RU2804592C1 - Method for assessing blood circulation of optic nerve and peripapillary region of retina in primary open-angle glaucoma - Google Patents

Abstract

FIELD: ophthalmology.

SUBSTANCE: used to assess the blood circulation of the optic nerve and the peripapillary region of the retina in primary open-angle glaucoma. To do this, laser speckle flowgraphy (LSFG) and ultrasound examination (U/S) are performed in the color Doppler mapping and pulsed Doppler mode. When the average image blur index (MBR) in the temporal sector of the optic disc and peripapillary retina is less than 20.30 a.u., the image blur index of the microvasculature (MT) of the optic disc and peripapillary retina is less than 14.50 a.u. and peak systolic velocity (PSV) in the lateral posterior short ciliary artery of the retina according to U/S data below 11.00 cm/s, blood circulation is assessed as impaired.

EFFECT: assessment of the state of blood circulation in the optic nerve and peripapillary region of the retina in this category of patients and, if necessary, timely adjustment of the management and treatment tactics of patients.

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Description

The invention relates to medicine, namely to ophthalmology, and is intended to assess the blood circulation of the optic nerve and the peripapillary region of the retina in primary open-angle glaucoma using laser speckle flowgraphy (LSFG) and ultrasound (US) in color Doppler mapping (CDC) modes and pulsed Dopplerography (PD).

Glaucoma is the leading cause of irreversible blindness worldwide. Today, there is a steady increase in both the number of patients and disability due to this pathology [Quigley N.A. 21st century glaucoma care. Eye (Lond). 2019; 33 (2): 254-60. doi:10.1038/s41433-018-0227-8].

Primary open-angle glaucoma (POAG) is a multifactorial disease characterized by a decrease in retinal ganglion cells (RGCs), which in turn leads to the progression of glaucomatous optic neuropathy (GON) with associated visual field defects. One of the leading factors involved in the pathophysiological processes in primary open-angle glaucoma (POAG) is impaired circulation of the optic nerve and peripapillary retina [Aizawa N., Kunikata N., Nitta F., et al. Age- and Sex-Dependency of Laser Speckle Flowgraphy Measurements of Optic Nerve Vessel Microcirculation. PLoS One, 11(2). 2016. P. 1-9. doi:10.1371/journal.pone.0148812].

Currently, the issue of searching for optimal algorithms for studying the blood flow of the optic nerve and retina during GON in order to optimize the diagnosis of glaucoma is relevant.

There are various methods for studying ocular blood flow: invasive - scanning laser ophthalmoscopic angiography with fluorescein (FAG) and/or with indocyanine green dye (IAG); and non-invasive. Despite the proven diagnostic effectiveness of angiography, it is the invasive nature and possible side effects that prevent the frequent use of these methods in clinical settings [Inoue M., Jung J.J., Balaratnasingam C, Dansingani K.K., Dhrami-Gavazi E., Suzuki M., et al. A Comparison Between Optical Coherence Tomography Angiography and Fluorescein Angiography for the Imaging of Type 1 Neovascularization. Invest Ophthalmol Vis Sci 2016; 57(9): OST314-23].

Widely available non-invasive methods for studying blood flow are optical coherence tomography with angiography function and ultrasound examination of blood flow in the color Doppler mapping (CDC) and pulsed Doppler (PD) modes.

Optical coherence tomography with angiography (OCT-A) is an informative method for studying the microvascular bed and is convenient for use in clinical practice. However, this technique makes it possible to visually assess the angioarchitecture of the optic disc area without determining quantitative volumetric parameters of blood supply in the studied area [Neroev V.V., Okhotsimskaya T.D., Fadeeva V.A. Assessment of microvascular changes in the retina in diabetes mellitus using OCT angiography. Russian ophthalmological journal. 2017; 10 (2): 40-45. doi.org/10.21516/2072-0076-2017-10-2-40-45].

Color Doppler and ID ultrasound is used to record peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistance index (RI) in retrobulbar vessels, including the ophthalmic artery (OA), central retinal artery (CRA), and posterior short ciliary vessels. arteries (MCCA) medial and lateral. [Kiseleva T.N. Z.M.S., Ramazanova K.A., Lugovkina K.V. Possibilities of color duplex scanning in the diagnosis of vascular pathology of the eye. Russian Ophthalmological Journal 2018; 11 (3): (84-94)].

These methods, with varying degrees of reliability, allow one to estimate the volume and speed of blood flow in the vessels of the eye. There are significant limitations in assessing hemodynamics in capillaries, taking into account their localization, as well as in interpreting the results obtained (artifacts due to eye movements, loss of signal due to large scanning depths, state of optical media) [Sampson D.M., Dubis A.M., Chen F.K., et al. Towards standardizing retinal optical coherence tomography angiography: a review. Light Sci Appl 2022; 11(1): 63; Kurysheva N.I., Maslova E.B. Optical coherence tomography with angiography function in the diagnosis of glaucoma. Bulletin of Ophthalmology. 2016; 132(5):98-102].

