[Efficiency and Therapy Safety of Fractionated Cyclophotocoagulation with up to Ten Laser Spots for Advanced Primary Open-Angle and Pseudoexfoliation Glaucoma]. / Effektivität und Therapiesicherheit der fraktionierten Zyklophotokoagulation mit bis zu 10 Herden für fortgeschrittene primäre Offenwinkel- und Pseudoexfoliationsglaukome.

BACKGROUND: Various procedures are available for the treatment of advanced glaucoma. We examined the efficacy and safety of fractionated cyclophotocoagulation (CPC) with up to ten laser spots for advanced primary open-angle glaucoma (POAG) and pseudoexfoliation (PEX) glaucoma treated with maximal topical therapy or eye-drop intolerance. MATERIAL UND METHODS: This retrospective study evaluated data from 297 eyes with advanced POAG and PEX glaucoma which received 10 applications of CPC between February 2012 and June 2017. Intraocular pressure (IOP), number of topical eye drops and postoperative complications were evaluated. Data were collected preoperatively, four weeks postoperatively, and at the last documented contact (six months postoperative visit). The paired Wilcoxon rank sum test was used to analyse the changes. RESULTS: The IOP for open-angle glaucoma decreased from 16.66 ± 4.36 mmHg preoperatively to 13.87 ± 3.59 mmHg at the last visit (6 months postoperative visit; p < 0.05). The IOP for the PEX glaucoma decreased significantly from 20.76 ± 9.55 mmHg preoperatively to 15.50 ± 5.93 mmHg at the last visit (p < 0.003). The number of hypotensive agents in the POAG was 2.51 ± 1.00 preoperatively and at the last visit 2.27 ± 1.03. In PEX glaucoma, the number of hypotensive agents was 2.46 ± 1.07 preoperatively and at the last visit 1.88 ± 0.97. Treatment-related complications occurred in three eyes - two cases of postoperative macular oedema, which were treated well with systemic steroids, and one case of pretreated anterior chamber irritation with hyphema, which was also treated with topical steroids. CONCLUSION: In our group of patients, the mild CPC performed by us with a maximum of 10 applications (vs. the conventional 20 - 30 applications) produced a good reduction of intraocular pressure, as well as a reduction in topical medication, with a low complication rate.

In vivo Histology of the Cornea - from the "Rostock Cornea Module" to the "Rostock Electronic Slit Lamp" - a Clinical "Proof of Concept" Study. / In-vivo-Histologie der Hornhaut ­ vom "Rostocker Cornea Modul" zur "Rostocker Elektronischen Spaltlampe" ­ eine klinische "Proof-of-Concept"-Studie.

INTRODUCTION: Confocal in vivo microscopy is an established method in ophthalmology research. As it requires contact coupling and calibration of the instruments is suboptimal, this method has been only rarely used in clinical routine work. As a result of close collaboration between physicists, information scientists and ophthalmologists, confocal laser scanning microscopy (CLSM) of the eye has been developed in recent years and a prototype can now be used in patients. The present study evaluates possible clinical uses of this method. MATERIAL AND METHODS: The essential innovations in CLSM are (1) a newly designed coupling element with superficial adaptation to corneal curvature and (2) the use of a dual computerised piezo drive for rapid and precise focusing. In post-processing and after elastic imaging registration of the individual images parallel to the surface, it is also possible to produce sagittal sections resembling a split lamp and with resolution in the micrometer range. The concept was tested on enucleated pig bulbi and tested on normal volunteers and selected patients with diseases of the cornea. RESULTS: Simultaneous imaging in planes parallel to the surface and in sagittal planes provided additional information that can help us to understand the processes of wound healing in all substructures of the cornea and the role of immune competent cells. Possible clinical uses were demonstrated in a volunteer with healthy eyes and several groups of patients (keratoconus after CXL, recurrent keratitis, status after PRK). These show that this new approach can be used in morphological studies at cellular level in any desired and appropriate test plane. CONCLUSIONS: It could be shown that this new concept of CLSM can be used clinically. It can provide valuable and novel information to both preclinical researchers and to ophthalmologists interested in corneal disease, e.g. density of Langerhans cells and epithelial stratification in ocular surface diseases.

