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PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p

Administration of low doses of Escherichia coli endotoxin (LPS) to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate the retinal vascular reactivity after LPS infusion. In a randomized placebo-controlled cross-over study, 18 healthy male volunteers received 20 IU/kg LPS or placebo as an intravenous bolus infusion. Outcome parameters were measured at baseline and 4h after LPS/placebo administration. At baseline and at 4h after administration a short period of 100% oxygen inhalation was used to assess retinal vasoreactivity to this stimulus. Perimacular white blood cell velocity, density and flux were assessed with the blue-field entoptic technique, retinal branch arterial and venous diameters were measured with a retinal vessel analyzer and red blood cell velocity in retinal branch veins was measured with laser Doppler velocimetry. LPS is associated with peripheral blood leukocytosis and increased white blood cell density in ocular microvessels (p0.001). In addition, retinal arterial (p=0.02) and venous (p0.01) diameters were increased. All retinal hemodynamic parameters showed a decrease during 100% oxygen breathing. This decrease was significantly blunted by LPS for all retinal outcome parameters except venous diameter (p=0.04 for white blood cell velocity, p=0.0002 for white blood cell density, p0.0001 for white blood cell flux, p=0.01 for arterial diameter, p=0.02 for red blood cell velocity and p=0.006 for red blood cell flux). These data indicate that LPS-induced inflammation induces vascular dysregulation in the retina. This may provide a link between inflammation and vascular dysregulation. Further studies are warranted to investigate whether this model may be suitable to study inflammation induced vascular dysregulation in the eye.

OBJECTIVE—The aim of the present study was to investigate the effect of intravenous C-peptide infusion on ocular blood flow in patients with type 1 diabetes under euglycemic conditions. RESEARCH DESIGN AND METHODS—The study was performed in a randomized, placebo-controlled, double-masked, two-way, crossover design in 10 type 1 diabetic patients. C-peptide was intravenously administered at two different dosages (dosage 1: 25 pmol · kg−1 · min−1 bolus followed by 5 pmol · kg−1 · min−1 continuous infusion; dosage 2: six times higher than dosage 1), each for 60 min. Physiologic saline solution was used as a control for C-peptide on a different study day. On both study days, euglycemic clamps were performed. To assess retinal blood flow, laser Doppler velocimetry (blood flow velocities) and retinal vessel analyzer (vessels diameters) measurements were performed. Laser interferometric measurements of fundus pulsation were used to assess pulsatile choroidal blood flow. Blood velocities in the ophthalmic artery were measured using color Doppler imaging. RESULTS—Eight patients (two female and six male) completed the study according to the protocol and without adverse events. One patient developed an anaphylactic reaction to C-peptide, which resolved without sequelae. The following results originate from the remaining eight subjects. Systemic hemodynamic parameters remained stable during both study days. Infusion of C-peptide did not affect any ocular hemodynamic parameter. CONCLUSIONS—The data of the present study indicate that exogenous C-peptide exerts no effect on ocular hemodynamic parameters in type 1 diabetic patients under euglycemic conditions. The maximum detectable change in these parameters was

Administration of low doses of Escherichia coli endotoxin [a lipopolysaccharide (LPS)] to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate whether the blue-field entoptic technique may be used to quantify the increase in circulating leukocytes in the ocular microvasculature after LPS infusion. In addition, combined laser Doppler velocimetry and retinal vessel size measurement were used to study red blood cell movement. Twelve healthy male volunteers received 20 IU/kg iv LPS as a bolus infusion. Outcome parameters were measured at baseline and 4 h after LPS administration. In the first protocol (n = 6 subjects), ocular hemodynamic effects were assessed with the blue-field entoptic technique, the retinal vessel analyzer, and laser Doppler velocimetry. In the second protocol (n = 6 subjects), white blood cell (WBC) counts from peripheral blood samples and blue-field entoptic technique measurements were performed. LPS caused peripheral blood leukocytosis and increased WBC density in ocular microvessels (by 49%; P = 0.036) but did not change WBC velocity. In addition, retinal venous diameter was increased (by 9%; P = 0.008), but red blood cell velocity remained unchanged. The LPS-induced changes in retinal WBC density and leukocyte counts were significantly correlated (r = 0.87). The present study indicates that the blue-field entoptic technique can be used to assess microvascular leukocyte recruitment in vivo. In addition, our data indicate retinal venous dilation in response to endotoxin.

