ABSTRACT
Color Doppler Imaging is a recent advance in Ultrasonography that allows two dimensional study of tissues and simultaneous evaluation of blood flow and has a considerable diagnostic potential to evaluate numerous vascular parameters in vessels of whatever size. The Author has examined the average systolic speed in central retinal artery and in posterior ciliary arteries in normal subjets and compared with glaucomatous eyes. Studies on the variations in blood flow have shown significant alterations in the blood rate of patients affected by POAG.
Moreover pharmacological influence of a betablocker on blood flow were evaluated in 12 patients after 3 minutes from instillation and after 3 hours; it was not founded significant changes in the systolic and diastolic flows, nor in the resistance and pulsatility index in the two eyes. A second group of 10 chronic simple glaucoma patients were colordoppler examined after a month of washout. The results after a month of Carteol 2% local administration revealed a significant increase in the rate of blood flow compared to basal tests. We can assume that the drug acts on the alpha-receptors of vessels by performing a slight vasodilatation and on the beta-receptors of the heart thus reducing the cardiac output. Values obtained show an increase of the systolic peak with a slowering of resistance index to confirm that the drug performs a local improvement of vascular parameters.
KEY WORDS
OPEN ANGLE GLAUCOMA
COLOR DOPPLER IMAGING
CENTRAL RETINAL ARTERY
CARTEOLOL
POSTERIOR CILIARY ARTERY.
INTRODUCTION
Ophthalmologists have long felt the need of a non-invasive method to quantify eye blood supply of choroid and retina to identify the vascular role in ocular pathologies and, in particular, to study the open angle glaucoma pathogenesis. Glaucomatous pathogenesis has been discussed for a long time. We can observe many subjects with high IOP without serious perimetral damages. However, other patients develop severe glaucomatous damages with slight hypertone or with normal IOP.
Ocular hypertension is not the only pathogenetic factor of POAG as assumed by the “Mechanical Hypothesis” or by the “Vascular – Mechanical hypothesis”. According to the latter, ocular hypertension causes the compression of small vessels of the pre-laminar and laminar portions of the optic nerve head. The “pure vascular hypothesis” suggests that the pathogenetic factor is the primary ischaemic affection of the optic nerve: occlusion of a part of choroidal vessels induces an increase of the pressure gradient in the remaining pervious ducts thus determining their dilatation and an increase of the uveal tissue thickness.
Obviously, we have to take into account that personal factors can also play an importante role in the pathogenesis of the glaucomatous disease because they can alter the perfusion pressure and peripheral resistance. We refer to systemic hypotension, carotid and ophthalmic artery stenosis, reduction of vascular compliance and vessel diameter, an increase of hematic viscosity and vasoconstriction.
A number of techniques to quantify eye blood supply have been developped but the results obtained, though permitting topographical evaluation of the vessels, do not give blood flow rate (fluoroangiography), or permit indirectly the evaluation by computerized extrapolation of the choroidal flow (Langham’s Ocular Blood Flow System and oculo-oscillo-dynamography), or make an evaluation of the Central Retinal Artery (CRA) flow possible only when the dioptric medium is perfectly transparent (Laser Doppler Velocimetry).
Colour Doppler Imaging is a method which, by means of a colour module, visualizes blood flow, even in small diameter vessels, superimposed in colour on the two-dimensional image. With the coloured image as a guide, the Doppler spectral analysis enables quantitative evaluation of the blood flow in the vessels.
By positioning the pulsed doppler beam electronic cursor on the various orbital areas, we can display slender vascular formations such as those irrorating the eye. Red indicates the flow towards the probe and blue the flow away from it .
The basic velocity measuring unit consists of a main systolic peak followed by a minor peak which represents the vascular systole, it corresponds to aortic valve closing. There follows the protodiastolic reflux corresponding to the cardiac diastole, an index of artery distensibility, and the vascular diastolic wave which represents the vessel’s elasticity.