[Glaucoma-Related Sleep Disorder and Associated Diseases]. / Schlafstörungen und schlafassoziierte Erkrankungen beim Glaukom.

The simultaneous occurrence of sleeping disorders and glaucoma is caused by multiple factors and, until today, the underlying mechanisms are not completely understood. There seems to be correlations, either between sleeping disorders in patients with a diagnosed glaucoma and between the onset of a glaucoma in patients with certain sleeping habits, but no precise data has been collected so far.

An Automated Approach for Localizing Retinal Blood Vessels in Confocal Scanning Laser Ophthalmoscopy Fundus Images.

In this work, we present a rules-based method for localizing retinal blood vessels in confocal scanning laser ophthalmoscopy (cSLO) images and evaluate its feasibility. A total of 31 healthy participants (17 female; mean age: 64.0 ± 8.2 years) were studied using manual and automatic segmentation. High-resolution peripapillary scan acquisition cSLO images were acquired. The automated segmentation method consisted of image pre-processing for gray-level homogenization and blood vessel enhancement (morphological opening operation, Gaussian filter, morphological Top-Hat transformation), binary thresholding (entropy-based thresholding operation), and removal of falsely detected isolated vessel pixels. The proposed algorithm was first tested on the publically available dataset DRIVE, which contains color fundus photographs, and compared to performance results from the literature. Good results were obtained. Monochromatic cSLO images segmented using the proposed method were compared to those manually segmented by two independent observers. For the algorithm, a sensitivity of 0.7542, specificity of 0.8607, and accuracy of 0.8508 were obtained. For the two independent observers, a sensitivity of 0.6579, specificity of 0.9699, and accuracy of 0.9401 were obtained. The results demonstrate that it is possible to localize vessels in monochromatic cSLO images of the retina using a rules-based approach. The performance results are inferior to those obtained using fundus photography, which could be due to the nature of the technology.

Depression, anxiety, and disturbed sleep in glaucoma.

Although it has been suggested that glaucoma is associated with circadian misalignment, sleep disorder, anxiety, and depression, these comorbid conditions have not received much attention. This study provides evidence for a significantly higher prevalence of depression, trait anxiety, and sleep disturbances in patients with progressed glaucoma, as compared with glaucoma patients with no or minor visual field defects (VFD). Logistic-regression analyses suggest that severe VFD constitute a significant predictor of depression, trait-anxiety, and sleep disturbance. Results indicate the necessity of regular screening and psychochronobiological treatment in glaucoma patients.

The effect of reactive oxygen species on the myogenic tone of rat ophthalmic arteries with and without endothelium.

BACKGROUND: Reactive oxygen species (ROS) play an important role in the pathogenesis of various ocular diseases. ROS can induce vasodilation or vasoconstriction depending on the species, the tested vessel bed, and the condition of the vessel. This study investigates the effect of different dosages of ROS on the tone of rat ophthalmic arteries. METHODS: Freshly dissected rat ophthalmic arteries were pressurized in a perfusion setup in steps of 10 mmHg to 180 mmHg in three consecutive cycles. The first cycle was run under mostly physiological conditions, the second cycle was run after ROS treatment, and the third cycle as passive dilation after all Ca(2+) was removed from the solution. ROS-induced dilation or constriction was calculated in relation to the passive dilation. All experiments were performed with or without endothelium. RESULTS: For vessels with endothelium, dilation in control experiments was 20.0 ± 0.1%; after 5 s of ROS dilation was 74.4 ± 0.6%, and after 20 s 87.4 ± 0.3%. ANOVA revealed significant differences between these groups (P = 0.048). For vessels without endothelium, a slight dilation was seen in control experiments (14.5 ± 0.4%), which was also present after 5 s of ROS treatment (15.4 ± 0.4%). Treatment with ROS for 20 s led to a constriction of the vessel preparations (-16.6 ± 0.5%; P = 0.831). CONCLUSIONS: ROS led to a vasodilation in vessels with endothelium that was not seen in vessels without endothelium. Endothelial function seems to determine the effect of ROS on the vessel tone in isolated rat ophthalmic arteries.

