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Tonometry

Distribution by Scientific Domains

Medical Sciences	95%
Life Sciences	4%

Kinds of Tonometry

applanation tonometry

arterial tonometry

Selected Abstracts

Functional Electrical Stimulation-Induced Surface Muscle Stiffness Captured by Computer-Controlled Tonometry

ARTIFICIAL ORGANS, Issue 3 2002
Dietmar Rafolt
Abstract: A new tonometric test system to assess surface stiffness over relaxed and activated calf muscles was developed. The mechanical arrangement consists of a skin indentor driven by a torque motor (galvo-drive) that is rigidly connected to an ankle dynamometer. The indentation depth is measured by a displacement transducer. Software routines for cyclic indentation (recording of stiffness curves), static indentation (sensing of twitch responses), and vibration (skin resonance) were implemented. A visual interface is used to capture surface stiffness during target contractions and during controlled relaxation. For functional electrical stimulation (FES) applications, the software includes a pulse train synthesizer to generate arbitrary stimulation test patterns. The system's performance was tested in FES and voluntary contraction procedures. [source]

Dynamic contour tonometry in corneal oedema

ACTA OPHTHALMOLOGICA, Issue 2007
CA RENNINGS
Purpose: Tonometry in corneal oedema is a current problem. In clinical routine intraocular pressure (IOP) may be measured erroneously too low in edematous thickened cornea using Goldmann applanation tonometry. To compare Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT, Pascal, Technomed, Germany) in postsurgical corneal oedema. Methods: Fifty patients with cataract were included in a prospective study. IOP was measured by means of GAT and DCT before and one day after cataract surgery. Corneal thickness was determined using a Scheimpflug camera system (Pentacam, Oculus, Germany). Results: After surgery corneal thickness increased significantly (pre-surgery: 548 ,m, post-surgery: 677 ,m, p<0.0001). No significant difference of IOP values measured with DCT compared to GAT was detected before and after cataract surgery (pre-surgery: GAT: 17 ±5 mmHg, DCT: 17 ±6 mmHg; post-surgery: GAT 15 ± 7 mmHg, DCT: 15 ±7 mmHg). IOP measured with DCT and GAT were significantly correlated (pre-surgery: r=0.808, p<0.0001; post-surgery: r=0.767, p<0.0001). The difference between GAT and DCT pre-surgery compared to post-surgery was not significantly different. The IOP difference using GAT or DCT pre-surgery compared to post-surgery was not correlated to the change in corneal thickness. Conclusions: DCT does not give any additional information compared to GAT in patients with corneal oedema. However, a marked difference in IOP values using GAT or DCT is apparent in some subjects. [source]

Evaluation of the new Ocuton S tonometer

ACTA OPHTHALMOLOGICA, Issue 2 2002
Giorgio Marchini
ABSTRACT. Purpose:, To evaluate the intra- and interobserver variability of the Ocuton S tonometer, its correlation with Goldmann tonometry, the reliability of self-tonometry and the safety of the instrument. Methods:, Thirty-five healthy subjects and 45 patients with primary open-angle glaucoma (POAG), aged from 38 to 80 years (mean age: 64.6 ± 12.2 years), underwent tonometry with the Ocuton S tonometer in one eye chosen at random. The intra- and interobserver variability between two operators (kappa coefficient), the Ocuton S/Goldmann correlation and the reliability of self-tonometry were evaluated by performing two tonometries on each patient in subgroups. Each tonometry was considered as the mean of three consecutive measurements. Central ultrasonic pachymetry, keratometry and corneal biomicroscopy were also evaluated. Results:, The intra- and interobserver variability ranged from 0.38 to 0.66. The difference between the means of intraocular pressure (IOP) with the Ocuton S (24.4 ± 4.7 mmHg) and the Goldmann tonometer (18.1 ± 4.7 mmHg) was statistically significant (p < 0.0001). Linear regression analysis revealed a good Ocuton S/Goldmann correspondence (r = 0.88, p = 0.0001). However, IOP values detected with the Ocuton were consistently overestimated, compared to those detected with the Goldmann tonometer. The correlation between corneal thickness and IOP was statistically significant both for the Goldmann (r = 0.510, p = 0.021) and for the Ocuton S tonometer (r = 0.520, p = 0.019). No correlation was found between keratometry and IOP. The mean measurement obtained by self-tonometry (21.9 ± 3.6 mmHg) showed no statistically significant difference when compared to the mean measurement obtained by an expert operator (21.3 ± 3.4 mmHg). Conclusion:, The Ocuton S tonometer is a safe instrument that can be used easily by the patient. However, in comparison to the Goldmann tonometer , it overestimates IOP and requires further technical and methodological refinements in order to ensure greater reliability. [source]

Subclinical vascular alterations in young adults with type 1 diabetes detected by arterial tonometry

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2009
I. Barchetta
Abstract Background Diabetes mellitus is characterized by a very high prevalence of atherosclerotic disease. Aims of this study were to determine arterial compliance parameters in type 1 diabetes (T1D) patients as an expression of early pre-clinical endothelial dysfunction and to evaluate the impact of glucose exposure parameters such as the duration of diabetes and glycosylated haemoglobin (HbA1c) on the risk of developing alterations in vascular compliance. Methods 23 patients with uncomplicated type 1 diabetes (mean age: 32.78 ± 9.06 years, mean disease duration: 10.78 ± 7.51 years, mean HbA1c levels: 7.7 ± 1.9) and 26 age- and sex-matched healthy subjects (mean age: 32.3 ± 8.51 years) were recruited. In these subjects, we evaluated arterial compliance by calibrated tonometry (HDI/PulsewaveÔ CR-2000). Parameters included the following: large artery elasticity (C1), small artery elasticity (C2), systemic vascular resistance (SVR) and total vascular impedance (TVI). Results Patients with longer duration of T1D (>10 years) showed significant alterations in C2 (4.97 ± 2.7 mL/mmHg × 100) and in SVR (1464.67 ± 169.16 dina × s × cm,5) when compared with both healthy individuals (C2: 8.28 ± 2.67 mL/mmHg × 100, p = 0.001; SVR: 1180.58 ± 151.55 dina × s × cm,5, p = 0.01) and patients with recent-onset disease (,10 years) (C2: 10.02 ± 3.6 mL/mmHg × 100, p < 0.001; SVR: 1124.18 ± 178.5 dina × s × cm,5, p < 0.000). Both disease duration and HbA1c independently predicted impaired arterial compliance. Conclusions Young adult T1D patients with no signs of disease complication have detectable vessel wall abnormalities, particularly of small arteries, suggestive of hyperglycaemia-related early endothelial dysfunction. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Comparison of in vivo effects of nitroglycerin and insulin on the aortic pressure waveform

