Measurement of the retinal venous pressure with a new instrument in patients with primary open angle glaucoma.

PURPOSE: To compare the results of retinal venous pressure (RVP) measurement performed with contact lens dynamometry (CLD) and with the new IOPstim. METHODS: In this cross-sectional study, we included 36 patients with primary open angle glaucoma with a median age (Q25; Q75) of 74 (64; 77) years (m/f = 18/18), baseline intraocular pressure (IOP): 13.9 (12.2; 15.1) mmHg. Median mean defect: - 5.8 (- 11.9; - 2.6) db. Principle of the IOPstim: an empty balloon with a diameter of 8 mm is positioned on the eye, laterally of the limbus. Under observation of the central retinal vein (CRV), the examiner inflates the balloon. As soon as the CRV starts pulsation, the inflation is stopped and the IOP is measured, equaling the RVP at this moment. In the CLD, the pulsation of the CRV is observed with a contact lens. The RVP is calculated from the attachment force applied when pulsation appears. COURSE OF EXAMINATIONS: Three single measurements of RVP in quick succession with both methods. The sequence of the two methods was randomized. The means of the three RVP measurements were compared. RESULTS: Pressures in mmHg. RVP: IOPstim: 19.4 ± 5.4 (mean ± SD), CLD: 20.3 ± 5.9. Range of three single measurements: IOPstim: 2.9 ± 1.5, CLD: 2.2 ± 1.1. The differences were RVPIOPstim - RVPCLD = - 0.94 ± 1.15, and approximately normally distributed. Bland-Altman analysis: only one data point was 0.5 mmHg higher than the upper line of agreement. The confidence interval of this line was 0.65 mmHg. Concordance correlation coefficient according to Lin (CCC): 0.96. Intraclass correlation coefficient: both methods, 0.94. CONCLUSION: In both methods, the range of the single measurements may be taken as a sign of good reliability, the CCC of 0.96 as a sign of a very good agreement. At the mean, the IOPstim RVP values were 1 mmHg lower than those obtained with the CLD. This difference may be due to the different directions of the prevailing force vectors induced by the instruments. The IOPstim seems applicable in glaucoma diagnostics.

The retinal venous pressure at different levels of airway pressure measured with a new method.

PURPOSE: This study is to investigate the increase in retinal venous pressure (RVP) induced by a stepwise increase in airway pressure (AirP) using the new IOPstim method, which is designed to artificially increase the intraocular pressure (IOP) and thus to stimulate vascular pulsation. METHODS: Twenty-eight healthy subjects were examined in the left eye. The RVP was measured at baseline and at four different levels of AirP (10, 20, 30, and 40 mmHg) using the new IOPstim method: a half balloon of 8 mm diameter is inflated laterally to the cornea under observation of the central retinal vein. As soon as the vein pulsates at a certain AirP level, the IOP is measured with a commercially available tonometer, which then corresponds to the RVP. RESULTS: Spontaneous venous pulsation was observed in all study participants. The mean RVP values at baseline and at the AirP levels of 10, 20, 30, and 40 mmHg were 17.6 ± 2.8 mmHg; 20.1 ± 3.0 mmHg; 22.1 ± 3.5 mmHg; 24.3 ± 3.7 mmHg, and 26.6 ± 4.2 mmHg, respectively. The mean RVP values of each AirP level were statistically significantly different from each other in pairwise comparison. In a linear mixed model, the effect of AirP on RVP was highly significant (p < 0.001). In the model, a 10-mmHg increase in AirP resulted in a linear increase in RVP of 2.2 mmHg. CONCLUSION: An increase in AirP was accompanied by a linear increase in RVP. The influence of AirP on RVP, and thus on retinal perfusion pressure during the Valsalva maneuver, is less than was assumed based on previous studies in which contact lens dynamometry was used.

Measurement of the retinal venous pressure with a new instrument in healthy subjects.

