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Vascular deregulation (VD) or Vasospastic Syndrome is defined as an inappropriate constriction or insufficient dilatation in the microcirculation. Primary VD is highly prevalent in subpopulations of young people and can potentially predispose healthy individuals to severe disorders (neurodegeneration and cancer) being, therefore, particularly attractive for predictive diagnostics and primary prevention in targeted sub-populations [1], namely it occurs more frequently in females and is manifested at puberty, moderating with age this phenomenon is even more frequent in the Japanese population compared to Caucasians usually, academics are more affected by VD in addition to clinical signs there is an inborn increased sensitivity to any kind of stress provocation (mechanical, cold, emotion, etc.), altered drug sensitivity, frequently cold extremities, altered sleep behaviour, reduced feeling of thirst but increased smell perception, low blood-pressure, reduced body-mass-index, more frequent migraine compared to general population Compared to the general population, vasospastic individuals tend to have a meticulous personality and successful professional career, Figure 1. Open image in new window Figure 1 Symptoms and typical attitude of individuals with Vasospastic Syndrome: individuals with primary vasospastic deregulation tend to a meticulous personality and successful professional career such as the young female on the left image [2]

PURPOSE: To evaluate the relationship between the circadian blood pressure rhythm and the retrobulbar blood flow in glaucoma patients. DESIGN: Cross-sectional study. METHODS: Circadian blood pressure measurements and color Doppler imaging (CDI) in the ophthalmic artery as well as the central retinal artery of one randomly selected eye were obtained in 193 primary open-angle glaucoma patients. CDI parameters were compared by means of analysis of covariance between patients with a nocturnal decrease in mean systemic blood pressure (MBP) below 20% of the average daytime MBP (over-dippers), patients with a decrease between 10% to 20% (dippers), and patients with a decrease of less than 10% (nondippers), using age, intraocular pressure (IOP), and MBP during color Doppler measurement as covariates. RESULTS: An analysis of covariance disclosed, after correcting for age, IOP, and MBP during color Doppler imaging, a significantly lower EDV ( P = .0096) and a significantly higher RI ( P = .033) in the central artery of over-dipping glaucoma patients compared with nondippers or dippers. This effect seemed independent of the use of vasoactive drugs. CONCLUSIONS: Glaucoma patients with a marked drop in nocturnal systemic blood pressure seem to have altered retrobulbar blood flow parameters, suggesting that an abnormal systemic blood pressure profile may be the manifestation of some kind of systemic vascular dysregulation relevant for the ocular circulation.

Purpose: To investigate contractions evoked by the thromboxane A 2 analog U 46619 and by the inhibitor of nitric oxide formation N G -nitro-L-arginine methyl ester (L-NAME) in isolated porcine ciliary arteries and vortex veins. Material and Methods: In a myograph system (for isometric forces measurement), vessels were exposed (at different levels of wall tension) to 100 mM potassium chloride (KCI). At their optimal tension, vessels were exposed (in a cumulative manner) to increasing concentrations of U 46619 (0.1 nM - 1 μM) in the absence or in the presence of L-NAME (0.1 mM). Contractions were expressed in mN or in percent of a 100 mM KCI-induced contraction. Results: Optimal tension was higher in arteries (7 mN) than in veins (3 mN). Maximal contractions induced by KCI were stronger in arteries (24.4 ± 3.6 mN; n=8) than in veins (1.8 ± 0.2 mN; n = 8). In contrast, maximal contractions evoked by U 46619 were proportionally higher (p < 0.001) in veins (178.3 ± 8.9%; n=8) than in arteries (108.4 ± 2.6%; n=5) and were not significantly affected by L-NAME. Sensitivity to U 46619 was not significantly different between arteries (pD 50 = 7.7 ± 0.1) and veins (pD 50 = 7.9 ± 0.1). In quiescent vessels, L-NAME evoked contractions that were higher (p < 0.001) in veins (43 ± 7.9%; n = 13) than in arteries (7.5 ± 1.7 %; n = 10). Conclusions: When compared with KCI-induced contractions, contractions evoked by U 46619 or L-NAME are proportionally higher in porcine vortex veins than in ciliary arteries.

PURPOSE. The Susac syndrome is a microangiopathy that leads to visual symptoms, hearing loss and neurological symptoms. CASE REPORT. We report on a young woman suffering from this syndrome who also presented the following signs and symptoms typical of a vasospastic syndrome; 1) a history of cold hands, low blood pressure and migraine; 2) a typical alteration of conjunctival vessels; 3) prolonged flow arrest time after cooling in nailfold capillaromicroscopy; 4) increased resistivity in the orbital vessels measured by color Doppler imaging; and 5) an increased plasma level of endothelin-1. CONCLUSIONS. We postulate that the Susac syndrome is a manifestation of the vasospastic syndrome. (Eur J Ophthalmol 2001; 11: 175-9)

Background: Because intraocular pressure-lowering agents should have a good safety profile with regard to ocular hemodynamics, the innocuousness of unoprostone isopropyl 0.15% with regard to ocular hemodynamics in vasospastic patients with normal-tension glaucoma was assessed in a pilot study. Methods: Corneal temperature as a parameter of ocular blood flow and choroidal and optic nerve blood flow as assessed by means of laser Doppler flowmetry techniques were evaluated in 12 vasospastic normal-tension glaucoma patients in a prospective, randomized, observer-masked, two-period crossover, placebo-controlled pilot trial. Results: Statistical analysis in 2×2 two-way analysis of variance models with two treatments (placebo and unoprostone isopropyl) and two assessments (baseline and after 1 week of treatment) as within-subject factors disclosed a lack of difference between eyes, between the treatment (placebo/unoprostone isopropyl) periods, and between baseline and after 1 week of treatment in corneal temperature, choroidal blood flow, and optic nerve blood flow. The differences between the results at baseline and after 1 week of treatment in these parameters were not significantly different between the placebo treatment period and the unoprostone isopropyl treatment period, and this was comparable in fellow eyes for all the parameters. Conclusion: Unoprostone isopropyl did not induce any alterations in ocular hemodynamics in this pilot study with vasospastic normal-tension glaucoma patients.

