Normal Pressure Glaucoma Patients Research Articles

Cell-Based Therapies for Trabecular Meshwork Regeneration to Treat Glaucoma.

Glaucoma is clinically characterized by elevated intraocular pressure (IOP) that leads to retinal ganglion cell (RGC) and optic nerve damage, and eventually blindness if left untreated. Even in normal pressure glaucoma patients, a reduction of IOP is currently the only effective way to prevent blindness, by either increasing aqueous humor outflow or decreasing aqueous humor production. The trabecular meshwork (TM) and the adjacent Schlemm’s canal inner wall play a key role in regulating IOP by providing resistance when aqueous humor drains through the tissue. TM dysfunction seen in glaucoma, through reduced cellularity, abnormal extracellular matrix accumulation, and increased stiffness, contributes to elevated IOP, but current therapies do not target the TM tissue. Stem cell transplantation for regeneration and re-functionalization of damaged TM has shown promise in providing a more direct and effective therapy for glaucoma. In this review, we describe the use of different types of stem cells for TM regeneration in glaucoma models, the mechanisms of regeneration, and the potential for glaucoma treatment using autologous stem cell transplantation.

Comparison of T Helper Cell Patterns in Primary Open-Angle Glaucoma and Normal-Pressure Glaucoma.

BackgroundHSP60-related immunological activities are found in normal-pressure glaucoma (NPG) patients, in whom an elevated intraocular pressure (IOP) found in primary open-angle glaucoma (POAG) is not observed. HSP60 was found in POAG and NPG patients, while anti-HSP60 level was mainly found to be higher in NPG patients. The purpose of this study was to compare the percentages of Th cells and levels of related cytokines, attempting to provide evidence to explain this discrepancy.Material/MethodsBlood samples from POAG, NPG, and normal control (NC) groups were collected and peripheral blood monocytes were isolated and cultured with or without the stimulation of HSP60. Flow cytometry and enzyme-linked immunosorbent assay were used to assess the percentages of Th1, Th2, Th17, and Treg cells, as well as HSP60 antibody levels and related cytokine levels, before and after culture.ResultsSignificantly higher titers of anti-HSP60 were observed only in NPG patients. Comparable Th1 and Th2 cell frequencies, IL-4 level, and IFN-γ level were found in POAG and NPG patients, while higher Treg cell frequency was only found in POAG patients. After culturing with HSP60, increased Th2 frequencies and decreased Th1 frequencies were observed in the POAG, NPG, and NC groups, while increased Treg frequency was only identified in the POAG and NC groups.ConclusionsDifferent Th cell patterns were observed among POAG, NPG, and NC groups. Lack of induction of Treg cells and imbalance of the pro-inflammatory and anti-inflammatory response patterns of Th cells exist in some NPG patients.

Electrophysiological evaluation in normal-tension glaucoma suspects: a pilot study

Purpose: To evaluate the variations of intraocular pressure (IOP), morphometric papillary characteristics, perimetric indices and electrophysiological parameters (Pattern electroretinogram and visual evoked potentials) before and after topic hypotonization therapy in patients with suspect normal tension glaucoma.Methods: we evaluated 38 eyes of 20 patients with intraocular pressure < 21 mmHg (measured with Goldman applanation tonometry), initial glaucomatous optic neuropathy (valued with HRT: retinal fiber layer (RNFL) and/or linear cup/disk (linear C/D), minimal visual defects (Octopus 101: G2 program), visual acuity more than 15/20 with best correction and pathological electrophysiological parameters (valued with pattern electroretinogram and visual evoked potentials), free of systemic or other ocular diseases. All parameters were evaluated at the beginning of the study (T0) and after 12 months from the beginning of the therapy (T12). A randomized normal control group (27 eyes of 14 subjects) with apparent larger disc cupping underwent all exams at initial of study and after 12 months. Results:At T0, P100 Latency VEPs in LTG was slightly increased either at 15’ (12,9 msec) and 30’ (8,9 msec). At T0, P100 Amplitude VEPs in LTG group were reduced compared to normal subjects, with average differences of: -6.4 µV (95% C.I.: (-9.8, -3.0) µV) for 15'; and: -5.4 µV (95% C.I.: ( -8.9, -2.0) µV) for 30’. P50N95 complex amplitude PERG was reduced at T0 in LTG, with average differences: -0.9 (95% C.I.: ( -1.4, -0.4) µV), -0.8 (-1.3, -0.3) µV) for 15’ and 30’, respectively; than it improved after therapy, with average differences between T12 and T0 of 0.3 µV (95% C.I.: (0.1, 0.6) µV) and 0.5 µV (95% C.I.: ( 0.2, 0.8) µV). So IOP decreased at T12 in LTG group, with an average difference between T12 and T0 of -5.2 mmHg (95% C.I.: (-5.9, -4.4). mmHg). Finally, CRT was slight delayed in LTG group at T0. Conclusion: In a viewpoint of an integrated diagnostic, electrophysiological tests (VEPs and PERG) could provide a more sensitive measure of retinal ganglion cell integrity and help to distinguish between suspect normal-pressure glaucoma patients before perimetric alterations are evident and normal subjects with apparent larger disc cupping.

