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ORIGINAL ARTICLE
Year : 2003  |  Volume : 51  |  Issue : 2  |  Page : 133-138

Pulsatile ocular blood flow among normal subjects and patients with high tension glaucoma


Dr. R P Centre for Ophthalmic Sciences, All Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Harish C Agarwal
Dr. R P Centre for Ophthalmic Sciences, All Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


PMID: 12831143

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  Abstract 

Purpose: To estimate pulsatile ocular blood flow (POBF) among normal subjects and to compare various parameters in eyes of primary open angle glaucoma with high intraocular pressure (IOP).
Methods: POBF was estimated in 95 eyes of 95 normal subjects above the age of 40 years and in 35 eyes of 35 primary open angle glaucoma patients using the OBF system (OBF Labs Ltd., UK). Correlation of age, gender, IOP, pulse amplitude, pulse volume and pulse rate with POBF was studied. POBF values were measured in glaucomatous patients before IOP control and one month later after control of IOP to <22mmHg.
Results: The mean POBF among normal subjects was 1382.2 + 413ml/min (range 636-2291m/min). Females had a significantly higher mean POBF (1512 + 347ml/min) than males (1193 + 312ml/min). The mean IOP among normal subjects was 12.6mmHg and in glaucoma patients, 29.1mmHg. Mean POBF in glaucomatous eyes with initially elevated IOP was 718.9 + 322.6 ml/min, which improved after IOP control to 1129 + 291ml/min. IOP had a strong (P<.01) negative correlation with POBF
(r = -0.667)
Conclusions: POBF among eyes of normal subjects in this study is higher than reported among Caucasian eyes. Primary open angle glaucoma eyes with high IOP have significantly reduced ocular blood flow. Therapy aimed at lowering IOP has a positive effect on ocular haemodynamics.

Keywords: Pulsatile ocular blood flow, normal subjects, intraocular pressure, primary open angle glaucoma.


How to cite this article:
Agarwal HC, Gupta V, Sihota R, Singh K. Pulsatile ocular blood flow among normal subjects and patients with high tension glaucoma. Indian J Ophthalmol 2003;51:133-8

How to cite this URL:
Agarwal HC, Gupta V, Sihota R, Singh K. Pulsatile ocular blood flow among normal subjects and patients with high tension glaucoma. Indian J Ophthalmol [serial online] 2003 [cited 2019 Dec 11];51:133-8. Available from: http://www.ijo.in/text.asp?2003/51/2/133/14715



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Pulsatile ocular blood flow (POBF) is due to the pulsatile waveform created as blood passes through the eye with each heart beat. Pulsatile ocular blood flow measures 70% of the total blood flow to the eye and it is known that 85% of the total blood flow is choroidal circulation.[1],[2] Since it is the choroidal flow which supplies the optic nerve, POBF assumes importance in the evaluation of glaucomatous damage. POBF can also be affected by systemic and local drugs and in conditions like retinitis pigmentosa, diabetic retinopathy and carotid artery stenosis.[3],[4],[5] The OBF system calculates the ocular blood flow based on the amplitude of IOP variation. Several studies have been done to assess POBF in normal subjects among Caucasian eyes, [6],[7],[8] including testing of its reproducibility.[6],[9] However, there are limited reports of POBF values among Asians.[10] In this study we estimated POBF values among normal Indian subjects and in primary open angle glaucoma patients with high IOP and again after IOP control.


  Material and Methods Top


Ninety-five normal subjects who reported for routine presbyopic check up and satisfied the inclusion criteria were enrolled in the study, which was carried out over 6 months. Inclusion criteria were age above 40 years, IOP<20 mmHg, and no ocular abnormalities. Exclusion criteria for normal subjects were hazy media, refractive error greater than or equal to + 2 DSph, relatives of glaucoma patients, those with any fundus pathology and those with systemic diseases or on systemic drugs. Only one eye of each subject was selected randomly (computerised randomisation) for inclusion in the study.

Thirty five patients of bilateral primary open angle glaucoma (POAG) reporting to the glaucoma clinic for the first time were included. Diagnostic criteria for POAG was a record of IOP > 22mmHg on two successive occasions, optic disc cupping greater than 0.5 in the presence of glaucomatous field defects, and open angles on gonioscopy. Visual field examination was performed with central 30-2 full threshold program of the Humphrey field analyser 645 (Humphrey Instruments, San Leandro, CA, USA). The minimum criterion for defining a glaucomatous field defect was the presence of a cluster of 3 abnormal points in the expected area of the same hemifield with pattern deviation probability less than 2% and at least one point less than 1% or at least 2 adjacent points with a pattern deviation less than 1% and glaucoma hemifield outside normal limits. Patients had similar exclusion criteria as normal subjects. Patients were recruited only if their IOP readings on previous occasions was >22mmHg without antiglaucoma therapy and was confirmed high on applanation tonometry and OBF tonography. Only one eye of each patient was selected randomly (by computer generated randomisation) for inclusion in the study. Glaucoma patients and normal subjects were matched for comparison by age, gender and refraction. All patients were re-examined after control of IOP to less than 22mmHg one month later.