PURPOSE To evaluate the effect of 0.5% timolol maleate on the capillary circulation of the anterior optic nerve head in patients with primary open-angle glaucoma and to compare the results with those obtained in a healthy control group. PATIENTS AND METHODS Twelve patients with nonprogressive glaucoma and 12 age- and sex-matched healthy volunteers were included in this prospective study. Optic nerve head perfusion was examined by the Heidelberg Retina Flowmeter (HRF) in both groups. A 3-week washout period preceded the baseline measurement in the glaucoma group, and ONH blood flow was assessed again after 3 weeks of bilateral topical timolol treatment and 2 hours after timolol application. RESULTS Intraocular pressure decreased significantly with timolol (P < 0.001). The HRF flow values for patients with glaucoma were comparable to those for a control group at baseline (P = 0.25), 3 weeks after timolol therapy (P = 0.09), and 2 hours after timolol instillation (P = 0.15). The glaucoma group showed no statistically significant change in the HRF parameter flow as compared with baseline, either after 3 weeks of timolol treatment or 2 hours after timolol instillation (P = 0.40). The heart rate and arterial systolic and diastolic blood pressure values showed no alteration after timolol therapy. CONCLUSIONS Patients with nonprogressive glaucoma seem not to have an altered optic nerve blood flow as assessed by the HRF, and timolol treatment does not seem to alter the latter blood flow parameter in such patients.

Pigmentation of the iris is caused by varying amounts of melanin pigment granula in a constant number of melanocytes in the superficial stroma. Melanin has been shown to act as antioxidant. We have now investigated lipid peroxidation in dependence on stromal pigmentation in isolated porcine irises.The same number of lightly and heavily pigmented porcine irises (visual selection) were homogenized (1 : 20 w/v) in buffer (50 mmol/l phosphate buffer and 4 mmol/l sodium azide). 500 microl homogenate were incubated at 37 degrees C in duplicate for 5, 10, 20 and 40 min in absence and presence of Fe2+ as inducer of lipid peroxidation. The amount of lipid peroxidation was assayed by the thiobarbituric acid (TBA) test. The results are expressed as nmol of TBA reactive material (TBAR) produced/mg protein. Fe2+ concentration of the supernatant was determined spectrophotometrically with 1,10 orthophenanthroline. Concentrations of D-glucose and D -fructose in iris tissue homogenates were determined spectrophotometrically by enzymatic bioanalysis.70, 180 and 360 micromol/l Fe2+ induced lipid peroxidation. A plateau region was reached after 20 min. The amount of lipid peroxidation differed in dependence on stromal pigmentation in porcine irises. The effect was most significant at 180 micromol/l Fe2+, which induced 1.373 +/- 0.138 nmol TBAR/mg protein in lightly compared to 0.491 +/- 0.125 nmol TBAR/mg protein in heavily pigmented irises after 10 min incubation (p0.0001, n = 4). Similar effects (factor 2-3) were also measured after 20 and 40 min incubation. On the other hand, the content of Fe2+ in the supernatant was the same within error. Sugar concentrations (D-glucose and D-fructose) did not differ significantly for the two differently pigmented iris tissues.There is a stronger induction of lipid peroxidation in lightly compared to heavily pigmented porcine irises. This effect may be related to the difference in stromal melanin content and its antioxidant activity.

The aim of this study was to assess the olfactory function of primary open-angle glaucoma patients.We analyzed odour threshold, identification, and discrimination in 30 primary open-angle glaucoma patients and 30 age- and gender-matched healthy control subjects. The "Sniffin' Sticks" test battery was applied sequentially on both sides, scores of two nostrils were averaged and means were compared with Mann-Whitney U-test between the groups.Scores for odour threshold were 5.9 +/- 2.2 and 7.4 +/- 2.1 in glaucoma and control group, respectively (p = 0.01), for odour discrimination 10.5 +/- 2.0 and 10.8 +/- 1.6 (p = 0.65), and for odour identification 11.8 +/- 2.1 and 10.6 +/- 1.6 (p = 0.008). Comparing within glaucoma group between those with (n = 18) and without history (n = 12) of cold hands and feet, the former had significantly better odour threshold scores, 6.6 +/- 1.5, than the latter, 4.8 +/- 2.6 (p = 0.036); no difference in other two olfactory modalities were detected.Changes of olfactory function have been described in neurodegenerations such as Alzheimer and Parkinson diseases. Complex alterations of olfactory performance seem to be present in POAG patients as well.

To evaluate the correlation between interocular difference in progression of glaucomatous damage and interocular differences in retrobulbar blood flow.On the basis of a retrospective analysis of visual fields, progressive damage was identified in 20 patients with primary open-angle glaucoma. As a parameter of interocular difference in progression of visual field damage, the angle (gamma) between the regression lines of the visual field index mean defect over time per eye was calculated for each subject. The relationship between the angle gamma and interocular differences in intraocular pressure and retrobulbar color Doppler imaging parameters was analyzed by a multiple linear regression analysis in a stepwise forward approach.With larger interocular differences in progression of glaucomatous damage, lower mean blood flow velocities in the ophthalmic artery (partial r = -.69; P. 0016), higher resistivity indices in the central retinal artery (partial r =.48; P.0456), and higher peak systolic velocities in the ophthalmic artery (partial r =.52; P.0285) were noted in the eyes with more marked progression of damage (multiple r =.71; P. 0099). Interocular differences in progression of visual field damage were not related to intraocular pressure or extent of visual field damage.Independent of the extent of the interocular difference in glaucomatous damage and intraocular pressure, interocular difference in progression of glaucomatous visual field damage correlates with interocular difference in retrobulbar hemodynamic parameters.

Low-density lipoprotein (LDL) concentrations have been linked to altered responses to endogenous vasodilators and vasoconstrictors. We evaluated retrospectively the relationship between LDL and vasoconstrictor (endothelin-1, phenylephrine) responsiveness of the forearm vasculature in 15 elderly healthy volunteers with apolipoprotein B and LDL levels in the normal range. In contrast to phenylephrine, changes in forearm vascular resistance induced by endothelin-1 were correlated with apolipoprotein B, LDL, and total cholesterol concentrations in women but not in men. These findings might suggest that lipids may increase vascular tone through both impaired endothelial vasodilation and increased vasoconstriction to endothelin-1 at least in women.

Some in vitro and in vivo evidence, as well as rare observations in human eyes with glaucoma, suggests that retinal ganglion cells could be lost by apoptosis during the course of glaucomatous optic neuropathy. There exist also observations indicating that in the vitreous of patients with glaucoma it is possible to measure an increased concentration of glutamate (an excitotoxic amino acid known to induce neuronal apoptosis in animal models). These observations, among others, suggest the possibility of an excitotoxicity mechanism in the pathogenesis of glaucoma and as a consequence the potential for a neuroprotective approach to treating this disorder. Amazingly, not only in glaucoma but also in other neurodegenerative disorders (Parkinson's disease, amyotrophic lateral sclerosis, stroke, etc.) it has been postulated that neurons could be lost through an excitotoxic mechanism. In these non-glaucomatous disorders, quite a large number of clinical trials have already been conducted to determine the potential benefit of different neuroprotective therapies. Unfortunately, with a few rare exceptions, the results of these clinical studies have been very disappointing (in contrast to encouraging results obtained in preclinical trials). The experience acquired in other neurodegenerative disorders should probably be kept in mind when addressing the question of neuroprotection in glaucoma. In particular, the hope raised by preclinical studies showing that drugs could have a beneficial effect on the survival of retinal ganglion cells should certainly be tempered until such an effect is confirmed by clinical trials conducted in patients with glaucoma.

