Establishing the Calibration Curve of a Compressive Ophthalmodynamometry Device.

The relationship between externally applied force and intraocular pressure was determined using an ex-vivo porcine eye model (N=9). Eyes were indented through the sclera with a convex ophthalmodynamometry head (ODM). Intraocular pressure and ophthalmodynamometric force were simultaneously recorded to establish a calibration curve of this indenter head. A calibration coefficient of 0.140 ± 0.009 mmHg/mN was established and was shown to be highly linear (r = 0.998 ± 0.002). Repeat application of ODM resulted in a 0.010 ± 0.002 mmHg/mN increase to the calibration coefficient.Clinical Relevance- ODM has been highlighted as a potential method of non-invasively estimating intracranial pressure. This study provides relevant data for the practical performance of ODM with similar compressive devices.

Empirical retinal venous pulse wave velocity using modified photoplethysmography.

OBJECTIVE: Using the novel imaging method of high-speed modified photoplethysmography we measured the retinal venous pulse wave velocity in a single case. RESULTS: A healthy 30-year-old subject underwent high-speed modified photoplethysmography (120 frames per second) with simultaneous ophthalmodynamometry at 26 Meditron units. A video of the optic nerve was analyzed using custom software. A harmonic regression model was fitted to each pixel in the time series and used to quantify the retinal vascular pulse wave parameters. Retinal venous pulsation at the optic disc was observed as a complex dynamic wall motion, whereas contraction commenced at a point in the vein at the center of the optic disc, and progressed centrifugally. The empirically estimated retinal venous pulse wave velocity at this segment was approximately 22.24694 mm/s. This measurement provides an estimate for future studies in the field.

Non-Invasive Measurement of Intracranial Pressure Through Application of Venous Ophthalmodynamometry.

Non-invasive intracranial pressure (ICP) monitoring is possible using venous ophthalmodynamometry to observe a pulsation in retinal blood vessels when intraocular pressure (IOP) exceeds ICP. Here, we identify features in the eye - optic disc and retinal blood vessel locations - and identify pulsation in large retinal blood vessels. The relationship between force and the magnitude of pulsation is used to estimate ICP when force is applied to the eye to gradually increase IOP over time. This approach yields 77% accuracy in automatically observing vessel pulsation.Clinical Relevance - Non-invasive ICP monitoring is desirable to improve patient outcome by reducing potential trauma and complications associated with invasive assessment with intracranial sensors or lumbar puncture.

Corneal Biomechanical Changes Caused by Acute Elevation of IOP in Eyes with and without Glaucoma.

SIGNIFICANCE: Although corneal biomechanical parameters are well linked with glaucoma, their clinical utility has not yet been fully elucidated. This study was designed to provide unique evidence about the dynamic nature of corneal biomechanical parameters and their potential prognostic ability for glaucoma. PURPOSE: This study aimed to evaluate the effect of acute intraocular pressure (IOP) elevation on corneal hysteresis (CH) and corneal resistance factor (CRF) and the associations of these biomechanical parameters with glaucomatous disease. METHODS: Subjects participating in a prospective, longitudinal glaucoma research study had CH and CRF measured before and during ophthalmodynamometry during visits in the years 2011 to 2012. All participants were diagnosed with primary open-angle glaucoma, ocular hypertension, glaucoma suspect, or normal eyes and had a minimum of 3 years of study participation with at least five reliable visual field (VF) tests. Changes in CH, CRF, and IOP induced by ophthalmodynamometry were compared between diagnostic groups and evaluated for relationships with existing and future glaucomatous VF loss. RESULTS: In 248 eyes of 248 subjects followed up for 7.7 ± 2.3 years, ophthalmodynamometry induced a mean IOP increase from 15.1 to 29.9 mmHg, causing a mean 34 ± 28% increase in CRF and 21 ± 25% decrease in CH. Magnitude of CH change did not differ between diagnostic groups or between eyes that did (n = 20) and did not (n = 95) develop new VF loss during the study period, nor was it related to rate of future VF progression. CONCLUSIONS: Ophthalmodynamometry-induced IOP elevation resulted in significant acute changes in CH and CRF in this study; this suggests accounting for IOP may be important in clinical interpretation of these parameters. However, because the degree of CH change was not related to glaucoma or its progression, acute changes in CH and CRF do not seem to have a prognostic value for glaucoma.