BACKGROUND: The retinal venous pressure (RVP) is a determining factor for the blood supply of the retina as well as the optic nerve head and until recently has been measured by contact lens dynamometry (CLD). A new method has been developed, potentially offering better acceptance. The applicability and the results of both methods were compared. METHODS: The type of this study is cross sectional. The subjects were 36 healthy volunteers, age 26 ± 5 years (mean ± s). Tonometry: rebound tonometer (RT) (iCare). The measurements were performed during an increase in airway pressure of 20 mmHg (Valsalva manoeuvre). Principle of RVP measurement: the central retinal vein (CRV) is observed during an increase of intraocular pressure (IOP) and at the start of pulsation, which corresponds with the RVP. Two different instruments for the IOP enhancement where used: contact lens dynamometry and the new instrument, IOPstim. PRINCIPLE: a deflated balloon of 8 mm diameter-placed on the sclera laterally of the cornea-is filled with air. As soon as a venous pulsation occurs, filling is stopped and the IOP is measured, equalling the RVP. Examination procedure: randomization of the sequence: CLD or IOPstim, IOP, mydriasis, IOP three single measurements (SM) of the IOP with RT or of the pressure increase with CLD at an airway pressure of 20 mmHg, 5 min break, IOP, and three SM using the second method at equal pressure (20 mmHg). RESULTS: Spontaneous pulsation of the CRV was present in all 36 subjects. Pressures are given in mmHg. IOP in mydriasis 15.6 ± 3.3 (m ± s). Median RVP (MRVP)) of the three SM: CLD/IOPstim, 37.7 ± 5.2/24.7 ± 4.8 (t test: p < 0.001). Range of SM: 3.2 ± 1.8/2.9 ± 1.3 (t test: p = 0.36). Intraclass correlation coefficient (ICC) of SM: 0.88/0.83. ANOVA in SM: p = 0.48/0.08. MRVP CLD minus MRVP IOPstim: 13.0 ± 5.6. Ratio MRVP CLD/MRVP IOPstim: 1.56 ± 3.1. Cooperation and agreeability were slightly better with the IOPstim. CONCLUSION: This first study with the IOPstim in humans was deliberately performed in healthy volunteers using Valsalva conditions. As demonstrated by ICC and ANOVA, reproducible SM can be obtained by both methods and the range of the SM does not differ greatly. The higher MRVP in CLD could be explained by the different directions of the force vectors.

The Oxygen Saturation in the Retinal Vessels of Patients with Diabetes Mellitus - The Search for Determinants. / Die Sauerstoffsättigung in den Gefäßen der Netzhaut von Patienten mit Diabetes mellitus ­ die Suche nach Einflussfaktoren.

INTRODUCTION: Oxygen saturation in retinal vessels can be non-invasively measured by a new method. It is known that oxygen extraction is lowered in diabetic retinopathy. In the cross-sectional study presented here, it has been investigated whether diabetes-specific changes and typical accompanying diseases could influence the measurements in oximetry. METHODS: During a time span of seven months, 237 diabetics were included who came to our clinic for an intravitreal injection, who met the inclusion criteria, who showed no exclusion criteria and gave written consent. 203 eyes of 203 patients were evaluated. The oxygen saturation (SO2) was measured in digitally stored fundus images taken with a fundus camera (Zeiss 450 FF). In its illumination beam, a filter was inserted with two transmission maxima at 584 nm and 610 nm (bandwidth 10 nm). With the program "Oximetry" (Imedos Systems, Jena, Germany), the venous and the arterial SO2 were measured. The values were stored in a spreadsheet. Diabetes related data, clinical parameters and accompanying diseases were documented in the predefined scheme. RESULTS: In the whole patient sample, the venous oxygen saturation (vSO2) was 69 ± 12%, the arterial saturation (aSO2) 99 ± 5% and the arteriovenous difference 31 ± 9%. A statistically significant association could not be found between the measurement values of oximetry and age, duration of diabetes and HbA1c (Kruskal-Wallis ANOVA: p > 0.05). The differences in oximetry values between units of analysis (UOA) e.g. hypertension and non units of analysis (NOA) were analysed. Descriptive testing showed significant differences in vSO2% in the following units of analysis: allergies n = 47: UOA vs. NUOA: 64 vs. 69 (t test: p < 0.02); sartan therapy n = 46: UOA vs. NUOA: 64 vs. 70 (p = 0.003); state after intravitreal injections n = 144: 68 vs. 71 (p = 0.02). Oxygen extraction from the retinal capillaries was improved in patients who had injections with VEGF inhibitors. An improvement in oxygen extraction is also seen in patients with allergies and hypertension in comparison to those without these units of analysis. CONCLUSION: The clinically observed improvement in the retinal state situation after intravitreal injections with VEGF inhibitors may be seen in association with the improved oxygen extraction. It seems reasonable to study whether a switch to sartans in the therapy of hypertension may improve retinal function.

