study, and in areas of the fovea and ONH, the normalized blur (NB), a quantitative index of blood velocity, was measured, together with blood pressure, heart rate, and intraocular pressure (IOP), before and 1.5, 3, 6, and 9 hours after administration. RESULTS: Blood flow in the rabbit retina increased significantly in the lomerizine-treated group, but blood flow changed little in the choroid or iris-ciliary body. Blood flow in the rabbit ONH also showed a significant increase in the lomerizine-treated group. In human studies, the NB obtained from the ONH during the experimental period showed a small but significant increase in the lomerizine-treated group compared with the placebo-treated group, but no significant intergroup difference was detected in the NB obtained from the fovea or in blood pressure, heart rate, or IOP. CONCLUSIONS: Lomerizine increases blood velocity, and probably blood flow, in the ONH and retina in rabbits, and it also increases blood velocity in the ONH in healthy humans, without significantly altering blood pressure or heart rate.     

Effect of topical unoprostone on circulation of human optic nerve head and retina.

The purpose of the present study was to study the effect of topical unoprostone on the circulation of human optic nerve head (ONH) and retina in normal subjects. Using laser-speckle tissue blood flow analysis, normalized blur (NB), a quantitative index of tissue blood velocity, was measured every 0.125 sec at a temporal ONH site, free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). Color Doppler imaging (CDI) was also used to evaluate peak systolic blood velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) in the central retinal artery (CRA) and mean blood velocity (MV) in the central retinal vein (CRV). For baseline comparison (Day 0), recordings of bilateral NB(ONH) and intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were recorded in healthy volunteers before, and 45, 90, 180, and 270 min after instillation of one drop of unoprostone vehicle. On Day 1 (the day after baseline measurements), and twice daily for 7 days, one drop of 0.12% unoprostone was instilled into one eye and its vehicle into the other in a double-blinded manner. Measurements as on Day 0 were recorded on Days 1 and 7. CDI measurements were performed before and at 45 and 180 min after morning instillation on Days 1 and 7. During baseline recordings, there were no significant changes in any parameters. After administration of topical unoprostone, IOP was significantly lower bilaterally with more reduction in the unoprostone-treated eyes on Day 7. On Day 7, the NB(ONH) of the unoprostone-treated eyes was significantly higher 45 min after instillation than baseline (P = 0.035 with Bonferroni's correction). Analysis of variance for repeated measurements also revealed significant difference between Day 0 and Day 7 (P = 0.0017). BP, PR, NB(ONH) in the eye that received only the vehicle, PSV, EDV, and RI in the CRA in both eyes, and MV in the CRV in both eyes changed little. Tissue blood velocity in the ONH increased, at least temporarily, following instillation of unoprostone twice daily for 7 days. Although the clinical implication of the increase is unclear, the effects of topical unoprostone on human ONH circulation deserve further consideration.     

Effect of topically applied iganidipine dihydrochloride, a novel Ca2+ antagonist, on optic nerve head circulation in rabbits

PURPOSE: We studied the effect of topically applied iganidipine dihydrochloride, a novel water-soluble calcium channel blocker on the blood flow of optic nerve head (ONH), intraocular pressure, and blood pressure in rabbits. METHODS: 1. 0.1% iganidipine (20 microliters) was instilled into a normal eye. The change in blood flow in the ONH was measured using a hydrogen gas clearance flowmeter. 2. Iganidipine (0.0001%-0.1%) was instilled into a circulation-disordered eye before or after the intravitreal injection of endothelin-1, and change in the blood flow in the ONH was measured. 3. Changes in intraocular pressure and blood pressure after instillation of 0.1% iganidipine were measured. In all experiments, physiological saline was instilled in each contralateral eye as a control. RESULTS: 1. Instillation of iganidipine significantly increased the blood flow in the ONH by 40% at 45 minutes after instillation. 2. Pre-instillation of 0.01 and 0.1% iganidipine almost completely inhibited the decrease of blood flow in the ONH in the circulation-disordered model. The decrease of blood flow in the ONH was corrected with post-instillation of 0.1% iganidipine. These effects were continuous. 3. Instillation of 0.1% iganidipine did not change either intraocular pressure or blood pressure. CONCLUSION: It was shown that instillation of iganidipine continuously increased and maintained the blood flow in the ONH in normal and circulation-disordered rabbit eye models.     