Integrated electrophysiological evaluation in early normal-tension glaucoma

Purpose: To evaluate the variations of intraocular pressure (IOP), morphometric optic nerve head characteristic, perimetric indices and electrophysiological parameters (pattern electroretinogram and visual evoked potentials) before and after topical IOP lowering in patients with early normal-tension glaucoma.Methods: we evaluated 38 eyes of 20 patients with IOP < 21 mmHg, initial glaucomatous optic neuropathy (valued with HRT: retinal nerve fiber layer thickness (RNFL) and linear cup/disk ratio (linear C/D ratio)), minimal visual field defects (Octopus 101: G2 program), best correct visual acuity more than 15/20 and pathological electrophysiological parameters (valued with pattern electroretinogram (PERG) and visual evoked potentials (VEPs)), free of systemic or other ocular diseases. All parameters were evaluated at the beginning of the study (T0) and after 12 months of therapy (T12). A randomized normal control group (27 eyes of 14 subjects) with apparent larger disc cupping underwent all exams at initial of study (T0) and after 12 months (T12).Results: Among electrophysiological parameters, at the beginning of the study NTG P100 VEPs latency is slightly increased and P100 amplitude is reduced compared to normal subjects. There are not significant variations after 12 months. P50 PERG latency in NTG is quite similar respect normal and do not modify after therapy. P50N95 complex PERG amplitude in NTG is reduced compared to normal subjects and slightly increases after 12 months (1.8 vs 1.5 ; 2.4 vs 1.9 micronvolts, with different checkboard spatial frequency). Cortical retinal time (CRT) is slightly delayed in NTG and does not modify. Among visual field indices, MD and CLV is slightly higher in NTG and do not significantly modify after therapy. Among morphometric optic nerve head characteristics, linear C/D and RNFL thickness are quite similar in NTG and do not modify. IOP is quite similar between NTG and control group and modifies in NTG after therapy.Conclusion: In a viewpoint of an integrated diagnostic, electrophysiological tests (VEPs and PERG) could provide a more sensitive measure of retinal ganglion cell integrity and help to distinguish between early normal-pressure glaucoma patients with no or minimal visual field alterations and normal subjects with apparent larger disc cupping.

Ophthalmology and mathematics: crossroad or scientific interface?

Ophthalmology and mathematics: crossroad or scientific interface?

Back to the Future – Has Medical Treatment of Glaucoma Improved?

These proceedings are based on a symposium that were presented at the European Society of Ophthalmology 2015 Congress in Vienna, Austria on 8 June 2015. The symposium was arranged to bring together leaders in ophthalmology to explore advances in the medical treatment of glaucoma. Many patients with glaucoma require combination therapy. Fixed-dose combinations represent a significant improvement in the medical treatment of glaucoma, being advantageous in terms of their association with good compliance and elimination of the wash-out effect. While preservatives are a historic necessity, their use is associated with increased ocular surface disease and higher indirect cost. The novel preservative-free tafluprost/timolol fixed-dose combination provides mean diurnal intraocular pressure (IOP) lowering of up to 40 % from baseline and demonstrates similar efficacy with other prostaglandin/timolol fixed-dose combinations, is superior to its individual components and non-inferior to its individual components given concomitantly. The tafluprost/timolol fixed-dose combination is well-tolerated with low prevalence of hyperaemia. It is generally accepted that function loss follows structural damage and that normal-pressure glaucoma (NPG) and high-pressure glaucoma (HPG) represent that same disease, separated by an arbitrary pressure level. However, functional damage (pattern electroretinogram) is detectable prior to structural damage and NPG patients show less retinal nerve fibre layer and visual field loss compared with the same optic nerve head morphology HPG patients. NPG patients seem to lose connective tissue first whereas, in HPG, patients seem to lose retinal nerve fibres first. Thus, whether NPG and HPG are the same disease is an open question.

