Effect of NO synthase inhibition on retinal vessel reaction to isometric exercise in healthy humans.

PURPOSE: It has been shown that retinal blood flow is autoregulated, meaning that flow is independent of perfusion pressure within a certain range. We tested the hypothesis that nitric oxide (NO) synthase inhibition alters the response of retinal arterial and venous vessels during isometric exercise. METHODS: In this study, nine healthy subjects were included. Each subject received the NO synthase inhibitor Ng-monomethyl-l-Arginine (l-NMMA, the α-receptor agonist phenylephrine or placebo intravenously on three study days. Retinal vessel diameter was assessed with the retinal vessel analyser (RVA), at baseline and during a squatting period of 6-7 min in absence or presence of l-NMMA, phenylephrine or placebo. RESULTS: Mean arterial pressure (MAP) and pulse rate (PR) increased significantly during all pretreatment squatting periods (p < 0.001) Retinal venous and arterial diameters showed a continuous decrease during squatting (p < 0.001). Phenylephrine increased MAP and PR but did not alter the retinal vessel diameter response to squatting. Administration of l-NMMA lead to a significant decrease in venous diameter before isometric exercise (p = 0.004). In addition, the retinal venous diameter response during administration of the NO synthase inhibitor was less pronounced than during phenylephrine or placebo (p < 0.001). CONCLUSION: Our study confirms that NO plays an important role in the control of retinal vascular tone at rest. In addition, the present data indicate a role of NO in retinal autoregulation, because the response of retinal venous diameters was altered after NO synthase inhibition. The nature of involvement, however, appears to be complex and requires further studies.

Effect of nifedipine on choroidal blood flow regulation during isometric exercise.

PURPOSE: To determine whether nifedipine, an L-type calcium channel blocker, alters choroidal blood flow (ChBF) regulation during isometric exercise in healthy subjects. METHODS: The study was carried out in a randomized, placebo-controlled, double-masked, two-way crossover design. Fifteen healthy male subjects were randomly assigned to receive either placebo or nifedipine on two different study days. Subfoveal ChBF was measured with laser Doppler flowmetry while the study participants performed isometric exercise (squatting). This was performed before drug administration and during infusion of nifedipine and placebo, respectively. Mean arterial pressure (MAP) and intraocular pressure (IOP) were measured noninvasively, and ocular perfusion pressure (OPP) was calculated as ⅔ MAP-IOP. RESULTS: MAP and OPP increased significantly during all squatting periods (P < 0.01). The increase in ChBF was less pronounced than the increase in OPP during isometric exercise. Nifedipine did not alter the OPP increase in response to isometric exercise, but it significantly augmented the exercise-induced increase in ChBF (P < 0.001 vs. placebo). Although ChBF increased by a maximum of 14.2% ± 9.2% during the squatting period when placebo was administered, the maximum increase during administration of nifedipine was 23.2% ± 7.2%. CONCLUSIONS: In conclusion, the data of the present study suggest that nifedipine augments the ChBF response to an experimental increase in OPP. In addition, it confirms that the choroidal vasculature has a significant regulatory capacity over wide ranges of OPPs during isometric exercise. (ClinicalTrials.gov number, NCT00280462.).

Posterior optic buttonholing prevents intraocular pressure peaks after cataract surgery with primary posterior capsulorhexis.

BACKGROUND: The performance of a primary posterior capsulorhexis (PPC) with and without posterior optic buttonholing (POBH) may significantly influence the intraocular pressure (IOP) after cataract surgery in age-related cataract patients. METHODS: The prospective randomized clinical study was performed at the department of Ophthalmology, Medical University of Vienna, Austria. Thirty consecutive cataract patients with bilateral same-day cataract surgery (60 eyes) under topical anesthesia were enrolled. In randomized order, cataract surgery with combined PPC/POBH was performed in one eye; in the other eye, cataract surgery was performed with PPC and in-the-bag implantation of the intraocular lens (IOL). Standardized IOP measurements by Goldmann applanation tonometry were performed preoperatively, 1, 2, 4, 6, 8 and 24 hours postoperatively, as well as 1 week and 1 month postoperatively. RESULTS: During the first 24 hours after surgery, all IOP measurements were significantly lower in eyes with combined PPC/POBH when compared to eyes with solitary PPC (p < 0.001). No IOP peaks of more than 27 mmHg were observed with combined PPC/POBH. In contrast, in eyes with PPC and in-the-bag IOL implantation, seven patients had an IOP peak of more than 27 mmHg and four IOP peaks of more than 30 mmHg. One week and 1 month postoperatively, IOP measurements were statistically comparable, and no significant differences could be observed between the two groups (p > 0.05). CONCLUSION: Postoperative IOP peaks after cataract surgery with sole PPC can be effectively prevented by the buttonholing of the IOL through the posterior capsulorhexis.