We can study in the orbital area: the ophthalmic artery in its course and its flexion round the optic nerve until the superior orbit angle; the central retinal artery within the optic nerve; the central retinal artery as it emerges from the optic disc, where it bends and branches; the posterior ciliary arteries in the areas of their insertion into the sclera; the set of vessels around the optic nerve head (Zinn-Haller’s Circle); the newly-formed vessels inside endobulbar or orbital neoformations; the newly-formed vessels on proliferative vitreous outgrowths. Blood flow may be evaluated in these vessels obtaining the value of : systolic peak, diastolic peak, resistance index (RI), pulsatility index (PI).
An interesting application of color doppler examination is the real time evaluation of the vascular effects of a drug on the orbital circulation and the opportunity it gives of monitoring those effects in time. The aim of this study was to evaluate the vascular action of a long-acting, non-selective adrenergic beta-blocking agent with intrinsic sympathomimetic activity the Carteolol hydrochloride (Carteolol) ( FIG. IV Pilot studies in volunteers and patients with glaucoma demonstrated that the ocular hypotensive effects of carteolol were approximately equal to those of timolol. It is not clear whether the topically instilled carteolol reduces intraocular pressure (IOP) in its original, unmetabolized form or its metabolites play a significant role in lowering IOP.
METHODS
The instrument used was a Color Doppler Imaging ATL UltraMark 9 H.D.I. with a 5-10 MHz linear array multifrequency probe and a 5-9 MHz convex microprobe. The colour module threshold was set to reduce to a minimum the spurious readings caused by eyelid movements and involuntary eye movements. The sampling volume was 0.2 x.0.3 mm and the wall filter used was 25 Hz.
The patient supine, examination was carried out by laying the echodoppler probe on the eyelid surface of the closed eye, previously smeared with sterile echograph gel.
The study of 90 normal subjects ( 180 eyes ) shows for the central retinal artery (CRA) VEL.SYS.= 11.8 cm/sec +/- 1.9, R.I.= 65 +/- 4, P.I.= 1.2 +/- 0.3; for the long and short posterior ciliary arteries (PCA) VEL.SYS.= 13.2 cm/sec +/- 2.7, R.I.= 68 +/- 5, P.I.= 1.1 +/- 0.4, and for the fine vascular structures of Zinn-Haller’s Circle VEL.SYS.= 10.7 cm/sec +/- 1.8 .
A color doppler study on 110 eyes (55 patients) affected by chronic simple open angle glaucoma has shown characteristic alterations of morphologic shapes with a rounded point systolic peak and a decrease of diastolic flow. The values obtained for the central retinal artery systolic mean flow were 7.4 cm per sec (+/- 1.9) with a resistance index of O.65 (+/- 0.03 ) and a pulsatility index of 1 (+/- 0.08). In the posterior ciliary arteries, mean flow is 12.0 cm per sec (+/- 2.4) with a resistance index of 0.70 (+/- 0.07 ) and pulsatility index of 1.1 (+/- 0.1 ).
The difference in the central retinal artery mean flow between healthy and glaucomatous patients is statistically significant ( p < 0.002) ( FIG.I ), converselly the difference in the meanflow of the posterior ciliary arteries, as well as the difference between the resistance index values are not statistically significant. Color doppler investigation on carteol action has proven its vascular effects which have been already pointed out in many reports in the literature.
A color doppler examination was performed on 12 patients, with ocular hypertension, whose provocation tests were positive, but who had no perimetric or papillary damage. At the end of the examination, one drop of Carteol 2% was instilled in one eye, while its fellow was treated with placebo. The examination was repeated three minutes and three hours after instillation.
A second group of 10 chronic simple glaucoma patients were colordoppler examined after a month of washout. Then it was performed a Carteolol 2% local administration twice a day and the colordoppler was repeated after one month of therapy.