The Distribution of Retinal Venous Pressure and Intraocular Pressure Differs Significantly in Patients with Primary Open-Angle Glaucoma.

INTRODUCTION: Until now, venous pressure within the eye has widely been equated with intraocular pressure (IOP). Measurements with dynamometers calibrated in instrument units or in force showed that the retinal venous pressure (RVP) may be higher than the IOP in glaucoma patients. In this study, the RVP was measured with a contact lens dynamometer calibrated in mmHg. METHODS: Study type: cross-sectional. SUBJECTS: Fifty consecutive patients with primary open-angle glaucoma (POAG) who underwent diurnal curve measurement under medication. Age: 69 ± 8 years. Measurement of RVP: contact lens dynamometry. IOP measurement: dynamic contour tonometry. RESULTS: Pressures are given in mmHg. In all 50 patients, the IOP was 15.9 (13.6; 17.1) [median (Q1; Q3)], and the RVP was 17.4 (14.8; 27.2). The distribution of the IOP was normal and that of the RVP was right skewed. In the subgroup of 34 patients with spontaneous pulsation of the central retinal vein (SVP), the IOP and therefore, by definition, the RVP was 16.5 (13.7; 17.4). In the subgroup of 16 patients without SVP, the IOP was 14.8 (13.3; 16.4), and the RVP was 31.3 (26.2; 38.8) (p ≤ 0.001). In systemic treatment, the prescribed drugs were (the number of patients is given in parentheses): ACE inhibitors (20), ß-blockers (17), angiotensin II-receptor blockers (13), calcium channel blockers (12), diuretics (7). No difference in RVP was observed between patients receiving these drugs and not receiving them, except in the ß-blocker group. Here, the 17 patients with systemic ß-blockers had a median RVP of 15.6 mmHg and without 20.2 mmHg (p = 0.003). In the 16 patients with a higher RVP than IOP, only one patient received a systemic ß-blocker. The median IOP was 15.7 mmHg with systemic ß-blockers and 16.1 mmHg without (p = 0.85). CONCLUSION: In a subgroup of 16 of the 50 patients studied, the RVP was greater than the IOP by a highly statistically and clinically significant degree. According to the widely accepted thinking on the pathophysiology of retinal and optic nerve head circulation, the blood flow in these tissues may be much more compromised in this group of patients than has been assumed. They may be identified by a missing SVP. Topical and systemic medications showed no statistically significant influence on the RVP, except for the systemic ß-blockers, in which the RVP was lower by 4.6 mmHg than for the patients who did not receive these drugs (p = 0.003).

The retinal venous pressure at different levels of airway pressure.

PURPOSE: To investigate retinal venous pressure (RVP) as a function of airway pressure (AirP) during the Valsalva maneuver (VM) in human subjects. METHODS: Forty-three healthy volunteers (age, 22.0 (2.3) years) (median and interquartile range) were investigated using the following instruments: dynamic contour tonometer, contact lens dynamometer (CLD), and aneroid manometer. The following measurements were performed in their left eyes: tonometry and dynamometry during VM at different levels of airway pressure (AirP = 0, 10, 20, 30, and 40 mmHg). RESULTS: The median RVP during spontaneous breathing (AirP = 0) was 19.7 (6.4) (median in mmHg (interquartile range)) and the intraocular pressure (IOP) in mydriasis was 16.3 (3.1) mmHg. Spontaneous pulsation occurred in 58.1% of the subjects. RVP increased nonlinearly. The coefficient of variation of four individual measurements of RVP at each pressure level averaged 8.1 (7.6) %. At different AirP levels of 10, 20, 30, and 40 mmHg, the following RVPs were measured: 29.6 (12.6); 34.2 (12.8); 38.0 (10.5); and 40.3 (11.0), respectively. The rise of RVP (Δ RVP) during VM was significantly higher than that of Δ IOP (p < 0.0001, Wilcoxon test). Δ RVP between 0 and 40 mmHg AirP was 20.6 mmHg and Δ IOP 1.5 mmHg. The steepest slope of the RVP/AirP curve was observed at the first step from 0 to 10 mmHg of AirP (∆ RVP = 9.9 mmHg). CONCLUSION: A nonlinear relationship between RVP and AirP was found during VM. Small rises in AirP increase the RVP and affect retinal circulation.