Update on the natural history of glaucoma

Glaucoma is a progressive disease, and the rate of visual field (VF) progression is an important parameter that determines management decisions and is frequently used as an outcome measure in clinical trials. Different scoring systems have been used in the large randomized clinical studies, and have been found to vary in terms of sensitivity and specificity. All these systems measure change in VF from baseline, and the measurements are confounded by variability due to learning effect and test fatigue. For better patient management, the rate of change needs to be considered as well as the time to progression. Rate can be evaluated using trend analysis, as mean deviation (MD), clusters or points. Trend analysis suggests that the linear model is the ‘best fit’, at least for normal tension glaucoma. Using this model, it has been shown that the rate of progression in untreated normal-pressure glaucoma patients varies greatly despite similar ages and MD at baseline.

Aqueous Humor sCD44 Concentration and Visual Field Loss in Primary Open-angle Glaucoma

To correlate aqueous humor soluble CD44 (sCD44) concentration, visual field loss, and glaucoma risk factors in primary open-angle glaucoma (POAG) patients. Aqueous samples were obtained by paracentesis from normal and glaucoma patients who were undergoing elective surgery and analyzed for sCD44 concentration by enzyme-linked immunosorbent assay. In normal aqueous (n=124) the sCD44 concentration was 5.88+/-0.27 ng/mL, whereas in POAG aqueous (n=90) the sCD44 concentration was 12.76+/-0.66 ng/mL, a 2.2-fold increase (P<0.000001). In POAG patients with prior successful filtration surgery (n=13), the sCD44 concentration was decreased by 43% to 7.32+/-1.44 (P=0.001) in comparison with POAG patients without filtration surgery; however, the sCD44 concentration in the prior successful filtration subgroup with no medications and normal intraocular pressure was 12.62+/-3.81 (P=0.05) compared with normal. The sCD44 concentration of normal pressure glaucoma patients was 9.19+/-1.75 ng/mL, a 1.6-fold increase compared with normal (P=0.02). Race and intraocular pressure pulse amplitude were significant POAG risk factors in this cohort of patients. In both normal and POAG patients with mild and moderate visual field loss, sCD44 concentration was greater in African Americans than in whites (P=0.04). sCD44 concentration in the aqueous of POAG patients correlated with the severity of visual field loss in all stages in white patients and in mild to moderate stages in African American patients. sCD44 concentration in aqueous is a possible protein biomarker of visual field loss in POAG.

Visual Evoked Potentials of the Blue-Sensitive Pathway Under Cold Provocation in Normals and Glaucomas

Vascular dysregulation in open-angle glaucomas can be identified by measuring the blood circulation during exposure to cold water. Aim of this study was to find out whether the same cold stimulus would lead to functional changes in the visual evoked potentials (VEP) of the short-sensitive pathway in normals and glaucoma patients. Blue-on-yellow pattern-visual evoked potentials were studied in 22 healthy control persons and 47 patients with primary open-angle glaucoma (25 high-pressure glaucomas, 22 normal pressure glaucomas with clinical signs of vasospastic hyperreactivity). A blue stripe pattern, presented in onset-offset mode on a yellow adaptation light served as the stimulus. Cold provocation was initiated by dipping one hand of the patient into cold water of 3 degrees C to 5 degrees C. The onset amplitudes and peak times were measured without cold exposition as well as two and four minutes after the cold exposition began. In the group of vasospastic glaucoma patients a significant reduction of visual evoked potential-amplitudes was observed during cold provocation (amplitude before ice exposition: 4.17 microV, amplitude following two minutes of ice exposition: 3.52 microV; paired test: P < 0.01). Other subject groups showed no significant amplitude reductions after cold provocation. Peak times of both open-angle glaucoma groups (132.3 +/- 18.7 milliseconds in high pressure, 132.7 +/- 14.5 milliseconds in normal pressure) were significantly increased in comparison to normals (117.4 +/- 8.0 milliseconds). However, no significant influence of the cold provocation on peak times could be found in all groups. Peak times of the blue-on-yellow visual evoked potentials are significantly prolonged in patients with primary open-angle glaucomas. Cold provocation causes a significant amplitude reduction of the blue-on-yellow visual evoked potential in the present normal-pressure glaucoma patients and reflects vascular dysregulation in patients with vasospastic hyperreactivity.