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2004
J. Westerbacka
Abstract Background, Individuals whose platelets are resistant to the antiaggregatory effects of insulin in vitro are also resistant to the antiaggregatory effects of nitroglycerin (GTN). We have previously shown that insulin acutely diminishes central wave reflection in large arteries and that this action of insulin is blunted in insulin-resistant subjects. However, as yet, no studies have compared the haemodynamic effects of insulin and GTN on large arterial function in the same group of subjects. The aim of this study was to determine whether resistance to the haemodynamic effects of insulin is a defect specific to insulin or whether individuals resistant to the vascular actions of insulin are also resistant to GTN. Design and results, Dose,response characteristics of insulin and GTN on the aortic waveform were determined using applanation tonometry and pulse wave analysis (PWA) in seven healthy men (age 26 ± 1 year, BMI 25 ± 2 kg m,2). Three doses of sublingual GTN (500 µg for 1, 3 or 5 min) and insulin (0·5, 1 or 2 mU kg,1 min,1 for 120 min) were administered on three separate occasions. Both agents dose-dependently decreased central pulse pressure and the augmentation index (AIx) without changing brachial artery blood pressure. We next compared responses to insulin (2 mU kg,1 min,1 for 120 min) and sublingual GTN (500 µg for 5 min) in 20 nondiabetic subjects (age 50 ± 2 year, BMI 21·0,36·3 kg m,2). Again, both agents significantly decreased AIx. Although the vascular effects of insulin and GTN vascular were positively correlated [Spearman's r = 0·92 (95% confidence interval 0·81,0·97), P < 0·0001], the time-course for the action GTN was faster than that of insulin. Brachial systolic blood pressure remained unchanged during the insulin infusion (122 ± 3 vs. 121 ± 3 mmHg, 0 vs. 120 min) but aortic systolic blood pressure decreased significantly by 30 min (111 ± 3 vs. 107 ± 3 mmHg, 0 vs. 30 min, P < 0·01). Similarly, GTN decreased aortic systolic blood pressure from 119 ± 4 to maximally 112 ± 3 mmHg (P < 0·001) without significantly decreasing systolic blood pressure in the brachial artery. Conclusions, The effects of insulin and GTN on large arterial haemodynamics are dose-dependent and significantly correlated. The exact mechanisms and sites of action of insulin and GTN in subjects with insulin resistance remain to be established. [source]

Variations in carotid arterial compliance during the menstrual cycle in young women

EXPERIMENTAL PHYSIOLOGY, Issue 2 2006
Koichiro Hayashi
The effect of menstrual cycle phase on arterial elasticity is controversial. In 10 healthy women (20.6 ± 1.5 years old, mean ±s.d.), we investigated the variations in central and peripheral arterial elasticity, blood pressure (carotid and brachial), carotid intima,media thickness (IMT), and serum oestradiol and progesterone concentrations at five points in the menstrual cycle (menstrual, M; follicular, F; ovulatory, O; early luteal, EL; and late luteal, LL). Carotid arterial compliance (simultaneous ultrasound and applanation tonometry) varied cyclically, with significant increases from the values seen in M (0.164 ± 0.036 mm2 mmHg,1) and F (0.171 ± 0.029 mm2 mmHg,1) to that seen in the O phase (0.184 ± 0.029 mm2 mmHg,1). Sharp declines were observed in the EL (0.150 ± 0.033 mm2 mmHg,1) and LL phases (0.147 ± 0.026 mm2 mmHg,1; F= 8.51, P < 0.05). Pulse wave velocity in the leg (i.e. peripheral arterial stiffness) did not exhibit any significant changes. Fluctuations in carotid arterial elasticity correlated with the balance between oestradiol and progesterone concentrations. No significant changes were found in carotid and brachial blood pressures, carotid artery lumen diameter, or IMT throughout the menstrual cycle. These data provide evidence that the elastic properties of central, but not peripheral, arteries fluctuate significantly with the phases of the menstrual cycle. [source]

Vasopressin decreases intestinal mucosal perfusion: a clinical study on cardiac surgery patients in vasodilatory shock

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009
A. NYGREN
Background: Low to moderate doses of vasopressin have been used in the treatment of cathecholamine-dependent vasodilatory shock in sepsis or after cardiac surgery. We evaluated the effects of vasopressin on jejunal mucosal perfusion, gastric-arterial pCO2 gradient and the global splanchnic oxygen demand/supply relationship in patients with vasodilatory shock after cardiac surgery. Methods: Eight mechanically ventilated patients, dependent on norepinephrine to maintain mean arterial pressure (MAP) ,60 mmHg because of septic/post-cardiotomy vasodilatory shock and multiple organ failure after cardiac surgery, were included. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h for 30-min periods. Norepinephrine was simultaneously decreased to maintain MAP at 75 mmHg. At each infusion rate of vasopressin, data on systemic hemodynamics, jejunal mucosal perfusion, jejunal mucosal hematocrit and red blood cell velocity (laser Doppler flowmetry) as well as gastric-arterial pCO2 gradient (gastric tonometry) and splanchnic oxygen and lactate extraction (hepatic vein catheter) were obtained. Results: The cardiac index, stroke volume index and systemic oxygen delivery decreased and systemic vascular resistance and systemic oxygen extraction increased significantly, while the heart rate or global oxygen consumption did not change with increasing vasopressin dose. Jejunal mucosal perfusion decreased and the arterial-gastric-mucosal pCO2 gradient increased, while splanchnic oxygen or lactate extraction or mixed venous,hepatic venous oxygen saturation gradient were not affected by increasing infusion rates of vasopressin. Conclusions: Infusion of low to moderate doses of vasopressin in patients with norepinephrine-dependent vasodilatory shock after cardiac surgery induces an intestinal and gastric mucosal vasoconstriction. [source]

Hemodynamic effects of PEEP in a porcine model of HCl-induced mild acute lung injury