Review of non-invasive intracranial pressure measurement techniques for ophthalmology applications.

Assessment and monitoring of intracranial pressure (ICP) are important in the management of traumatic brain injury and other cerebral pathologies. In the eye, ICP elevation and depression both correlate with optic neuropathies, the former because of papilledema and the latter related to glaucoma. While the relationship between ICP elevation and papilledema is well established, the relationship between low ICP and glaucoma is still poorly understood. So far, ICP monitoring is performed invasively, but this entails risks including infection, spurring the study of non-invasive alternatives. We review 11 methods of non-invasive estimation of ICP including correlation to optic nerve sheath diameter, intraocular pressure, ophthalmodynamometry and two-depth transcranial Doppler of the ophthalmic artery. While none of these methods can fully replace invasive techniques, certain measures show great potential for specific applications. Although only used in small studies to date, a MRI based method known as MR-ICP, appears to be the best non-invasive technique for estimating ICP, with two-depth transcranial ultrasound and ophthalmodynamometry showing potential as well.

In Vivo Three-Dimensional Lamina Cribrosa Strains in Healthy, Ocular Hypertensive, and Glaucoma Eyes Following Acute Intraocular Pressure Elevation.

Purpose: To compare in vivo lamina cribrosa (LC) strains (deformations) following acute IOP elevation in healthy, glaucoma, and ocular hypertensive subjects. Methods: There were 20 healthy, 20 high-tension primary open-angle glaucoma (POAG), 16 primary angle-closure glaucoma (PACG), and 20 ocular hypertensive (OHT; with normal visual fields) eyes studied. For each test eye, the optic nerve head was imaged three times (at baseline IOP, following an acute elevation of IOP to approximately 35 then 45 mm Hg using an ophthalmodynamomter) using optical coherence tomography (OCT). A three-dimensional (3D) strain-mapping algorithm was applied to both sets of baseline and IOP-elevated OCT volumes to extract IOP-induced 3D strains. Octant-wise LC strains were also extracted to study the pattern of local deformation. Results: The average LC strain in OHT subjects (3.96%) was significantly lower than that measured in healthy subjects (6.81%; P < 0.05). On average, POAG subjects experienced higher strain than the PACG subjects (4.05%), healthy subjects experienced higher strains than the POAG and PACG subjects, but these difference were not statistically significant. Local LC deformations showed lowest strain in the infero-temporal and temporal octant in the POAG and OHT subjects. Conclusions: We demonstrate measurable LC strains in vivo in humans as a response to acute IOP elevation. In this population, our data suggest that OHT LCs experience lower IOP-induced strains than healthy LCs.

Changes in Choroidal Blood Flow and Morphology in Response to Increase in Intraocular Pressure.

Purpose: The purpose of this study was to determine the effects of an elevation in IOP on the choroidal blood flow and morphology. Methods: We studied 27 healthy subjects. The mean blur rate (MBR) determined by laser speckle flowgraphy was used to measure the choroidal blood flow. The subfoveal choroidal thickness (SFCT) was measured in the optical coherence tomographic images of the macular region. The luminal and stromal areas of the choroid were determined by the binarization method before, during, and after the IOP was elevated 20 and 30 mm Hg with pressure using an ophthalmodynamometer. Results: The ocular perfusion pressure (OPP) was significantly reduced by the elevation of the IOP by 20 (-52.0%, P < 0.001) and 30 mm Hg (-77.9%, P < 0.001). The percentage reduction in the macular choroidal MBR was -32.5% at an IOP elevation of 20 mm Hg (P < 0.001) and -46.6% at an IOP elevation of 30 mm Hg (P < 0.001). The SFCT was reduced by -3.8% (P = 0.014) and -7.7%, (P < 0.001) during an elevation of IOP of 20 and 30 mm Hg, respectively. The luminal area of the choroid was reduced during an elevation of the IOP of 20 (P = 0.001) and 30 mm Hg (P < 0.001). However, the stromal area did not change significantly. There was no significant correlation between the reduction ratio of OPP and other factors during the elevation of 20 mm Hg, but the correlation between the reduction ratio of OPP and the choroidal MBR during the elevation of 30 mm Hg was significant. The choroidal MBR had recovered significantly at 7 (P = 0.037) and 10 minutes (P = 0.022) compared with that immediately after the IOP elevation of 30 mm Hg. Conclusions: The choroid can autoregulate its blood flow in response to experimental changes in the OPP induced by IOP elevations.