Central retinal venous pressure is higher than intraocular pressure during amateur trumpet playing.

BACKGROUND: It has been shown in the literature that the Valsalva manoeuvre influences ocular perfusion by changing intraocular pressure and central retinal venous pressure (CRVP). High-resistance wind instrument (HRWI) playing is a common situation resembling a Valsalva manoeuvre. The aim of this investigation was to explore the influence of amateur trumpet playing on CRVP. METHODS: The left eyes of 20 healthy non-professional trumpet players (median age 26, range 19-52 years; 17 males, 3 females) were included in this investigation. Subjects, sitting at a slit lamp, were asked to play the tone b' flat with their own mouthpiece on the same trumpet for at least 30 s with moderate loudness. The following data were obtained: intraocular pressure (IOP) by applanation tonometry before and during playing, CRVP by contact lens dynamometry before and during playing, airway pressure (AirP) using a pressure sensor during playing and blood pressure and heart rate using the common cuff method before and during playing. RESULTS: The results are presented as the medians before vs during playing: a calculated mean ophthalmic artery pressure of 66 vs 72 mmHg, heart rate of 76 vs 82 beats per minute, airway pressure of 0 vs 17 mmHg, IOP 12 vs 13 mmHg and CRVP of 24 vs 55 mmHg (Wilcoxon test: p = 0.00009), respectively. A correlation between the CRVP during playing and the height of the spontaneous CRVP is noted (Spearman rank correlation coefficient: ρ = 0.68). CONCLUSIONS: Amateur trumpet playing increases CRVP, airway pressure and IOP. The increase in CRVP is greater than that of the intraocular pressure. The increase in CRVP seems to be more important for retinal perfusion changes during trumpet playing than the increase of IOP. It can be hypothesised that high airway pressure during playing may cause a permanent increase in CRVP, at least in a subgroup of trumpet players.

Diameter of retinal vessels in patients with diabetic macular edema is not altered by intravitreal ranibizumab (lucentis).

PURPOSE: To investigate the effect(s) of intravitreally injected ranibizumab on retinal vessel diameter in patients with diabetic macular edema. METHODS: Participants of this prospective study were 14 men and 16 women (30 eyes) aged 60 ± 11 years (mean ± standard deviation), all with clinically significant diabetic macular edema. Treatment comprised 3 intravitreal injections of ranibizumab given at 4-week intervals. Examinations were conducted before the first (baseline), before the second (Month 1), before the third (Month 2) injections, and 3 months after baseline (Month 3). Measured parameters included systemic blood pressure, static retinal vessel analysis (central retinal artery equivalent and central retinal vein equivalent), and dynamic retinal vessel analysis, as measured by the change in vessel diameter in response to flicker stimulation during three measurement cycles. Flicker stimulation was accomplished using a 50-second baseline recording, followed by an online measurement during 20-second flicker stimulation and 80-second online measurements in both arteriolar and venular vessel segments. RESULTS: Static retinal vessel analysis showed a reduction of central retinal artery equivalent from 186.25 ± 51.40 µm (baseline) to 173.20 ± 22.2 µm (Month 1), to 174.30 ± 27.30 µm (Month 2), and to 170.56 ± 22.89 µm (Month 3), none of which was statistically significant (P = 0.23, 0.12, and 0.14, respectively). Central retinal vein equivalent was reduced from 216.21 ± 25.0 µm (baseline) to 214.48 ± 25.4 µm (Month 1), to 214.80 ± 24.30 µm (Month 2), and to 211.41 ± 24.30 µm (Month 3), revealing no statistically significant differences between examination time points (P = 0.54, 0.06, and 0.24, respectively). Dynamic vessel analysis yielded a mean retinal arterial diameter change of +1.47% ± 2.3 (baseline), +1.91% ± 2.5 (Month 1), +1.76% ± 2.2 (Month 2), and +1.66% ± 2.1 (Month 3), none of which showed statistically significant differences (P = 0.32, 0.49, and 0.70, respectively). Mean retinal venous diameter changes were +3.15% ± 1.7 (baseline), +3.7% ± 2.3 (Month 1), +4.0% ± 2.0 (Month 2), and +4.95% ± 1.9 (Month 3), none of which showed statistically significant differences (P = 0.12, 0.17, and 0.14, respectively). Central retinal thickness, as measured by spectral domain optical coherence tomography, decreased significantly from 435.2 ± 131.8 µm (baseline) to 372.3 ± 142.8 µm (Month 3), P = 0.01. Regression analysis of arteriolar and venular diameters indicated that there was no significant correlation between these 2 parameters (r = 0.053; P = 0.835 and r = 0.06; P = 0.817, respectively). Also, no significant correlation was observed between the difference in the central retinal thickness and change in arteriolar or venular dilatation (r = 0.291, P = 0.241 and r = 0.06, P = 0.435, respectively). CONCLUSION: Intravitreally applied ranibizumab did not significantly affect retinal vessel diameter in patients with diabetic macular edema. Decline in the central foveal thickness after ranibizumab therapy, as measured by spectral domain optical coherence tomography, was not linked to any change in retinal vessel diameter or dilatatory response, neither for arterioles nor venules.