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2009
C. K. MARUMO
Background: Positive end-expiratory pressure (PEEP) and sustained inspiratory insufflations (SI) during acute lung injury (ALI) are suggested to improve oxygenation and respiratory mechanics. We aimed to investigate the hemodynamic effects of PEEP with and without alveolar recruiting maneuver in a mild ALI model induced by inhalation of hydrochloric acid. Methods: Thirty-two pigs were randomly allocated into four groups (Control,PEEP, Control,SI, ALI,PEEP and ALI,SI). ALI was induced by intratracheal instillation of hydrochloric acid. PEEP values were progressively increased and decreased from 5, 10, 15 and 20 cmH2O in all groups. Three SIs maneuvers of 30 cmH2O for 20 s were applied to the assignable groups between each PEEP level. Transesophageal echocardiography (TEE), global hemodynamics, oxygenation indexes and gastric tonometry were measured 5 min after the maneuvers had been concluded and at each established value of PEEP (5, 10, 15 and 20 cmH2O). Results: The cardiac index, ejection fraction and end-diastolic volume of right ventricle were significantly (P<0.001) decreased with PEEP in both Control and ALI groups. Left ventricle echocardiography showed a significant decrease in end-diastolic volume at 20 cmH2O of PEEP (P<0.001). SIs did not exert any significant hemodynamic effects either early (after 5 min) or late (after 3 h). Conclusions: In a mild ALI model induced by inhalation of hydrochloric acid, significant hemodynamic impairment characterized by cardiac function deterioration occurred during PEEP increment, but SI, probably due to low applied values (30 cmH2O), did not exert further negative hemodynamic effects. PEEP should be used cautiously in ALI caused by acid gastric content inhalation. [source]

Effects of levosimendan on indocyanine green plasma disappearance rate and the gastric mucosal,arterial pCO2 gradient in abdominal aortic aneurysm surgery

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2008
H. LEPPIKANGAS
Background: Levosimendan has a dual mechanism of action: it improves myocardial contractility and causes vasodilatation without increasing myocardial oxygen demand. In a laboratory setting, it selectively increases gastric mucosal oxygenation in particular and splanchnic perfusion in general. The aim of our study was to describe the effects of levosimendan on systemic and splanchnic circulation during and after abdominal aortic surgery. Methods: Twenty abdominal aortic aneurysm surgery patients were randomized to receive either levosimendan (n=10) or placebo (n=10) in a double-blinded manner. Both the mode of anaesthesia and the surgical procedures were performed according to the local guidelines. Automatic gas tonometry was used to measure the gastric mucosal partial pressure of carbon dioxide. Systemic indocyanine green clearance plasma disappearance rate (ICG-PDR) was used to estimate the total splanchnic blood flow. Results: The immediate post-operative recovery was uneventful in the two groups with a comparable, overnight length of stay in the intensive care unit. Cumulative doses of additional vasoactive drugs were comparable between the groups, with a tendency towards a higher cumulative dose of noradrenaline in the levosimendan group. After aortic clamping, the cardiac index was higher [4(3.8,4.7) l/min/m2 vs. 2.6(2.3,3.6) l/min/m2; P<0.05] and the gastric mucosal,arterial pCO2 gradient was lower in levosimendan-treated patients [0.9(0.6,1.2) kPa vs. 1.7(1.2,2.1) kPa; (P<0.05)]. However, the total splanchnic blood flow, estimated by ICG-PDR, was comparable [29(21,29)% vs. 20(19,25)%; NS]. Organ dysfunction scores (sequential organ dysfunction assessment) were similar between the groups on the fifth post-operative day. Conclusion: Levosimendan favours gastric perfusion but appears not to have a major effect on total splanchnic perfusion in patients undergoing an elective aortic aneurysm operation. [source]

Central corneal thickness in European (white) individuals, especially children and the elderly, and assessment of its possible importance in clinical measures of intra-ocular pressure

OPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 6 2002
Michael J. Doughty
Purpose:,To ascertain the impact of central corneal thickness (CCT, as assessed by pachometry) and central corneal curvature (as assessed by keratometry) on clinical measures of intra-ocular pressure (IOP, as assessed by tonometry), especially in the young and elderly. Methods:,Pachometry, keratometry and tonometry were carried out on three groups, namely children aged 5,15 years, adults aged 32,60 years, and elderly individuals aged between 61 and 82 years. For children, ultrasound pachometry was combined with non-contact tonometry (NCT), specular microscopy was used with Perkins tonometry in the adults, and ultrasound pachometry was used with Perkins tonometry for the elderly. Central corneal curvature was assessed by keratometry. Results:,The average CCT in children was 0.529 ± 0.034 mm (n=104, ±S.D.), averaged 0.533 ± 0.033 in adults (n=75) and 0.527 ± 0.034 mm (n=91) in the elderly. Tonometry values averaged 16.7 ± 2.9 mm in children, 13.0 ± 3.5 mmHg in adults and 13.6 ± 2.5 mm in the elderly group. Central corneal thickness values were not predictably different in relation to central corneal curvature values. Regression analyses indicated that the tonometry values were higher in both children and the elderly who had thicker corneas (and vice versa) (p , 0.003), with the measures increasing by 1.3 ± 0.4 and 2.6 ± 0.4 mmHg for a 10% difference in CCT in children and the elderly, respectively. For adults, no statistically significant difference in tonometry values could be demonstrated with respect to CCT (<1 mmHg for a 10% difference in CCT), and for no group were the CCT or tonometry values predictably different in relation to central corneal curvature values. Conclusions:,The results of these studies, albeit relatively small scale, indicate that in young or elderly individuals with essentially normal IOP and CCT measures, the tonometry values show only small differences with respect to CCT. The slope in the observed relationship was not that different from an average of 1.5 mmHg for a 10% different in CCT, as obtained from a literature analysis over a 30-year period. The magnitude of the effect does not provide evidence that pachometry needs to be routinely performed in glaucoma screening protocols based on tonometry. Notwithstanding, the finding of higher than expected tonometry values should be further investigated, by pachometry, especially in very young children and in the elderly. [source]

Effects of deep and superficial experimentally induced acute pain on muscle sympathetic nerve activity in human subjects

