The acute effects of stellate ganglion block on circulation in human ocular fundus

PURPOSE: To study the acute effects of local-anesthetic stellate ganglion block (SGB) on tissue circulation in the human fundus. METHODS: Eleven patients with Bell's palsy (age 56+/-6 y, mean+/-SD) who underwent SGB for its treatment participated in the study. Using the laser speckle method, normalized blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 s over an area located halfway between the macula and the optic nerve head (ONH) with no discrete visible vessels and averaged over 3 pulses when fixation was satisfactory (NB(ch-ret)). NB(ch-ret) and intraocular pressure (IOP) in both eyes, blood pressure (BP), and pulse rate (PR) were measured before, and 10, 20, 30, and 60 min after SGB. SGB was induced by injecting 1% mepivacaine hydrochloride (5 ml) into the vicinity of the seventh cervical vertebra on the paralyzed side. RESULTS: The IOP in the blocked side significantly decreased between 20 and 60 min following SGB, compared to the baseline, while IOP in the unblocked side remained unchanged. The NB(ch-ret) was significantly increased after 10 min by about 8% in the blocked side, but its effect almost disappeared at 60 min. There was no significant change in NB(ch-ret) in the unblocked side, BP or PR throughout the experimental period. CONCLUSION: SGB increased tissue circulation in the fundus in the blocked side, but its effect was thought to be small and transient.     

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.     

Optic nerve head circulation after intraocular pressure reduction achieved by trabeculectomy

OBJECTIVE: To study the effects of trabeculectomy and needling revision of poorly functioning blebs on the optic nerve head (ONH) circulation in patients with primary open-angle glaucoma (POAG). DESIGN: Prospective, nonrandomized, self-controlled trial. PARTICIPANTS: Nineteen POAG patients (age range, 52 +/- 12 years; mean +/- standard deviation) undergoing trabeculectomy and six POAG patients (age range, 62 +/- 14 years) undergoing needling revision of the bleb. METHODS: Using the laser speckle method, the normalized blur (NB) value, a quantitative index of blood velocity, was determined every 0.125 seconds and averaged more than three cardiac pulses in the optic nerve head (NB(ONH)). MAIN OUTCOME MEASURES: The NB(ONH) and intraocular pressure (IOP) in both eyes, and blood pressure (BP) and pulse rate (PR) were measured before and 2 days and 1, 4, and 8 weeks after trabeculectomy, and also before and 10 and 40 min after needling procedures. RESULTS: Intraocular pressure in the operated eye was significantly decreased after trabeculectomy or needling procedures, and the ocular perfusion pressure was significantly increased by a maximum of 38%. The IOP in the unoperated eye, BP, and PR did not significantly change. The NB(ONH) did not significantly change in either the operated or unoperated eye. CONCLUSIONS: Trabeculectomy and needling procedures induced little change in the ONH circulation.     

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.     

Effect of topical carteolol on tissue circulation in the optic nerve head

The effect of topical 2% carteolol on tissue circulation in the albino rabbit optic nerve head (ONH) was investigated using a laser speckle tissue circulation analyzer. In the first experiment, the normalized blur (NB) value, a quantitative index of tissue blood flow velocity in the ONH, intraocular pressure (IOP), blood pressure (BP), and pulse rate were measured under general anesthesia before as well as 30, 60, 90, and 120 minutes after a 20-μL instillation of carteolol in one eye and the vehicle in the other eye in a masked, randomized manner. In the second experiment, one eye of a rabbit received carteolol twice daily for 20 days and the fellow eye received the vehicle in a masked, randomized manner. The IOP was measured every 5 days, and the NB in the ONH and IOP were measured before treatment and 2 hours after the last instillation on the 20th day. After a single instillation of carteolol, pulse rate showed a maximum reduction of 15%, and IOP in the carteolol-treated eyes showed a maximum decrease of 22%. The NB in the ONH and BP did not show any significant change during the experiment. After 20-day treatment with carteolol, IOP showed a maximum decrease of 25% in the carteolol-treated eyes and 21% in the vehicle-treated eyes. The NB showed a significant increase of 15% (P < 0.01) in the carteolol-treated eyes and 11% (P < 0.01) in the vehicle-treated eyes. It was indicated that long-term topical carteolol increased the blood velocity in the ONH tissue both in the carteolol- and vehicle-treated contralateral eyes in albino rabbits.     