[Use of antiglaucomatous drugs in the urban adult population : New Insights into the prevalence of glaucoma from the Hamburg City Health Study]. / Anwendung von Antiglaukomatosa in der urbanen erwachsenen Bevölkerung : Erkenntnisse zur Glaukomprävalenz aus der Hamburg City Health Study.

BACKGROUND: Glaucoma is a widespread ophthalmological disease. Knowledge about the spread of the disease in the population is necessary with respect to further questions on comorbidities, risk factors and the provision of care. OBJECTIVE: An analysis of the use of glaucoma medications and the prevalence of glaucoma in an urban adult population was carried out. MATERIAL AND METHODS: The Hamburg City Health Study (HCHS) is a prospective, long-term, population-based cohort study that includes a random sample of 45,000 participants aged between 45 and 79 years from the general population of Hamburg, Germany. Apart from various medical parameters, data include premedication and the medical history of the participants. The use of antiglaucomatous medication among the first 10,000 study participants was analyzed and the prevalence of glaucoma was estimated according to the use of medications as well as by the self-reported history of glaucoma. Descriptive analysis and logistic regression analysis were performed to analyze the data and to calculate correlations by age and gender. RESULTS: In the study population 319 persons were on medication to lower the intraocular pressure (IOP, mean age 67.1 years, SD = 7.57 years), which is equivalent to an estimated prevalence of 3.35% (95% confidence interval, CI 3.00-3.70%). A positive correlation was observed between age and the use of IOP-lowering medication, which is statistically highly significant (p = < 0.001). The analysis by gender showed a slightly higher prevalence among women, which was not statistically significant. The estimated prevalence according to glaucoma medication and history were only partly congruent. DISCUSSION: This estimated prevalence of glaucoma is comparable to other epidemiological studies. The study results cover not only patients with manifest glaucoma but also persons who were treated for ocular hypertension. The inconsistency between the prevalence of glaucoma medication and the diagnosis of glaucoma can be explained by different treatment strategies and also by information deficits.

Scleral Inflammation around Collector Channels in Eyes with Primary Open-Angle Glaucoma.

Purpose: Investigating the existence of inflammation in the distal outflow system posterior of the Schlemm's canal in primary open-angle glaucoma (POAG).Methods: Scleral biopsies (n = 62) from POAG-patients were taken during deep sclerectomy and fixed either in formalin or RNAlater®. Histologic (hematoxylin & eosin) and immunohistological staining for CD 3 and CD 45RO were performed.Results: Cellular infiltration of immunocompetent cells (CD 3 and CD 45RO positive cells) exists around collector channels (CC). This inflammation is limited to the area around the CCs. Ninety-two percent of the biopsies are positive for inflammation. Untreated, dysgenetic glaucoma eyes and 8% of POAG eyes were negative for inflammation. Neither the use of benzalkonium chloride nor the number and type of preoperative antiglaucomatous medication correlated to the immunohistological result.Conclusion: In POAG a diverse cellular infiltration exists around the CCs in the vast majority of biopsies. This could have major diagnostic and therapeutic consequences for the treatment of POAG.Abbreviations: POAG: primary open-angle glaucoma; CC: collector channel; AH: aqueous humor; TM: trabecular meshwork; SC: Schlemm's canal; HE: hematoxylin & eosin; APC: antigen-presenting cell.

Morphological characterization of the human corneal epithelium by in vivo confocal laser scanning microscopy.