It has recently been reported that light/dark transitions lead to changes in choroidal blood flow. Several observations indicate that these changes in choroidal perfusion are triggered at least in part by neural mechanisms. In the present study we hypothesised that the choroidal blood flow response to changes in retinal illumination may be modified by either the muscarinic receptor antagonist atropine or by the β-receptor antagonist propranolol. In 15 healthy subjects the response of choroidal perfusion was studied in a randomised placebo-controlled three way cross-over study using laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude. Before drug administration a transition from light to dark reduced both choroidal haemodynamic parameters by 8%–12%. Neither propranolol nor atropine altered basal choroidal blood flow or choroidal blood flow responses to light/dark transitions. Our data indicate that neither muscarinic nor β-receptors are involved in the choroidal blood flow response to changes in retinal illumination. Further studies are required to elucidate which mechanisms contribute to this blood flow behaviour of the choroid.

Purpose: To evaluate the long-term difference in lens epithelial cell (LEC) outgrowth on the anterior surface of a hydrogel intraocular lens (IOL) after curettage of the entire or one half of the circumference of the anterior capsule. Setting: Department of Ophthalmology, University of Vienna, Austria. Methods: Forty eyes with senile cataract only were randomly assigned to Group A, which had curettage of the entire anterior capsule, or Group B, which had curettage of the nasal half of the anterior capsule. Rentsch capsule curettes (Geuder) were used, a straight one for the nasal half and a bent model for the temporal half. One surgeon performed all standardized procedures with a temporal clear corneal incision, phacoemulsification, and in-the-bag implantation of a hydrogel IOL. Two years after surgery, the anterior surface of the IOL was examined by specular microscopy in a double-blinded fashion, and LEC outgrowth was graded semiquantitatively. Anterior capsule opacification (ACO) was also graded semiquantitatively. Results: In Group A, grade 2 ACO was observed in 53% of patients and grade 1 ACO in 47%. Similar results were achieved in Group B (59% and 41%, respectively). Two years after IOL implantation, the typically circumferential monolayer outgrowth of LECs on the hydrogel IOL surface was present in 80% in Group A and 60% in Group B. The ongrowth was less dense in the other IOLs; however, no significant differences between the groups were observed. Conclusions: Mechanical removal of residual LECs with a Rentsch capsule curette from the entire or from one half of the anterior capsule did not reduce LEC outgrowth 2 years after IOL implantation. Furthermore, the ACO grade was not significantly different. Lens epithelial cell proliferation in the germinative region and consecutive migration might be the cause of this outgrowth.

Purpose: To compare the clinical performance of 2 foldable intraocular lenses (IOLs) with sharp optic edges in terms of uveal and capsular biocompatibility. Setting: Department of Ophthalmology, University Hospital of Vienna, Vienna, Austria. Methods: Fifty eyes scheduled for cataract surgery were included in this comparative study. A standardized surgical protocol was used, and all operations were performed by 1 experienced surgeon. Two posterior chamber lens types of similar design with a 6.0 mm sharp-edged optic and poly(methyl methacrylate) haptics were used. Twenty-five eyes received an AcrySof® acrylic IOL (Alcon), and 25 eyes received a CeeOn® 911A® silicone IOL (Pharmacia). Relevant data were collected at a 3-year follow-up examination. To evaluate uveal biocompatibility, anterior chamber laser flare and cell measurements and inflammatory cell reactions were monitored. Cellular biocompatibility was investigated by examining anterior capsule opacification (ACO), posterior capsule opacification (PCO), and lens epithelial cell (LEC) ongrowth on the IOL’s anterior surface. Factors such as intralenticular glistenings and IOL decentration were also evaluated. Results: Anterior chamber flare and cells and the inflammatory cell reaction were significantly lower in the CeeOn 911A group. There was no statistically significant difference in ACO, PCO, and LEC ongrowth between the 2 groups. The AcrySof lenses showed significantly better centration and a higher density of intralenticular glistening. Conclusions: The findings show that a sharp-edged optic design is, to date, the most effective method of reducing the rate of PCO. Despite a subclinical foreign-body reaction in the AcrySof group, both lenses had a high degree of capsular and uveal biocompatibility.