Choroidal blood flow and progression of age-related macular degeneration in the fellow eye in patients with unilateral choroidal neovascularization.

PURPOSE: Cardiovascular risk factors such as smoking, hypertension, and atherosclerosis seem to play an important role in the development of choroidal neovascularization (CNV). Recent studies have also provided evidence suggesting that choroidal and retinal blood flow is decreased in patients with AMD. On the basis of these results, the hypothesis for this study was that lower choroidal blood flow is associated with an increased risk of CNV in patients with AMD. METHODS: Forty-one patients with unilateral choroidal neovascular AMD were included in this observational longitudinal study. The fellow eyes of the patients served as study eyes. Subfoveal choroidal blood flow (FLOW) and fundus pulsation amplitude (FPA) were assessed with laser Doppler flowmetry and laser interferometry, respectively. A multivariate COX-regression model was used to test the hypothesis that low choroidal perfusion parameters are associated with the development of CNV. RESULTS: Of the 37 patients that were followed up until the end of the study, 17 developed CNV and 20 did not. The univariate COX-regression analysis shows that lower FLOW, systolic blood pressure, intraocular pressure, and FPA are risk factors for development of CNV. Moreover, the more advanced the AMD in the study eye, the higher the risk for CNV to develop in the fellow eye. Multivariate COX regression analysis indicated that only FLOW (P = 0.0071), FPA (P = 0.0068), and staging (P = 0.031) had statistically significant influences on the progression to CNV. CONCLUSIONS: The present study indicates that lower choroidal perfusion is a risk factor for the development of CNV in the fellow eye of patients with unilateral CNV.

Acute effects of intravenously administered ethanol on retinal vessel diameters and flicker induced vasodilatation in healthy volunteers.

There is evidence from several vascular beds that acute alcohol consumption causes ocular hypotension and peripheral vasodilatation. The current study investigated the effects of intravenously administered ethanol on retinal vessel diameters and on flicker induced retinal vasodilatation. For this purpose, ethanol (0.35 g/kg) or placebo (physiologic saline solution) was administered intravenously for 40 min in a randomized, double masked, two way cross-over design to 12 healthy male volunteers. Retinal vessel diameters and flicker induced vasodilatation were measured before administration of ethanol as well as 30, 50, 90 and 130 min after the start of infusion with a retinal vessel analyzer. Intraocular pressure, systemic blood pressure and blood ethanol concentration were determined at the same time points. Intravenous administration of ethanol increased blood ethanol concentration from 0.0 g/l to 0.56+/-0.10 g/l. Ethanol reduced IOP, but did not change ocular perfusion pressure. After cessation of the infusion blood ethanol concentration started to drop reaching a blood ethanol concentration of 0.22+/-0.06 g/l 130 min after the start of infusion. Retinal arterial diameters increased significantly after administration of ethanol by a maximum of +4.2+/-4.0%, whereas no change was observed in retinal veins. Neither arterial nor venous diameters were influenced by administration of placebo. Flicker stimulation induced a significant dilatation in both arterial and venous diameters. Ethanol did not change flicker responses in arteries or in retinal veins. In conclusion, intravenous administration of ethanol increases retinal arterial diameters, whereas venous diameters remained unchanged. Whether this is related to a direct vasodilator effect or to a hitherto unidentified mechanism remains to be clarified.