Informed consent was obtained from each healthy volunteer and from patients after explaining the procedure. A detailed history to rule out any systemic illness or intake of systemic drugs was taken. Blood pressure was recorded in all subjects. Slitlamp and fundus examination were performed. Axial length was measured with the Sonomed Inc (Lake Success, NY, USA). POBF was recorded in sitting position after instillation of 4% topical lignocaine. The subjects were tested twice over a period of one hour and the mean of the two readings was considered for data analysis

We used an OBF system (OBF Labs Ltd, UK) which has a pneumotonometer that transmits IOP change signals as changes in ocular blood flow. The POBF measurements are derived assuming a standard scleral rigidity and assuming that the outflow of blood from the eye is nonpulsatile. The signals can be recorded over a period of 5-20 seconds; we used the 20-second cycle. The attached computer automatically selects 5 representative pulses; other pulses which do not approximate these are discarded. The IOP, pulse amplitude, pulse volume, pulse rate and the POBF are recorded and stored in a database.

Statistical analysis

The Shapiro-Wilks test was used to determine whether POBF values among healthy subjects conformed to a normal distribution. Mean and standard deviation were calculated for males and females in both the groups. Multiple stepwise linear regression analysis was performed to determine the influence of age, IOP, pulse amplitude, pulse volume and pulse rate on POBF among normal subjects. The 't' test was used to compare whether differences between the normal and glaucoma subjects were statistically significant. A p-value of <0.05 was considered significant. Mean POBF values among groups of 5 mmHg of IOP were compared with each other in both normal and glaucoma subjects using ANOVA and posthoc tests. SPSS version 7.0 was used for the statistical analysis.


  Results Top


The 95 normal subjects included 41 males and 54 females. [Table - 1] gives the distribution of mean age, axial length, IOP, pulse amplitude (PA), pulse volume (PV), pulse rate (PR) and POBF among males and females in normal and glaucoma subjects. The mean age of glaucoma patients was 51.3 + 9.7 years. The mean IOP was 29.1 + 6.8 mmHg and mean axial length was 22.72 + 1.2 mm. The mean PA, PV and PR were 3.4 + 1.46mmHg, 4.3 + 1.9ml, and 77.9 + 17 per minute respectively. The mean POBF among glaucoma subjects was significantly lower [719.9 + 322ml/min (range 139-1504ml/min)] than among normal subjects (P<0.05), as was the mean PV. There was no statistically significant difference with respect to age, IOP, PR and PA between males and females. But the mean PV and POBF values were significantly higher among females ( P<0.05).

Among normal subjects the mean age was 49.2 + 8.6 years and mean IOP was 12.6 + 4 mmHg. Mean axial length was 22.84 + 1.1mm. The mean values of PA, PV, PR were 3.5 + 1.3mmHg, 8.5 + 3ml, and 79 + 13 per minute respectively. The mean POBF among the normal subjects was 1382.2 + 387ml/min (range 636-2291ml/min). The histogram [Figure - 1] of POBF among normal subjects assumes a normal distribution curve (Shapiro-Wilks test, P=0.09). Univariate and multivariate regression analysis was done with POBF as the dependent variable; and age, IOP, mean blood pressure, pulse amplitude (PA), pulse volume (PV) and pulse rate (PR) as independent variables. Age did not show correlation with POBF. IOP had a statistically significant (P<0.01) negative correlation with POBF (r=-0.667). The mean blood pressure also did not show correlation with POBF (r=0.012). Both PA and PR had weak correlation with POBF (r=0.11) which was statistically not significant (P=0.45). However, PV had a significantly ( P<0.01) positive correlation with POBF (r = 0.883). POBF increased in all eyes in whom IOP reduction was achieved to ­ 22mmHg [Figure - 2]. There was a 44% IOP reduction from mean 29.1 + 6.8 mmHg to 16.2 + 2.3mmHg after therapy. Mean POBF increased from 719.9 + 322ml/min to 1129 + 291.4ml/min after therapy (P<0.05), a 57% increase. In 20 eyes IOP was controlled on topical timolol 0.5% twice daily and pilocarpine 2% three times a day. In another 15 eyes systemic acetazolamide 250mg three times daily was added along with the above two medications to control the IOP.

POBF values in IOP ranges of 5 mmHg were analysed [Table - 2]. Multiple comparisons were made between and among groups using the posthoc test. Subjects within 15mmHg range of IOP had significantly different mean POBF values compared to those with IOP in the range of 16-20 mmHg and those with IOP in the range of 21-30 mmHg had significantly different POBF values from those with IOP ranging above 31 mmHg (P<0.05).