Purpose: Many physiological parameters, including blood pressure, show circadian variations. Diurnal fluctuations of the optic nerve head (ONH) circulation have not yet been studied. The purpose of the present study was to determine the pattern of ONH blood flow variations over a 24-hour period in healthy subjects. Methods: The subject group comprised 15 healthy volunteers (6 women, 9 men) aged 22 to 43 years (mean ± SEM: 28.2 ± 1.3 years). Blood flow in the ONH was measured by laser Doppler flowmetry (LDF) over a 24-hour period at 08:00, 12:00, 16:00, 20:00, 24:00 hours, and at 08:00 hours the following morning. Results: ONH perfusion varied significantly over time. The mean LDF-flow during daytime ranged from 8.2 to 8.9 arbitrary units (AU) and fell at midnight to 7.1 AU ( P = .0015). The mean LDF-volume during daytime was 0.23 to 0.24 AU and decreased at midnight to 0.20 AU ( P = .04). The mean LDF-velocity ranged from 0.39 to 0.41 kHz with no significant differences at any time point. Conclusions: Our study in normal subjects reveals small mean changes of ONH perfusion during daytime and a significant reduction at night. The physiological and clinical relevance of the nocturnal dip in the ONH perfusion needs to be determined in future studies.

In glaucoma there is a loss of retinal ganglion cells. There is evidence that this loss can occur by apoptosis. The signal transduction leading to retinal ganglion cell apoptosis in glaucoma is not yet clear. The present study compares the gene expression in lymphocytes of normal tension glaucoma patients (NTG-patients) with the one of healthy controls.Subtractive hybridization was used to compare mRNA in lymphocytes of six vasospastic NTG-patients with six age and sex matched healthy subjects.Genes coding for p53-protein, NTP (neural thread protein) and 20 S proteasome subunit XAPC7 were overexpressed, whereas those coding for XPGC (Xeroderma pigmentosum gene), the survivin protein as well as one type of ABC transport protein were underexpressed.In comparison to healthy controls, patients with vasospastic NTG seem to over- as well as under-express certain genes in their lymphocytes.

We studied the localization and distribution of connective tissue growth factor (CTGF) in corneal scar tissue and membranes using in situ hybridization in 8 corneas from keratoplasty and 4 normal corneas. Identification of the cells was done with immunohistochemistry for SM-α-actin, vimentin, and Lu5. CTGF mRNA was found in activated corneal fibroblasts in 7 of 8 scars, 7 of 8 retrocorneal membranes and 2 subepithelial membranes, whereas the control corneas showed no CTGF mRNA expression. Vimentin was positive in all scars, retrocorneal and subepithelial membranes, SM-α-actin in 7 of 8 scars and 6 of 8 retrocorneal membranes. These results suggest that CTGF plays a crucial role in corneal wound healing and membrane formation.

Objectives: To study the influence of different illumination levels on the results of the hue-discrimination test, Roth 28-Hue desaturated. Subjects and methods: The cap-sorting test, Roth 28-Hue desaturated, was conducted using four different illumination levels and four groups of patients taken from a total test cohort of 172 ocularly and generally healthy subjects: 4800 lux (Group 1: 76 subjects; mean age±SD: 30±9 years); 2000 lux (Group 2: 35 subjects; mean age±SD: 31±5 years); 1000 lux (Group 3: 34 subjects; mean age±SD: 31±8 years); and 100 lux (Group 4: 26 subjects; mean age±SD: 30±7 years). The illumination levels were determined with the Minolta Chroma Meter XY-1. Illumination was provided by fluorescent light sources with a balanced spectral distribution and a color-rendering index of 93 (Osram L36W/12 LDL Daylight). Results: No differences could be detected between the illumination level of 4800 lux (average error sum=median±MAD; 42±18) and 2000 lux (average error sum: 40±22). However, examinat...

The Heidelberg Retina Flowmeter (HRF) is intended to assess ocular blood flow by scanning laser doppler flowmetry. In the retina and possibly in the optic nerve head, carbogen increases blood flow, whereas pure oxygen or high intraocular pressure (IOP) decrease it. This study addresses whether at the papilla of healthy volunteers, the HRF parameter flow, is modulated by breathing 5 % carbogen (5 % carbon dioxide + 95 % oxygen) for 7 minutes, breathing 100% oxygen for 7 minutes, increasing IOP to 50 mm Hg with a suction cup, or decreasing IOP with a single topical ocular instillation of the β-blockers 0.5 % betaxolol (betoptic) or 0.5 % timolol (timoptic). At the papilla (20° × 5°, 256 × 64 pixels), values of HRF parameter, flow (50 × 50) pixels, increased after carbogen (N = 5, P

Purpose: To assess the variability of corneal temperature and the reproducibility of its measurement by means of a noncontact infrared thermometer in healthy subjects. Methods: The THI-500 noncontact infrared thermometer (Tasco Japan, Osaka, Japan) was used for the measurement of corneal temperature. The reproducibility of corneal temperature measurements was assessed for 5 consecutive temperature readings obtained within 45 min or within 5 days. In addition, the interocular difference in corneal temperature and the diurnal temperature changes of the cornea were assessed. For each experiment, 10 healthy subjects were recruited. Results: The reliability of 5 consecutive corneal temperature measurements obtained within 45 min and within 5 days was 97.92 and 85.35%, respectively. Interocular differences in corneal temperature were not statistically significant (p = 0.70). Average corneal temperature varied significantly during the day (p < 0.0001), with lower corneal temperature readings during the morning hours compared to those obtained during the afternoon. Conclusion: The assessment of corneal temperature by means of noncontact infrared thermometry is highly reproducible. Corneal temperature varies throughout the day, and this variation is independent of variations in environmental temperature.