THE JOURNAL OF PHYSIOLOGY, Issue 1 2009
A. R. Burton
Human studies conducted more than half a century ago have suggested that superficial pain induces excitatory effects on the sympathetic nervous system, resulting in increases in blood pressure (BP) and heart rate (HR), whereas deep pain is believed to cause vasodepression. To date, no studies have addressed whether deep or superficial pain produces such differential effects on muscle sympathetic nerve activity (MSNA). Using microneurography we recorded spontaneous MSNA from the common peroneal nerve in 13 awake subjects. Continuous blood pressure was recorded by radial arterial tonometry. Deep pain was induced by intramuscular injection of 0.5 ml hypertonic saline (5%) into the tibialis anterior muscle, superficial pain by subcutaneous injection of 0.2 ml hypertonic saline into the overlying skin. Muscle pain, with a mean rating of 4.9 ± 0.8 (s.e.m.) on a 0,10 visual analog scale (VAS) and lasting on average 358 ± 32 s, caused significant increases in MSNA (43.9 ± 10.0%), BP (5.4 ± 1.1%) and HR (7.0 ± 2.0%) , not the expected decreases. Skin pain, rated at 4.9 ± 0.6 and lasting 464 ± 54 s, also caused significant increases in MSNA (38.2 ± 12.8%), BP (5.1 ± 2.1%) and HR (5.6 ± 2.0%). The high-frequency (HF) to low-frequency (LF) ratio of heart rate variability (HRV) increased from 1.54 ± 0.25 to 2.90 ± 0.45 for muscle pain and 2.80 ± 0.52 for skin pain. Despite the different qualities of deep (dull and diffuse) and superficial (burning and well-localized) pain, we conclude that pain originating in muscle and skin does not exert a differential effect on muscle sympathetic nerve activity, both causing an increase in MSNA and an increase in the LF : HF ratio of HRV. Whether this holds true for longer lasting experimental pain remains to be seen. [source]

Relationship of asymmetric dimethylarginine and homocysteine to vascular aging in systemic lupus erythematosus patients

ARTHRITIS & RHEUMATISM, Issue 6 2010
Michelle Perna
Objective Systemic lupus erythematosus (SLE) is independently associated with accelerated atherosclerosis and premature arterial stiffening. Asymmetric dimethylarginine (ADMA) and homocysteine are mechanistically interrelated mediators of endothelial dysfunction and correlates of atherosclerosis in the general population. The aim of this study was to assess the relationship of ADMA and homocysteine to subclinical vascular disease in patients with SLE. Methods One hundred twenty-five patients with SLE who were participating in a study of cardiovascular disease underwent clinical and laboratory assessment, carotid artery ultrasonography to detect atherosclerosis, and radial artery applanation tonometry to measure arterial stiffness. Results Neither ADMA nor homocysteine correlated with the presence or extent of carotid atherosclerosis. In contrast, ADMA was significantly related to the arterial stiffness index. Independent correlates of arterial stiffening included the ADMA concentration, the presence of diabetes mellitus, older age at the time of diagnosis, longer disease duration, and the absence of anti-Sm or anti-RNP antibodies. A secondary multivariable analysis substituting homocysteine for ADMA demonstrated comparable relationships with arterial stiffness (r2 = 0.616 for homocysteine and r2 = 0.595 for ADMA). Conclusion ADMA and homocysteine are biomarkers for and may be mediators of premature arterial stiffening in patients with SLE. Because arterial stiffness has independent prognostic value for cardiovascular morbidity and mortality, its predictors may identify patients who are at increased risk of cardiovascular disease. [source]

Independent association of rheumatoid arthritis with increased left ventricular mass but not with reduced ejection fraction

ARTHRITIS & RHEUMATISM, Issue 1 2009
Rebecca L. Rudominer
Objective Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature atherosclerosis, vascular stiffening, and heart failure. This study was undertaken to investigate whether RA is associated with underlying structural and functional abnormalities of the left ventricle (LV). Methods Eighty-nine RA patients without clinical cardiovascular disease and 89 healthy matched controls underwent echocardiography, carotid ultrasonography, and radial tonometry to measure arterial stiffness. RA patients and controls were similar in body size, hypertension and diabetes status, and cholesterol level. Results LV diastolic diameter (4.92 cm versus 4.64 cm; P < 0.001), mass (136.9 gm versus 121.7 gm; P = 0.004 or 36.5 versus 32.9 gm/m2.7; P = 0.01), ejection fraction (71% versus 67%; P < 0.001), and prevalence of LV hypertrophy (18% versus 6.7%; P = 0.023) were all higher among RA patients versus controls. In multivariate analysis, presence of RA was an independent correlate of LV mass (P = 0.004). Furthermore, RA was independently associated with presence of LV hypertrophy (odds ratio 4.14 [95% confidence interval 1.24, 13.80], P = 0.021). Among RA patients, age at diagnosis and disease duration were independently related to LV mass. RA patients with LV hypertrophy were older and had higher systolic pressure, damage index scores, C-reactive protein levels, homocysteine levels, and arterial stiffness compared with those without LV hypertrophy. Conclusion The present results demonstrate that RA is associated with increased LV mass. Disease duration is independently related to increased LV mass, suggesting a pathophysiologic link between chronic inflammation and LV hypertrophy. In contrast, LV systolic function is preserved in RA patients, indicating that systolic dysfunction is not an intrinsic feature of RA. [source]

Central corneal thickness in children with growth hormone deficiency

ACTA OPHTHALMOLOGICA, Issue 6 2010
Fulvio Parentin
Acta Ophthalmol. 2010: 88: 692,694 Abstract. Purpose:, To evaluate central corneal thickness (CCT), intraocular pressure (IOP) and eye refraction in patients with congenital growth hormone (GH) deficiency. Methods:, Retrospective case series. Forty-five patients with growth defect treated with recombinant GH and 45 healthy children underwent ophthalmological examination, including CCT measurements, applanation tonometry and cycloplaegic refraction. Results:, The average CCT in the GH deficiency group was 570.6 ,m [standard deviation (SD) 37.4]. In the control group, it was 546.0 (SD 24.9). The average IOP in the GH deficiency group was 18.2 mmHg (SD 3.4). In the control group, it was 14.6 (SD 2.0). The mean refractive error (spherical equivalent) in the GH deficiency group was 0.59 D (SD 1.9). In the control group, it was 0.11 (SD 2.1). Conclusion:, GH and insulin-like growth factor 1 are involved in ocular growth by influencing the synthesis of the extracellular matrix of the sclera. Children with congenital GH deficiency or insensitivity have a mean hyperopic defect related to a shorter axial length. A number of studies have demonstrated that CCT in newborns is significantly greater than in adults; a decrease in CCT is closely correlated with an increase in corneal diameter. This finding suggests that the growth of the eye, with possible remodelling and stretching of collagen fibres, may play an important role in the reduction of corneal thickness in the first years of life. Therefore, we conclude that a greater CCT can represent a sign of a delayed growth of the eye in patients with GH deficiency. Finally, our study confirms the influence of corneal thickness on IOP measures, and the prevalence of hyperopia among children with growth defect. [source]