Effect of the consumption of ethanol on the microcirculation of the human optic nerve head in the acute phase

PURPOSE: The effect of the consumption of ethanol on the circulation of the optic nerve head (ONH) in the human eye in the acute phase and its mechanism were studied. METHODS: Eleven volunteers drank a bottle of beer (633 ml) with or without ethanol (29.5 g). Normalized blur (NB), a quantitative index of blood flow velocity, was measured in the temporal site of the ONH. NB, blood pressure (BP) and pulse rate (PR) were measured before, immediately after, and every 15 minutes for 90 minutes after consumption. Intraocular pressure (IOP) and plasma ethanol concentration were measured before, and 30 and 90 minutes after consumption. Genotyping of the aldehyde dehydrogenase (ALDH) 2 gene was also performed. RESULTS: NB in the ONH increased significantly from 15 to 45 minutes after consumption of ethanol and the maximum increase was 14% at 15 minutes. IOP was lowered at 90 minutes after consumption, but it was not significant. Mean BP was lowered significantly after 60 minutes. PR and ocular perfusion pressure did not change. A significant correlation was found between plasma ethanol concentration at 30 minutes and maximum NB. NB in the ALDH 2-deficient group was significantly larger from 15 to 45 minutes after consumption than in the proficient group. CONCLUSION: It appeared that the consumption of ethanol can increase the blood flow in the human ONH in the acute phase through decreased resistance in blood vessels induced by acetaldehyde, a metabolite of ethanol.     

Effect of the consumption of ethanol on the microcirculation of the human optic nerve head in the acute phase

Purpose: The effect of the consumption of ethanol on the circulation of the optic nerve head (ONH) in the human eye in the acute phase and its mechanism were studied.Methods: Eleven volunteers drank a bottle of beer (633 mL) with or without ethanol (29.5 g). Normalized blur (NB), a quantitative index of blood flow velocity, was measured in the temporal site of the ONH. NB, blood pressure (BP) and pulse rate (PR) were measured before, immediately after, and every 15 minutes for 90 minutes after consumption. Intraocular pressure (IOP) and plasma ethanol concentration were measured before, and 30 and 90 minutes after consumption. Genotyping of the aldehyde dehydrogenase (ALDH) 2 gene was also performed.Results: NB in the ONH increased significantly from 15 to 45 minutes after consumption of ethanol and the maximum increase was 14% at 15 minutes. IOP was lowered at 90 minutes after consumption, but it was not significant. Mean BP was lowered significantly after 60 minutes. PR and ocular perfusion pressure did not change. A significant correlation was found between plasma ethanol concentration at 30 minutes and maximum NB. NB in the ALDH 2-deficient group was significantly larger from 15 to 45 minutes after consumption than in the proficient group.Conclusions: It appeared that the consumption of ethanol can increase the blood flow in the human ONH in the acute phase through decreased resistance in blood vessels induced by acetaldehyde, a metabolite of ethanol.     