Modulation of Human Intraocular Pressure Using a Pneumatic System.

Purpose: To technically validate a novel pneumatically based system and method for modulation of intraocular pressure (IOP) and to test its application in the human eye. Special attention was paid to the applicability of the pneumatically driven balloon, which realizes the modulation of the IOP through its contact with the conjunctiva. Methods: A force sensor as key component of a customized measurement setup was used to check the applied pressure through the balloon. The IOP of 10 healthy subjects (4 female, 6 male, aged 28.8 ± 6.64 years) was modulated and increased linearly to at least 40 mmHg. At this point, the pressure inside the balloon was kept constant for 2 minutes, with IOP measurements taken every 40 seconds using a rebound tonometer. Results: The technical setup led to an IOP decrease of 0.71 mmHg within 2 minutes at an operating point of 40 mmHg. For all subjects, the IOP could be increased up to 42.8 ± 3.6 mmHg, whereby a mean pressure decrease of 2.4 mmHg/min was determined, which seems to be caused mainly by physiological processes. Conclusions: With the new pneumatically based setup, a targeted modulation in terms of level and constancy of the IOP can be realized. Translational Relevance: Additional and, compared with the technique according to Löw, a more precise and more constant methodology for the modulation of the IOP, can significantly simplify the determination of retinal vessel pressures for clinical application. It is suitable for practical questions concerning an enhanced retinal venous pressure.

Retinal venous pressure is higher than the airway pressure and the intraocular pressure during the Valsalva manoeuvre.

PURPOSE: The aims of this prospective experimental study were to explore the influence of the Valsalva manoeuvre (VM) on retinal venous pressure (RVP) in human volunteers in a university setting and to establish correlations for RVP with the increase in airway pressure (∆AirP) and in intraocular pressure (∆IOP). METHODS: In total, 31 healthy young volunteers (age: 24 ± 1.7 years) were investigated. The instruments used included a dynamic contour tonometer, a contact lens dynamometer (Imedos) and an electronic pressure transducer for measuring airway pressure. The following measurements were successively performed in left eyes: tonometry, dynamometry, repeated simultaneous dynamometry and airway pressure measurement during the VM and tonometry during the VM. The pressures obtained during the VM were determined at 10, 20 and 30 seconds after onset of the VM by linear interpolation. RESULTS: The pressures (in mmHg) at baseline and during the VM (median and range with outliers) were as follows: ∆AirP: 10 seconds: 10.0 (7.5); 20 seconds: 12.5 (11.0); and 30 seconds: 11.0 (10.0); and RVP: Start: 17.1 (2.4); 10 seconds: 26.0 (7.5); 20 seconds: 25.0 (6.5); and 30 seconds: 24.0 (6.0). During the VM, the RVP was significantly increased compared with the ∆AirP (p = 0.0017). The IOP during the VM was 13.5 (2.7), and the increase in IOP (∆IOP) was 0.8 (5.6). CONCLUSION: During the VM, the RVP was increased compared with the ∆AirP. The increase in RVP (∆RVP) was significantly greater than the ∆IOP. During the VM, the calculated retinal perfusion pressure may be more strongly reduced by the ∆RVP than by the ∆IOP. These properties may influence retinal and optic nerve head pathophysiology.

Assessment of Optic Nerve Head Pallor in Primary Open-Angle Glaucoma Patients and Healthy Subjects.