2352: The influence of central corneal thickness and corneal biomechanics in glaucoma

ACTA OPHTHALMOLOGICA, Issue 2010
FC LAM
Purpose To look at the impact that central corneal thickness and corneal biomechanics can have on intraocular pressure (IOP) measurements and their effect on visual fields. Methods Written and informed consent from patients and guidance from the local research ethics committee was obtained. Ocular diagnoses and ocular medications were recorded. IOPs were recorded using Goldmann applanation tonometry (GAT)followed by dynamic contour tonometry with the Pascal tonometer. Central corneal thickness(CCT) was measured using ultrasound. Visual fields were recorded using Humphries perimetry. Bland-Altman plots were used to compare the 2 methods. Results 92 eyes of 46 patients were included. Median CCT 556µm(range:427µm-634µm). Despite a good correlation of the IOP measurements usin the two different techniques(r=0.7; p< 0.01), there was a significant difference in limits of agreement(LOA) of DCT to GAT on the Bland-Altman analysis. The LOA was 8.6mmHg to -4.8mmHg with a mean bias of 1.9mmHg. This persisted even after correction for CCT. Ocular hypertensives had a wider LOA than glaucoma patients. Conclusion DCT IOP measurements can be significantly different from GAT IOPs even after taking into account central corneal thickness. Compared to CCT, corneal hysteresis appears to have a greater impact on IOP measurements. This could have important prognostic implications. [source]

2353: The influence of corneal thickness and curvature on IOP measurement by IcareTM rebound tonometer and applanation tonometry in glaucoma patients and normal subjects.

ACTA OPHTHALMOLOGICA, Issue 2010
P KRZYZANOWSKA-BERKOWSKA
Purpose To evaluate the influence of central corneal thickness (CCT) and radius of the corneal curvature (R) on IOP measurements obtained with the ICare rebound tonometer and the Goldmann applanation tonometer (GAT). Methods Eighty four eyes of 48 subjects (65 eyes of glaucoma patients and 19 eyes of healthy volunteers) were examined with ICare and Goldmann tonometers. Central corneal thickness was determined by ultrasound pachymetry. Corneal radius of curvature was determined using corneal topography. Results There was no significant difference between IOP readings with ICare and GAT. Intraocular pressure measurements were found to be higher with the ICare tonometer, both in glaucoma patients (15,3±4,0 mmHg) and normal subjects (14,4±3,0 mmHg). ICare-GAT mean difference was 1.1±3.6mmHg (95% CI, -6.1-8.3mmHg) for glaucoma patients and 1.8±3.2mmHg (95% CI, -4.6-8.2mmHg) for healthy volunteers. Using CCT patients were divided into 2 groups: 1) thinnest corneas - CCT<556 ,m (mean CCT 531±23 ,m), 39 eyes and 2) thickest corneas - CCT >556 ,m (mean CCT 578±17 ,m), 45 eyes. In the group of thinnest corneas there was no correlation between IOP, CCT and R. In thickest corneas there was significant correlation between IOP readings obtained by ICare and CCT (r=-0.4, p<0.01), and mean radius (R) (r=0.5, p<0.001). Conclusion Measurements of IOP using the ICare rebound tonometer are in good agreement with Goldmann applanation tonometer in glaucoma patients and normal subjects, although influenced by CCT. [source]

2355: Biomechanical analysis of the pressure-volume relationship in a statically loaded human eye

ACTA OPHTHALMOLOGICA, Issue 2010
AA STEIN
Purpose To develop an approach for estimating the mechanical characteristics of the individual eye in the ophthalmologic procedures based on static load application (tonometry, et al.). Methods The fibrous coat is mathematically modeled as a soft elastic shell (cornea) connected with an elastic system that mainly consists of the sclera and is characterized by a single elastic constant describing its response to the intraocular pressure. A function representing the intraocular volume as a function of two variables, the intraocular pressure and the load applied, called the volume function is introduced. This function is then specified on the basis of a simple model characterized by two elastic constants in the case of an applanating load. Results A general method of estimating the integral elastic behavior of the individual eye is developed and specific relationships between elastic constants important in different loading processes are obtained. Conclusion The method developed makes it possible to reliably estimate the integral elastic behavior of the fibrous coat and, as a result, to obtain more correct data on the intraocular pressure and other mechanical characteristics. Although in different loading processes (for example, in tonometry and inflating the eye by a liquid volume) different integral elastic contacts are involved, the model proposed provides a means for obtaining efficient approximate relationships between these constants. [source]

Effect of acute postural variation on diabetic macular oedema

ACTA OPHTHALMOLOGICA, Issue 2 2010
Martin Vinten
Abstract. Purpose:, This study aimed to study the pathophysiology of diabetic macular oedema (DMO) by analysis of concomitant changes in macular volume (MV), mean arterial blood pressure (MABP), intraocular pressure (IOP), and retinal artery and vein diameters in response to acute postural changes in patients with DMO and healthy subjects. Methods:, Thirteen patients with DMO (13 eyes) and five healthy subjects (five eyes) were examined after resting in a chair for 15 mins using optical coherence tomography to measure MV and fundus photography to assess retinal vessel diameters. The patients then lay down for 60 mins, during which they were examined repeatedly before they were reseated and examined again. Intraocular pressure was measured using pulse-air tonometry, arterial blood pressure by sphygomanometry and fluid columns using rulers and a spirit level. Results:, In healthy subjects, retinal artery (p = 0.02) and vein (p = 0.001) diameters decreased when subjects lay down, whereas MV remained stable. In patients with DMO, no orthostatic variation in retinal vessel diameters could be demonstrated, whereas MV had increased by 2.4 ± 0.6% (mean ± standard error of the mean; p = 0.006) 50 mins after assuming a recumbent position. In both healthy subjects and DMO patients, MABP decreased and IOP increased in a recumbent position, with no significant difference between the groups. Conclusions: The increase in MV that occurs in DMO when changing from a seated to a recumbent position is associated with a failure of retinal artery contraction, a response seen in healthy subjects that appears to counter-regulate the increase in ocular perfusion pressure caused by assuming a recumbent position. [source]