[Intracranial Pressure Evaluation by Ophthalmologist]. / Hodnotenie intrakraniálneho tlaku oftalmológom.

The value of ICT is important in diagnosis of the diseases of the eye and orbit Methods for direct measurement of intracranial pressure (ICT) are exact, but they are invasive and there is some risk of infection and damage of the tissue. Currently there are 2 valid indirect methods of mesurement of IKT. Digital Ophthalmodynamometry (D-ODM) and Transcranial Doppler ultrasonography (TDU). D-ODM is a non-invasive method for measuring of the Pulsating Venous Pressure (VPT). We can measure VPT by the pulse phenomena. Physiologically (to be maintained blood flow) VPT not be less than the ICT and intraorbital pressure (IorbitT). If we raise the VPT to compensate the current IKT (or IorbitT) - there is a pulsation VCR. We can calculate aproxymative IKT with the formula: IKT = 0.903 - (VPT) - 8.87, or IKT = 0.29 + 0.74 (VOT / PI (AO)). [VOT = intraocular pressure. PI - pulsatility index arteriae ophthalmic from Color Doppler ultrasonography.] IKT can be approximate calculate with mathematical formulas: IKT = 0:55 × BMI (kg / m2) + 0.16 × KTD (mmHg) - 0:18 x age (years) - 1.91. [KTD - diastolic blood pressure, BMI - Body master index] or: IKT = 16.95 x 0.39 x OSASW09 + BMI + 0.14 + TKS - 20.90. [OSASW095: width of the orbital arachnoid space at a distance of 9 mm behind the eyeball (nuclear magnetic resonance). BMI: Body Mass Index. TKS: mean arterial pressure]. Normal values of VPT are under 15 torr. The risk of increased intracranial pressure is above 20 torr. Under physiological conditions, there is intraocular pressure lower in about 5 torr than VPT. CONCLUSION: D-ODM is a useful screening method in the evaluation of IKT for hydrocephalus, brain tumors, cerebral hemorrhage after brain trauma and also in ocular diseases: Glaucoma, Ocular hypertension, orbitopathy (endocrine orbitopathy), ischemic / non-ischemic occlusion of blood vessels of the eye, indirect detection ICT carotid artery-cavernous fistula, amaurosis fugax, optic neuropathy. D-ODM is suitable for immediate evaluation of IKT, but is not suitable for continuous monitoring. As it can be repeated, it is useful for a patient suspected of having an increased ICT.Key words: central retinal artery, central retinal vein, colour Doppler ultrasonography, digital ophthalmodynamometry, intracranial pressure, pressure of cerebrospinal fluid, transcranial Doppler ultrasonography, intraocular pressure, venous pulsation pressure, venous outflow pressure, retinal venous pressure.

Non-invasive intracranial pressure assessment.

Assessing intracranial pressure (ICP) remains a cornerstone in neurosurgical care. Invasive techniques for monitoring ICP remain the gold standard. The need for a reliable, safe and reproducible technique to non-invasively assess ICP in the context of early screening and in the neurocritical care environment is obvious. Numerous techniques have been described with several novel advances. While none of the currently available techniques appear independently accurate enough to quantify raised ICP, there is some promising work being undertaken.

Intraocular Pressure Reduction Is Associated with Reduced Venous Pulsation Pressure.