Ocular haemodynamic changes after single treatment with photodynamic therapy assessed with non-invasive techniques.

PURPOSE: To investigate in patients with neovascular age-related macular degeneration (ARMD) the changes in ocular perfusion caused by single treatment with photodynamic therapy (PDT) by different non-invasive methods; to evaluate correlations between relative changes of ocular haemodynamic parameters after PDT among each other and compared to morphological parameters; and to assess this in relation to early changes of visual acuity. STUDY POPULATION: 17 consecutive patients with subfoveal choroidal neovascularization (CNV) caused by ARMD scheduled for PDT without previous PDT treatment (four patients with predominantly classic CNV and 13 patients with occult CNV). OBSERVATION PROCEDURES: best-corrected visual acuity (before PDT, 6 and 8 weeks after PDT), fundus photography, fluorescein angiography, haemodynamic measurements with laser Doppler flowmetry (LDF), laser interferometry and ocular blood flow (OBF) tonometry (baseline and 1, 2, 6 and 8 weeks after treatment). MAIN OUTCOME MEASURES: choroidal blood flow (CHBF), fundus pulsation amplitude (FPA), pulsatile ocular blood flow (POBF), visual acuity. Changes smaller than 20% were considered clinically irrelevant. RESULTS: Ocular haemodynamic parameters did not change significantly in the follow-up period. Changes of haemodynamic parameters showed no correlation to treatment spot, morphological changes or visual acuity. Changes of visual acuity were comparable to results of earlier studies. CONCLUSION: Single treatment with PDT did not modify ocular blood flow parameters above 20% as assessed with different non-invasive methods.

Effect of primary posterior continuous curvilinear capsulorhexis with and without posterior optic buttonholing on postoperative anterior chamber flare.

PURPOSE: To evaluate the effect of primary posterior continuous curvilinear capsulorhexis (PCCC) with and without posterior optic buttonholing (POBH) on the anterior chamber reaction after small-incision cataract surgery. SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: Consecutive patients with age-related cataract having cataract surgery in both eyes under topical anesthesia were prospectively enrolled in a randomized clinical trial. In randomized order, cataract surgery with combined primary PCCC and POBH was performed in 1 eye; in the other eye, cataract surgery was performed with primary PCCC and in-the-bag implantation of an intraocular lens. Intraocular flare was measured with an FC-1000 laser flare-cell meter preoperatively and postoperatively at 1, 4 to 6, and 24 hours, 1 week, and 1 month. RESULTS: Thirty patients (60 eyes) were evaluated. The peak of intraocular flare was 1 hour postoperatively in all study eyes. In both groups, the response steadily decreased thereafter. Anterior chamber flare was statistically significantly higher in eyes with primary PCCC without POBH than in eyes with combined primary PCCC-POBH at all postoperative testing points (P<.001), including at 1 month (P = .01). CONCLUSIONS: Cataract surgery with combined primary PCCC-POBH led to significantly lower postoperative anterior chamber reaction than conventional in-the-bag implantation during a 4-week follow-up. The tight capsule-optic diaphragm effectively prevented the ophthalmic viscosurgical device captured behind the optic from entering the anterior chamber postoperatively.

Effects of vitamin C on hyperoxia-induced reduction of retinal blood flow.

OBJECTIVE: Breathing of 100% oxygen causes vasoconstriction in retinal vessels paralleled by a decrease in blood flow. The mechanism underlying this effect is still unclear, but may be related to the increased generation of reactive oxygen species during hyperoxia. Thus, the purpose of the present study was to investigate whether vitamin C, an agent with strong antioxidative properties, modifies the retinal vasoconstrictor response to hyperoxia. METHODS: A randomized, double-masked, placebo controlled, two-way crossover study was performed in 12 healthy young volunteers. 100% oxygen was administered via a breathing mask for 12 min. Retinal blood flow was measured before and during oxygen breathing in the presence of either ascorbic acid (3 g) or placebo on two different study days. Retinal blood flow was determined based on measurement of retinal vessel diameters and red blood cell velocity. RESULTS: Breathing of 100% oxygen induced a pronounced reduction of retinal arterial (-7.6%+/-6.5%) and venous diameters (-12%+/-6%). Hyperoxia induced vasoconstriction was not altered by co-administration of vitamin C (-8.6%+/-4.8% in arteries and -15%+/-7% in veins). Likewise, RBV and retinal blood flow decreased in response to oxygen by -24%+/-53% and -38%+/-42%. Again, the reduction of retinal hemodynamic parameters was not altered by co-administration of vitamin C. CONCLUSIONS: Oxygen induced blood flow response in the human retina is not altered by a single dose of vitamin C in healthy, young subjects. Whether this indicates that ROS are not involved in hyperoxia induced vasoconstriction of retinal vessels or is related to other factors has yet to be determined.