BACKGROUND: Regarding the growing interest and importance of understanding the cellular changes of the cornea in diseases, a quantitative cellular characterization of the epithelium is becoming increasingly important. Towards this, the latest research offers considerable improvements in imaging of the cornea by confocal laser scanning microscopy (CLSM). This study presents a pipeline to generate normative morphological data of epithelial cell layers of healthy human corneas. METHODS: 3D in vivo CLSM was performed on the eyes of volunteers (n=25) with a Heidelberg Retina Tomograph II equipped with an in-house modified version of the Rostock Cornea Module implementing two dedicated piezo actuators and a concave contact cap. Image data were acquired with nearly isotropic voxel resolution. After image registration, stacks of en-face sections were used to generate full-thickness volume data sets of the epithelium. Beyond that, an image analysis algorithm quantified en-face sections of epithelial cells regarding the depth-dependent mean of cell density, area, diameter, aggregation (Clark and Evans index of aggregation), neighbor count and polygonality. RESULTS: Imaging and cell segmentation were successfully performed in all subjects. Thereby intermediated cells were efficiently recognized by the segmentation algorithm while efficiency for superficial and basal cells was reduced. Morphological parameters showed an increased mean cell density, decreased mean cell area and mean diameter from anterior to posterior (5,197.02 to 8,190.39 cells/mm2; 160.51 to 90.29 µm2; 15.9 to 12.3 µm respectively). Aggregation gradually increased from anterior to posterior ranging from 1.45 to 1.53. Average neighbor count increased from 5.50 to a maximum of 5.66 followed by a gradual decrease to 5.45 within the normalized depth from anterior to posterior. Polygonality gradually decreased ranging from 4.93 to 4.64 sides of cells. The neighbor count and polygonality parameters exhibited profound depth-dependent changes. CONCLUSIONS: This in vivo study demonstrates the successful implementation of a CLSM-based imaging pipeline for cellular characterization of the human corneal epithelium. The dedicated hardware in combination with an adapted image registration method to correct the remaining motion-induced image distortions followed by a dedicated algorithm to calculate characteristic quantities of different epithelial cell layers enabled the generation of normative data. Further significant effort is necessary to improve the algorithm for superficial and basal cell segmentation.

Optical Coherence Tomography-Based Scattering Properties of Retinal Vessels in Glaucoma Patients.

PURPOSE: Clinical trials have demonstrated that retinal blood flow deficiencies are present in patients with open-angle glaucoma (OAG). We introduce a method for facilitating retinal vessel analysis: The intensity of the distal shadow of vessels in optical coherence tomography (OCT) caused by the scattered signal is analyzed, compared between healthy subjects and OAG patients and correlated with OCT angiography (OCT-A) flow density. PATIENTS AND METHODS: We recruited 80 patients with diagnosed OAG (mean age 63.4 ± 13.2 years) and 80 healthy age-matched control subjects for comparison, and 20 patients for the correlation with OCT-A flow density. Patients received perimetry, peripapillary OCT measurements, and selected patients OCT-A of the papillary area. The vessel shadow intensity (VSI) is based on peripapillary OCT scans: the intensity of the distal vessel shadow was automatically compared to its surroundings, separated by arteries and veins. Flow density of the OCT-A scan was calculated by binarization and quantification of the pixel density. RESULTS: The VSI for arteries was in OAG patients with 7.52 ± 2.62 [%] significantly lower compared to healthy subjects (9.03 ± 3.38 [%], p = 0.0029). In veins, the VSI was as well significantly lower for OAG patients (14.9 ± 3.59 [%]) compared to healthy subjects (17.46 ± 4.45 [%], p < 0.0001). Furthermore, in OAG patients there was a significant correlation of mean deviation of the visual field results with the veins' VSI (p = 0.0006; r = -0,454). There was no significant correlation of scattering properties with OCT-A flow density (p > 0.05). CONCLUSIONS: We conclude that the OCT-based analysis of the scattering properties of retinal vessels differs significantly between patients with OAG and healthy subjects. Furthermore, changes in the scattering properties of veins correlated with the stage of the disease in terms of visual field deficits. These properties might complement existing measurements of ocular blood flow including OCT-A flow density.

Association between optical coherence tomography based retinal microvasculature characteristics and myocardial infarction in young men.

Incident myocardial infarction (MI) is a leading cause of adult mortality in the United States. However, because MI has a relatively low incidence in the young population, little information exists on the disease in younger adults. Because the retina has the unique quality that its vasculature is readily and noninvasively visible, the retina is frequently studied to evaluate correlations between vessels and cardiovascular diseases. In the current study, we evaluated the retinal microvasculature of patients who had experienced an MI before 50 years of age (n = 53 subjects) and age- and sex-matched patients who had not experienced an MI (n = 53 patients). We used circular optical coherence tomography (OCT) scans to image peripapillary venules and arterioles. The diameter of each vessel was measured and the respective arterial-venous ratio (AVR) was calculated. We did not detect any significant differences between MI and control subjects in retinal vessel calibre or AVR.