Doppler-Sonographie bei Normaldruckglaukompatienten

Ocular hemodynamics is of great interest in glaucoma, especially since vascular disturbances may play a pathogenetic role in disease development. To investigate the hemodynamic differences between normal pressure glaucoma patients and normal volunteers, flow velocities of the retrobulbar vessels were measured by colour Doppler imaging. 15 patients with normal pressure glaucoma (NPG) and 15 healthy volunteers underwent colour Doppler imaging (CDI) of the retrobulbar vessels. The patients and the volunteers were especially gender- and age-matched. Peak systolic velocities (PSV), end-diastolic velocities (EDV), and resistive indices (RI) of the ophthalmic artery and central retinal artery were obtained. In NPG patients, PSV and EDV in the central retinal artery were significantly decreased, whereas RI was increased in central retinal artery and the ophthalmic artery. Colour Doppler imaging is a non-invasive technique that allows further estimation of the ocular circulatory status. Particularly in the group of patients with disturbed hemodynamics, like NPG patients, it was able to show a reduction of the retrobulbar hemodynamics.

Dynamic cerebral autoregulation is impaired in glaucoma

Objectives: Autonomic and endothelial dysfunction is likely to contribute to the pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma (POAG). Although there is evidence of vasomotor dysregulation with decreased peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been evaluated. The aim of our study was to assess dynamic CA in patients with NPG and POAG. Materials and Methods: In 10 NPG patients, 11 POAG patients and 11 controls, we assessed the response of cerebral blood flow velocity (CBFV) to oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz. CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz oscillations in MAP and CBFV. Results: 0.1 Hz spectral powers of MAP did not differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients with NPG (5.68±1.2 cm 2 s −2) and POAG (6.79±2.1 cm 2 s −2) than in controls (2.40±0.4 cm 2 s −2). Furthermore, the MAP–CBFV gain was higher in NPG (2.44±0.5 arbitrary units [a.u.]) and POAG (1.99±0.2 a.u.) than in controls (1.21±0.1 a.u.). Conclusion: Enhanced transmission of oscillations in MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and might contribute to an increased risk of cerebrovascular disorders in these diseases.

Helicobacter pylori infection and the risk for open-angle glaucoma

Purpose To determine the frequency of exposure to Helicobacter pylori infection in glaucoma patients. Design Prospective case-control study. Participants Ninety-seven consecutive patients attending a glaucoma clinic. These included 38 patients with primary open-angle glaucoma (POAG), 19 with normal pressure glaucoma (NPG), 16 with pseudoexfoliation glaucoma (PXE), and 24 with ocular hypertension (OHT). Ninety-four age-matched participants without glaucoma served as a control population. Methods Serum was analyzed for the presence of H. pylori–specific immunoglobulin G antibodies by enzyme-linked immunosorbent assay. Main outcome measures Serologic analysis for H. pylori. Results Seropositivity for H. pylori was higher in patients with glaucoma (26.0%) than in controls (20.2%), but this did not achieve statistical significance ( P = 0.46). A total of 26.3% of POAG patients, 26.3% of NPG patients, 25.0% of PXE patients, and 25.0% of OHT patients were seropositive. Conclusions This study suggests that exposure to H. pylori infection is not associated with open-angle glaucoma.

Impaired cardiovascular responses to baroreflex stimulation in open-angle and normal-pressure glaucoma

Autonomic neuropathy may contribute to the pathophysiology of both open-angle and normal-pressure glaucoma. However, autonomic function has not been studied extensively in these diseases. We evaluated baroreflex control of the heart and blood vessels in open-angle and normal-pressure glaucoma. We studied 14 patients with open-angle glaucoma, 15 with normal-pressure glaucoma and 17 controls. Sinusoidal neck suction (0 to -30mmHg) was applied at 0.1Hz to assess the sympathetic modulation of the heart and blood vessels, and at 0.2Hz to assess the effect of parasympathetic stimulation on the heart. Baseline recordings showed no significant differences between the groups. The RR-interval response of the controls to neck suction at 0.1Hz (3.88±0.32 to 6.65±0.44lnms2) was significantly greater than that of the open-angle glaucoma patients (4.22±0.28 to 5.56±0.26lnms2) and the normal-pressure glaucoma patients (4.53±0.27 to 5.53±0.37lnms2) (P&lt;0.05). The low-frequency power of diastolic blood pressure increased significantly in the controls (0.48±0.08 to 2.76±0.72mmHg2; P&lt;0.01) during 0.1Hz neck suction, but did not change significantly in patients with either open-angle glaucoma or normal-pressure glaucoma. The RR-interval response in the control group (3.45±0.52lnms2) to neck suction at 0.2Hz was significantly greater than that of the normal-pressure glaucoma patients (1.84±0.32lnms2) and the open-angle glaucoma patients (1.58±0.35lnms2) (P&lt;0.05). The decreased sympathetic and parasympathetic modulation during baroreceptor stimulation in patients with open-angle glaucoma and normal-pressure glaucoma suggests that autonomic dysfunction may contribute to the pathogenesis of both diseases.