PURPOSE: To investigate optic nerve head (ONH) pallor quantitatively in patients with primary open-angle glaucoma (POAG) and in healthy subjects, and to examine the relationship to mean deviation in perimetry (MD), cup-disk ratio (CDR), and diameters of retinal vessels. METHODS: A total of 89 POAG patients (67.6 ± 11.1 years) and 48 healthy subjects (63.3 ± 14 years) were included. A dual-bandpass transmission filter was introduced in the illumination path of the fundus camera of the Dynamic Vessel Analyzer (Imedos Systems UG) and two monochromatic images at different wavelenghts (548 ± 10 and 610 ± 10 nm) were recorded simultaneously. ONH pallor was defined as the quotient of light reflection in both spectral channels. Pallor values were averaged over four fields which were positioned on the ONH. The mean of these measurements was calculated. In 47 of 89 POAG patients diameters of retinal vessels were determined peripapillary. RESULTS: In POAG, the ONH showed a significantly higher pallor value compared to healthy subjects (82.34 ± 19.28 vs. 62.67 ± 10.41, p < 0.001). ONH pallor was correlated to indicators used to estimate disease severity: MD (r = -0.565, p < 0.001) and CDR (r = 0.561, p < 0.001). The pallor value was associated to diameters of retinal arterioles (r = -0.313, p = 0.032) and venules (r = -0.397, p = 0.006). CONCLUSIONS: Pallor determined by this method was higher in POAG patients than in healthy subjects and increased in patients with advanced disease. ONH pallor might result from a reduced blood perfusion of the ONH or tissue atrophy accompanied by vessel obliteration in POAG. By measuring ONH pallor additional diagnostic information about the vitality of the neuroretinal rim might be gained in glaucoma patients.

The short-term effect of flavonoid-rich dark chocolate on retinal vessel diameter in glaucoma patients and age-matched controls.

PURPOSE: To investigate the effect of flavonoid-rich dark chocolate and non-flavonoid-rich white chocolate on retinal vessel diameter in glaucoma patients and age-matched controls. METHODS: Thirty glaucoma patients and 30 age-matched subjects were assigned to dark or white chocolate by randomization with forced equal distribution. The number in each of the four groups was 15. Measured parameters included systemic blood pressure (BP), blood glucose levels, static retinal vessel analysis, as measured by central retinal artery equivalent (CRAE) (which relates to the diameter of the central retinal artery), central retinal vein equivalent (CRVE) (which relates to the diameter of central retinal vein) and the arterio-venous ratio (AVR), which represents the CRAE/CRVE ratio, dynamic retinal vessel analysis as measured by the change in vessel diameter in response to flicker light stimulation. Three recording cycles from each were averaged. RESULTS: Blood pressure parameters (systolic BP, diastolic BP and pulse), IOP and blood glucose levels did not differ significantly between both groups before and after consumption of white or dark chocolate. Static vessel analysis did not show any significant changes in CRAE, CRVE or AVR before and after dark or white chocolate in both groups (p > 0.05). Mean dilatation of the venules in the control group was 3.2 ± 0.9 % before dark chocolate and 4.2 ± 1.4 % after dark chocolate intake, which was statistically significantly different (p = 0.01). Mean dilatation of the arterioles in the control group was 2.8 ± 1.8 % before dark chocolate and 3.5 ± 1.8 % after dark chocolate intake with a trend to statistical significance (p = 0.14), but not reaching the significance level. Mean diameter changes in the glaucoma group did not show any significant differences after dark chocolate consumption. CONCLUSION: The present study showed a significant improvement of venous vasodilatation 2 hr after dark chocolate intake in the control group, but not in the glaucoma group. This effect might be indicative of an increased bioavailability of nitric oxide (NO) after dark chocolate consumption. The lack of finding a significant venous response after dark chocolate in the glaucoma group might be related to the already impaired endothelial function in these patients.

Central retinal venous pulsation pressure in different stages of primary open-angle glaucoma.