The many smoking-induced changes are diffuse and include, but are not limited to, coronary artery disease and cerebrovascular accidents. Cigarette smoking has even been suggested to be an important risk factor in the development of nonarteritic anterior ischemic optic neuropathy. The purpose of the present investigation was to compare confocal scanning laser Doppler flowmeter parameters between otherwise healthy smokers and healthy nonsmokers. Confocal scanning laser Doppler flowmeter parameters were assessed in 58 healthy non-smokers and 20 otherwise healthy smokers in a middle-aged population. An analysis of covariance (covariate: age) disclosed decreased values for all confocal scanning laser Doppler flowmeter parameters (`Volume': p

Background: Fludrocortisone is a potent mineralocorticoid, whichhas no known direct vasoactive properties, and is the first-line drug fortreatment of orthostatic hypotension. The present study evaluated thesystemic hemodynamic effects of fludrocortisone treatment in glaucomapatients. Patients and methods: A retrospective analysis of the charts of glaucoma patients of the University Eye-Clinic Basel was performed. Twenty-two patients with open-angle glaucoma under treatment withfludrocortisone were selected. The selected patients had one 24-hblood pressure recording immediately prior to treatment with fludrocortisoneand one recording at least 2 months after starting the treatment. Parallel to blood pressure recordings, diurnal intraocular tension curve recordings and visual field testings were carried out. In addition, twelve patients also had nail-fold video-capillaroscopy. Results: IOP and visual fields remained stable. The average values for all systemic blood-pressure readings showed an improvement in the follow-up compared to primary examination. Mean (±SD) night-to-day ratio (`nocturnal dips')of systolic, diastolic and mean arterial bloodpressure decreased from 13.6 ± 4.3%, 16.9 ± 5.2% and 15.9 ± 3.5%, respectively, to 9.9 ± 5.9% (p=0.01), 13.2 ± 4.3% (p = 0.044) and 11.7 ± 3.9% (p = 0.0004). Baseline capillary blood-flow velocity increased and capillary blood-flow standstill time after cold provocation decreased significantlyunder fludrocortisone therapy. Conclusion: Hemodynamic parameters show a tendency towards improvement in a magnitude which might be of clinical relevance.

The relationship between blood flow velocities in retrobulbar vessels and blood flow at the optic nerve in glaucoma patients was assessed in a prospective study. The Heidelberg retina flowmeter (HRF) was used to assess optic nerve head blood flow in 13 open-angle glaucoma patients. In the same patients, color Doppler imaging (CDI) measurements were obtained from the ophthalmic artery, the central retinal artery and the posterior ciliary arteries. Using data for one randomly selected eye per subject, correlations between HRF recordings and CDI measurements were evaluated by means of Spearman’s rank correlation factor. All three HRF parameters correlated with CDI measurements obtained from retrobulbar vessels. The most marked correlations were those of the HRF parameter ‘volume’ with the end-diastolic velocity in the ophthalmic artery and the medial posterior ciliary artery (R = 0.79, p = 0.0012 and R = 0.81, p = 0.0007, respectively), and the peak systolic velocity in the lateral posterior ciliary artery (R = 0.82, p = 0.0006). The present study suggests that glaucoma patients with altered blood flow in retrobulbar vessels are likely to show an alteration in optic nerve blood flow as measured with the HRF.

Purpose To assess the Heidelberg Retina Flowmeter (HRF) parameters “volume”, “flow”, and “velocity”, at the papilla in healthy subjects. Methods HRF measurements were taken at the papilla (5° × 20°), superficially at level of the retina and at the bottom of the excavation. The effect of increasing frame size (1×1 to 50×50 pixels) on HRF values was assessed in ten subjects. HRF parameters were calculated (50×50 pixels) for 150 eyes of 150 subjects. To assess short-term reliability, measurements were repeated five times in ten subjects. Results With 50×50 pixels the location of the frame had no influence on HRF values. Reliability was > 90%. Values were significantly higher (p2>0.85). Conclusions A low magnification (5°×20°) and a 50×50 frame allows a global assessment of HRF parameters at the papilla with high reliability. In healthy eyes, the HRF values are influenced by the level where measurements are made at the papilla. This might be of importance in glaucoma patients with excavated papilla.

BACKGROUND: A correlation between a thin cornea and the presence of vascular risk factors has recently been reported in normal-tension glaucoma patients. The present study intended to investigate the correlation between central corneal thickness and basal retrobulbar blood flow in glaucoma patients. PATIENTS AND METHODS: Corneal pachymetry and colour Doppler imaging (CDI) of the retrobulbar arteries (ophthalmic, central retinal and cilliary) were performed in 63 glaucoma patients. Linear mixed effect models were used to evaluate the association of central corneal thickness and retrobulbar blood flow. RESULTS: There was no significant correlation between central corneal thickness and blood flow in any of the assessed arteries (p = 0.13-0.88). CONCLUSIONS: A statistical relationship between central corneal thickness and retrobulbar blood flow could not be found in the examined sample of glaucoma patients.

Many risk factors associated with glaucoma have been identified recently. The best known of these is increased intraocular pressure (IOP). Among the others, however, vascular risk factors play a major role. Although such vascular factors were already postulated more than 100 years ago, only recent technical developments have afforded systematic investigations of associated microcirculatory disturbances and basic principles of blood flow regulation. In glaucoma, besides IOP, vascular dysregulation (such as local vasospasm and systemic hypotension, resulting in impaired autoregulation of blood flow in the optic nerve head, the choroid, and other ocular tissues) seems to be a major risk factor. However, multiple coacting factors, which are not limited to the eye but are, rather, symptoms of a systemic disease, seem to be involved in the damaging process.

Glaucoma is a progressive optic neuropathy that has a multi-factorial etiology. The most important risk factor is certainly an increased intraocular pressure. However, clinical observations have indicated that factors other than increased intraocular pressure also damage the neural tissue in glaucomatous optic neuropathy. The most prominent of these to be vascular dysregulation. Vascular tone is permanently regulated by a number of regulatory systems and factors, and the endothelial cell layer acts as an important mediator for the response to these factors. According to recent evidence, glaucomatous optic neuropathy may be associated with changes in endothelium-dependent vascular regulation. Consequently, therapeutic approaches based on vasodilator drugs acting via endothelium-derived substances are being developed. Although promising preliminary studies have been performed, the clinical relevance of such treatment remains to be clarified.

Glaucoma can be defined as an optic nerve disease with typical morphological and functional changes. There are many risk factors associated with this neuropathy. The best known factor is an increased intraocular pressure. There are, however, many other risk factors. Among them, vascular factors play a major role. Although such vascular factors have been postulated more than hundred years ago, it is only recently that the physiology and pathophysiology of the optic nerve head circulation is, to some extent, understood. New instruments have been developed to measure ocular blood flow including blood flow in the optic nerve head. Although most of the studies indicate that circulation is changed in glaucoma patients, there is little association between glaucoma and arteriosclerosis. The main cause for the circulation disturbance in glaucoma seems rather to be a vascular dysregulation leading to local vasospasm and to systemic hypotension.

