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Methods of visualization and diagnosis of glaucoma
Last reviewed: 06.07.2025
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It has been established that the goal of glaucoma treatment is to prevent further symptomatic vision loss with maximum reduction of side effects or complications after surgical interventions. In the context of pathophysiology, this means reducing intraocular pressure to a level that does not damage the axons of the retinal ganglion cells.
Currently, the “gold standard” for determining the functional state of ganglion cell axons (their stress) is automated static monochromatic visual field imaging. This information is used to make a diagnosis and assess the effectiveness of treatment (progression of the process with cell damage or its absence). The study has limitations depending on the degree of axonal loss, which must be determined before conducting the study, which identifies changes, makes a diagnosis and compares indicators to establish progression.
Retinal Thickness Analyzer
The Retinal Thickness Analyzer (RTA) (Talia Technology, MevaseretZion, Israel) calculates the retinal thickness in the macula and takes measurements of 2D and 3D images.
How does a retinal thickness analyzer work?
In retinal thickness mapping, a green 540 nm HeNe laser beam is used to image the retina using a retinal thickness analyzer. The distance between the laser intersection with the vitreoretinal surface and the surface between the retina and its pigment epithelium is directly proportional to the retinal thickness. Nine scans are made with nine separate fixation targets. When these scans are compared, the area in the central 20° (measured as 6 by 6 mm) of the fundus is covered.
Unlike OCT and SLP, which measure SNV, or HRT and OCT, which measure the optic disc contour, the retinal thickness analyzer measures the retinal thickness at the macula. Because the highest concentration of retinal ganglion cells is in the macula and the ganglion cell layer is much thicker than their axons (which make up the SNV), retinal thickness at the macula can be a good indicator of the development of glaucoma.
When to use a retinal thickness analyzer
The retinal thickness analyzer is useful in detecting glaucoma and monitoring its progression.
Restrictions
A 5 mm pupil is required to perform retinal thickness analysis. Its use is limited in patients with multiple floaters or significant opacities in the ocular media. Because of the short-wavelength radiation used in ATS, this device is more sensitive to nuclear dense cataracts than OCT, confocal scanning laser ophthalmoscopy (HRT), or SLP. To convert the obtained values into absolute retinal thickness values, corrections must be made for refractive error and axial length of the eye.
Blood flow in glaucoma
Increased intraocular pressure has long been associated with progression of visual field loss in patients with primary open-angle glaucoma. However, despite reduction of intraocular pressure to target levels, many patients continue to experience visual field loss, suggesting that other factors are at play.
Epidemiological studies show that there is a connection between blood pressure and risk factors for glaucoma. Our studies have shown that autoregulatory mechanisms alone are not enough to compensate for and reduce blood pressure in glaucoma patients. In addition, the results of the studies confirm that some patients with normotensive glaucoma experience reversible vasospasm.
As research has progressed, it has become increasingly clear that blood flow is an important factor in understanding the vascular etiology of glaucoma and its treatment. The retina, optic nerve, retrobulbar vessels, and choroid have been found to have abnormal blood flow in glaucoma. Since there is currently no single method available that can accurately examine all of these areas, a multi-instrument approach is being used to better understand the blood circulation of the entire eye.
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Scanning laser ophthalmoscopic angiography
Scanning laser ophthalmoscopic angiography is based on fluorescein angiography, one of the first modern measurement technologies for collecting empirical data on the retina. Scanning laser ophthalmoscopic angiography overcomes many of the shortcomings of traditional photographic or videoangiographic techniques by replacing the incandescent light source with a low-power argon laser to achieve better penetration through the lens and corneal opacities. The laser frequency is selected according to the properties of the injected dye, fluorescein or indocyanine green. When the dye reaches the eye, the reflected light exiting the pupil hits a detector, which measures the light intensity in real time. This creates a video signal, which is passed through a video timer and sent to a video recorder. The video is then analyzed offline to obtain parameters such as arteriovenous transit time and average dye velocity.
Fluorescence scanning laser scanning laser ophthalmoscopic ophthalmoscopic angiography with indocyanine green angiography
Target
Evaluation of retinal hemodynamics, especially arteriovenous transit time.
Description
Fluorescein dye is used in combination with low-frequency laser radiation to improve visualization of retinal vessels. High contrast allows individual retinal vessels to be seen in the upper and lower parts of the retina. At a light intensity of 5x5 pixels, as the fluorescein dye reaches the tissue, areas with adjacent arteries and veins are revealed. Arteriovenous transit time corresponds to the difference in time when the dye passes from the arteries to the veins.
TargetEvaluation of choroidal hemodynamics, especially comparison of optic disc and macula perfusion.