Twelve-hour reproducibility of retinal and optic nerve blood flow parameters in healthy individuals.

PURPOSE: The aim of the present study was to investigate the reproducibility and potential diurnal variation of optic nerve head and retinal blood flow parameters in healthy individuals over a period of 12 hr. METHODS: We measured optic nerve head and retinal blood flow parameters in 16 healthy male non-smoking individuals at five time-points during the day (08:00, 11:00, 14:00, 17:00 and 20:00 hr). Outcome parameters were perimacular white blood cell flux (as assessed with the blue field entoptic technique), blood velocities in retinal veins (as assessed with bi-directional laser Doppler velocimetry), retinal arterial and venous diameters (as assessed with the retinal vessel analyser), optic nerve head blood flow, volume and velocity (as assessed with single point and scanning laser Doppler flowmetry) and blood velocities in the central retinal artery (as assessed with colour Doppler imaging). The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter. RESULTS: No diurnal variation in optic nerve head or retinal blood flow was observed with any of the techniques employed. Coefficients of variation were between 1.6% and 18.5% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 3.7% to 78.2%. CONCLUSION: Our data indicate that in healthy individuals the selected techniques provide adequate reproducibility to be used in clinical studies. However, in patients with eye diseases and reduced vision the reproducibility may be considerably worse.

Strategies for reducing variance in laser Doppler flowmetry measurements.

BACKGROUND: Scattering of blood flow data as assessed with laser Doppler flowmetry (LDF) in humans is a problem in many studies using this technique. We set out to reduce variability in LDF data by eliminating the effect of the total returning light level (DC) on LDF parameters in the choroid through partial regression analysis. METHODS: In 20 healthy subjects, choroidal blood flow parameters were measured at different DC values using a portable confocal LDF device. We used two different strategies to reduce scattering of data eliminating the effect of yield, which is defined as DC/gain. On the one hand, we used a previously described method based on a third-order polynomial fit, which combines all obtained data. On the other hand, we applied a new method based on a linear fit for each individual subject. RESULTS: Variability of data during changes in DC is higher for LDF parameters volume and flow than for velocity. Both methods were successful in reducing scattering of LDF parameters with varying DC. CONCLUSIONS: The present study indicates that both methods to correct for changes in yield were successful in reducing the variability of LDF measurements. When systematic changes in DC occur after an intervention, one needs to be careful in interpreting the obtained data and it remains to be shown if either of the two techniques is capable of correcting for this effect. The approach presented here may, however, represent an effective, easily applicable and valid approach to reduce scattering of data from using LDF to assess blood flow in the posterior pole of the human eye.

Anterior chamber depth and change in axial intraocular lens position after cataract surgery with primary posterior capsulorhexis and posterior optic buttonholing.