Compromised autoregulatory control of ocular hemodynamics in glaucoma patients after postural change.

PURPOSE: The autoregulatory control of retrobulbar blood flow in response to postural challenge was investigated in normal-tension glaucoma (NTG) patients in comparison with primary open-angle glaucoma (POAG) patients and healthy volunteers. DESIGN: Prospective cohort study. PARTICIPANTS AND CONTROLS: Twenty POAG patients, 20 NTG patients, and 20 control subjects. METHODS: Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI) in the short posterior ciliary artery (SPCA), central retinal artery (CRA) and ophthalmic artery (OA) were recorded after a change from sitting upright to a supine body position using color Doppler imaging. MAIN OUTCOME MEASURES: Peak systolic velocity, EDV, and RI. RESULTS: Ten minutes after postural change to a supine position, blood flow velocities in the SPCA remained unchanged in controls, whereas a significant increase of PSV and EDV was found in both glaucoma groups. The RI in the SPCA was significantly lowered in the NTG group. Recordings for the OA and CRA showed a significant increase in EDV and significant decrease in RI in all 3 groups; a significant increase in PSV in the CRA was detected only in the NTG group. CONCLUSIONS: The unaltered flow velocities in the SPCA of healthy controls may indicate tight autoregulatory control, whereas the flow velocities in the CRA and OA appeared to follow alterations in hydrostatic pressure. In contrast, NTG and POAG patients demonstrated an insufficient compensatory response to postural change, leading to accelerated flow in the SPCA. This compromised autoregulatory control could represent another contributing factor in the pathogenesis of glaucoma.

Effects of glaucoma drugs on ocular hemodynamics in normal tension glaucoma: a randomized trial comparing bimatoprost and latanoprost with dorzolamide [ISRCTN18873428].

BACKGROUND: Reduced choroidal perfusion is hypothesized to play a role in the pathogenesis of normal tension glaucoma. Thus the impact of antiglaucomatous eye drops on ocular perfusion has been the focus of recent research and the subject of intensive investigations. The present study investigates whether topically applied latanoprost or bimatoprost influence ocular perfusion in patients with normal tension glaucoma and compares these effects with that changes detected after the treatment with dorzolamide. METHODS: Ocular hemodynamics were assessed by color Doppler imaging (CDI) shortly before and after a one-month treatment with either latanoprost, bimatoprost or dorzolamide. Primary end-points of the study were peak systolic and end-diastolic blood flow velocities in the short posterior ciliary artery (SPCA) under the new therapy. Intraocular pressure (IOP) and additional perfusion parameters in the SPCA and other retrobulbar vessels were tracked as observational parameters. n = 42 patients with normal tension glaucoma were enrolled in the study. RESULTS: Systolic and diastolic blood flow velocities in the SPCA showed no significant alteration after the treatment with latanoprost or bimatoprost. Dorzolamide lead to increase of peak systolic velocity. IOP was reduced by all three agents in a range reported in the literature. CONCLUSION: Topically applied latanoprost and bimatoprost act in a hemodynamically neutral manner and have the capability to lower IOP even in patients with normal tension glaucoma and low initial IOP level. Dorzolamide accelerates blood flow in systole. None of the tested compounds has a negative impact on hemodynamics in the short posterior ciliary arteries.

Estimation of choroid perfusion by colour Doppler imaging vs. other methods.

Ocular haemodynamics play a prominent role in several ocular diseases. Recently, new methods for the determination of ocular perfusion were developed. Colour Doppler imaging (CDI) of orbital vessels has come up in the past decade and was shown to be useful in ophthalmological diagnostics. Little is known about measurement of choroid perfusion by CDI in comparison with other methods. Therefore, 49 eyes were examined with CDI, laser Doppler flowmetry (LDF) and the method of Langham (LOBF). Correlations between the methods were identified by the Spearman correlation coefficient (r). LDF readings correlated with time-averaged mean velocity assessed by CDI in the long posterior ciliary artery (r = 0.47; p = 0.039; n = 20), but not in the short posterior ciliary artery. LOBF measurements correlated with pulsatility index (PI) of CDI in short (r = 0.50; p = 0.005; n = 30) and long posterior ciliary arteries (r = 0.41; p = 0.024; n = 30). Methods strengthened each other by partial correlation. The study demonstrates that CDI allows a more detailed insight into ocular perfusion.