Purpose: To evaluate the influence on postoperative inflammation of lens epithelial cell (LEC) removal after phacoemulsification. Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria. Methods: This randomized prospective single-surgeon study comprised 60 patients with senile cataract only. After a temporal clear corneal incision was made and phacoemulsification performed, no LECs were removed in Group A, LECs in the nasal half were removed in Group B, and LECs were removed from the entire anterior capsule in Group C. The LECs were removed with a Rentsch capsule curette (Geuder). In all eyes, a foldable hydrogel intraocular lens (Hydroview®, Bausch & Lomb) was implanted. Anterior chamber flare was evaluated through dilated pupils in a double-masked fashion using a Kowa FC-1000 laser flare-cell meter (LFCM). Measurements were done preoperatively as well as 1, 3, 7, 14, and 28 days and 3, 6, 12, and 24 months postoperatively. Results: In all 3 groups, the flare and cell values increased on the first postoperative day followed by a successive decrease thereafter. One month after surgery, the blood-aqueous barrier (BAB) was nearly restored in all groups. Between the first and fourth week, the flare values in Groups B and C were slightly lower than in Group A; however, mean flare and cell values among groups were not statistically significantly different at any measurement. Conclusion: The removal of LECs from the anterior capsule with a Rentsch curette did not influence postoperative BAB changes detected using an LFCM.

Background: The early postoperative inflammation after cataract surgery is mainly caused by surgical trauma. Patients and Methods: 450 data-sheets of patients, who were operated for senile cataract with small-incision phacoemulsification and in-the-bag implantation of a foldable intraocular lens were retrospectively analysed. Postoperative inflammation was evaluated with the Laser Flare-Cell Meter Kowa FC-1000 on day 1, 3, 7 and 28. All the operations were done with the same phacomachine model Orbit Oertli. The absolute phacotime was measured, the data classified in steps of 20 seconds. Statistical analysis was made with the student's t-test. Results: In the first postoperative week there is a statistical significant difference in the flare-values between the groups with short phacotime (up to 39 seconds) and the group with long phacotimes (over 80 seconds). One month after operation this significance was absent. Conclusions: The early postoperative inflammation is influenced by the duration of phacoemulsification. Surgical techniques and phacomachines that may reduce phacotime are helpful with respect to early postoperative inflammation.

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, placebocontrolled, 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 2⁄3 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.) (Invest Ophthalmol Vis Sci. 2012;53:374‐378) DOI:10.1167/iovs.11-8536

PURPOSE. The purpose of the present study was to investigate whether the nucleoside adenosine is involved in the regulatory processes of choroidal blood flow (ChBF) during an experimental decrease in ocular perfusion pressure (OPP). METHODS. In this randomized, double-masked, placebo-controlled, two-way crossover study, 14 subjects received either intravenous adenosine or placebo on two different study days. The suction cup method was used for a stepwise increase in intraocular pressure (IOP). Subfoveal ChBF was measured by laser Doppler flowmetry. Mean arterial pressure (MAP) and IOP were measured noninvasively. Ocular perfusion pressure was calculated as OPP 2⁄3MAP IOP. RESULTS. Adenosine increased ChBF significantly versus placebo before application of the suction cup (P 0.05). When the suction cup was applied, a significant decrease in OPP was observed. This effect was comparable on all study days. The decrease in OPP was paralleled by a significant decrease in ChBF (maximum between 43% and 52%) which was less pronounced than the decrease in OPP (maximum between 62% and 64%). Neither placebo nor adenosine influenced the ChBF increase during suction cup‐induced changes in OPP. CONCLUSIONS. The data of the present study confirm that the human choroid shows some regulatory capacity during a decrease in OPP. Adenosine influences basal vascular tone in the choroid but is not involved in the regulatory mechanisms during an increase in IOP. (ClinicalTrials.gov number, NCT00712764.) (Invest Ophthalmol Vis Sci. 2011;52: 6035‐6039) DOI:10.1167/iovs.11-7491