• Background: The present study was performed to investigate the influence of extracellular magnesium on changes in contractile tone induced by endothelin-1, and on relaxations to bradykinin in isolated porcine ciliary arteries. • Methods: Vessels were studied in a myograph system for measurement of isometric forces.Concentration-response curves (10−10–10−7 M) to endothelin-1 were constructed in the presence of different concentrations (0, 1.2, 2, 10 mM) of magnesium (MgSC4). Endothelin-1-precontracted vessels (∼10−8M) were exposed to magnesium (10−5–10−2 M) in the presence or absence of either the inhibitor of nitric oxide formation L-NAME (∼10−4 M), or different concentrations of calcium (2.5, 5, 10 mM). In endothelin-1-precontracted vessels (10−8 M), relaxations to bradykinin (10−10–10−6 M) were conducted in the presence of different concentrations of magnesium (0, 1.2, 10 mM). • Results: Contractions to endothelin-1 were reduced only in the presence of 10 mM magnesium. (1.2 mM vs 10 mM, P = 0.001). In endothelin-1 -precontracted vessels, magnesium evoked complete concentration-dependent relaxations (pD2 = 3.1 ± 0.1), which were shifted to the right by increasing extracellular concentrations of calcium (2.5 vs 5 mM, P

Purpose: To evaluate the intraocular pressure (IOP) in a population without known glaucoma as measured by means of a noncontact tonometer (NCT). Methods: IOP values of 842 persons, measured by means of a Pulsair 2000 NCT ® (Keeler Instruments, Inc., Broomhall, Pennsylvania) by 5 investigators were evaluated. Three consecutive measurements were taken first on the right eye and then on the left eye in each subject. Topical anesthesia was not used. Results: The distribution of the measured IOP values was significantly different from a normal distribution. The median IOP was 15.0 mm Hg (lower quartile/upper quartile 12.5/17.2). There were no differences in IOP values between male and female subjects or between right and left eyes. There was no correlation between age and IOP values. Ninety percent of the subjects had an IOP within a range of 9–24 mm Hg in both eyes. Among the examined subjects, the IOP was above 24 and 21 mm Hg in 4,6 and 11%, respectively, in at least one eye. The median range of consecutive IOP measurements in one eye was 3 mm Hg (lower quartile/upper quartile 2.0/4.0). The median interocular IOP difference was 1.7 mm Hg (0.7/2.7). The median individual coefficient of variation (CV) values were 10.0% for the right eyes, –10.8% for the left eyes. Among the 5 different examiners, the IOP values, range of 3 consecutive IOP readings in one eye, interocular asymmetry and CV values were statistically comparable. Conclusion: The Pulsair 2000 NCT is very simple to use and its handling is mostly independent of the operator. The results of the present investigation might be of some value for future screening programs.

An ideal glaucoma drug reduces intraocular pressure profoundly and long-lastingly without known major side effects. Latanoprost, a new prostaglandin F2 alpha-analogue, indeed has these properties. However, we need long-term experience to exclude major, clinically relevant side effects. The influence of latanoprost on ocular circulation also needs further evaluation. Nevertheless, the clinician does have a new and very potent drug to reduce intraocular pressure. Literature search by Medline.

• Background: The potent vasoconstrictor peptide endothelin-I has been shown to participate in the control of peripheral vascular tone and in the regulation of ocular perfusion. In glaucoma patients vasospasms and arterial hypotension have been identified as risk factors for the progression of glaucomatous damage, and the regulation of endothelin-1 release is disturbed in some of these patients. The aim of this study was to assess the relationship between resting blood pressure and cutaneous vascular responsiveness to endothelin-1 and phenylephrine in patients with glaucoma and in matched controls. • Methods: In 9 patients with primary open-angle glaucoma (POAG), 7 patient with normal tension glaucoma (NTG), and 16 age- and sex-matched controls, endothelin-1 and phenylephrine responses were assessed in the human forearm microcirculation using laser Doppler flowmetry during intra-arterial drug administration. Blood pressure was measured intra-arterially. • Results: In contrast to α1-adrenergic effects, endothelin-1 responses were inversely correlated to both systolic (r 2 = 0.27,P = 0.05) and diastolic (r 2 = 0.54,P = 0.001) blood pressure in glaucoma patients, whereas there was no such correlation in controls. Patients with lower blood pressure values were more sensitive to the vasoconstrictor effects of endothelin-1. Cutaneous responsiveness to endothelin-1 and phenylephrine was similar in glaucoma patients and in controls. • Conclusion: These results reveal that glaucoma patients appear to have peripheral microvascular abnormalities which are exhibited as altered responsiveness to endothelin-1. Thus, this study supports the hypothesis that endothelin-l-related microvascular dysfunction may be involved in the pathogenesis of glaucomatous damage

Visual field defects caused by vasospasm are often encountered in ophthalmology as a feature of glaucoma with poor response to conventional treatment. Combination therapy with drugs acting via different mechanisms might be more effective. Therefore, the effects of the calcium antagonist amlodipine and the angiotensin converting enzyme (ACE) inhibitor benazeprilat at low and high dose combination on contractions to endothelin-1 and endothelium-dependent relaxations to bradykinin were examined in porcine ciliary arteries.Segments of the arteries were suspended in myographs for isometric tension recording.Pretreatment of the vessels with either amlodipine, the low or high dose combination significantly reduced the sensitivity to endothelin-1 as compared to control (concentration shift 18.3-fold, 14.2-fold, 23.3-fold respectively; p0.05), while benazeprilat was ineffective. The maximal response to endothelin-1 (10(-7) M) was most inhibited by the high dose combination which reduced the contractions by 49% as compared to control (p0.05). The low dose combination and amlodipine alone were less effective (reduction: 25%; p0.05 and 20%; n.s., respectively). On the other hand, benazeprilat enhanced the sensitivity (concentration shift 73-fold; p0.05) and maximal relaxation to bradykinin (by 27%; p0.01), whereas amlodipine or the low or high dose combination were ineffective.These findings indicate that amlodipine and benazeprilat differently affect vascular function of ciliary arteries. A high dose combination of both substances was most effective in inhibiting contractions to endothelin-1, suggesting a potentiating effect of the two compounds. In contrast, endothelium-dependent relaxations to bradykinin were enhanced by benazeprilat alone, but not when combined with amlodipine.