T cell subsets and sIL-2R/IL-2 levels in patients with glaucoma

PURPOSE: We hypothesize that cellular immunity may have a previously unrecognized role in glaucomatous optic neuropathy. The purpose of this study is to analyze subsets of T cells and the levels of cytokine IL-2 and the soluble IL-2 receptor in peripheral blood from patients with normal pressure glaucoma (NPG) or primary open angle glaucoma (POAG) in comparison to age-matched control subjects. METHODS: In this study, 38 patients (20 NPG; 18 POAG) and 19 controls were included. sIL-2R and IL-2 were assayed by ELISA. T cell subsets were analyzed by flow cytometry and lymphocyte proliferation was used to measure the reactive ability of T cells to phytohemagglutinin (PHA). RESULTS: The frequency of CD8 +HLA-DR + lymphocytes were increased in patients with NPG ( P = 0.008), and CD3 +CD8 + lymphocytes increased in both NPG ( P = 0.03) and POAG patients ( P = 0.0004). CD5 + lymphocytes were higher only in POAG patients ( P = 0.0012). In comparison to controls, the ratio of CD4 +/CD8 + lymphocytes was similar in both groups. The mean concentrations of sIL-2R in NPG ( P = 0.011) and POAG ( P = 0.0023) patients were higher than that found in control subjects although IL-2 concentrations were similar in these groups. In addition, the reactive ability of T lymphocytes to the non-specific reagent (PHA) was reduced significantly in NPG ( P = 0.02) and POAG patients ( P=0.04). CONCLUSION: The alterations of the cellular immune system in patients with glaucoma support our hypothesis that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy in some patients.

Longitudinal nerve fibre layer thickness change in normal-pressure glaucoma.

To investigate longitudinal retinal nerve fibre layer (RNFL) thickness change in patients with normal-pressure glaucoma (NPG) and to assess how this may be related to visual fields. NPG patients and normal subjects who had had serial GDx nerve fibre layer Analyzer II imaging and Humphrey visual fields performed at least 18 months apart were selected for study. These measurements were compared between groups at baseline and at subsequent follow-up, for change over time. Seventy-five NPG patients and 35 normal subjects were studied. Significant differences in RNFL thickness were found between NPG patients and normal controls at baseline (P < or = 0.001). Over the same time, there was greater RNFL thinning in NPG patients than in normal subjects (P < or = 0.0001). RNFL thinning in NPG was negatively correlated with visual field log MD at baseline (P < 0.001) and change in MD over time (P < 0.001). Reduction of RNFL thickness over time was significantly greater in NPG patients than in normal subjects, indicating that NPG patients' RNFL had thinned at a faster rate. NPG patients with initially better visual fields had a greater reduction in RNFL thickness than did those with initially more advanced visual field defects, suggesting that more RNFL change may be observed when glaucoma is at an earlier stage. There was a direct relationship between RNFL thinning and visual field deterioration.

Glaucomatous optic disc changes in the contralateral eye of unilateral normal pressure glaucoma patients

Objective To evaluate the optic disc for structural abnormalities in the contralateral eye of unilateral normal pressure glaucoma patients. Design Cross-sectional study. Participants Fifty-three unilateral normal pressure glaucoma patients. Testing Optic disc imaging with the Heidelberg Retina Tomograph (HRT). Main outcome measures Optic disc structural parameters. Results Of the contralateral (normal visual field) eyes, 79.2% were found to have an abnormal optic disc by HRT analysis. Of the glaucomatous (abnormal visual field) eyes, 94.3% were found to have an abnormal disc. The patterns of disc abnormality were defined as marked or moderate diffuse thinning of the neuroretinal rim (NRR) or broad or narrow focal thinning of the NRR. The most common pattern in the contralateral eyes was moderate diffuse thinning of the NRR (45.2%). The most frequently abnormal segments were the nasal superior (73.8%) followed by the nasal inferior and the global NRR parameter (both 54.8%). Conclusions A high frequency of NRR thinning was found in the contralateral (normal visual field) eyes of unilateral normal pressure glaucoma patients by HRT analysis. Knowing whether these abnormalities predict future progression to the development of visual field abnormality must wait until longitudinal studies are completed. If a disc abnormality is shown to predict future field loss, then early identification will allow early treatment.