To compare dynamic autoregulation in the central retinal artery (CRA) and the posterior ciliary arteries (PCAs) after a step decrease in systemic blood pressure.Ten healthy male young subjects were studied. Flow velocities in retrobulbar vessels and systemic blood pressure were recorded in each subject before, during, and after a step decrease in blood pressure. Continuous blood pressure recordings were made with a finger plethysmograph system and flow velocities in the CRA and the PCAs were continuously measured with color Doppler imaging. Large bilateral thigh cuffs were inflated and a pressure approximately 20 mm Hg above peak systolic blood pressure was maintained for 3 minutes. A decrease in blood pressure was induced by rapid deflation of bilateral thigh cuffs. Experiments were performed separately for the CRA and the PCAs.Systemic blood pressure showed a step decrease between -9% and -12% (p0.001 each) immediately after thigh cuff release and returned to baseline 6 to 7 pulse cycles later. Peak systolic flow velocity in the CRA decreased by - 10 ± 7% (p=0.043) and returned to baseline earlier than systemic blood pressure, showing a delay of 3 pulse cycles after the blood pressure decrease. Peak systolic and end diastolic flow velocities in the PCAs decreased by - 13 ± 3% (p=0.004) and by - 10 ± 1% (p=0.0009), respectively and returned to baseline with a comparable time course to systemic blood pressure, reflecting no change in peripheral vascular resistance. There was a statistically significant difference in the time course of the velocity changes in the two selected arteries after thigh cuff release (p=0.008).The results of the present study indicate differences in the autoregulatory behavior of the vascular beds peripheral to the CRA and the PCAs. Our data indicate that the vascular bed distal to the CRA shows better autoregulatory properties as compared to the PCAs. Whether this is related to a myogenic mechanism remains to be investigated. The thigh cuff technique represents an interesting approach to study dynamic autoregulation in the human eye.

There is evidence that vascular beds distal to the ophthalmic artery (OA) show vasoconstriction in response to a step decrease in systemic blood pressure (BP). The mediators of this response are mostly unidentified. The aim of the current study was to test the hypothesis that α2-adrenoreceptors may contribute to the regulatory process in response to a decrease in BP. In this randomized, double-masked, placebo-controlled study 14 healthy male volunteers received either 22mg yohimbine hydrochloride or placebo. Beat-to-beat BP was measured by analysis of arterial pressure waveform; blood flow velocities in the middle cerebral artery (MCA) and the OA were measured with Doppler ultrasound. Measurements were done before, during and after a step decrease in BP. The step decrease in BP was induced by bilateral thigh cuffs at a suprasystolic pressure followed by a rapid cuff deflation. After cuff deflation, BP returned to baseline after 7-8 pulse cycles (PC). Blood velocities in the MCA returned to baseline earlier (4 PC) than BP indicating peripheral vasodilatation. Blood velocities in the OA returned to baseline later (15-20 PC) indicating peripheral vasoconstriction. Yohimbine did not affect the blood velocity response in the MCA, but significantly shortened the time of OA blood velocities to return to baseline values (6-7 PC, p