PURPOSE: To explore whether alterations in intraocular pressure (IOP) affect vein pulsation properties using ophthalmodynamometric measures of vein pulsation pressure. PATIENTS AND METHODS: Glaucoma patients had two retinal vein pulsation pressure (VPP) measurements from upper and lower hemiveins performed by ophthalmodynamometry at least 3 months apart. All subjects had VPP and IOP recorded at two visits, with standard automated perimetry, central corneal thickness (CCT) recorded at the initial visit. Where venous pulsation was spontaneous ophthalmodynamometry could not be performed and VPP was considered equal to IOP. Change in VPP was calculated and binarized with reduction in pressure scored 1 and no change or increase scored as 0. Data analysis used a mixed logistic regression model with change in VPP as response variable and change in IOP, visual field loss (mean deviation), CCT and time interval as explanatory variables. RESULTS: 31 subjects (20 females) with mean age 60 years (sd 11) were examined with change in VPP being significantly associated with change in IOP (odds ratio 1.6/mmHg, 95% CI 1.2 to 2.1 in the glaucoma patients but not suspect patients (p = 0.0005). CONCLUSION: Change in VPP is strongly associated with change in IOP such that a reduced intraocular pressure is associated with a subsequent reduction in VPP. This indicates that reduced IOP alters some retinal vein properties however the nature and time course of these changes is not known.

Twenty-four-hour efficacy of preservative-free tafluprost for open-angle glaucoma patients, assessed by home intraocular pressure (Icare-ONE) and blood-pressure monitoring.

PURPOSE: To evaluate the effect of preservative-free (PF) tafluprost on diurnal variation of intraocular pressure (IOP) and ocular perfusion pressure (OPP), measured by use of home IOP and blood-pressure (BP) monitoring devices, for primary open angle glaucoma (POAG) patients. METHODS: Twenty-two eyes from 22 patients with POAG were studied. Initially, IOP was measured at the hospital by Goldmann applanation tonometry (GAT) and Icare-ONE rebound tonometry. Each patient was then instructed how to use the Icare-ONE and BP home monitoring devices. IOP and BP were measured at home by the patients, every 4 h, before and 2 weeks after once daily treatment with PF tafluprost (0.0015%) ophthalmic solution. RESULTS: Intraclass correlations between different IOP measurements were greater than 0.8. PF tafluprost reduced mean diurnal IOP significantly for patients with POAG, from 15.7 ± 1.2 mmHg at baseline to 12.5 ± 0.6 mmHg 2 weeks after treatment (p < 0.001). It increased mean diurnal OPP from 48.5 ± 7.3 mmHg at baseline to 51.3 ± 7.0 mmHg post-treatment (p < 0.017). CONCLUSIONS: Icare-ONE enables glaucoma patients to measure their own diurnal IOP fluctuations. Patient-measured Icare-ONE IOP readings showed that PF tafluprost effectively reduced diurnal IOP in eyes with POAG.

Trabecular Meshwork Response to Pressure Elevation in the Living Human Eye.

The mechanical characteristics of the trabecular meshwork (TM) are linked to outflow resistance and intraocular pressure (IOP) regulation. The rationale behind this technique is the direct observation of the mechanical response of the TM to acute IOP elevation. Prior to scanning, IOP is measured at baseline and during IOP elevation. The limbus is scanned by spectral-domain optical coherence tomography at baseline and during IOP elevation (ophthalmodynamometer (ODM) applied at 30 g force). Scans are processed to enhance visualization of the aqueous humor outflow pathway using ImageJ. Vascular landmarks are used to identify corresponding locations in baseline and IOP elevation scan volumes. Schlemm canal (SC) cross-sectional area (SC-CSA) and SC length from anterior to posterior along its long axis are measured manually at 10 locations within a 1 mm segment of SC. Mean inner to outer wall distance (short axis length) is calculated as the area of SC divided by its long axis length. To examine the contribution of adjacent tissues to the effect IOP elevations, measurements are repeated without and with smooth muscle relaxation with instillation of tropicamide. TM migration into SC is resisted by TM stiffness, but is enhanced by the support of its attachment to adjacent smooth muscle within the ciliary body. This technique is the first to measure the living human TM response to pressure elevation in situ under physiological conditions within the human eye.

The effect of nifedipine on retinal venous pressure of glaucoma patients with the Flammer-Syndrome.