Effect of topical timolol on tissue circulation in optic nerve head

The effects of topical 0.5% timolol on tissue circulation in the albino rabbit optic nerve head (ONH) were investigated using a laser speckle tissue circulation analyzer. In the first experiment, the normalized blur (NB) value, a quantitative index of tissue blood flow velocity in the ONH, intraocular pressure (IOP), blood pressure, and pulse rate were measured under general anesthesia before, and 30, 60, 90, and 120 minutes after a 20 μL instillation of timolol in one eye and the vehicle in the other eye in a masked, randomized manner. In the second experiment, one eye of a rabbit received timolol twice daily for 20 days and the fellow eye received the vehicle in a masked, randomized manner. Every 5 days IOP was measured and the NB in the ONH and IOP were measured before treatment and 2 hours after the last instillation on the 20th day. After a single instillation of timolol, PR showed a maximum reduction of 12% and IOP in the timolol-treated eyes showed a maximum decrease in 25%. NB in the ONH and BP did not show any significant change during the experiment. After a 20-day treatment with timolol, IOP showed a maximum decrease of 25% in the timolol-treated eyes and 16% in the vehicle-treated eyes. The NB in the timolol-treated eyes increased significantly by 16% (P < 0.01), whereas that in the vehicle-treated eyes showed no significant change. It was suggested that long-term topical timolol with a normal drug regimen caused a significant increase in the peripheral blood velocity in the ONH only in the timolol-treated eyes, at least partly, by local penetration of the drug. Ocular penetration of topically applied timolol is thought to be similar between rabbit and human eyes. Therefore, the present results may have clinical implications.     

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 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.     

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 nitric oxide synthase inhibitor on optic nerve head circulation in conscious rabbits

PURPOSE: To study the effect of a nitric oxide synthase inhibitor on tissue circulation in the optic nerve head (ONH) of conscious rabbits. METHODS: N(G)-nitro-L-arginine methyl ester (L-NAME) (1, 10, or 100 mg/kg), D-NAME (10 mg/kg), or physiological saline was administered intravenously to albino rabbits. A quantitative index of blood velocity, the normalized blur (NB), was measured in the ONH by laser speckle tissue circulation analyzer. The intraocular pressure (IOP) and blood pressure (BP) were also measured. L-arginine (10 mg/kg) was intravenously administered 20 minutes after L-NAME (10 mg/kg) injection. Acetylcholine (ACh; 10 microg/kg per minute) was infused for 15 minutes, with or without pretreatment of L-NAME (1 mg/kg). RESULTS: L-NAME induced a continuous decrease of the NB in a dose-dependent manner, but D-NAME caused no significant change. At 100 mg/kg, L-NAME significantly increased the IOP, mean BP, and ocular perfusion pressure, but the other doses caused no significant changes. When L-arginine was administered after L-NAME injection, the NB returned to its initial level and remained there. Pretreatment with L-NAME inhibited the increase of NB induced by ACh. CONCLUSIONS: These results indicate that nitric oxide regulates basal tissue circulation in the ONH of conscious rabbits and suggest that ACh increases the circulation by promoting nitric oxide synthesis.     

Effect of topical latanoprost-timolol combined therapy on retinal blood flow and circulation of optic nerve head tissue in cynomolgus monkeys

PURPOSE: To evaluate the effects of topical latanoprost and timolol in combined therapy on retinal blood flow and tissue circulation in the optic nerve head (ONH) of the cynomolgus monkey. METHODS: Latanoprost (30 microL, 0.005%) was instilled once daily and timolol (30 microL, 0.5%) twice daily for 6 days into 1 eye, and physiological saline into the other eye to serve as control. Blood velocity through retinal veins was determined using Kowa Laser Speckle Blood Flow Meter. The ONH tissue blood velocity (NB(ONH)) was determined using the Laser Speckle Tissue Circulation Analyzer. Retinal blood flow and NB(ONH) determinations were carried out before the first instillation and 4 hours after the first instillation on the 2nd experimental day, and the last instillation at the same sites at the same time of day. The intraocular pressure (IOP) was also measured periodically. RESULTS: After the first instillation, on the 2nd experimental day, the retinal blood flow decreased compared with the baseline, but 6-day instillation caused no significant change from the baseline. Six-day instillation increased the NB(ONH) in the treated eyes by 10% from the baseline and by 7% from that in the fellow control eye. After 6-day instillation, the IOP was lowered by 7.8+/-2.7 mm Hg and 3.6+/-4.3 mm Hg in the treated and control eyes, respectively. CONCLUSIONS: Combined 6-day instillation of latanoprost once daily and timolol twice daily has no significant effect on the retinal blood flow, but significantly increases the ONH tissue blood velocity in monkey eyes. Jpn J Opthalmol 2000;44:227-234     

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.     