PURPOSE. The study was conducted to investigate whether the L-arginine/nitric oxide system plays a role in choroidal blood flow (ChBF) regulation during a decrease in ocular perfusion pressure (OPP). METHODS. Experiments were performed on 3 days in a randomized double-masked, placebo-controlled, three-way crossover design. On different study days, subjects received intravenous infusions of N G -monomethyl-L-arginine (L-NMMA), phenylephrine, or placebo. Intraocular pressure was raised in stepwise increments using the suction cup method. Choroidal blood flow (ChBF, laser Doppler flowmetry), mean arterial blood pressure (MAP), and IOP were assessed. Ocular perfusion pressure was calculated as OPP = 2/3(MAP - IOP). For correlation analysis all OPP/ChBF data pairs from all subjects were pooled independent of time point of measurement. Then, the pooled data were sorted according to OPP, and correlation analyses were performed. RESULTS. L-NMMA and phenylephrine increased resting OPP by +17% ± 18% and +14% ± 21%, respectively (P < 0.05). L-NMMA reduced resting ChBF by -21% ± 17% (P < 0.05). The relative decrease in OPP during suction cup application was comparable with all drugs administered. The decrease in OPP was paralleled by a significant decrease in ChBF (maximum between - 39% and - 47%), which was less pronounced, however, than the decrease in OPP (maximum between -69% and -74%). Neither placebo nor L-NMMA, nor phenylephrine, influenced the OPP/ChBF relationship. CONCLUSIONS. The data confirm previously published observations that the choroid shows some regulatory capacity during reduced OPP. The L-arginine/nitric oxide-system plays a role in the maintenance of basal vascular tone but seems not to be involved in the choroidal vasodilator response when IOP is increased.

PURPOSE Several studies have recently shown that a transition from light to dark is associated with a reduction in choroidal blood flow. The mechanism underlying this effect is unclear but may be related to changes in neural input. In the present study, the authors hypothesized that either the alpha-receptor agonist phenylephrine or the nitric oxide synthase (NOS) inhibitor L-NMMA may alter the choroidal blood flow response during a transition from light to dark. METHODS In 15 healthy male nonsmoking subjects, the response of choroidal perfusion was studied in a randomized placebo-controlled three-way crossover study. Phenylephrine, L-NMMA or placebo was administered on different study days, and the effect of a light/dark transition on choroidal perfusion parameters was studied. Subfoveal choroidal blood flow and fundus pulsation amplitude were assessed with laser Doppler flowmetry and laser interferometry, respectively. RESULTS Before drug administration, a transition from light to dark reduced both choroidal hemodynamic parameters by 11% to 20%. Neither phenylephrine nor placebo altered basal choroidal blood flow or choroidal blood flow responses to the light/dark transitions. By contrast, the NOS inhibitor L-NMMA significantly reduced basal choroidal blood flow by 20.5% +/- 5.9% (P < 0.001) and basal fundus pulsation amplitude by 21.5% +/- 4.8% (P < 0.001). In addition, the response of subfoveal choroidal blood flow (-6.2% +/- 3.2%; P = 0.008) and fundus pulsation amplitude (-4.2% +/- 2.4%; P < 0.001) to the light/dark transition was significantly diminished. CONCLUSIONS The present study indicates that NO plays a role in the choroidal blood flow decrease during a transition from light to dark. Given that L-NMMA is a nonspecific inhibitor of NOS, the present study does not clarify whether this NO is from endothelial or neural sources.

SummaryC-reactive protein (CRP) protects against bacterial pathogens and is a predictor of cardiovascular events. CRP is produced by vascular and organ-specific cells but the generation of CRP from peripheral blood mononuclear cells (PBMC) is poorly established. In a randomized, double-blind, placebo-controlled, two-way cross-over trial six healthy volunteers received a bolus infusion of 20 IU/kg Escherichia coli endotoxin [lipopolysaccharide (LPS)] or placebo. Intracellular CRP protein and CRP secretion of peripheral blood mononuclear cells (PBMC) was measured at baseline and 6 h after LPS by flow cytometry and enzyme-linked immubosorbent assay (ELISA), respectively. CRP mRNA expression was determined by real-time polymerase chain reaction (PCR). Regulation of the expression pathway was assessed using specific inhibitors in vitro. Small amounts of CRP protein and mRNA were detectable in PBMC, which were up-regulated between two- and eightfold by endotoxaemia in vivo. Augmented expression and release of CRP by LPS was consistent in PBMC cell culture experiments. LPS, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-α increased and IL-10 reduced CRP expression in PBMC. Toll-like receptor (TLR)-4, nuclear factor (NF)-κB and protein kinase C (PKC) activation were identified as intracellular signal transduction pathways of LPS-induced CRP expression. Constitutive CRP expression and release in PBMC is enhanced by inflammatory stimuli in vivo and in vitro. LPS might induce CRP generation via activation of TLR-4, NF-κB and PKC.