Effects of adenosine on optic nerve head circulation in rabbits

This study was performed to determine whether intravitreal or intravenous adenosine can alter the microcirculation in the optic nerve head (ONH) of rabbits. Capillary blood flow in the ONH was measured serially with a laser speckle tissue analyser for 2 hr after the intravitreal (0.1, 1.0 and 10 nmol) or intravenous (0.2 and 0.6 mg kg(-1)min) injections of adenosine. In addition, the effect of specific adenosine A(1) and A(2a) antagonists and an adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel blockers on the adenosine-induced changes on the ONH blood flow was analysed. Intravitreal adenosine increased the capillary blood flow in the ONH in a dose-dependent manner, while intravenous adenosine had no effect. Co-administration of the specific adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nmol) significantly suppressed (P=0.006, ANOVA) the increase in the ONH blood flow induced by adenosine (10 nmol). The specific A(2a) receptor antagonist, 8-(3-chlorostyryl) caffeine (CSC, 10 nmol), had a weak effect in inhibiting the increase but the change was not significant (P=0.08, ANOVA). Both specific A(1) and A(2a) receptor agonists, N(6)-cyclopentyladenosine (CPA, 10 nmol) and 2-p-(2-carboxyethyl) phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680, 10 nmol), increased the ONH tissue blood flow (P<0.01, ANOVA). Glibenclamide (10 nmol), a selective K(ATP) channels antagonist, suppressed the increase of ONH blood flow induced by 10 nmol adenosine significantly (P<0.001, ANOVA). On the other hand, 10 nmol of 8-Br-cAMP, a cAMP analog, failed to enhance the capillary blood flow in the ONH. These results indicate that adenosine increases the capillary blood flow in the ONH of rabbits, and it acts through A(1) and A(2a) receptors from the ablumenal side where pericytes are located. Activation of K(ATP) channels is strongly related to the mechanism of adenosine-induced increase in ONH blood flow, while the participation of adenylate cyclase is less likely.     

Effects of topical latanoprost on optic nerve head circulation in rabbits, monkeys, and humans.

PURPOSE: To evaluate the effect of topically administrated latanoprost on optic nerve head (ONH) circulation in Dutch rabbits, cynomolgus monkeys, and normal humans. METHODS: The ONH tissue blood velocity (NB(ONH)) was determined using the laser speckle method. Latanoprost (0.005%, 30 microl) was instilled into one eye, and vehicle into the other eye as a control. In rabbits, NB(ONH) was measured for 90 minutes after a single instillation and before and after a 7-day once-daily instillation regimen. In monkeys, NB(ONH) was measured before and after 1, 4, and 7 days of a once-daily instillation regimen. The effect of intravenous indomethacin on the latanoprost-induced NB(ONH) change was also studied in rabbits and monkeys. In humans, the time-course changes in NB(ONH) were measured for 4.5 hours before and after a 7-day once-daily instillation regimen. Intraocular pressure (IOP) and systemic parameters were simultaneously studied in each experiment. All measurements were performed by investigators masked to the experimental condition. RESULTS: Latanoprost significantly increased NB(ONH) 10% to 19% in treated eyes after a single instillation (P = 0.035) or 7-day instillation regimen (P = 0.035) in rabbits, after a 4-day (P = 0.035) or 7-day (P = 0.035) instillation regimen in monkeys, and after a 7-day (P = 0.013) instillation regimen in humans, whereas there were no significant changes in the vehicle-treated eyes in any of the experiments (P > 0.5). Pretreatment with indomethacin (5 mg/kg) abolished the NB(ONH) increase but not the IOP reduction in latanoprost-treated eyes in rabbits and monkeys. IOP remained unchanged in both eyes in rabbits (P > 0.4), whereas it significantly decreased only in latanoprost-treated eyes in monkeys (P < 0.05) and humans (P < 0.05). CONCLUSIONS: Topical latanoprost significantly increased ONH blood velocity only in treated eyes in rabbits, monkeys, and humans. This effect was independent of the IOP-reducing effect of latanoprost and probably was associated with local penetration of the drug and the production of endogenous prostaglandins.     