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.     

Time course of the change in optic nerve head circulation after an acute increase in intraocular pressure

PURPOSE: To investigate the time course of changes in optic nerve head (ONH) circulation after an acute increase in intraocular pressure (IOP), by using the laser speckle method, and to evaluate the effects of a calcium antagonist, the nitric oxide synthetase inhibitor, indomethacin, or sympathetic nerve amputation on the response in ONH circulation after an acute increase in IOP. METHODS: In rabbits, the normalized blur (NB) level, a quantitative index of tissue blood velocity in the ONH, was monitored for 60 minutes after an increase in IOP from 20 mm Hg to 40, 50, or 60 mm Hg and for 25 seconds after increase in IOP from 20 mm Hg to 50 or 60 mm Hg with high time resolution. The effects of systemic administration of 1 micro g/kg per hour nilvadipine (a calcium antagonist), 30 mg/kg N(omega)-nitro-L-arginine (L-NAME), or 5 mg/kg indomethacin, or those of sympathetic nerve amputation on the time course of the changes in NB were studied. RESULTS: NB showed a quick recovery within several seconds after increase in IOP to 40 or 50 mm Hg, whereas no or little recovery occurred after an increase to 60 mm Hg. The nilvadipine treatment significantly increased NB at IOP of 20 mm Hg (baseline NB, P = 0.045) and apparently impaired the recovery of NB after the increase in IOP. After L-NAME administration, baseline NB significantly decreased (P = 0.028), and the NB recovery time was slightly but significantly prolonged (P = 0.012). Indomethacin showed no effects on baseline NB or NB recovery. Sympathetic nerve amputation increased baseline NB (P = 0.027), but did not influence NB recovery. CONCLUSIONS: The current results showed a quick recovery response in the ONH circulation after an acute increase in IOP in rabbits. A calcium antagonist impaired the response. Production of nitric oxide or prostaglandins or the sympathetic nervous system is probably not mainly responsible for the reaction.     

Oxygen saturation in optic nerve head structures by hyperspectral image analysis

PURPOSE: A method is presented for the calculation and visualization of percent blood oxygen saturation from specific tissue structures in hyperspectral images of the optic nerve head (ONH). METHODS: Trans-pupillary images of the primate optic nerve head and overlying retinal blood vessels were obtained with a hyperspectral imaging (HSI) system attached to a fundus camera. Images were recorded during normal blood flow and after partially interrupting flow to the ONH and retinal circulation by elevation of the intraocular pressure (IOP) from 10 mmHg to 55 mmHg in steps. Percent oxygen saturation was calculated from groups of pixels associated with separate tissue structures, using a linear least-squares curve fit of the recorded hemoglobin spectrum to reference spectra obtained from fully oxygenated and deoxygenated red cell suspensions. Color maps of saturation were obtained from a new algorithm that enables comparison of oxygen saturation from large vessels and tissue areas in hyperspectral images. RESULTS: Percent saturation in retinal vessels and from the average over ONH structures (IOP = 10 mmHg) was (mean +/- SE): artery 81.8 +/- 0.4%, vein 42.6 +/- 0.9%, average ONH 68.3 +/- 0.4%. Raising IOP from 10 mmHg to 55 mmHg for 5 min caused blood oxygen saturation to decrease (mean +/- SE): artery 46.1 +/- 6.2%, vein 36.1 +/- 1.6%, average ONH 41.9 +/- 1.6%. The temporal cup showed the highest saturation at low and high IOP (77.3 +/- 1.0% and 60.1 +/- 4.0%) and the least reduction in saturation at high IOP (22.3%) compared with that of the average ONH (38.6%). A linear relationship was found between saturation indices obtained from the algorithm and percent saturation values obtained by spectral curve fits to calibrated red cell samples. CONCLUSIONS: Percent oxygen saturation was determined from hyperspectral images of the ONH tissue and retinal vessels overlying the ONH at normal and elevated IOP. Pressure elevation was shown to reduce blood oxygen saturation in vessels and ONH structures, with the smallest reduction in the ONH observed in the temporal cup. IOP-induced saturation changes were visualized in color maps using an algorithm that follows saturation-dependent changes in the blood spectrum and blood volume differences across tissue. Reduced arterial saturation at high IOP may have resulted from a flow-dependent mechanism.     