There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT).One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude.Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p0.001 versus timolol).This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma.

PURPOSE. To compare dynamic autoregulation in the middle cerebral artery (MCA) and the ophthalmic artery (OA) after a step decrease in systemic blood pressure. METHODS. Eighteen healthy male young subjects were studied. Ultrasound parameters and systemic blood pressures were recorded in each subject before, during, and after a step decrease in blood pressure. Continuous blood pressure recordings were made with a finger plethysmograph system, and flow velocities in the MCA and the OA were continuously measured with Doppler ultrasound. Large bilateral thigh cuffs were inflated and a pressure approximately 20 mm Hg above peak systolic blood pressure was maintained for 3 minutes. A decrease in blood pressure was induced by rapid deflation of bilateral thigh cuffs. Experiments were performed separately for the OA and the MCA. RESULTS. Systemic blood pressure showed a step decrease immediately after thigh cuff release (9%-15%) and returned to baseline 7 to 10 pulse cycles later. Flow velocities in the MCA returned to baseline earlier than systemic blood pressure, indicating peripheral vasodilatation, with a maximum of five to six pulse cycles after the blood pressure decrease. By contrast, flow velocities in the OA returned to baseline later than systemic blood pressure, reflecting peripheral vasoconstriction with a maximum 10 to 15 pulse cycles after cuff release. There was a statistically significant difference in the time course of the resistance changes in the two selected arteries after thigh cuff release (P < 0.001). CONCLUSIONS. The results of the present study suggest substantial differences in the autoregulatory behavior of the vascular beds peripheral to the MCA and the OA. Results in the MCA would be compatible with either metabolic or myogenic vasodilatation, whereas the results in the OA could reflect sympathetic vasoconstriction. Further studies are needed to support this hypothesis. The thigh cuff technique may represent an interesting approach to the study of autoregulation in patients with ocular vascular disease.

Purpose: To compare the course of inflammation after small-incision cataract surgery with implantation of 1 of 3 types of foldable intraocular lenses (IOLs) in eyes with uveitis. Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria. Methods: Seventy-four eyes with uveitis and cataract and 68 control eyes with cataract were prospectively selected to receive a foldable hydrophilic acrylic (Hydroview®, Bausch & Lomb), hydrophobic acrylic (AcrySof®, Alcon), or silicone (CeeOn® 911, Pharmacia) IOL. All surgery was performed by the same surgeon using a standardized protocol: clear corneal incision, capsulorhexis, phacoemulsification, and in-the-bag IOL implantation. Preoperative and postoperative inflammation was evaluated by measuring aqueous flare preoperatively and 1, 3, 7, 28, 90, and 180 days after surgery using the Kowa FC-1000® laser flare-cell meter. All uveitic eyes were in remission for at least 3 months before surgery. Results: In the uveitic eyes, there was no statistically significant difference in the postoperative course of flare and cell among the 3 IOL groups. Six months after surgery in uveitic eyes, flare values reached preoperative levels and the cell count was lower than preoperatively in all 3 IOL groups. Relative flare values were higher in the eyes with uveitis and a CeeOn 911 IOL; however, the difference between this group and the 2 acrylic IOL groups was not significant. Conclusions: There were no significant differences in inflammation after implantation of foldable IOLs in uveitic eyes. Although absolute flare values and cell counts in eyes with uveitis were higher than in control eyes, primarily because of a damaged blood-aqueous barrier (BAB), BAB recovery was similar between the 2 groups. The changes in the BAB indicate that foldable IOL implantation is safe in uveitic eyes.