Accumulating low level mitochondrial insults are thought to be key to aging processes and neurodegeneration. Among other stressors, protein damage due to nitrosative stress negatively impacts mitochondrial function and is linked to neurodegeneration. Using biotin switch technique, we show that mitochondrial proteins are S-nitrosylated not only in the presence but also in the absence of exogenous nitrosative stress. In addition, we revealed a role for the ubiquitin-proteasome system and the outer mitochondrial membrane associated degradation (OMMAD)-component p97 in the quality control of S-nitrosylated mitochondrial. Taken together, constant proteasome-mediated clearance of nitrosatively-damaged proteins from mitochondria is likely important for maintaining organelle function.

Purpose: To study the influence of retinal structural changes on oxygen saturation in retinitis pigmentosa (RP) patients. Methods: Oximetry measurements were performed on 21 eyes of 11 RP patients and compared to 24 eyes of 12 controls. Retinal oxygen saturation was measured in all major retinal arterioles (A-SO2) and venules (V-SO2) with an oximetry unit of the retinal vessel analyser (IMEDOS Systems UG, Jena, Germany). Oximetry data were compared with morphological changes measured by Cirrus optical coherence tomography (OCT) (Carl Zeiss Meditec, Dublin, CA, USA, macular thickness protocol). Results: In RP patients, the retinal A-SO2 and V-SO2 levels were higher at 99.3% (p = 0.001, ANOVA based on mixed-effects model) and 66.8% (p < 0.001), respectively, and the difference between the two (A-V SO2) was lower at 32.5% (p < 0.001), when compared to the control group (92.4%; 54.0%; 38.4%, respectively). With the RP group, the A-V SO2 correlated positively, not only with central macular thickness, but also with retinal thickness, in zones 2 and 3 (p = 0.006, p = 0.007, p = 0.014). Conclusion: These data indicate that oxygen metabolism was altered in RP patients. Based on our preliminary results, retinal vessel saturation correlated with structural alterations in RP. This method could be valuable in monitoring disease progression and evaluating a potential therapeutic response.

Background The JAK/STAT (Janus Tyrosine Kinase, Signal Transducers and Activators of Transcription) pathway is associated with cytokine or growth factor receptors and it is critical for growth control, developmental regulation and homeostasis. The use of porcine ocular cells as putative xenotransplants appears theoretically possible. The aim of this study was to investigate the response of various porcine ocular cells in vitro to human cytokines in regard to the activation of JAK-STAT signaling pathways. Methods Porcine lens epithelial cells, pigmented iris epithelial cells and pigmented ciliary body cells were used in this study. These cells were isolated from freshly enucleated porcine eyes by enzymatic digestion. Cultured cells between passages 3–8 were used in all experiments. Electromobility shift assay (EMSA), proliferation assay, immunofluorescence staining and flow cytometry were used to evaluate the JAK-STAT signaling pathway in these cells. Results JAK/STAT signaling pathways could be activated in porcine pigmented epithelial ciliary body cells, in pigmented iris epithelial cells and in lens epithelial cells in response to porcine and human interferons and cytokines. All cells showed very strong STAT1 activation upon stimulation with porcine interferon-gamma. Porcine ocular cells also respond to human cytokines; IFN-alpha induced strong activation of STAT1 in EMSA, flow cytometry and immunofluorescence experiments whereas activation of STAT3 was less strong in EMSA, but strong in flow cytometry and immunofluorescence. Human recombinant IL-6 activated STAT3 and human IL-4 activated STAT6. With the help of immunofluorescence assay and flow cytometry we observed nuclear localization of STAT proteins after activation of porcine ocular cells with cytokines and interferons. Human IFN-α had an inhibitory effect on porcine ocular cells in proliferation assays. Conclusion Our study demonstrated that some types of human cytokines and interferon activate intracellular JAK-STAT signaling pathways in porcine ocular cells. We hypothesize that direct stimulation of the JAK-STAT pathway in porcine cells in response to human cytokines will lead to complications or failure, if pig-to-human ocular tissue xenotransplantation were to be carried out. For successful xenotransplantation among other obstacles there must be new approaches developed to regulate signaling pathways.

Purpose Differences in the gene expression of leukocytes between patients with normal-tension glaucoma (NTG) and controls have been described. This study was performed in order to detect the differences in gene expression in peripheral lymphocytes in patients with primary open-angle glaucoma (POAG), patients with pseudoexfoliation glaucoma (PEX), and patients with NTG, and in healthy subjects.Ten patients with POAG, 11 patients with PEX, 10 patients with NTG, and 42 sex- and age-matched healthy persons were recruited. All study subjects were Caucasian. Twenty-two preselected genes were chosen and their expression in blood lymphocytes was quantified by real-time PCR. First, a univariate comparison among all groups was performed using the nonparametric Friedman test. Second, an L1 penalized logistic regression was performed.Using the Friedman test to compare the 4 groups, 9 genes showed a different expression (plt;0.05). Comparing the controls vs patients with POAG, 8 genes were differently expressed (plt;0.05). Comparing patients with PEX vs controls, 9 genes were significantly different (p≤0.05). The statistical analysis of patients with NTG vs controls showed a difference in gene expression of 7 genes (p≤0.05). All these genes were upregulated in the glaucoma groups compared with the controls. The genes RhoGDI and RAR showed the most significant statistical difference in the L1-penalized logistic regression. The genes overexpressed in POAG/PEX differed from the ones in NTG.In this masked study among the preselected 22 genes, several genes are overexpressed in the blood lymphocytes of Caucasian patients with glaucoma compared with the controls. The genes upregulated in POAG/PEX differed from the ones in NTG.

PURPOSE: Endothelin-1 (ET) is an important molecule in vascular physiology. After an acute stimulation with ET, vessels are to some extent temporarily refractory to further stimulation. However, few details are known about this phenomenon. The aim of our study was to verify the existence of refractoriness in ophthalmic ciliary arteries and, if present, to analyze its time course. METHODS: Twenty freshly isolated porcine ciliary arteries were placed in a myograph system to measure isometric forces. Each vessel was stimulated with 10(-7) M ET twice. The experiment was performed in 5 groups of vessels, which differed in the time interval between the initial and the second stimulation with ET. The intervals were 15 min, 30 min, 1 h, 2 h, and 4 h, respectively. RESULTS: The vasoconstrictive response to re-exposure to ET was time-dependently reduced. The response was lowest after 15 min (22% of baseline response), and then the sensitivity slowly recovered and was finally normal again after 4 h. CONCLUSIONS: Our experiment with isolated porcine ophthalmic ciliary arteries revealed a refractoriness phase to ET after an acute stimulation with ET. This refractoriness was transient and disappeared after 4 h. The lowest response was observed in the group of vessels re-exposed 15 min after the first stimulation.