Effects of caffeine on microcirculation of the human ocular fundus

PURPOSE: To determine the effect of caffeine on microcirculation in the human ocular fundus. METHODS: The microcirculation in the ocular fundus of 10 healthy volunteers (10 eyes) was studied using a laser speckle tissue circulation analyzer. Caffeine or placebo (100 mg) was administered orally in a double-masked manner. Square blur rate (SBR), a quantitative index of blood flow velocity, was measured in a temporal site of the optic nerve head (ONH) free of surface vessels and in a middle site of the choroid-retina between the ONH and macula. Intraocular pressure (IOP), blood pressure (BP), pulse rate (PR), and central critical fusion frequency (CFF) were also measured. These parameters were measured before and for 2 hours after administration. The area under curve (AUC) of SBR was calculated for each area. Ocular perfusion pressure (OPP) was also calculated from BP and IOP. RESULTS: The time-course of change in SBR value showed much individual difference. Caffeine decreased the AUC of SBR in the ONH (P =.0218) as well as in the choroid-retina (P =.0469) significantly. IOP, mean BP, PR, OPP, and central CFF did not change significantly. CONCLUSIONS: These results suggest that caffeine may increase blood vessel resistance and decrease blood flow in the human ONH and choroid-retina.     

Effects of semotiadil, a novel calcium antagonist, on the retina and optic nerve head circulation.

The effects of semotiadil, a novel benzothiazine calcium antagonist, on the retinal and optic nerve head (ONH) tissue circulation were evaluated using the noninvasive laser speckle method. In urethane-anesthetized Dutch or albino rabbits, before and up to 90 min following intravenous injection of 400 microg/kg semotiadil fumarate (semotiadil group) or vehicle (control group), normalized blur value, a quantitative index of tissue blood velocity, in the retina (NB(retina)) or ONH (NB(onh)), was serially obtained with monitoring intraocular pressure (IOP) and systemic parameters: arterial pressure, pulse rate, arterial blood gas, and body temperature. There were no significant differences in IOP and the systemic parameters except arterial pressure between semotiadil and control groups during the experiments. Arterial pressure showed an acute and transient drop during the first 5 min after semotiadil administration. The time courses of the normalized blur value were significantly different between semotiadil and control groups in the retina (P = 0.0001, repeated measures two-way ANOVA), but not in the ONH (P = 0.6724). Changes in NB(retina) from the baseline in the semotiadil group was significantly greater than those in the control group 50 min or later after the administration (P < 0.0500, Mann-Whitney test). NB(onh) showed no significant differences between the two groups except during the first few min when arterial pressure acutely decreased in the semotiadil group. In conclusion, intravenously injected semotiadil increased the tissue blood velocity in the retina, but not in the ONH. This vascular selectivity in the ocular neural tissues differs from those of other calcium antagonists, such as nicardipine.     

Effect of topical timolol on optic nerve head circulation in the cynomolgus monkey

PURPOSE: To evaluate the effect of topical timolol on the optic nerve head (ONH) circulation in the cynomolgus monkey. METHODS: Eight cynomolgus monkeys were used. Timolol (0.5%, 30 microL) was instilled twice daily into 1 eye and physiological saline into the other eye for 7 consecutive days. The ONH tissue blood velocity (NB(ONH)) was determined using the laser speckle method. The determinations of NB(ONH) were carried out before the first instillation and 4 hours after the first, the seventh and the last instillation. The IOP was measured periodically. All measurements were performed in a masked manner. RESULTS: Twice daily 7-day instillation of 0.5% timolol showed no significant effect on the NB(ONH) in either eye, while the IOP was significantly decreased in both eyes. CONCLUSION: In the cynomolgus monkey, the ONH circulation was not affected by 7-day twice daily topical timolol treatment.