PURPOSE: The purpose was to measure the retinal venous pressure (RVP) in both eyes of primary open-angle glaucoma (POAG) patients before and 3 weeks after treatment with low-dosed Nifedipine. METHODS: This retrospective study included 20 POAG patients who were treated with Nifedipine (5 mg daily) and 20 untreated control POAG patients. In both the treated and untreated control group, a distinction was made between those patients who had the Flammer-Syndrome (FS) and those who did not. The RVP was measured in all patients bilaterally at baseline and 3 weeks later by means of contact lens ophthalmodynamometry and the RVP measurements of the treated POAG patients were compared to the RVPs of the untreated POAG controls. Ophthalmodynamometry is done by applying an increasing force on the eye via a contact lens. The minimum force required to induce a venous pulsation is called the ophthalmodynamometric force (ODF). The RVP is defined and calculated as the sum of ODF and intraocular pressure (IOP) [RVP = ODF + IOP]. RESULTS: The RVP decreased significantly after 3 weeks in both eyes of patients treated with low-dosed Nifedipine compared to the untreated group (mean decrease of 12.5 mmHg (SD 12.5), P < 0.001). A larger response to therapy was found in patients with the FS compared to patients lacking the FS (mean decrease of 16.07 vs. 7.28 mmHg, confidence Interval (CI): 5.2 to 9.3 vs. 12.3 to 19.7; P < 0.001). No significant differences were accounted for in the IOP's of the patients after treatment. In the untreated control group, no significant differences were accounted for either in the RVP or the IOP after 3 weeks. CONCLUSIONS: Treatment with low-dosed Nifedipine decreases RVP in both eyes of glaucoma patients, particularly in those with the Flammer-Syndrome. This effect may be due to the partial inhibition of Endothelin-1 (ET-1) by Nifedipine.

Ultrasound-assisted periconal ocular blockade in rabbits.

OBJECTIVE: This study aimed to evaluate the benefit and specifically the feasibility of using ultrasound in ophthalmologic periconal block, and the occurrence of complications. STUDY DESIGN: Prospective experimental study. ANIMALS: Ten healthy New Zealand White rabbits (6-8 months of age), weighing 2.0-3.5 kg. METHODS: Rabbits were anesthetized by intramuscular injection of acepromazine (1 mg kg(-1)), ketamine (30 mg kg(-1)) and xylazine (3 mg kg(-1)). Ultrasound-assisted periconal block with lidocaine was performed on 18 eyes. Intraocular pressure was measured by applanation tonometry whereas corneal sensitivity was assessed using an esthesiometer, before and after each periconal anesthesia. RESULTS: In all 18 eyes, it was possible to adequately visualize the needle shaft within the periconal space, as well as muscular cone, optic nerve and local anesthetic solution spread. Lidocaine 2% without epinephrine (0.79 ± 0.19 mL) was injected into the periconal space. There was no statistical difference between the intraocular pressure (mean ± SD) measured before (10.9 ± 2.9 mmHg) and after (11.9 ± 3.8 mmHg) the periconal anesthesia (p = 0.38). The effectiveness of the ultrasound-assisted technique was shown according to the values for corneal sensitivity, assessed before and after periconal anesthesia (p < 0.0001). Complications were not observed in this study. CONCLUSIONS: Eye ultrasonography allowed visualization of all anatomic structures necessary to perform a periconal block, as well as the needle insertion and anesthetic spread in real time. Further studies are required to prove the real potential of ultrasound for reducing the incidence of complications associated with ophthalmic blocks, especially when anatomic disorders of the eye could potentially increase the risk. CLINICAL RELEVANCE: Ultrasonography is a painless, noninvasive tool that may improve safety of ophthalmic regional blocks, potentially by reducing the prevalence of globe perforation or penetration of the optic nerve associated with the needle-based techniques.

The effect of flammer-syndrome on retinal venous pressure.