Purpose: To evaluate the uveal and capsular biocompatibility of hydrophilic acrylic (Hydroview®) and hydrophobic acrylic (AcrySof®) intraocular lenses (IOLs) after phacoemulsification in eyes with pseudoexfoliation syndrome (PEX) or uveitis and compare the results with those in a control group. Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria. Methods: This prospective nonrandomized comparative trial comprised 143 eyes recruited consecutively. Of these, 49 eyes had PEX, 43 had uveitis, and 51 served as controls. A standardized surgical protocol was used. Cell reaction, anterior (ACO) and posterior (PCO) capsule opacification, and flare were evaluated 1 year after cataract surgery. Results: Regarding uveal biocompatibility, the number of foreign-body giant cells (FBGCs) increased in proportion to associated ocular pathologies in both IOL groups. The difference between the Hydroview control and Hydroview uveitis groups was statistically significant. The number of FBGCs was greater on AcrySof IOLs than on Hydroview IOLs in all 3 groups. The difference in FBGCs between the 2 IOL types was statistically significant in the control and PEX groups. Regarding capsular biocompatibility, lens epithelial cell (LEC) outgrowth was inversely correlated with intraocular inflammation. Outgrowth was statistically significantly higher with Hydroview IOLs, occurring in 85% in the control group, 45% in the PEX group, and 28% in the uveitis group (P < .0001). With AcrySof lenses, the percentages were 0%, 8%, and 4%, respectively. The PEX and uveitis groups were more likely to develop ACO than the control group (P < .012). There was no statistically significant difference in ACO between the 2 IOL types in the 3 patient groups. The PCO was statistically significantly greater in the uveitis group than in the control group (P < .026) and statistically significantly more dense on Hydroview than on AcrySof IOLs in all 3 patient groups (P < .002). Flare was statistically significantly higher in the uveitis group than in the PEX and control groups with both IOL types (P < .012). There was no statistically significant difference in flare between the 2 IOL types. Conclusions: Uveal and capsular biocompatibility depends on the intensity of ocular inflammation. The greater the inflammation, the less the biocompatibility of hydrophilic and hydrophobic acrylic materials. AcrySof stimulated more FBGCs. The Hydroview material had better uveal but poorer capsular biocompatibility than AcrySof. The sharp optic edge effect of the AcrySof IOL and the advantages of the Hydroview lens in normal eyes are less apparent in compromised eyes.

Purpose: To evaluate the influence of heparin sodium in the irrigation solution on postoperative inflammation and cellular reaction on the anterior surface of a hydrophilic intraocular lens (IOL). Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria. Methods: This randomized prospective single-surgeon study included 50 patients with senile cataract only. Half the patients received 1 mL of heparin sodium (concentration 10 IU/mL) in addition to the regular irrigating solution. In all other respects, the procedure was standardized: clear corneal incision, phacoemulsification, and implantation of a Hydroview® foldable hydrogel IOL (Bausch & Lomb). The parameters of inflammation—anterior chamber flare and cells—were evaluated with the pupil dilated in a masked fashion using a Kowa FC-1000 laser flare-cell meter 1, 3, 7, 14, and 28 days and 3, 6 and 12 months postoperatively. The cellular reaction was semiquantitatively examined and analyzed by specular microscopy. Results: In both groups, flare and cell values increased on the first postoperative day and successively decreased thereafter. In the first week, the flare and cell values were significantly higher in the group without heparin sodium in the irrigating solution. Subsequently, there were no differences between the 2 groups in flare or cells. At 1 day, the heparin sodium group had statistically significantly fewer IOLs with no cells on the surface. Subsequently, no differences in cellular reaction on the IOL were observed. Conclusions: Heparin sodium added to the standard irrigating solution reduced disturbances of the blood-aqueous barrier in the early postoperative period. There seemed to be no long-term effect, especially on cellular reaction, on the hydrophilic IOL surface.