BACKGROUND: To evaluate the central retinal venous pulsation pressure (CRVPP) in patients with intraocular pressure (IOP)-controlled early, moderate and advanced open-angle glaucoma and a healthy control group. METHODS: CRVPP was measured with a contact lens dynamometer calibrated in mm Hg (Meditron GmbH, Voelklingen, Germany) in 34 patients with IOP-controlled open-angle glaucoma who were selected consecutively and according to the stage of their visual fields and 27 age-matched healthy controls. If a spontaneous venous pulsation was seen, CRVPP was considered to be equal to IOP. Visual fields were tested with the Humphrey 30-2 SST programme. The ocular perfusion pressure was conventionally calculated as OPP1=2/3MAP - IOP (MAP=systemic mean arterial blood pressure) and, using the measured CRVPP in the formula, as OPP2=2/3MAP - CRVPP. Statistical analysis was performed using the Kruskal-Wallis and the Mann-Whitney U test. RESULTS: Median CRVPP was 14.0 mm Hg (IQR 12.0-16.0) in controls, 15.0 mm Hg (IQR 14.0-17.0) in early, 38.9 mm Hg (IQR 29.9-48.4) in moderate and 34.6 mm Hg (IQR 23.9-51.0) in advanced glaucoma cases. The conventionally calculated OPP1 was 49.8 mm Hg (IQR 42.7-57.6) for controls, 56.9 mm Hg (IQR 55.3-58.8) for early, 56.6 mm Hg (IQR 51.2-64.4) for moderate and 59.3 mm Hg (IQR 53.9-61.6) for advanced cases. OPP2 was equal to OPP1 in the control group, 56.1 mm Hg (IQR 54.5-57.9) in early, 25.1 mm Hg (IQR 15.7-38.6) and 34.2 mm Hg (IQR 20.4-47.5) in moderate and advanced cases. This difference was statistically significant for moderate (OPP2 lower; p=0.003) and advanced (OPP2 lower; p=0.002) cases. CONCLUSIONS: In more advanced cases of glaucoma, CRVPP seems to be much higher than previously thought. This might further compromise the perfusion pressure in the prelaminar region of the optic nerve head and be of clinical importance, especially in IOP-controlled more advanced cases. This should be considered as a possible risk factor for progression. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT01503996.

Ocular perfusion pressure in glaucoma.

This review article discusses the relationship between ocular perfusion pressure and glaucoma, including its definition, factors that influence its calculation and epidemiological studies investigating the influence of ocular perfusion pressure on the prevalence, incidence and progression of glaucoma. We also list the possible mechanisms behind this association, and discuss whether it is secondary to changes in intraocular pressure, blood pressure or both. Finally, we describe the circadian variation of ocular perfusion pressure and the effects of systemic and topical medications on it. We believe that the balance between IOP and BP, influenced by the autoregulatory capacity of the eye, is part of what determines whether an individual will develop optic nerve damage. However, prospective, longitudinal studies are needed to better define the role of ocular perfusion pressure in the development and progression of glaucoma.

Enhanced pressure in the central retinal vein decreases the perfusion pressure in the prelaminar region of the optic nerve head.

PURPOSE: The pressure in the central retinal vein (CRVP) has been shown to be higher in glaucoma patients than in controls. Until now, these measurements have been performed in arbitrary units or in units of ophthalmodynamometric force. In our study, a contact lens dynamometer, calibrated in mm Hg, was used to calculate the retinal perfusion pressure. METHODS: A total of 27 patients with primary open angle glaucoma (POAG) and 27 healthy control subjects were included in the study. The IOP measurement included Goldmann applanation tonometry, whereas the pressure enhancement measurement consisted of contact lens dynamometry. results: the pressures are given in mm hg, and are expressed as the mean ± SD for the control subjects versus the POAG patients: IOP 14.4 ± 2.7 vs. 15.4 ± 2.9, systolic blood pressure 141 ± 20.1 vs. 153 ± 16.5 (P = 0.013), central retinal vein threshold pressure (CRVTP) 11.9 ± 3.8 vs. 16.8 ± 5.0, CRVP 15.0 ± 2.7 vs. 17.9 ± 4.2, and retinal perfusion pressure (PPret) standard 84 ± 12.2 vs. 94 ± 9.1 and new 83 ± 12.2 vs. 91 ± 9.6. The differences in PPret between using the new versus the standard method are 0.55 ± 1.33 vs. -2.5 ± 3.89 (P = 0.041 and P = 0.002, respectively). The PPret was at least 5.0 mm Hg lower in 5 of the 27 POAG patients when the new calculation method was used. CONCLUSIONS: The perfusion pressure in the retina and prelaminar region of the optic nerve head (ONH) may be lower than expected because the CRVP may be higher. The pressure measurement in the central retinal vein may be a step toward a better understanding of ONH pathophysiology.