Ocular blood flow and oxygen delivery to the retina in primary open-angle glaucoma patients: the addition of dorzolamide to timolol monotherapy

ACTA OPHTHALMOLOGICA, Issue 1 2010
Brent Siesky
Abstract Purpose:, To assess the effects of adding dorzolamide to timolol monotherapy on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (POAG). Methods:, Twenty-four patients (12 healthy, 12 with POAG) were treated with dorzolamide/timolol combination (DT) versus timolol maleate 0.5% twice daily in a randomized, crossover, double-blind study conducted over a period of 18 months. Patients received each treatment for 8 months then crossed over to the other treatment after a 1-month washout and second baseline. Goldmann applanation tonometry, Heidelberg retinal flowmetry (HRF), colour Doppler imaging (CDI) and retinal photographic oximetry were performed at each visit. Results:, DT significantly reduced intraocular pressure (IOP) in both glaucomatous [right eye (OD) ,13.15%, left eye (OS) ,14.43%; p < 0.036] and non-glaucomatous (OD ,12.4%, OS ,13.88%; p < 0.039) patients compared to timolol after 8 months of treatment. DT significantly reduced the number of zero blood flow pixels in the superior (,39.72%; p < 0.014) and inferior (,51.44%; p < 0.008) retina in the non-glaucomatous group and inferior retina in the glaucomatous group (,55.38%, p < 0.006). The continuation of timolol monotherapy from baseline did not change (p < 0.05) any measured parameter and neither treatment had a significant effect (p < 0.05) on retinal oximetry or CDI parameters. Conclusion:, The addition of dorzolamide to timolol monotherapy decreases IOP and increases retinal blood flow in the superficial retinal vasculature in both glaucomatous and healthy patients following 8 months of treatment. The combination of increased retinal blood flow with consistent oxygen saturation may potentially increase oxygen delivery to the retina. [source]

Association between corneal hysteresis and central corneal thickness in glaucomatous and non-glaucomatous eyes

ACTA OPHTHALMOLOGICA, Issue 8 2009
George Mangouritsas
Abstract. Purpose:, We aimed to determine corneal hysteresis values (CH) using the ocular response analyser (ORA) in non-glaucomatous and glaucomatous eyes and their relationship with central corneal thickness (CCT). Methods:, Corneal hysteresis, intraocular pressure (IOP) as measured by Goldmann applanation tonometry (GAT) and CCT were prospectively evaluated in 74 non-glaucoma subjects with IOP < 21 mmHg and in 108 patients with treated primary open-angle glaucoma (POAG). One eye in each subject was randomly selected for inclusion in the analysis. Results:, Mean (± standard deviation [SD]) age was 59.2 ± 14.2 years in the non-glaucoma group and 62.4 ± 9.8 years in the glaucoma group. Mean (± SD) GAT IOP was 15.7 ± 2.65 mmHg and 16.38 ± 2.73 mmHg in the non-glaucoma and glaucoma groups, respectively. There was no statistically significant difference between the two groups in mean age (p = 0.396) or mean GAT IOP (p = 0.098). Mean (± SD) CH was 10.97 ± 1.59 mmHg in the non-glaucoma and 8.95 ± 1.27 mmHg in the glaucoma groups, respectively. The difference in mean CH between the two groups was statistically significant (p < 0.0001). There was a strong positive correlation between CH and CCT in the non-glaucoma group (r = 0.743) and a significantly (p = 0.001) weaker correlation (r = 0.426) in the glaucoma group. Conclusions:, Corneal hysteresis was significantly lower in eyes with treated POAG than in non-glaucomatous eyes. The corneal biomechanical response was strongly associated with CCT in non-glaucoma subjects, but only moderately so in glaucoma patients. It can be assumed that diverse structural factors, in addition to thickness, determine the differences in the corneal biomechanical profile between non-glaucomatous and glaucomatous eyes. Corneal hysteresis could be a useful tool in the diagnosis of glaucoma. [source]

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

ACTA OPHTHALMOLOGICA, Issue 6 2009
Noemi Maar
Abstract. Purpose:, To investigate in patients with neovascular age-related macular degeneration (ARMD) the changes in ocular perfusion caused by single treatment with photodynamic therapy (PDT) by different non-invasive methods; to evaluate correlations between relative changes of ocular haemodynamic parameters after PDT among each other and compared to morphological parameters; and to assess this in relation to early changes of visual acuity. Methods:, Study population: 17 consecutive patients with subfoveal choroidal neovascularization (CNV) caused by ARMD scheduled for PDT without previous PDT treatment (four patients with predominantly classic CNV and 13 patients with occult CNV). Observation procedures: best-corrected visual acuity (before PDT, 6 and 8 weeks after PDT), fundus photography, fluorescein angiography, haemodynamic measurements with laser Doppler flowmetry (LDF), laser interferometry and ocular blood flow (OBF) tonometry (baseline and 1, 2, 6 and 8 weeks after treatment). Main outcome measures: choroidal blood flow (CHBF), fundus pulsation amplitude (FPA), pulsatile ocular blood flow (POBF), visual acuity. Changes smaller than 20% were considered clinically irrelevant. Results:, Ocular haemodynamic parameters did not change significantly in the follow-up period. Changes of haemodynamic parameters showed no correlation to treatment spot, morphological changes or visual acuity. Changes of visual acuity were comparable to results of earlier studies. Conclusion:, Single treatment with PDT did not modify ocular blood flow parameters above 20% as assessed with different non-invasive methods. [source]

Why do we need a biomechanical approach to the ocular rigidity concept?