Effects of lomerizine, a novel Ca2+ channel blocker, on the normal and endothelin-1-disturbed circulation in the optic nerve head of rabbits.

We examined the effects of lomerizine, a new diphenylmethylpiperazine Ca2+ channel blocker, on the normal circulation in the optic nerve head and long posterior ciliary artery, and on endothelin-1-induced hypoperfusion in the optic nerve head in anesthetized rabbits using a hydrogen gas clearance method and laser Doppler flowmetry. These effects were compared with those of nilvadipine and pranidipine. Lomerizine (0.1 and 0.3 mg/kg, i.v.) significantly increased tissue blood flow in the optic nerve head and the putative blood flow in the long posterior ciliary artery with smaller reduction of blood pressure (0.3 mg/kg, i.v.) and without change in heart rate. On the other hand, nilvadipine (0.003 and 0.01 mg/kg, i.v.) and pranidipine (0.003 and 0.01 mg/kg, iv.) each significantly increased blood flow and lowered blood pressure. Moreover, lomerizine (0.1 and 0.3 mg/kg, i.v.) and nilvadipine (0.01 mg/kg, i.v.), when administered 5 min before an endothelin-1 injection (10(-6) M, 100 microl), inhibited the hypoperfusion in the optic nerve head. These results suggest that lomerizine improves the ocular circulation with minimal cardiovascular side effects. Therefore, lomerizine may have clinical potential for the treatment of eye diseases associated with local circulatory disturbances, such as normal-tension glaucoma.     

Malignant lymphoma involving the optic nerve head and the retina

A previously healthy 27-year-old man presented with a history of progressive paraplegia and blurred vision within one year. Physical examination revealed marked posterior column sign. Cerebrospinal fluid (CSF) contained a white blood count of 1,940 microL, all lymphocytes. Fundi revealed yellowish infiltration (candle-wax drippings) along retinal vessels and tumefaction of the optic nerve head. He was initially misdiagnosed as suffering from tuberculosis meningitis on the basis of the CSF findings. Sarcoidosis was then suspected because of the unusual fundus appearance. Malignant lymphoma was confirmed by inguinal lymph node biopsy.     

Optic cup enlargement followed by reduced optic nerve head circulation after optic nerve stimulation.

PURPOSE: To investigate changes in optic nerve head (ONH) circulation, visual evoked potentials (VEPs), and ONH cupping after stimulation of the optic nerve. METHODS: Electrodes were fixed above the optic chiasma in rabbits under general anesthesia. Screw-type electrodes for VEP recording were fixed on the dura. ONH circulation, intraocular pressure (IOP), and blood pressure (BP) were measured after the passage of a current of 0.1 mA for 0.1 second (weak stimulation), 1 mA for 1 second (moderate), 5 mA for 10 seconds (strong), or 25 mA for 10 seconds (severe). Normalized blur (NB), indicative of tissue blood flow and velocity, was measured in the ONH after each stimulation, by using a laser speckle circulation analyzer. Changes in VEP and ocular fundus were also recorded. The ratio of cup area (CA) to disc area (DA) was measured before and 4 weeks after stimulation. After all experiments, the ONH was histologically examined. RESULTS: Weak stimulation increased NB in ONH for 10 minutes, whereas strong or severe stimulation significantly decreased NB for a longer time, in a dose-dependent manner. BP showed no significant change, except with severe stimulation. IOP was not significantly changed. VEP amplitude was reduced 30 minutes after strong stimulation. The CA-to-DA ratio was significantly increased 4 weeks after strong stimulation. In some rabbits, disc hemorrhage occurred, followed by enlargement of disc cupping, with slight gliosis. CONCLUSIONS: Electrical stimulation of the optic nerve changed ONH circulation and VEPs and increased disc cupping. This technique warrants further investigation as an experimental model for normal-tension glaucoma.     