To compare the outgrowth of lens epithelial cells (LECs) on 3 types of intraocular lenses (IOLs) to determine the influence of lens material and lens design (optic edge) on this phenomenon.Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria.Ninety eyes scheduled for cataract surgery were included in a prospective comparative study. A standardized surgical procedure was performed by 1 experienced surgeon. Patients received 1 of 3 types of posterior chamber IOLs of similar design with a 6.0 mm optic and poly(methyl methacrylate) haptic: AcrySof (Alcon), HydroView (BauschLomb), or Sensar (Allergan). Each IOL type was implanted in 30 eyes. Postoperative biomicroscopic examinations were performed 1, 3, 7, 30, 90, and 180 days and 1 year after surgery. Lens epithelial cells in each quadrant of the anterior lens surface were subjectively graded. The product with the highest density and the number of quadrants with this density were used to measure LEC outgrowth.Statistically significant differences (P.05) were seen between the hydrophilic IOL and the 2 hydrophobic lenses from day 30 until the final examination. The HydroView lens had a higher number of LECs on its anterior surface than the AcrySof or Sensar IOL. There were no statistically significant differences between the 2 acrylic IOLs at any measurement.The findings suggest that lens surface properties have a greater influence on LEC outgrowth than lens design (ie, sharp optic edge).

Purpose The current approach to the prevention of diabetic retinopathy relies on intensive anti-diabetes treatment and is only partially successful. A marker of retinopathy risk would enable strategies of surveillance, screening of adjunct drugs, and targeted drug interventions. The authors sought to identify early abnormalities of retinal vessels that are not prevented by the current therapeutic approach. Methods Retinal thickness (an informer of vascular permeability) and hemodynamic parameters at baseline and longitudinally were measured in 27 subjects (age, 32 ± 9 years [mean ± SD]) with well-controlled type 1 diabetes of 12.4 ± 6.4 years' duration and no retinopathy, and in 27 control subjects. In a subset of 17 patients and 11 controls, the hemodynamic response to reclining, a postural change that increases retinal perfusion pressure, was measured. Results Baseline foveal thickness and hemodynamic parameters were similar in the diabetic and control subjects. Foveal thickness increased over 12 months in the diabetic subjects, from 217 ± 22 μm to 222 ± 20 μm (P = 0.0036), remaining however within the normal range. Reclining uncovered in 47% of diabetic subjects (P = 0.016 compared with controls) an absent myogenic response (i.e., unchanged or increased arterial diameter instead of the normal decrease). The patterns were repeatable. Only the diabetic group with defective vasoconstriction showed widening arterial diameter over 12 months, a change presaging vascular dilatation in diabetic retinopathy. Conclusions Defective myogenic response to pressure was the first detectable abnormality of retinal vessels in subjects with well-controlled type 1 diabetes. Because of its selective occurrence, interpretability in individual patients, and pathogenic potential, the abnormality deserves evaluation as a risk marker for retinopathy.

To test the hypothesis that human choroidal blood flow (ChBF) may depend, not only on ocular perfusion pressure (OPP), but also on absolute mean arterial pressure (MAP) and intraocular pressure (IOP).There were two study days in an open design. On the first day, OPP was varied by elevating IOP during a squatting-induced increase in MAP (28 subjects). On the second day, only the IOP was increased (17 subjects). IOP was raised in stepwise increments by using the suction cupSubfoveal ChBF (laser Doppler flowmetry), MAP, and IOP were assessed, and OPP was calculated as (2/3)(MAP - IOP). For correlation analysis, data from all subjects were pooled according to IOP and MAP, and correlation analyses were performed.When data from study day 1 were grouped according to IOP, no correlation was observed between ChBF and MAP; but ChBFs were lower, the higher the IOP (P0.001). When data were grouped according to MAP, a significant correlation was found between ChBF and IOP (P0.001), but correlations were independent of MAP. When data of study day 2 were pooled according to IOP, a correlation between ChBF and OPP was seen only at IOP40 mm Hg (P0.05).The data confirm previously published observations that the choroid shows some autoregulatory capacity during changes in OPP. In addition, the data indicate that the choroid regulates its blood flow better during exercise-induced changes in MAP than during an experimental increase in IOP.