ACTA OPHTHALMOLOGICA, Issue 2009
KE KOTLIAR
Ocular rigidity in ophthalmology is generally assumed to be a measurable surrogate parameter related to the biomechanical properties of the whole globe. Clinical tonometry and tonography, as well as recently developed methods to assess the ocular pulse amplitude and pulsatile ocular blood flow and measurements with the ocular response analyzer are based on the concept of ocular rigidity. Clinical concepts of ocular rigidity describe a resulting effect without considerations of possible diverse morphology and material properties of the different ocular tissues. It is commonly accepted that ocular rigidity is related to the elasticity of the sclera. Many formulations are however dependent on the internal volume of the globe, intraocular pressure, corneal biomechanics and thickness of the corneoscleral shell. Sometimes this is extended to biomechanical properties of the ocular vasculature and perfusion pressure. Therefore ocular rigidity is expressed in various units and has different physical meanings but the same name is used which is confusing. Ocular biomechanics introduces parameters of elasticity and viscoelasticity of the sclera, cornea and other tissues which consider the morphology of the different tissues describing their mechanical properties such as: Young's modules of the sclera and Poisson's ratios of the cornea. When applying these rigorous statements and methods of biomechanical modeling a unified concept for ocular rigidity can be developed in order to link the limited clinical concepts, to improve them and to better understand the results of clinical measurements. [source]

Ocular pulse amplitude under pressure: what happens to OPA in glaucoma before and after surgery?

ACTA OPHTHALMOLOGICA, Issue 2009
I STALMANS
Purpose To investigate whether trabeculectomy, besides its intraocular pressure (IOP) - lowering effect, has an effect on the ocular pulse amplitude (OPA). To determine if OPA changes are influenced by IOP changes. Methods Forty-eight glaucoma patients (48 eyes) scheduled for unilateral first-time trabeculectomy were prospectively enrolled from October 2007 to April 2008. The eye undergoing trabeculectomy was considered as study eye, whereas the non-operated fellow eye was used as control eye. OPA, IOP, blood pressure and heart rate were measured prior to and 4 weeks following trabeculectomy by means of Pascal dynamic contour tonometry (DCT), Goldmann applanation tonometry (GAT) and sphygmomanometry. A regression model for repeated measures was used. Results Preoperative GAT, DCT and OPA were 20.92 ±8.55 mmHg, 21.33 ±7.06 mmHg and 3.23 ±1.58 mmHg, respectively. One month following trabeculectomy, GAT, DCT and OPA were 11.23 ±5.03 mmHg, 14.45 ±4.79 mmHg and 2.12 ±1.07 mmHg, respectively. There was a significant decrease in OPA after filtering surgery in the study eye compared to the control eye (P<0.0001). Changes in OPA were correlated with changes in IOP (Spearman rho = 0.49, P=0.0004). When the IOP change caused by filtering surgery was taken into account, no significant difference in effect on the OPA following trabeculectomy could be demonstrated in the study eye compared to the control eye (P=0.18). Conclusion OPA changes were strongly correlated with IOP changes. There was no evidence for an effect of filtering surgery on the OPA when the concomitant IOP decrease after trabeculectomy was taken into account. [source]

Consequences of dietary omega-3 polyunsaturated fatty acid deficiency on retinal function and intraocular pressure in the rat

ACTA OPHTHALMOLOGICA, Issue 2009
B BARDET
Purpose Omega-3 polyunsaturated fatty acids (,3) are key components in nervous structures but their dietary intakes in the overall population are often below nutritional requirements. A chronic deficiency in ,3 is recognized to be associated with functional impairment of the retina. At the opposite, ,3 supplementation is associated with a reduced risk for AMD. The consequences of ,3 deficiency on other eye structures than the retina, such as ciliary bodies, are scarce. The purpose of our study was to compare the response of the retina and ciliary bodies to dietary ,3 deficiency in terms of fatty acid profile and eye functionality. Methods Two successive generations of Lewis rats (G1 and G2) were obtained under either a standard or ,3-deficient diet. Intraocular pressure (IOP) was measured by rebound tonometry throughout the experiment. Retinal functionality was assessed by scotopic electroretinography (ERG). Gas chromatography was used to determine the fatty acid profile of the ciliary bodies and retina. Results A 2-fold fall in DHA content of the retina was observed in ,3-deficient G1 animals. This decrease was accentuated in G2 (-66%) and counterbalanced by an increase in DPA,6 in the retina. The b-wave amplitude of the ERG was decreased by 50% at 9mcds/m² in ,3-deficient rats. In ciliary body DHA was reduced by 80% in ,3-deficient in G1 animals but not in G2. Meanwhile, animals from the ,3-deficient diet had increased IOP (18 vs 12mmHg, p<0.0001). Conclusion The crucial role of ,3 in retinal function was confirmed. The most relevant finding from our study is the rise in IOP, the major risk factor for glaucoma, which was observed in animals reared under dietary deficiency in ,3. [source]

Do patients with normal tension glaucoma have a thinner conjunctiva?

ACTA OPHTHALMOLOGICA, Issue 2009
R VAN GINDERDEUREN
Purpose The central cornea is thinner in patients with normal tension glaucoma (NTG). We had developed the surgical impression of thinner conjunctivas in patients with NTG. The purpose of this study was to determine whether there is a difference between the conjunctival thickness of patients with NTG and those with high tension primary open-angle glaucoma (POAG). Methods In this prospective study, 40 patients scheduled for trabeculectomy were categorized into NTG and POAG based on maximum intraocular pressure (IOP) as measured by Goldmann applanation tonometry. Ten (10) patients with NTG (max. IOP,21mmHg) and 30 patients with high tension POAG (max IOP>21mmHg) were included in the study. Conjunctival biopsies taken from the inferior fornix one month prior to trabeculectomy were fixed in formalin and embedded in Historesin. The conjunctival thickness was measured on a standardised way and compared between the two groups. Non-paired Student T test for two-tailed groups with equal variance was used for statistical analysis. Results The difference in mean conjunctival thickness between patients with NTG (66.4,±21.1) and patients with high tension POAG (104.6,±44.3) was statistically significant (P=0.045). The mean CCT in NTG (537,6±19.6) was lower than in POAG (548.3±38.0), but did not reach significancy in this study. Conclusion Patients with NTG have a thinner conjunctiva than those with high tension POAG [source]