Effect of topical amosulalol on tissue circulation in the optic nerve head.

The effect of topical 0.1% amosulalol on tissue circulation in the albino rabbit optic nerve head (ONH) was investigated using a laser speckle tissue circulation analyzer. Amosulalol was administered into one eye twice daily for 20 days, and vehicle was administered into the other eye in a masked, randomized manner. Intraocular pressure (IOP) was measured every 5 days. The normalized blur value (NB), a quantitative index of tissue blood flow velocity in the ONH, was measured before treatment and 2 hours after the last instillation on day 20. The IOP was also measured at 5-day intervals. Amosulalol decreased IOP by approximately 2 mmHg in the treated eyes (P < 0.01). There was no significant difference in NB between eyes before the first instillation, whereas NB was significantly greater (by approximately 16%) in the amosulalol-treated eye than in the control eye after completion of instillations (P < 0.01). The difference between NB after completion of instillations and that before the first instillation was significantly greater in the ONH of the amosulalol-treated eye than in the contralateral control eye (P < 0.01). Twice-daily instillation of 0.1% amosulalol for 20 days induced a significant increase in tissue blood velocity in the ipsilateral ONH in albino rabbits.     

Effects of topical travoprost and unoprostone on optic nerve head circulation in normal rabbits

PURPOSE: To evaluate the effect, and the duration of the effect, of topically administrated travoprost and unoprostone on optic nerve head (ONH) circulation in Dutch rabbits. METHODS: First, travoprost (0.004% solution) or unoprostone (0.12% solution) was unilaterally instilled once, or once daily (travoprost) or twice daily (unoprostone) for 7 days in Dutch rabbits. The ONH tissue blood velocity (NB(ONH)) was measured using the laser speckle method at 30 and 60 min after a single instillation of travoprost or unoprostone, and before and at 1, 6, and 12 hr (travoprost or unoprostone) and 24 hr (travoprost only) after the last instillation of the aforementioned 7-day instillation regimen. Second, similar experiments were conducted with indomethacin (5 mg/kg) pretreatment. RESULTS: Both travoprost and unoprostone significantly increased NB(ONH) only in the treated eyes after a single instillation (p = 0.011 to 0.038); this effect was abolished by indomethacin pretreatment. In the 7-day instillation regimen, NB(ONH) was increased by 11%, 40%, 17%, 16%, and 12% only in the treated eyes just before and at 1, 6, 12, and 24 hr after the final instillation of travoprost, respectively, and increased by 10%, 25%, 13%, and 14% only in the treated eyes just before and at 1, 6, 12 hr after the final instillation of the unoprostone, respectively. CONCLUSIONS: Topical travoprost or unoprostone significantly increased the ONH blood velocity with a single instillation and the effect persisted for 24 hr after a 7-day instillation. The effects of these drugs against retinal and ONH circulation are probably associated with the production of endogenous prostaglandins.     

Two dimensional mapping of the perfusion of the retina and optic nerve head.