BACKGROUND: The purpose of the study was to measure the retinal venous pressure (RVP) in the eyes of primary open-angle glaucoma (POAG) patients and healthy subjects with and without a Flammer-Syndrome (FS). METHODS: RVP was measured in the following four groups of patients and age- and sex-matched healthy controls: (a) 15 patients with a POAG and a FS (POAG/FS+); (b) 15 patients with a POAG but without a FS (POAG/FS-); (c) 14 healthy subjects with a FS (healthy/FS+) and (d) 16 healthy subjects without a FS (healthy/FS-). RVP was measured in all participants bilaterally by means of contact lens ophthalmodynamometry. Ophthalmodynamometry is done by applying increasing pressure on the eye via a contact lens. The minimum force required to induce a venous pulsation is called ophthalmodynamometric force (ODF). The RVP is defined and calculated as the sum of ODF and intraocular pressure (IOP) [RVP = ODF + IOP]. RESULTS: The participants with a FS (whether patients with POAG or healthy subjects), had a significantly higher RVP compared to subjects without a FS (p = 0.0103). Patients with a POAG and FS (POAG/FS+) had a significantly higher RVP compared to patients without a FS (POAG/FS-) (p = 0.0301). There was a notable trend for a higher RVP in the healthy/FS + group compared to the healthy/FS - group, which did not reach statistical significance (p = 0.0898). CONCLUSIONS: RVP is higher in subjects with a FS, particularly in glaucoma patients. The causal relationship needs to be further evaluated.

[Contact lens dynamometry influences the systemic blood circulation: clinical significance]. / Die Kontaktglasdynamometrie beeinflusst den Systemkreislauf: Folgerungen für die Praxis.

BACKGROUND: The diastolic and systolic pressure in the ophthalmic artery (OAPdia, OAPsys) as well as the venous pulsation pressure (VPP) can be determined by contact lens dynamometry (CLD). With these parameters, carotid artery stenosis, ocular perfusion, e.g., in glaucoma patients and the cerebrospinal pressure can be examined indirectly. In the underlying study comparative data were collected and it was investigated to what extent CLD itself leads to changes of the systemic blood pressure. SUBJECTS/METHODS: In the course of a prospective trial CLD was performed in 162 eyes of 81 healthy volunteers (mean age 41.0 ± 17.3 years). VPP, OAPdia and OAPsys were measured. A mean was calculated from 5 single readings. Directly before and after CLD automated blood pressure measurements according to Riva-Rocci (RR) and the heart rate were obtained in both arms. RESULTS: In the entire group, the mean VPP was 21 ± 9 mmHg on the right side and 19 ± 8 mmHg on the left side. The mean OAPdia was 60 ± 14 mmHg on the right and 67 ± 14 mmHg on the left side. The mean OAPsys was 91 ± 17 and 101 ± 21 mmHg, respectively. The mean variation coefficient from 5 single readings was 13/16 % for VPP (right/left), 7.4/8.2 % for OAPdia and 6.2/6.2 % for OAPsys. The difference between right and left eyes concerning OAPdia and OAPsys was statistically significant (Wilcoxon test; p < 0.001). VPP and OAPsys were not correlated with age, OAPdia showed a weak correlation with age on the right side (Spearman R = 0.23; p = 0.03). Blood pressure (RR) dropped from a mean 137/84 to 135/82 mmHg in the right arm and from 135/84 to 132/83 mmHg in the left arm. The change of the diastolic values of the right side and of the systolic values of the left side reached statistical significance (p < 0.05). The difference of the systolic blood pressure and the heart rate before and after CLD were weakly correlated (Spearman R = - 0.28; p = 0.01). The extent of the systemic blood pressure drop was not correlated with the maximum force affecting the globe. CONCLUSIONS: The slightly lower blood pressure after CLD could be related to the oculocardiac reflex. This has to be confirmed in further trials with continuous blood pressure determination. In agreement with literature reports, significant differences between right and left eyes were found regarding OAPdia and OAPsys.

Photoplethysmographic measurement of various retinal vascular pulsation parameters and measurement of the venous phase delay.