Basic sciences in ophthalmology : , Basic sciences in ophthalmology : , کتابخانه دیجیتال جندی شاپور اهواز

Background and scope: Pulsed rising amplitude perimetry (pulsed RAMP) is an improved strategy for automated static perimetry, developed to save examination time without accuracy loss. The aim of this study was to identify characteristic differences between the normal strategy (NS) and the pulsed RAMP strategy in standard automated perimetry, in order to evaluate the potential of the pulsed RAMP for threshold estimation. Methods: Visual fields from 33 glaucoma patients, 11 controls and 4 patients with other pathology were statistically analysed. A G pattern test using the pulsed RAMP and the NS were performed in randomised order. The MD (mean defect), the sLV (square root of loss variance), the test duration and the point-wise accuracy, related to a calculated reference pre- and post-study visual fields of each patient, were evaluated. Results: The mean examination time was 8.34 min (SD 2.02) for the pulsed RAMP, compared to 13.37 min (SD 2.67) for the NS. The Bland-Altman correlation plot for the MDs showed a trend (p=0.0018) towards higher MDs in the pulsed RAMP compared to the NS. The sLV of the pulsed RAMP was on average 1.49 dB higher than the sLV of the NS. The absolute mean local deviations, evaluated with the pulsed RAMP (r=0.38), deviated more from the references than those obtained with the NS. Conclusion: The pulsed RAMP strategy was faster than the NS, but took longer than other established fast strategies like the SITA, TOP and Dynamic. The gain in time, compared to the NS, was paired with reduced local accuracy.

• Background: Glaucoma and cataract are multifactorial diseases. They have been described to be associated with cardiovascular risk factors. • Methods: Twentyfour-hour ECG monitoring was done in 22 normal-tension glaucoma patients, 27 open-angle glaucoma patients, 25 cataract patients, and 20 normal controls. The frequency of silent myocardial ischemia (SMI) as well as that of ventricular extrasystoles (VES) was evaluated. • Results: At least one episode of significant asymptomatic ST-T segment depression occurred in 45% of the normal-tension glaucomas, in 25.9% of open-angle glaucomas, in 12% of cataract patients, and in 5% of normal controls. The frequency of VES was not significantly different among the groups. • Conclusions: Glaucoma, especially normal-tension glaucoma, is significantly associated with the occurrence of episodic asymptomatic myocardial ischemias. Cataract patients, however, had only a slightly, statistically not significantly increased frequency of both SMI and VES compared with normals.

Purpose To determine normal values of bloodflow velocities in extraocular vessels. Methods In one eye each in 189 healthy adult volunteers, blood-flow velocities in the ophthalmic artery (OA), central retinal artery (CRA), central retinal vein (CRV), short lateral posterior ciliary artery (LPCA), and short medial posterior ciliary artery (MPCA) were measured by color Doppler imaging. In the arteries, peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI) were calculated. In the CRV, maximal and minimal blood-flow velocities were measured. Influence of age, gender, blood pressure, and heart rate on blood-flow velocities and the resistivity index were analyzed. Results Mean outcomes ± S.D. cm/sec were as follows: in the OA, PSV was 39.2 ± 5.3, EDV was 9.1 ± 2.5, and RI was 0.77 ± 0.05. In the CRA, PSV was 11.0 ± 1.8, EDV was 3.3 ± 0.9, and RI was 0.71 ± 0.05. In the short LPCA, PSV was 11.2 ± 1.7, EDV was 3.7 ± 1.0, and RI was 0.68 ± 0.06. In the short MPCA, PSV was 11.2 ± 11.7, EDV was 3.6 ± 0.9, and RI was 0.68 ± 0.05. In the CRV, mean maximal velocity was 4.5 ± 0.9, and mean minimal velocity was 3.3 ± 0.7. Age, gender, systolic blood pressure, diastolic blood pressure, and heart rate had no consistent statistically significant influence on the measured and calculated variables. Conclusion Normal values for blood-flow velocities in the extraocular vessels serve as a basis in deciding whether a measured value of a patient is normal or abnormal.

The authors report two cases in which severe rubeosis iridis regressed after trabeculectomy with intraoperative application of mitomycin-C. Several days after the operation, the vessels were no longer perfused. Only white, empty ghost vessels were visible. This phenomenon was observed in one case with well-controlled intraocular pressure (IOP) after surgery, as well as in a case in which IOP rose again to high preoperative values. The authors conclude that the regression of the rubeosis may be caused by a local, intraocular pharmacologic side effect of mitomycin-C, not by the drop in IOP alone. [Ophthalmic Surg Lasers 1996;27:709-712.] Rubeosis iridis is a severe complication of diabetic retinopathy, as well as of central vein occlusion, often leading to very high intraocular pressure (IOP). The treatment of such a glaucoma is difficult, and the prognosis is extremely poor. Many of these eyes eventually need to be enucleated as a result of either painfully high IOP or painful phthisis. 1,2 Many different therapeutical approaches have been tried; drug therapy is mostly insufficient. Fistulating surgery reduces IOP usually for only a very limited period of time. Cyclodestructive therapy, such as cyclophotocoagulation 3 or cyclocryotherapy, 4,5 might be of some help. The risk for rubeosis iridis can be decreased by extensive retinal photocoagulation or cryocoagulation. 4,5 Even secondary regression or involution of the rubeosis iridis has been observed after panretinal coagulation.3 We observed a regression of the neovascularization in two cases after trabeculectomy combined with intraoperative application of mitomycin-C. In one of these patients, the IOP remained controlled; in the other, it rose again to the pretreatment values within a few days. Because a regression of the neovascularization could be observed in both of these cases, we hypothesized that this phenomenon might be caused by a local, intraocular pharmacologic side effect of mitomycin-C, and not by the drop in IOP alone.

In the cornea, iris, retina, and ciliary processes of porcine eyes the nitric oxide synthase (NOS) activity was assayed by measuring the transformation of L-[U-14C]-arginine into L-[U-14C]-citrulline: (1) in the absence or presence of the calcium-chelator, ethylene glycol tetra acetic acid (EGTA), and (2) in the presence of EGTA and the false precursor of L-arginine, NG-nitro-L-arginine methyl ester (L-NAME). In the retina and the iris a high calcium-dependent NOS activity was present, while in the cornea the activity was relatively low. In these three tissues no significant calcium-independent NOS activity was detected. In contrast, a marked calcium-independent NOS activity, but no calcium-dependent NOS activity, was found in the ciliary processes. The presence of a spontaneous calcium-independent NOS activity in the ciliary processes suggests that nitric oxide (NO) production is highly regulated in this tissue.