AIM--To present a new non-invasive method of performing a high definition topography of perfused vessels of the retina and the optic nerve head with simultaneous evaluation of blood flow. METHOD--By a combination of a laser Doppler flowmeter with a scanning laser system the perfusion of the retina and the optic nerve head is visualised. The principles of measuring blood flow by laser Doppler flowmetry are based on the optical Doppler effect: laser light scattered by a moving particle is shifted in frequency by an amount delta f. Our data acquisition and evaluation system is a modified laser scanning tomograph. The technical data are retinal area of measurement 2.7 mm x 0.7 mm, 10 degrees field with 256 points x 64 lines, measurement accuracy 10 microns, wavelength 670 nm and 790 nm, light power 100 microW and 200 microW, data acquisition time 2.048 s. Every line is scanned 128 times by a line sampling rate of 4000 Hz. By performing a discrete fast Fourier transformation over 128 intensities of each retinal point the laser Doppler shift is calculated for each retinal point. With these data a two dimensional map with 256 x 64 points of the retinal perfusion is created. The brightness of the pixel is coded by the value of the Doppler shift. Offline capillary blood flow is estimated in arbitrary units according to the theory of laser Doppler flowmetry in every region of interest of the perfusion picture. We estimated the reliability and the validity of the method. Retinal blood flow was measured by scanning laser Doppler flowmetry (SLDF) while varying intraocular pressure by a suction cup of three healthy volunteers. Measurements of retinal blood flow performed in 47 eyes by the presented method (SLDF) were correlated with data gained by a commercially available laser Doppler flowmeter. Perfusion pictures of the superficial retinal layer and of deep prelaminar layers in the optic nerve head are presented. RESULTS--The reliability coefficients r1 of 'flow', 'volume', and 'velocity' were 0.84, 0.85, and 0.84 respectively. We found a significant linear relation between SLDF flow and the ocular perfusion pressure (r = 0.84, p < 0.001). Comparative measurements of the retinal blood flow by SLDF and a commercially available laser Doppler flowmeter showed a linear and significant relation (flow r = 0.6, p < 0.0001, volume r = 0.4, p < 0.01). Capillaries of the retinal superficial vasculature or deep ciliary sourced capillaries of the optic nerve head became visible with a high resolution by the confocal technique dependent on the focus. Offline, the blood flow variables of areas of 100 microns x 100 microns were calculated. CONCLUSION--SLDF enables the visualisation of perfused capillaries and vessels of the retina and the optic nerve head in high resolution by two dimensional mapping of perfusion variables which are encoded by the Doppler signal. This method achieves simultaneously qualitative and quantitative evaluation of capillary blood flow of distinct areas of the capillary meshwork.     

Effect of timolol on human retinal, choroidal and optic nerve head circulation

In a double-masked, randomized, placebo-controlled study, we evaluated the effect of topical timolol maleate 0.5% on the retinal, choroidal, and optic nerve head circulation in 5 healthy volunteer subjects. Changes in the pulsatile component of choroidal blood flow (PCBF) were determined from measurements of the ocular pulse wave. Changes in the retinal arterial blood flow rate (RBF) and optic nerve head capillary blood speed (CBS) were determined by laser Doppler velocimetry and monochromatic photography. In timolol-treated eyes, PCBF decreased by 32 +/- 12% (p = 0.0007). Changes in RBF and CBS were not statistically significant. In the contralateral placebo-treated eyes, PCBF decreased by 15 +/- 8% (p = 0.006) and RBF increased by 18 +/- 10% (p = 0.002). The change in CBS was not statistically significant.     

Effects of scleral buckling and encircling procedures on human optic nerve head and retinochoroidal circulation

AIMS: To study the effects of segmental scleral buckling and encircling procedures on tissue circulation in the human optic nerve head (ONH) and choroid and retina. METHODS: Using the laser speckle method, the normalised blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 seconds and averaged over three pulses in the optic nerve head (NB(ONH)) and choroid and retina (NB(ch-ret)) in 10 patients with unilateral rhegmatogenous retinal detachment (mean age 52 (SD 17)). NB(ONH), NB(ch-ret), and intraocular pressure (IOP) in both eyes, and blood pressure (BP) were measured before, and 1, 4, and 12 weeks after the scleral buckling and encircling procedure. RESULTS: NB(ch-ret) on the buckled side was significantly reduced after surgery and smaller than that in the unoperated contralateral eye throughout the study period (ANOVA, p<0.0001). NB(ch-ret) on the unbuckled side, in the foveal area, NB(ONH), IOP, and BP showed no significant change. CONCLUSIONS: It was indicated that the segmental scleral buckling procedure with encircling elements decreased tissue blood velocity in the choroid and retina on the buckled side but caused no significant change on tissue circulation in other areas of the fundus or ONH.     