PURPOSE: To compare axial position changes of the intraocular lens (IOL) by measuring anterior chamber depth (ACD) after small-incision cataract surgery with primary posterior continuous curvilinear capsulorhexis (PPCCC) and posterior optic buttonholing (POBH) of the IOL and after conventional cataract surgery with phacoemulsification and in-the-bag IOL implantation. SETTING: Department of Ophthalmology, Medical University of Vienna, Austria. METHODS: This prospective comparative study comprised 23 patients (46 eyes) with age-related cataract who had bilateral cataract surgery and implantation of an acrylic IOL (YA-60BB, Hoya). In randomized order, cataract surgery with PPCCC and POBH of the IOL was performed in 1 eye of each patient. In the fellow eyes, conventional phacoemulsification cataract surgery with in-the-bag IOL implantation was performed. The ACD was measured 1 to 2, 6, and 24 hours as well as 7 and 30 days postoperatively using high-resolution partial coherence laser interferometry. A baseline measurement was taken preoperatively in all patients. RESULTS: Ten patients completed 10 to 12 months of follow-up. Postoperatively, the axial IOL position was stable in eyes with PPCCC-POBH (P>.05). In contrast, a significant axial shift of the IOL in the anterior direction was observed in control eyes with in-the-bag IOL implantation (P<.001). The resulting refractive shift was significantly higher in control eyes than in eyes with PPCCC-POBH (P<.001). CONCLUSION: Combined PPCCC and POBH for cataract surgery significantly reduced postoperative anterior movement of the IOL.

Macular morphology after cataract surgery with primary posterior capsulorhexis and posterior optic buttonholing.

PURPOSE: To evaluate possible changes in macular morphology after cataract surgery with combined primary posterior capsulorhexis and posterior optic buttonholing in comparison to conventional in-the-bag intraocular lens (IOL) implantation. DESIGN: Prospective randomized study. METHODS: Fifty consecutive age-related cataract patients with normal macular morphology and function waiting for bilateral cataract surgery were enrolled. Cataract surgery with combined primary posterior capsulorhexis and posterior optic buttonholing was performed in one eye; in the fellow eye cataract surgery was performed with in-the-bag IOL implantation, leaving the posterior lens capsule untouched. Optical coherence tomography measurements were performed one week and one month postoperatively. RESULTS: During follow-up, no statistically significant changes of macular morphology could be observed in any of the tested patients. Mean central retinal thickness, minimum and maximum retinal thickness, and central retinal volume were all statistically comparable between the eyes with combined primary posterior capsulorhexis and posterior optic buttonholing and the control eyes (P > .05). Best-corrected visual acuity was full in all patients (Snellen 20/25 and better). No cases of subclinical macular edema were observed. CONCLUSION: Cataract surgery with combined primary posterior capsulorhexis and posterior optic buttonholing apparently does not increase the risk for postoperative macular edema in patients with a normal macula, since no cases of biomicroscopically noticeable macular edema with visual loss were observed in the first 1,000 eyes with primary posterior capsulorhexis/posterior optic buttonholing cataract surgery and no case of subclinical macular edema was found in this prospective randomized study.

Comparison of the effect of Viscoat and DuoVisc on postoperative intraocular pressure after small-incision cataract surgery.

PURPOSE: To evaluate the effect of Viscoat (sodium chondroitin sulfate 4%-sodium hyaluronate 3%) and DuoVisc (Viscoat and Provisc [sodium hyaluronate 1%]) on postoperative intraocular pressure (IOP) after bilateral small-incision cataract surgery. SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This prospective randomized study comprised 60 eyes of 30 consecutive patients with age-related cataract in both eyes. Each patient's eyes were randomly assigned to receive Viscoat or DuoVisc during cataract surgery. DuoVisc is a packet containing 2 ophthalmic viscosurgical devices (OVDs): the dispersive Viscoat, which was used for intraocular lens (IOL) implantation. In the Viscoat group, the Viscoat was used during the entire surgery. The intraocular pressure (IOP) was measured preoperatively as well as 1, 6, and 20 to 24 hours postoperatively. RESULTS: One and 6 hours postoperatively, the mean IOP was significantly higher in the Viscoat group than in the DuoVisc group (25.8 mm Hg and 20.5 mm Hg, respectively, at 1 hour and 24.7 mm Hg and 21.1 mm Hg, respectively, at 6 hours) (P<.05). At 20 to 24 hours, the mean IOP was not statistically significantly different between the 2 groups. Intraocular pressure spikes to 30 mm Hg or higher occurred in 4 eyes in the DuoVisc group and 11 eyes in the Viscoat group (P<.05). CONCLUSIONS: Viscoat caused significantly higher IOP increases and significantly more IOP spikes than DuoVisc in the early postoperative period. Therefore, if Viscoat is used during cataract surgery, an additional cohesive OVD should be used for IOL implantation.