Vascular dysfunction in ocular blood flow regulation: impact of reactive oxygen species in an experimental setup.

PURPOSE: Glaucoma is associated with an altered blood flow and increased levels of reactive oxygen species (ROS). Reactive oxygen species can have opposing influences on the tone of a vessel; depending on the condition and type of the vessel, ROS can induce vasodilation or vasoconstriction. In the present study, we investigated the impact of ROS on the tone of rat ophthalmic arteries under various conditions and present data on the underlying mechanisms. METHODS: Freshly dissected rat ophthalmic arteries were pressurized in a perfusion setup to 80 mm Hg, at which a stable myogenic tone was observed. After various pretreatments (e.g., removal of endothelium, partial depolarization to -41 mV, blocking of the Na(+)/Ca(2+)-exchanger (NCX) in reverse mode by KB-R7943, or blocking of the Na(+)/K(+)-ATPase by ouabain), the vessels were exposed to ROS. Vessel diameter was continuously recorded and values before and after treatment compared. RESULTS: Stable myogenic tone of vessels with and without endothelium was established at a pressure of 80 mm Hg. At the physiological resting membrane potential, ROS exposure led to a significant vasodilatation, which was significantly reduced by pretreatment with ouabain. After depolarization to -41 mV, ROS exposure led to vasoconstriction. Blocking the NCX in reverse mode using KB-R7943 completely abolished this ROS-induced vasoconstriction. CONCLUSIONS: At resting potential, ROS provoke dilation; however, in precontracted vessels they act synergistically and induce further vasoconstriction. In diseases involving altered blood flow through altered vascular tone (e.g., vasospasms), ROS may influence blood flow and may thereby contribute indirectly to further disease progression.

Dose-response-relationship between number of laser burns and IOP reduction in cyclophotocoagulation: an animal study.

PURPOSE: The relationship between number of laser burns of cyclophotocoagulation (CPC) and intraocular pressure (IOP) reduction is unknown. This animal model was established to reveal a possible dose-response-relationship between the number of applied laser burns and the IOP lowering effect. METHODS: 30 chinchilla bastard rabbits were divided into 5 groups and treated with either 1, 5, 10, 20, or 30 CPC burns, respectively. IOP was followed up for 1 week. IOP reduction of a single 30-burn treatment was compared with a fractionated treatment (three sessions; one week in between; 10 burns/session). RESULTS: IOP reduction increases nonlinearly with the number of CPC burns (max. -6.1 ± 1.4 mmHg). Fractionated treatment shows similar IOP reduction with less complications and more constant results compared to single session treatment. CONCLUSIONS: The study reveals a complex relationship between IOP reduction and the number of CPC burns. Fractionated CPC gives comparable IOP reduction at a higher degree of safety.

Thirty years of cornea cultivation: long-term experience in a single eye bank.

PURPOSE: To evaluate donor demographics, trends in donor tissue procurement and tissue storage over a long period. METHODS: A retrospective, longitudinal, descriptive analysis was undertaken of data from the Hamburg Eye Bank Data Base (HEB-DB) that had been collected between 1981 and 2010. Data on 54 parameters of cornea donors [including clinical history, age, death cause, gender and death-to-explantation interval (DEI)] and of cultivated corneas (endothelial quality and development in culture, cultivation period, microbiological contamination) were retrieved. These data were analysed statistically, focusing on the historical development of the eye bank. RESULTS: At the time of retrieval (June 2010), the HEB-DB contained data on 10 943 corneas (5503 donors). Most donors were men (65%) and had died from cardiopulmonary (n = 801)/cerebral (n = 261) failure or as the result of a polytraumatic accident/suicide (n = 602). Within these years, donor age, DEI and storage time increased. The percentage of stored corneas suitable for transplantation displayed a variable but increasing trend; in 2007, almost 75% of the stored corneas were transplanted. Between 1995 and June 2010, the median microbiological contamination rate was 5.3%. A change in the procurement procedure from enucleation to corneoscleral explantation in 2008 led to a briefly increased contamination rate. CONCLUSION: Donor demographic data run parallel to the general demographic development. Our analysis indicates a dynamic development of the eye bank over the last 30 years and emphasizes the need for an active quality management in coping with the challenges of modern eye banking.