Topical latanoprost and optic nerve head and retinal circulation in humans.

The purpose of the present study was to study the effect of a single instillation of latanoprost on the human optic nerve head (ONH) and retinal circulation. Using laser-speckle tissue blood flow analysis, normalized blur (NB; a quantitative index of tissue blood velocity) was measured every 0.125 sec at a temporal ONH site free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). Color Doppler Imaging (CDI) was also used to evaluate peak systolic blood velocity (PSV), endo-diastolic velocity (EDV), and resistive index (RI) in the central retinal artery (CRA) and mean blood velocity (MV) in the central retinal vein (CRV). One drop of 0.005% latanoprost was instilled into one eye and its vehicle into the other in eleven healthy volunteers in a double-blinded manner. Measurements of bilateral NB(ONH), CDI parameters, intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were performed before, and 45, 90, 180, and 270 min after instillation. After a single instillation of latanoprost or the vehicle, there was no significant bilateral difference throughout the experimental period. The difference in NB(ONH) between that before and at each time point of measurement (delta NB(ONH)) in the latanoprost-treated eyes was significantly higher between 45 and 270 min after instillation than that in vehicle-treated eyes (P = 0.0003 to 0.0156); ANOVA for repeated measurements also revealed significant difference between both eyes (P < 0.00001). BP, PR, and NB(ONH) in the eye that received only the vehicle, PSV, EDV, and RI in the CRA in both eyes, and MV in the CRV in both eyes changed little. Tissue blood velocity in the ONH increased at least temporarily following a single instillation of topical latanoprost. Although the mechanism of the increase is unclear, the effects of latanoprost on ONH tissue circulation in humans may have clinical implications.     

Effect of topical betaxolol on tissue circulation in the human optic nerve head.

There have been no reports to date on long-term betaxolol instillation effects on the human optic nerve head (ONH) tissue circulation. The purpose of this study was to study the effect of topical 0.5% betaxolol on tissue blood velocity in the human ONH. Using a laser-speckle tissue blood flow analyzer, normalized blur (NB; a quantitative index of tissue blood velocity) was measured every 0.125 seconds at a temporal ONH site free of visible surface vessels. Measurements were averaged for 3 cardiac cycles (NB(ONH)). For baseline comparison (day 0), recordings of bilateral NB(ONH) and intraocular pressure (IOP), blood pressure (BP) and pulse rate (PR) were recorded in healthy volunteers before, and 2, 4.5, and 7 hr after, instillation of 30 microL of betaxolol vehicle, and again on day 21; IOP was also recorded on days 7 and 14. On day 1 (the day after baseline measurements), and twice daily for 3 weeks, 30 microL of 0.5% betaxolol into one eye and 30 microL vehicle was instilled into the other in a double-blind study. Measurements as on day 0 were again recorded on day 21; IOP was also recorded on days 7 and 14. During baseline recordings, no significant changes were noted in any parameters. After administration of topical betaxolol, IOP was significantly reduced, bilaterally, with greater reduction in the betaxolol-treated eyes on day 21. Also on day 21, the NB(ONH) of the betaxolol-treated eyes was significantly higher 4.5 hr after instillation than that of the comparable baseline recording (p = 0.035 with Bonferroni's correction); BP, PR, and NB(ONH) in the eye which received only the vehicle showed little change. Tissue blood velocity in the human ONH was increased at least temporarily by instillation of topical betaxolol twice daily for 3 weeks. Although the obtained increase is small and may be clinically insignificant, the potential of betaxolol that can affect the ONH tissue circulation in humans after 21 days of instillation is thought to deserve further investigation.