This study investigated the effects of dipyridamole in isolated porcine ciliary arteries (diameter 200-250 microns). Isolated porcine ciliary arteries were suspended in myograph chambers filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. Dipyridamole induced concentration-dependent relaxations of porcine ciliary arteries with endothelium precontracted with thromboxane analogue U-46619 (10(-6)M), KCl (50 mM), or endothelin-1 (10(-8)M). Removal of the endothelium of the ciliary vessels and preincubation of the arteries with L-NAME (10(-5)M), or indomethacin (10(-5)M), or the combination of the two drugs significantly reduced the relaxation to dipyridamole (p = 0.002-0.03). Similar vascular responses could be observed in a time-dependent analysis of the effect of a single concentration dipyridamole (10(-4)M). The stimulator of cAMP forskolin also caused relaxations. Endothelin-1 (10(-12)-10(-7)M) and U-46619 (10(-10)-10(-6)M) induced potent contractions of porcine ciliary arteries. Preincubation with dipyridamole (10(-5)M) reduced contractions to endothelin-1 as compared to control (p < 0.004), while contractions to U-46619 were only slightly affected under these conditions (n.s.). These findings demonstrate that dipyridamole is a vasodilator in porcine ciliary arteries. Endothelial nitric oxide and prostacyclin contribute importantly to the effects of dipyridamole. Further studies are required to show whether these properties of dipyridamole may also occur in vivo and offer clinical use in patients with ocular vasospasms and other ophthalmic vascular dysfunctions.

The cause of anterior ischemic optic neuropathy (AION) is thought to be occlusions of the posterior ciliary arteries, due to arteriosclerosis or emboli. The classical risk factors besides anatomical variants of the disc are those typically leading to arteriosclerosis. Whereas AION occurs mostly in elderly patients, it may also occur in young patients without relevant arteriosclerosis and even in the absence of risk factors. We report five young patients 12 to 44 years of age with typical AION. Extensive clinical and laboratory examination revealed no classical risk factors for arteriosclerosis. However, all patients had a vasospastic syndrome which included cold hands and feet, low blood pressure, migraine, and abnormal conjunctival vessels. The onset of symptoms under major stress, as well as the fast and relatively good recovery in most of the patients indicate that ischemia was due to local vasospasm in these young individuals.

Purpose: To compare thirst, drinking behaviour, and endothelin-1 (ET-1) plasma levels between vasospastic and non-vasospastic subjects. Methods: We compared 67 subjects with a primary vasospastic syndrome with 64 age- and sex-matched non-vasospastic control subjects. A detailed medical history was recorded, including a questionnaire containing queries about thirst and drinking behaviour, history of migraine or unspecific headache, history of episodes of low blood pressure, and smoking habits. Body mass index (BMI) was calculated and blood samples were drawn for ET-1 measurements. Results: Subjects with a vasospastic syndrome reported a reduced desire to drink and a lower estimated quantity of daily fluid intake, more often forgot to drink, more often had both migraine and unspecific headache, more often had episodes of low blood pressure, and had an increased plasma level of ET-1. These features differed statistically significantly between the two groups. There was also a non-significant trend among vasospastic subjects to smoke less and to have a smaller BMI. Conclusion: A reduced desire to drink is found frequently among vasospastic subjects.

Background: Primary intraocular lymphoma is a distinct subset of primary non-Hodgkin's lymphoma of the CNS. In general, the primary non-Hodgkin's lymphoma of the CNS is rare, accounting for 1 % of all non-Hodgkin's lymphomas and less than 1% of all intra-ocular tumors. History and signs: A 70-year-old man was hospitalized in June 2002 because of acute loss of vision on his left eye. A severe vitreous hemorrhage was observed. Ultrasound showed solid subretinal lesions at the posterior fundus. Diagnostic vitreous surgery including a biopsy was performed. An intraocular malignant B-cell lymphoma was determined by immunohistochemistry. General screening revealed no further manifestations of the lymphoma. Therapy and outcome: The patient initially refused any therapy until a painful secondary neovascular glaucoma with complete loss of visual function developed, thus prompting us to perform an enucleation. The following immunohistochemical examination confirmed the initial diagnosis. A chemotherapy with high-dose methotrexate and leucovorin rescue was initiated. Conclusions: Primary intraocular lymphoma can present as diffuse uveitis refractory to corticosteroids. Diagnosis can be difficult and is often delayed.

To investigate the intraocular pressure (IOP)-reducing effect and side effects of SDZ GLC-756, a novel dopamine D-1 antagonist and D-2 agonist, in control subjects and patients with open-angle glaucoma or ocular hypertension.A single-application, randomized, placebo-controlled, double-masked study was performed. SDZ GLC-756 eye drops at a concentration of 0.01% (n = 6) or 0.1% (n = 6) were administered to one eye in control subjects, vehicle alone (control) to the contralateral eye. In glaucoma patients the trial was designed as a crossover study administering SDZ GLC-756 (0.1%) eye drops and vehicle alone (control) to one eye in 12 patients with open-angle glaucoma or ocular hypertension.In control subjects, IOP decreased significantly by 2.0 +/- 0.4 mmHg (P0.01) after treatment with 0.01% SDZ GLC-756 and by 4.7 +/- 0.5 mmHg (P0.001) after treatment with 0.1% SDZ GLC-756. In the glaucoma group, IOP decreased by 6.8 +/- 0.6 mmHg (P0.001) (range, 4-11 mmHg). In both groups, treatment with 0.1% eye drops resulted in a significant IOP-lowering effect for 6 hours, and for 3 hours with treatment with 0.01% eye drops. A significant IOP-lowering effect (P0.05) also was found in the contralateral eye. Except for slight conjunctival hyperemia lasting up to 30 minutes after drug application, no ocular or systemic side effects were observed.SDZ GLC-756 reduced IOP significantly for approximately 6 hours. However, due to the study design with repeated IOP measurements before drug administration, the clinical efficacy of the preparation used remains unclear. The only systemic or local side effect observed was slight conjunctival hyperemia. The simultaneous D-1 antagonistic and D-2 agonistic properties of SDZ GLC-756 may provide a new pharmacologic approach to treating glaucoma and ocular hypertension, which deserves further investigation.

A variety of pathological processes at the level of the optic nerve head, such as papilledema, circulatory diseases, glaucoma, as well as certain inborn abnormalities, cause visual-field defects. The type of visual-field defect is dependent on the anatomic distribution of the nerve fibers involved and on the disease causing the optic nerve head damage. Therefore, the location and cause of the lesion determine the shape, extension, and depth of the visual-field defect.