Neuronal activity influences hemodynamics in the paraoptic short posterior ciliary arteries: a comparison between healthy and glaucomatous subjects.

PURPOSE: Perfusion of the retina adapts to metabolic demand by neurovascular coupling. The present study was an investigation of the presence of neurovascular coupling in the anterior part of the optic nerve in healthy subjects and patients with glaucoma. METHODS: Retrobulbar blood flow velocities were determined by color Doppler imaging (CDI). Peak systolic and end diastolic velocities (PSVs and EDVs) in the central retinal artery (CRA) or the short posterior ciliary artery (SPCA) were the primary readout. CDI measurements were performed shortly before, during, immediately after, 60 seconds after, and 120 seconds after a 10-Hz flicker stimulation of the retina. RESULTS: Thirty-five patients with glaucoma and 44 healthy control subjects were included in the study. In the SPCA of healthy control subjects, flicker stimulation led to an increase in PSV from 9.7 +/- 0.8 to 12.5 +/- 0.8 cm/s (P < 0.001; n = 24) and of EDV from 2.4 +/- 0.3 to 3.6 +/- 0.3 cm/s (P < 0.001; n = 24). This effect was not detectable in patients with glaucoma. In the CRA, flicker light led to an increase in EDV from 2.1 +/- 0.2 to 3.0 +/- 0.3 cm/s (P = 0.002; n = 20) in healthy volunteers and from 1.3 +/- 0.2 to 2.0 +/- 0.2 cm/s in patients with glaucoma (P = 0.004; n = 15). PSV was not affected by flicker stimulation in either the healthy volunteers or patients with glaucoma. CONCLUSIONS: The data indicate the presence of neurovascular coupling in the vascular bed supplied by the paraoptic SPCA. The response pattern to the flicker stimulus differs between healthy subjects and individuals with glaucoma.

Protective effects of nebivolol on oxygen free radical-induced vasoconstrictions in vitro.

BACKGROUND: Disturbed ocular hemodynamics and vasospasms might be involved in the pathogenesis of glaucoma. On a clinical level there are indications for an optimization of ocular perfusion parameters in hypertensive glaucoma patients by switching a beta-adrenoceptor-antagonist therapy to nebivolol. Aim of the present study is to investigate vasoactive properties of nebivolol on ocular vasculature in vitro. Besides vasorelaxing effects, the impact of nebivolol on oxygen free radical-induced vasoconstrictions is studied. MATERIAL/METHODS: The experiments were carried out with ring preparations from porcine ciliary arteries. The preparations were placed in a myograph system and were kept under physiological conditions (pH 7.4, 37 degrees C, Krebs-Henseleit-Buffer, 1.75 mM Ca2+) and were stimulated by K+ depolarizations. The experiments were performed at a Nernst potential of -41 mV, which reflects half-maximal activation. For radical exposure, the preparations were superfused for 20 s in a specifically designed set-up with hydroxyl radicals generated by the Fenton reaction from H2O2 and Fe3+. NO synthase activity was modulated by adding L-arginine to the buffer. RESULTS: At a concentration of 10-5 M nebivolol leads to a reduction of vascular tone by -8.5+/-3.4% (n=11; P=0.016) vs. +2.6+/-1.9% (n=11; n.s.) in presence of its solvent DMSO. Nebivolol (10-5 M) reduces hydroxyl radical-induced vasoconstrictions by 53+/-10% (n=11; P<0.001). Stimulation of the NO synthase by L-arginine saturation potentiates this effect. CONCLUSIONS: Nebivolol combines vasorelaxing properties with protection against oxidative stress-induced vasoconstrictions. Both effects may be attributed to NO-releasing properties of nebivolol independently of its beta-adrenoceptor-blocking effect.