Postoperative course of intraocular pressure after cataract surgery with combined primary posterior capsulorhexis and posterior optic buttonholing.

PURPOSE: To evaluate the natural course of intraocular pressure (IOP) after cataract surgery with combined primary posterior continuous curvilinear capsulorhexis (PPCCC) and posterior optic buttonholing (POBH) of the intraocular lens (IOL) in adult patients. SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: Fifty consecutive patients with age-related cataract awaiting cataract surgery under topical anesthesia in both eyes were enrolled prospectively. In randomized order, cataract surgery with combined PPCCC and POBH was performed in 1 eye. In the fellow eye, cataract surgery was performed conventionally with in-the-bag IOL implantation and the posterior lens capsule kept intact. Standardized IOP measurements by Goldmann applanation tonometry were performed 1, 2, 4, 6, 8, and 24 hours postoperatively. Follow-up IOP measurements were taken at 1 week and 1 month. Twenty-five patients received 1-time IOP-lowering medication immediately after cataract surgery; the other 25 did not receive IOP-lowering drops. RESULTS: During the first 24 hours postoperatively, no significant differences in IOP were observed between the PPCCC-POBH group and the conventional surgery group (P>.05). No IOP peaks greater than 27 mm Hg were observed in any eye. One week and 1 month postoperatively, no significant differences in IOP were found between groups (P>.05). The use of IOP-lowering drops significantly reduced postoperative IOP. However, no IOP spikes >27 mm Hg were found with and without the use of IOP-lowering drops. CONCLUSION: The course of IOP after cataract surgery with combined PPCCC and POBH showed the technique to be as safe as conventional cataract surgery with in-the-bag IOL implantation.

Intravenous administration of clonidine reduces intraocular pressure and alters ocular blood flow.

AIM: To evaluate the effect of intravenously administered clonidine on ocular blood flow in healthy volunteers. METHODS: A randomised, double-masked, placebo-controlled, two-way crossover study was performed in 12 healthy young volunteers. Clonidine (0.2 microg/kg/min) or placebo was administered intravenously over 10 minutes. The effects of clonidine were studied at baseline and up to 150 minutes after infusion. Ocular haemodynamics were measured using laser Doppler flowmetry, laser Doppler velocimetry and a retinal vessel analyser. RESULTS: Clonidine significantly decreased mean arterial pressure (MAP) and intraocular pressure (IOP). Calculated ocular perfusion pressure decreased significantly by -8.7+/-8.7% after infusion of clonidine (p<0.01 vs placebo). Retinal arterial diameters increased by +4.4+/-2.7% (p = 0.012 vs placebo), whereas no significant change was observed in retinal veins. Red blood cell velocity decreased by -16+/-14% (p<0.01 vs placebo) after infusion of clonidine. Hence, calculated retinal blood flow decreased by -14+/-12% (p = 0.033 vs placebo). Choroidal blood flow increased by +18+/-19% (p<0.01 vs placebo) and optic nerve head blood flow increased by +16+/-23% (p = 0.046 vs placebo) 30 minutes after administration of clonidine but both returned to baseline thereafter. CONCLUSION: The short-time increase in choroidal and optic nerve head blood flow indicates a transient vasodilatory effect of clonidine due to an unknown mechanism. The decrease in retinal blood flow indicates clonidine-induced vasoconstriction in the retinal microvasculature.

Altered nitric oxide system in patients with open-angle glaucoma.