Description
Indocyanine green dye is used in combination with deep-penetrating laser radiation to improve visualization of the choroidal vasculature. Two zones are selected near the optic disc and four zones around the macula, each 25x25 pixels. In the dilution zone analysis, the brightness of these six zones is measured and the time required to achieve predetermined brightness levels (10% and 63%) is determined. The six zones are then compared to each other to determine their relative brightness. Since there is no need to adjust for differences in optics, lens opacities, or movement, and all data is collected through the same optical system with all six zones imaged simultaneously, relative comparisons are possible.
Color Doppler mapping
Target
Evaluation of the retrobulbar vessels, especially the ophthalmic artery, central retinal artery and posterior ciliary arteries.
Description
Color Doppler mapping is an ultrasound technique that combines a grayscale B-scan image with a superimposed color Doppler-frequency-shifted blood flow image and pulse Doppler flow velocity measurements. A single multifunctional transducer is used to perform all functions, typically 5 to 7.5 MHz. Vessels are selected and deviations in the returning sound waves are used to make Doppler equalization blood flow velocity measurements. The blood flow velocity data are plotted against time, and the peak with the trough is defined as the peak systolic velocity and end diastolic velocity. The Pourcelot resistance index is then calculated to estimate the descending vascular resistance.
Pulse ocular blood flow
Target
Assessment of choroidal blood flow in systole using real-time intraocular pressure measurement.
Description
The device for measuring the pulse ocular blood flow uses a modified pneumotonometer connected to a microcomputer to measure the intraocular pressure approximately 200 times per second. The tonometer is applied to the cornea for several seconds. The amplitude of the pulse wave of intraocular pressure is used to calculate the change in ocular volume. It is believed that the pulsation of intraocular pressure is the systolic ocular blood flow. It is assumed that this is the primary choroidal blood flow, since it makes up approximately 80% of the circulation volume of the eye. It has been found that in patients with glaucoma, compared with healthy people, the pulse ocular blood flow is significantly reduced.
Laser Doppler Velocimetry
Target
Estimation of maximum blood flow velocity in large retinal vessels.
Description
Laser Doppler velocimetry is the predecessor of retinal laser Doppler and Heidelberg retinal flowmetry. In this device, low-power laser radiation is aimed at large retinal vessels of the fundus, and Doppler shifts observed in the scattered light of moving blood cells are analyzed. The maximum velocity is used to obtain the average velocity of blood cells, which is then used to calculate flow parameters.
Retinal laser Doppler flowmetry
Target
Evaluation of blood flow in retinal microvessels.
Description
Retinal laser Doppler flowmetry is an intermediate stage between laser Doppler velocimetry and Heidelberg retinal flowmetry. The laser beam is directed away from visible vessels to assess blood flow in microvessels. Due to the random arrangement of capillaries, only an approximate estimate of blood flow velocity can be made. The volumetric blood flow velocity is calculated using the Doppler spectrum shift frequencies (indicate the speed of blood cell movement) with the signal amplitude of each frequency (indicates the ratio of blood cells at each speed).
Heidelberg retinal flowmetry
Target
Evaluation of perfusion in peripapillary capillaries and optic disc capillaries.
Description
The Heidelberg Retinal Flowmeter has surpassed the capabilities of laser Doppler velocimetry and retinal laser Doppler flowmetry. The Heidelberg Retinal Flowmeter uses infrared laser radiation with a wavelength of 785 nm to scan the fundus. This frequency was chosen due to the ability of oxygenated and deoxygenated red blood cells to reflect this radiation with the same intensity. The device scans the fundus and reproduces a physical map of the retinal blood flow value without distinguishing between arterial and venous blood. It is known that the interpretation of blood flow maps is quite complex. Analysis of the computer program from the manufacturer when changing the localization parameters, even for a minute, gives a large number of options for reading the results. Using point-by-point analysis developed by the Glaucoma Research and Diagnostic Center, large areas of the blood flow map are examined, with a better description. To describe the "shape" of the blood flow distribution in the retina, including perfused and avascular zones, a histogram of individual blood flow values has been developed.
Spectral retinal oximetry
Target
Assessment of partial pressure of oxygen in the retina and optic nerve head.
Description
A spectral retinal oximeter uses the different spectrophotometric properties of oxygenated and deoxygenated hemoglobin to determine the partial pressure of oxygen in the retina and optic nerve head. A bright flash of white light hits the retina, and the reflected light passes through a 1:4 image splitter on its way back to the digital camera. The image splitter creates four equally illuminated images, which are then filtered into four different wavelengths. The brightness of each pixel is then converted to optical density. After removing camera noise and calibrating the images to optical density, an oxygenation map is calculated.
The isosbestic image is filtered by the frequency at which it reflects oxygenated and deoxygenated hemoglobin identically. The oxygen-sensitive image is filtered by the frequency at which the reflection of oxygenated oxygen is maximized and compared with the reflection of deoxygenated hemoglobin. To create a map reflecting the oxygen content in terms of the optical density coefficient, the isosbestic image is divided by the oxygen-sensitive image. In this image, the lighter areas contain more oxygen, and the raw pixel values reflect the oxygenation level.