RESULTS
The color doppler examination on 12 ocular hypertension registered a mean systolic flow rate of 10.4 cm per sec with a resistance index of 0.51 and a pulsatility index of 0.68 under basal conditions. In the following exemination after three minutes and after three hours, there were no significant changes in the systolic and diastolic flows, nor in the resistance and pulsatility index in the two eyes, but the repeatability of the examination was confirmed. ( Fig. III)
A second group of 10 chronic simple glaucoma patients were colordoppler examined after a month of washout. The values obtained averaged into a mean central retinal artery flow of 9.5 cm per sec, a resistance index of 0.76 and a pulsatility index of 1.25, while the corresponding means for the posterior ciliary arteries were 11.1 cm per sec, 0.71 and 1.1.
The results after a month of Carteol 2% local administration showed a significant increase of mean systolic blood flow of CRA to 10.9 cm per sec ( p = 0.02 ) ( Fig. IV a) with a significant reduction of the resistance index to 0.68 ( p < 0.001 ) (Fig. IV b) and of the pulsatility index to 1.06 ( p = 0.02 ). The mean blood flow posterior ciliary arteries was also increased, its value being 12.2 cm per sec ( p = NS ), while the resistance index was 0.72 ( p = NS ) and the pulsatility index was 1.2 ( p = NS ).
DISCUSSION
Color Doppler Imaging has a considerable diagnostic potential to evaluate numerous vascular parameters in vessels of whatever size. This method has revolutionized non-invasive diagnostic techniques, providing a new approach to study the vascular effects in different types of ocular pathologies.
Color Doppler Imaging reproduces two-dimensional images and produces specific Doppler data on small orbital vessels. The flow rate of the central retinal artery and the posterior ciliary arteries can therefore be evaluated with reliable results.
The average values of healthy subjects examined in this study were not significantly different from values quoted in literature.
Thanks to this high resolution two dimensional technique the flow rate of the examined vessels can be measured and statistical models can be created.
Studies on the variations in blood flow have shown significant alterations in the blood rate of patients affected by POAG.
The results have illustrated a considerable decrease in the flow rate probably due to structural changes in vascular endothelium (increase of pulsatility index ), connected to changes of blood perfusion ( decrease of systolic flow ) and with a reduction of perfusion pressure due to ocular hypertension ( increase of resistance index).
Color doppler was performed on several patients not being treated and repeated after administering Carteol 2% after 5 minutes. The Doppler test was repeated after 30 days of this treatment.
The Color Doppler evaluation of blood parameters obtained after treatment with this drug revealed a significant increase in the rate of blood flow compared to basal tests. We can assume that the drug acts on the alpha-receptors of vessels by performing a slight vasodilatation and on the beta-receptors of the heart thus reducing the cardiac output. Values obtained show an increase of the systolic peak with a slowering of resistance index to confirm that the drug performs a local improvement of vascular parameters.
This study has shown that Color Doppler technique can be repeatedly used with reliable results and it makes possible to continuosly asses the efficacy of the treatment. The drug used is significantly active on vessels by improving the values of Doppler parameters and reducing ocular hypertension.
During examination it is necessary to be careful not to increase IOP accidentally by probe pressure or flow readings will be affected. Take into account the patients’ blood pressure level and psychological stress during the examination, since systolic flow readings may be lifted by stress-induced vasoconstriction.
Remember that commonly-used drugs and beverages taken by the patient may cause changes in blood fluidity and lead to wrong flow evaluation (contraceptives, acetylsalicylic acid derivatives, antihypertensives, coffee, etc.).
CONCLUSION
Analysis of these results indicates how color-doppler examination allows an easy evaluation of the efficacy of a topical drug on the vascular component. Systolic blood flow increase along with a decrease of the resistance and pulsatility indices means a higher vascular blood flow in the eye and a better perfusion. This improvement shows up also in the morphological shape of the echo-doppler traces.
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