OBJECTIVE: To investigate the ocular blood flow response to systemic nitric oxide synthase inhibition in patients with primary open-angle glaucoma. METHODS: In 12 patients with glaucoma and 12 age-matched control subjects, subfoveal choroidal blood flow, optic nerve head blood flow, ocular fundus pulsation amplitude, intraocular pressure, and systemic hemodynamic parameters were measured at baseline and after inhibition of nitric oxide synthase by intravenous administration of NG-monomethyl-L-arginine. RESULTS: The increase in blood pressure in response to NG-monomethyl-L-arginine was comparable between the 2 study cohorts. In patients with glaucoma, the decrease of optic nerve head blood flow (P = .03) and fundus pulsation amplitude (P<.001) during nitric oxide synthase inhibition was significantly less pronounced than in healthy control subjects. A tendency toward a reduced response in choroidal blood flow was seen (P = .051 between groups) in patients with glaucoma. CONCLUSIONS: This is the first in vivo study providing evidence for an altered ocular L-arginine/nitric oxide system in patients with glaucoma. Normalization of the ocular nitric oxide production may be beneficial in terms of normalization of ocular blood flow and neuroprotection of retinal ganglion cells.

Influence of infusion volume on the ocular hemodynamic effects of peribulbar anesthesia.

PURPOSE: To test the hypothesis that ocular blood-flow response to peribulbar anesthesia can be reduced by using a smaller volume of anesthetic mixture. SETTING: Departments of Ophthalmology and Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. METHODS: Twenty patients scheduled for bilateral age-related cataract surgery were enrolled in a prospective randomized balanced observer-masked crossover study. Two study days with a 2 mL injection volume or 5 mL injection volume used for peribulbar anesthesia were scheduled. On 1 study day, patients received the 1-dose regimen and on the other study day, when the contralateral eye had surgery, patients received the other injection volume. On both study days, the anesthetic mixture consisted of an equal amount of lidocaine, bupivacaine, and hyaluronidase independently of the injection volume. Intraocular pressure (IOP), blood pressure, and pulse rate were measured noninvasively. Ocular fundus pulsation amplitude (FPA) and peak systolic and end diastolic flow velocities in the central retinal artery were measured with laser interferometry and color Doppler imaging, respectively. The results were recorded as means +/- SD. RESULTS: Peribulbar anesthesia increased IOP and reduced FPA and flow velocities in the central retinal artery. The effects on IOP (5 mL, 35.1% +/- 16.0%; 2 mL, 14.1% +/- 14.1%; P<.001) and ocular hemodynamic parameters (FPA: 5 mL, -17.5% +/- 7.8%/2 mL, -7.3% +/- 7.2%, P<.001; peak systolic velocity: 5 mL, -19.5% +/- 10.7%/2 mL, -10.6% +/- 9.8%, P = .013; end diastolic velocity: 5 mL, -16.7% +/- 6.2%/2 mL, -8.4% +/- 7.3%, P = .005) were more pronounced with the 5 mL injection volume than with the 2 mL injection volume. CONCLUSIONS: An injection volume of 2 mL instead of 5 mL reduced the ocular blood-flow response to peribulbar anesthesia. This procedure may be used in patients with ocular vascular disease to reduce the incidence of anesthesia-induced ischemia and loss of vision.

Treatment frequency and visual outcome in subfoveal choroidal neovascularization related to pathologic myopia treated with photodynamic therapy.

BACKGROUND: The purpose of this study was to examine the influence of treatment frequency on visual acuity of patients with PDT treatment for subfoveal predominantly classic CNV related to pathological myopia. DESIGN: Retrospective case series. METHODS: Thirty-seven patients with subfoveal predominantly classic CNV caused by pathologic myopia and treated with PDT were included. All patients received a full ophthalmic examination, including best-corrected visual acuity, slit-lamp biomicroscopy, fundus photography and fluorescein angiography, before first treatment and every 3 months thereafter. Photodynamic therapy was performed according to standard protocol. Main outcome measurements were visual acuity and treatment frequency. RESULTS: The number of treatments received was 3.35+/-1.83 (average: 1-7). In 12 eyes (32.43%); the BCVA was stable or increased during the entire follow-up period. In eight eyes (21.62%), the BCVA decreased and did not return to the baseline values. A transient loss of visual acuity (over 3-9 months) with subsequent improvement in visual function was found in 68% (17 eyes). A gain of three or more lines compared with lowest BCVA was found in 56% (14 eyes). The number of treatments did not correlate with baseline BCVA, greatest linear dimension of CNV at baseline or with the change of BCVA from baseline. In cases with transient worsening of BCVA, the recovery of visual acuity correlated significantly with the number of treatments (r=-0.522, P<0.05; Spearman rank correlation) received. CONCLUSION: Visual acuity recovery correlates with the number of PDT re-treatments; in many cases, an improvement in visual function after temporary decrease of BCVA can be observed after re-treatment according to current treatment guidelines. The number of PDT treatments has no negative effect on the visual outcome in subfoveal CNVs caused by pathological myopia.