The effect of caffeine on retinal vessel diameter in young healthy subjects.

PURPOSE: To investigate the effect of caffeine on retinal vessel diameter before and during flicker light stimulation in young healthy subjects. METHODS: Seventeen healthy subjects (mean age: 29.6 ± 3.73 years, range: 22-35 years) were included in this study. The diameter of retinal vessels was measured continuously with the retinal vessel analyzer (RVA) before and 1 hr after 200 mg oral caffeine intake. After baseline assessment, a green luminance flicker of 20-second duration was applied to stimulate retinal activity. The diameter of a segment of an arteriole and of a venule were measured during stimulation and 80 second after cessation of the stimulus. Flicker stimulation and 80-second measurement interval were carried out three times. Blood pressure parameters, systemic mean arterial pressure (MAP), ocular perfusion pressure (OPP) and intraocular pressure (IOP) were obtained before and after oral caffeine intake. RESULTS: The mean diameter of the arterioles at baseline before caffeine intake was 123.30 ± 14.0 µm (arithmetic mean standard deviation) and after caffeine 117.30 ± 13.0 µm which was significantly different (p=0.004). The mean diameter of the venules at baseline before caffeine intake was 147.60 ± 19.5 µm and after caffeine 137.73 ± 19.9 µm which was significantly different (p = 0.005). The mean diameter of the arterioles during flicker light stimulation before caffeine intake was 126.65 ± 13.24 µm and after caffeine intake 121.59 ± 12.12 µm (p = 0.012). The mean diameter of the venules during flicker light stimulation before caffeine intake was 151.87 ± 18.63 µm and after caffeine intake was 145.14 ± 19.82 µm (p = 0.027). The flicker response of the arterioles increased from 2.8% before caffeine to 3.8% after caffeine intake (p = 0.010). The flicker response of the venules increased from 3.4% before caffeine to 5.5% after caffeine intake (p = 0.0001). Baseline diameters and diameters during flicker light stimulation after caffeine intake showed a significant negative correlation to the MAP for the arterioles (baseline: r = -0.338, p = 0.049 and flicker: r = -0.345, p = 0.046) and the venules (baseline: r = -0.496, p = 0.003 and flicker: r =-0.479, p = 0.004). CONCLUSIONS: The present study showed a significant vasoconstrictory response of the retinal vessels 1 hr after caffeine intake in young healthy subjects. Retinal vessel diameter changes were negatively correlated with MAP after caffeine consumption. These effects seem to be elicited by an autoregulatory response of the retinal vessels to the increased blood pressure changes after caffeine.

Contact lens dynamometry: the influence of age.

PURPOSE: To examine the influence of age on systolic (systOAP) and diastolic (diastOAP) blood pressure in the ophthalmic artery (OA) measured by a new contact lens dynamometer (CLD). METHODS: In a prospective cross-sectional clinical trial, 106 eyes of 106 patients (58 women, 48 men) were examined. A nearly uniform age distribution was achieved by recruiting subjects in seven age groups, with at least 12 in each decade. Blood pressure in the OA was measured with a new CLD. Arterial blood pressure at the upper arm was measured by cuff, according to the Riva-Rocci (RR) METHOD: Main outcome measures were: SystOAP and diastOAP in the OA and systolic (systRR) and diastolic (diastRR) pressures in the subclavian artery. RESULTS: The blood pressures showed the following linear regression equations in association with age: systRR (mm Hg) = 115 + 0.45 × age (years) (R = 0.50; P < 0.00001); diastRR (mm Hg) = 72 + 0.28 × age (years) (R = 0.42; P < 0.00001); systOAP (mm Hg) = 61 + 0.93 × age (years) (R = 0.74; P < 0.0001); and diastOAP (mm Hg) = 44 + 0.37 × age (years) (R = 0.57; P < 0.0001). CONCLUSIONS: The relative slopes of the regression lines relating age to diastolic and systolic pressures are steeper in the ophthalmic than in the subclavian artery, indicating that the pressures in the ophthalmic artery increase faster with age than do the associated pressures in the subclavian artery, as measured by the standard sphygmomanometry. This phenomenon may be explained by progressive stiffening of the walls in the carotid and ophthalmic arteries. The effect of age should be taken into account whenever interpreting ophthalmodynamometric measurements for clinical diagnostic purposes.