  Discussion Top


In recent years a number of techniques have been used to measure the blood flow in the eye. Established clinical methods in human subjects include the laser doppler velocimetry that measures the optic nerve head flow,[11] but the depth of measurement is difficult to clarify. Laser speckle phenomenon is another method but it has not been extensively investigated. More recently the colour doppler ultrasound has been used to estimate blood flow in the ophthalmic artery, the central retinal artery and vein, and posterior ciliary arteries.[12],[13],[14] Though this method is easy to apply for central retinal vessels it is difficult and less reliable for the multiple tortuous posterior ciliary arteries. Pulsatile ocular blood flow can be measured using a pneumo-tonometer which utilizes the pressure-volume relationship. This technique, described by Langham and Toney, and Silver et al[15], [16] is relevant in investigating blood flow in choroidal circulation. The OBF tonograph used in our study is similar to the Langham tonograph but unlike the latter it gives a more objective, automatic calculation of POBF. This instrument can be used with ease by nurses or paramedical staff in outpatient clinics.

We studied the effect of age, gender and IOP on POBF. The influence of age on ocular perfusion has been debated. A study using the pneumotonometric method[9] did not find any correlation of age with POBF. Other studies based on POBF[17] and colour doppler imaging[18], however, report a decline in ocular perfusion in the elderly. Our results do not indicate any significant correlation of age with POBF. A probable reason could be that we selected only those subjects who were over 40 years. We found approximately 30% higher POBF in women than men, which may be due to a higher mean heart rate.

Raised IOP is known to cause reduction in blood flow to the uvea, retina and choroid.[19] Quaranta et al [20] reported reduction of POBF in both normal subjects and low tension glaucoma (LTG) patients with incremental IOP rise. They applied the Langham scleral cup on the temporal sclera to increase the IOP in the same eye. However, the decrease of POBF with increased IOP was greater in LTG eyes in their study. Our results confirm that ocular blood flow is lower in eyes with high IOP and a negative correlation exists between POBF and IOP even among subjects with IOP < 22 mmHg.

Although systemic blood pressure is, in theory, believed to influence ocular perfusion, autoregulatory mechanisms are known to exist to maintain retinal and choroidal blood flow against blood pressure changes.[21] Yang et al [6] did not find a relation between systemic blood pressure and POBF. Our study did not measure the effect of systemic blood pressure on POBF since presence of raised systemic blood pressure was an exclusion criterion. This study also confirms a previously noted fact that pulse volume has a direct correlation with POBF and that pulse amplitude is not a pertinent parameter.[21]

POBF values among normal subjects in this study were higher than previously reported among Caucasians. [6],[7] The possible explanation could be a higher mean IOP reported in other studies (IOP of 16.9 mmHg 6sub and 16.3 mmHg 7sub ) compared to ours. [Table - 3] compares the values of pulsatile ocular blood flow in normal subjects by previous authors with ours. The latest version of the OBF tonometer used in our study is different from the Langham tonometer used in two reports[6],[10] and the older version of the OBF system used in another study,[7] which could also account for differences in POBF measurements seen.

Axial length is shown to have a significant negative correlation with POBF.[10] This is because the pulse wave depends on the volume of choroidal vascular bed and the relationship between volume and pressure changes in the individual eye. A similar volume of blood entering the eye will thus produce greater pressure change in smaller hyperopic eyes than in larger myopic eyes. Axial length of the normal subjects was within normal range as we had excluded patients with refractive error of greater than ± 2D. This was probably the reason we did not find an association of this parameter associated with POBF.

Primary open angle glaucoma patients with high IOP underwent POBF measurement before IOP control measures were undertaken. Mean POBF was significantly lower in this group than in normal subjects. It has been experimentally confirmed that blood supply to the optic disc and peripapillary choroid is most susceptible to raised IOP.[22],[23] After IOP was controlled by antiglaucoma therapy in our study , POBF improved in each eye though the mean ocular blood flow in treated eyes of glaucoma patients remained lower than the normal subjects. Although the IOP of these eyes after treatment was higher than the mean IOP in the normal subjects, it is known that despite similar eye pressure, eyes of open angle glaucoma patients have lower perfusion than ocular hypertensives.[24],[25] The mode of treatment was not used for analysis. Nor did we aim to correlate the POBF with degree of glaucomatous defect in these eyes. It is possible that other forms of medical therapy can bring changes in POBF to a different extent.

Till date no direct method of clinically measuring the optic nerve circulation exists. The observations in this study, however, confirm the possibility of IOP rise contributing to optic nerve damage by reducing the blood flow. This study also assumes importance in providing reference values at different IOP ranges in normal and glaucomatous subjects and would be useful in evaluating further studies using the OBF tonograph.

 
  References Top

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    Figures

  [Figure - 1], [Figure - 2]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3]


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