Comparison of dynamic contour tonometry with Goldmann applanation tonometry in glaucoma practice

ACTA OPHTHALMOLOGICA, Issue 3 2009
Ioannis Halkiadakis
Abstract. Purpose:, To compare intraocular pressure (IOP) readings taken using dynamic contour tonometry (DCT) with IOP readings taken with Goldmann applanation tonometry (GAT) in eyes with glaucoma or ocular hypertension. Methods:, The present study included 100 eyes in 100 patients with glaucoma or ocular hypertension. After pachymetry DCT and GAT were performed. Intraocular pressures as measured with DCT and GAT were compared with one another and with central corneal thickness (CCT). Results:, Mean DCT IOP measurements (20.1 ± 4.3 mmHg) were significantly (p < 0.001) higher than GAT IOP values (17.9 ± 4.7 mmHg). The mean difference between DCT and GAT measurements was 2.1 mmHg (range , 3.4 to 9.7 mmHg). The difference followed a normal distribution. Measurements made with DCT and GAT correlated significantly with one another (Spearman's rho = 0.761, p < 0.001). Neither GAT nor DCT measurements showed a significant correlation with CCT (537 ± 39 ,m, range 458,656 ,m). Multivariate regression analysis has shown that the difference between DCT and GAT is influenced significantly by ocular pulse amplitude (r = , 0.334, p = 0.001) and it is not influenced by CCT (r = , 0.106, p = 0.292). Conclusions:, In eyes with glaucoma or ocular hypertension, DCT facilitates suitable and reliable IOP measurements which are in good concordance with GAT readings. Variation in CCT cannot by itself explain the differences in measurements taken with DCT and GAT in a number of eyes. [source]

Relationship between ocular pulse amplitude and systemic blood pressure measurements

ACTA OPHTHALMOLOGICA, Issue 3 2009
Matthias C. Grieshaber
Abstract. Purpose:, This study aimed to determine whether ocular pulse amplitude (OPA) measured with dynamic contour tonometry (DCT) is related to systemic blood pressure (BP) parameters. Methods:, Blood pressure was measured continuously and simultaneously with OPA in one randomly selected eye in 29 healthy subjects. Systemic parameters of interest were: systolic and diastolic BPs and their difference (BP amplitude), and left ventricle ejection time (LVET; defined as the time between the diastolic trough and the incisural notch in the BP curve). In addition, the axial length (AL) of the eye was measured. Associations between OPA, AL and systemic cardiovascular parameters were analysed in a multivariate regression model. Results:, Measurements of OPA ranged from 1.0 mmHg to 4.9 mmHg (mean 2.3 ± 0.9 mmHg, median 1.9 mmHg). In a univariate analysis with one predictor at a time, means of intraocular pressure (IOP) (p = 0.008), AL (p = 0.046) and LVET (p = 0.037) were significantly correlated with OPA, whereas systolic and diastolic BPs and their amplitude were not. A multiple linear regression analysis showed that mean IOP (p < 0.005), AL (p = 0.01) and LVET (p = 0.002) all independently contributed to OPA. Conclusions:, The OPA readings measured with DCT in healthy subjects were not related to BP levels and amplitude. It seems that the OPA strongly depends on the time,course of the cardiac contraction. Regulating mechanisms in the carotid system as well as scleral rigidity may be responsible for dampening the direct effect of BP variations. [source]

Re-examination of organ-cultured, cryopreserved human corneal grafts after 27 years

ACTA OPHTHALMOLOGICA, Issue 2 2009
Charlotte Corydon
Abstract. Purpose:, To determine the long-term fate of cryopreserved corneas. Review of 17 organ-cultered cryopreserved corneas grafted in 1978,1979. Methods:, We measured visual acuity and refraction and performed biomicroscopy, applanation tonometry and optical pachometri (CCT). Endothelial photos were taken, cells were counted and morphology was studied. Results:, Four of 16 grafted corneas were still clear after 27 years. Mean CCT was 0.52 mm, endothelial cell density was 882 cells/mm2 and visual acuity was 0.25 or better with an average of 0.6 in the four patients. Cell morphology showed irregularity in shape and size. Conclusion:, This study shows that cryopreserved endothelium can function as well as non-frozen corneas and that a regular hexagonal pattern is not essential for corneal clarity. The four grafts showed long-term durability despite the irregularity in shape and size. [source]

AER lecture: Some reflections on corneal thickness

ACTA OPHTHALMOLOGICA, Issue 2007
N EHLERS
The corneal thickness as an object for studies was recognized in the renaissance. A value of 1 mm, representing the maximally swollen human cornea, was reported. Optical in vivo measurements were done by Blix in 1880 reporting a thickness of about 0.5 mm, the value that we today know is correct. Blix lived in "the golden age of physiologic optics". His interest was the contribution of the cornea to the optical refraction of the eye, and was thus the distance between the anterior and the posterior surface rather than the thickness of the cornea as such. A biomechanical interest in corneal thickness was initiated by the studies of tonometry, in particular Hans Goldmann's development of applanation tonometry. He predicted correctly that corneal thickness would influence the estimated pressure reading. Another physiological aspect of the cornea is its transparency. Earlier explanations by equal refractive index was revolutionized by the interference theory by David Maurice. Optical transparency required a regular fiber pattern, and thus a stabilized thickness and stromal hydration. This led to extensive interest in the permeability of the limiting layers, in particular the transport of fluid across the endothelium. The physiological concepts required a regulated or stabilized thickness. The thickness as such became interesting. The human cornea is thinner in the center than more peripherally and the central, presumably regulated central thickness (CCT) became a biometric and clinical study object. The exact individual value became of interest. Several optical and later ultrasonic principles were presented. Questions addressed were: Is CCT a life-long, age independent characteristics. Is CCT diagnostic for certain disease conditions (e.g. Macular dystrophy of Groenouw). Is CCT a useful clinical parameter to follow disease processes (e.g. progression in keratoconus or acute changes in graft rejections). Today refractive surgery has revived the interest in biomechanical and optical properties of the cornea. Modern computer technology allows for a description of the "thickness profile" of the entire cornea. This gives us access to an overwhelming amount of data, and reopen many issues of the past. We must realize, however, that what we see is the pendulum swinging back to the problems of the last century. The machinery is smarter but many of the basic questions remain to be solved. [source]