Comparison of visual field progression in patients with normal pressure glaucoma between eyes with and without visual field loss that threatens fixation

AIMTo compare the frequency and site of visual field progression and changes in visual acuity in patients with normal pressure glaucoma (NPG) with and without pre-existing visual field loss.METHODPatients with...

Altitudinal visual field asymmetry is coupled with altered retinal circulation in patients with normal pressure glaucoma

AIMTo compare the effect of altitudinal asymmetric glaucomatous damage on retinal microcirculation in patients with normal pressure glaucoma (NPG).METHODSIn a prospective cross sectional study patients with NPG (washed out for...

Central and Peripheral Arteriovenous Passage Times of the Retina in Glaucoma

The purpose of this paper was to estimate arteriovenous passage (AVP) times, taking into account the non-uniform distribution of arrival times over the vessel diameter, and assessment of respective differences between 15 normal controls (N), 30 primary open-angle glaucoma (POAG) and 30 normal-pressure glaucoma (NPG) patients.Arrival times in retinal vessels were assessed from digitized scanning laser fluorescein angiograms. The arrival times were assessed as a function of position (juxtamural versus axial) in the vessel. This differentiation, based on the measurement position in the vessel, enabled the estimation of AVP times of the posterior pole and of the peripheral retina.The overall, juxtamural and axial AVP times were prolonged in POAG as compared to both N and NPG (P<0.03). The difference in axial AVP times between POAG and normal subjects was considerably larger than the juxtamural values. The distribution of AVP times was considerably larger in POAG patients than in N subjects and NPG patients.Retinal AVP times are prolonged in POAG patients as compared to N and NPG. The wider distribution of AVP times in POAG patients may point to a generalized microvascular alteration. Since the axial AVP times seem to provide the largest differences between NPG and POAG patients, this measurement may be preferred over more general AVP times. The axial AVP times may possibly reflect peripheral vascular changes, e.g. increased vascular resistance. The underlying mechanisms causing these differences are at present unknown.

Are there genuine and pseudo-normal pressure glaucomas? Body position-dependent intraocular pressure values in normal pressure glaucoma

Elevation of intraocular pressure in the supine position has been previously described in literature. Aim of this study is to investigate the elevation of intraocular pressure in normal tension glaucoma and its effect on the morphology of the optic disc, visual field function and capillary blood flow of the retina and optic disc. 56 eyes of 28 preperimetric and advanced normal tension glaucoma patients were prospectively evaluated. Ten eyes of ten normal patients served as a control group for the measurements of the intraocular pressure. In the course of a 24-h pressure profile applanation tonometry was performed in the morning in a supine and three and ten minutes later in a sitting position with Draeger's and Goldmann's tonometers. Arterial blood pressure was measured at the same time. The optic disc's morphology was evaluated by stereo photographs and Laser Scanning Tomography. As a sensory test computer perimetry was used. Capillary blood flow was measured at defined areas of the retina and optic disc. An intraocular pressure above 21 mm Hg in the supine position was used as a criterium to define two groups of normal tension glaucoma patients. In the supine position a statistically significant elevation of intraocular pressure was observed in 24 normal tension glaucoma patients by 6.2 +/- 2.8 mm Hg up to 21.8 +/- 3 mm Hg. Diastolic blood pressure in the supine position (80 +/- 10.5 mm Hg) was significantly lower than in the sitting position (94 +/- 11 mm Hg, p = 0.021). 12 of 28 normal tension glaucoma patients showed an intraocular pressure lower than 22 mm Hg in the supine position. In these patients a tendency towards a higher incidence for the occurrence of optic disc haemorrhages and significantly higher values for blood flow (p < 0.0005) and volume (p < 0.005) in the retina and optic nerve head could be shown. In this group of normal pressure glaucoma patients a higher incidence of migraine and vasospastic complaints was reported in the patients' history. In this study some normal tension glaucoma patients showed intraocular pressures in the supine position higher than 21 mm Hg and a lower diastolic arterial pressure. The higher incidence of haemorrhages and higher values for flow and volume parameters of the optic disc in normal tension glaucoma patients with an intraocular pressure lower than 22 mm Hg implicate the existence of two entities: real and pseudo normal tension glaucomas.