PURPOSE: Retinal vein pulsation properties are altered by glaucoma, intracranial pressure (ICP) changes, and retinal venous occlusion, but measurements are limited to threshold measures or manual observation from video frames. We developed an objective retinal vessel pulsation measurement technique, assessed its repeatability, and used it to determine the phase relations between retinal arteries and veins. METHODS: Twenty-three eyes of 20 glaucoma patients had video photograph recordings from their optic nerve and peripapillary retina. A modified photoplethysmographic system using video recordings taken through an ophthalmodynamometer and timed to the cardiac cycle was used. Aligned video frames of vessel segments were analyzed for blood column light absorbance, and waveform analysis was applied. Coefficient of variation (COV) was calculated from data series using recordings taken within ±1 unit ophthalmodynamometric force of each other. The time in cardiac cycles and seconds of the peak (dilation) and trough (constriction) points of the retinal arterial and vein pulse waveforms were measured. RESULTS: Mean vein peak time COV was 3.4%, and arterial peak time COV was 4.4%. Lower vein peak occurred at 0.044 cardiac cycles (0.040 seconds) after the arterial peak (P = 0.0001), with upper vein peak an insignificant 0.019 cardiac cycles later. No difference in COV for any parameter was found between upper or lower hemiveins. Mean vein amplitude COV was 12.6%, and mean downslope COV was 17.7%. CONCLUSIONS: This technique demonstrates a small retinal venous phase lag behind arterial pulse. It is objective and applicable to any eye with clear ocular media and has moderate to high reproducibility. ( http://www.anzctr.org.au number, ACTRN12608000274370.).

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.

Retinal venous pressure in the non-affected eye of patients with retinal vein occlusions.

BACKGROUND: To measure the retinal venous pressure (RVP) in both eyes of patients with unilateral central retinal vein occlusions and to compare these values to controls. METHODS: The study included 31 patients with unilateral central retinal vein occlusions (CRVO) and 31 controls who were matched by age, sex, and systemic disease. RVP was measured in all patients bilaterally by means of contact lens ophthalmodynamometry, and the RVP measurements of the affected and unaffected eyes of patients were compared to the RVPs of controls. Ophthalmodynamometry is done by applying an increasing pressure on the eye via a contact lens. The minimum force required to induce a venous pulsation is called ophthalmodynamometric force (ODF). The RVP is defined and calculated as the sum of ODF and intraocular pressure (IOP) [RVP = ODF + IOP]. RESULTS: The RVP group means ± SD were as follows: patient's affected eyes (45.0 ± 11.6 mmHg), patient's unaffected eyes (38.0 ± 11.1 mmHg) ,and (17.7 ± 6.7 mmHg) in the eyes of controls. The values of RVP, even in the patients unaffected eyes, were significantly higher than in the eyes of controls (P < 0.001). CONCLUSIONS: In patients with CRVO, the RVP is increased in both the affected as well as in the unaffected contralateral eye.

Oral proton pump inhibitors disrupt horizontal cell-cone feedback and enhance visual hallucinations in macular degeneration patients.

PURPOSE: Visual hallucinations (VHs) occur in macular degeneration patients with poor vision but normal cognitive function. The underlying mechanisms are poorly understood. We report the identification of pharmaceutical agents that enhance VH and use these agents to examine the contribution of retinal neurons to this syndrome. METHODS: We detail clinical observations on VH in five macular degeneration patients treated with proton pump inhibitors having the core structure, 2-pyridyl-methylsulfinyl-benzimidazole. We tested possible retinal mechanisms using paired whole cell recordings to examine effects of these compounds on feedback interactions between horizontal cells and cones in amphibian retina. RESULTS: Five patients with advanced wet macular degeneration described patterned VHs that were induced or enhanced by oral proton pump inhibitors. The abnormal images increased with light, disappeared in the dark, and originated in the retina, based on ophthalmodynamometry. Simultaneous paired whole cell recordings from amphibian cones and horizontal cells showed that 2-pyridyl-methylsulfinyl-benzimidazoles blocked the negative shift in voltage dependence and increase in amplitude of the calcium current (ICa) in cones that is induced by changes in horizontal cell membrane potential. These effects disrupt the negative feedback from horizontal cells to cones that is important for the formation of center-surround receptive fields in bipolar and ganglion cells, and thus for normal spatial and chromatic perception. CONCLUSIONS: Our study suggests that changes in the output of retinal neurons caused by disturbances in outer retinal feedback mechanisms can enhance patterned visual hallucinations.