ETa-receptor blockade, but not ACE inhibition, blunts retinal vessel response during isometric exercise.

Angiotensin II and endothelin-1 are potent vasoconstrictors that appear to play a role in retinal blood flow regulation. In the present study, we investigated the possible role of the angiotensin and the endothelin system in the regulation of retinal vessel diameters during isometric exercise in healthy humans. The study design was randomized, double-masked, placebo-controlled, and three-way cross over. Twelve healthy subjects performed squatting exercises for 6 min during infusion of either an angiotensin-converting enzyme inhibitor (enalapril), an ET(A)-receptor antagonist (BQ-123), or placebo. Retinal vessel diameters were measured continuously with the Zeiss retinal vessel analyzer. Systemic hemodynamics were assessed noninvasively, and intraocular pressure was measured with applanation tonometry. Squatting induced a significant increase in blood pressure and pulse rate, which was paralleled by a vasoconstriction in retinal arteries and veins. Intraocular pressure was only slightly increased during the squatting periods. BQ-123 significantly blunted the exercise-induced decrease in venous (P < 0.01) and arterial (P < 0.02, ANOVA) vessel diameters but had no effect on basal retinal diameters. By contrast, enalapril did neither influence vessel diameter at baseline conditions nor in response to isometric exercise. The data of the present study indicate that retinal vasoconstriction during isometric exercise is modified by ET(A)-receptor blockade, whereas it is not altered by angiotensin-converting enzyme inhibition. Hence, the present data indicate that endothelin-1, but not angiotensin II, is involved in retinal blood flow regulation during isometric exercise.

Effects of moderate changes in intraocular pressure on ocular hemodynamics in patients with primary open-angle glaucoma and healthy controls.

PURPOSE: There is some indirect evidence for altered autoregulation in patients with glaucoma, but only a few studies have measured ocular blood flow directly during changes in ocular perfusion pressure. The present study was designed to compare pulsatile choroidal blood flow and optic nerve head (ONH) blood flow during moderate increases in intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) and normal controls. DESIGN: Two nonrandomized studies comparing blood flow responses in glaucoma patients and controls in an open design. PARTICIPANTS AND CONTROLS: Sixteen patients with POAG glaucoma and 16 healthy gender-matched and age-matched controls were included in the choroidal blood flow experiments. The ONH blood flow experiment was performed in 14 POAG patients and 14 healthy gender-matched and age-matched controls. METHODS: In the first study, pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude (FPA). In the second study, ONH blood flow was measured using laser Doppler flowmetry. In both cohorts, the IOP was increased stepwise by 10 and 20 mmHg using a suction cup. MAIN OUTCOME MEASURES: Fundus pulsation amplitude and ONH blood flow. RESULTS: The baseline values of FPA and ONH blood flow were lower in glaucoma patients as compared with age-matched and gender-matched healthy controls. In patients with POAG, FPA decreased by -4.5+/-5.8% and -11.3+/-4.9% during elevation of IOP of 10 and 20 mmHg, respectively. These results were not different from the results in healthy controls, where FPA decreased by -5.1+/-3.4% and -12.2+/-4.9% at the 2 pressure levels (P = 0.23 between groups). Optic nerve head blood flow showed no changes during the increase of IOP of 10 and 20 mmHg in either of the 2 groups (glaucoma patients, +2.1+/-14.7% and -0.8+/-15.2%; healthy controls, +4.3+/-12.0% and +0.2+/-14.2%; P = 0.83 between groups). CONCLUSIONS: The present study does not provide evidence for altered autoregulation in patients with POAG during a moderate increase in IOP. However, these results do not necessarily contradict the concept of vascular dysregulation in glaucoma.