The closest analogue of the proposed method is a method for the same purpose, which consists in quantitative assessment of ocular blood flow using optical coherence tomography with angiography (SSADA, Angiovue, Optovue Inc.), which allows visualization of large vessels of the fundus, as well as the microvasculature of the retina and optic disc. The main parameter determined is the density of the vasculature of the region under study, namely, the radial peripapillary capillaries (RPC) in the retinal nerve fiber layer (RNFL) [Rao H.L., Pradhan Z.S., Suh M.N., et al. Optical coherence tomography angiography in glaucoma. J Glaucoma. 2020 Apr; 29 (4): 312-321. doi: 10.1097/IJG.0000000000001463].

However, with all the obvious advantages of assessing ocular blood flow and visualizing the microcirculation of the retina and optic disc, there is no information on quantitative volumetric indicators of blood circulation, and artifacts simulating blood vessels (shadows) arise, which reduces the reliability of the results obtained.

A promising innovative method for two-dimensional assessment of ocular blood flow is laser speckle flowtraffy (LSFG). The LSFG-RetFlow laser analyzer (Nidek) allows quantitative measurement of fundus perfusion in real time [Yamazaki R., Hashimoto R., Masahara H., et al. Time course in ocular blood flow and pulse waveform in a case of ocular ischemic syndrome with intraocular pressure fluctuation. Vision (Basel, Switzerland). 2020; 4 (2): 31. doi:10.3390/vision4020031]. When illuminated by a coherent radiation source - a laser, the surface of the fundus of the eye (ONH, retina and choroidal vessels) backscatters light, creating a rapidly changing “speckle field” pattern, which is dynamic in nature. The width of the fluctuation spectrum is directly proportional to the speed of blood flow. Laser speckle fluography can be considered as a screening research method in the diagnosis of eye diseases associated with impaired blood flow, since the technique is quite easy to use and has a high speed of image acquisition.

The objective of the present invention is to develop a quantitative objective method for assessing the blood circulation of the optic nerve and peripapillary region of the retina in primary open-angle glaucoma.

The technical result of the proposed method is the ability to evaluate volumetric and velocity parameters during speckle flowgraphy and ultrasound examination in the mode of color Doppler mapping and pulsed Doppler ultrasound with subsequent selection of patient management tactics.

The technical result is achieved through the use of a combination of certain parameters of LSFG and ultrasound in the Color Doppler and ID modes.

The method is carried out as follows.

Laser speckle flowgraphy (LSFG) and ultrasound examination (US) are performed in color Doppler mapping and pulsed Doppler modes. When the average image blur index (MBR) in the temporal sector of the optic disc and peripapillary retina is less than 20.30 a.u., the microvasculature blurriness index (MBR) is less than 14.50 a.u. and maximum systolic blood flow velocity (PSV) in the lateral posterior short ciliary artery of the retina according to ultrasound data below 11.00 cm/s, blood circulation is assessed as impaired.

In order to develop a method for assessing the blood circulation of the optic nerve and the peripapillary area of the retina in POAG, we analyzed data from 45 patients (90 eyes) aged 55 to 65 years (average age 59.36±6.23), of which 30 eyes were without ophthalmopathology and 60 eyes with initial and advanced stages of glaucoma. Staging of patients with glaucoma was carried out taking into account morphometric changes in the optic disc and visual field parameters. All subjects had normal blood pressure parameters, and patients with glaucoma received local antihypertensive therapy and had the necessary compensation of intraocular pressure (IOP). There were no significant differences between the groups in ophthalmopathology. Exclusion criteria were: mature cataracts, diseases of the retina or optic nerve other than glaucoma, high myopia, arterial hypertension without pressure compensation, diabetes mellitus, and taking medications that can alter ocular blood flow.

Laser speckle flowgraphy uses radiation from a semiconductor laser with a wavelength of 830 nm, which allows illumination of the heterogeneous surface of the fundus of the eye. The reflected radiation, returning to the optical system, gives the appearance of a consistent scattering pattern (“speckles”), which is captured as an image by a highly sensitive CCD camera. The received signals are processed by a computer to display images of the fundus and a two-dimensional map of blood flow, on which the distribution of the speed of movement of blood cells is visualized. To study blood flow in the target area, a total of 118 images are acquired at 30 frames per second with a shutter speed of 1/500 second over a 4 second period. The accompanying software (LSFG Analyzer) automatically captures images of the complete cardiac cycle [Anraku A., Enomoto N., Tomita G., et al. Ocular and systemic factors affecting laser speckle flowgraphy measurements in the optic nerve head. Transl Vis Sci Technol. 2021; 10 (1): 13. doi:10.1167/tvst.l0.1.13].

The first stage of blood flow measurement was carried out using the LSFG-RetFlow device (Nidek). The main indicator determined using LSFG is called the “average blurriness of the image” (Mean Blur Rate - MBR). In addition to the integral MBR indicator, you can separately calculate the MBR for large vessels (MBR of Vascular area, MV), microvascular bed (MBR of Tissue area, MT) and the area of interest (MBR of All area, MA). The average signal intensity was visualized as a “composite map” depicting the distribution of blood flow over a complete cardiac cycle.

The second stage was an ultrasound examination in the Color Doppler and ID modes in order to record blood flow and assess the main quantitative indicators of hemodynamics: maximum systolic velocity (PSV) and end-diastolic blood flow velocity (EVD) in the lateral and medial posterior short ciliary arteries (lat. CPCA and med. ZKCA).

A comprehensive examination (LSFG and ultrasound with assessment of blood circulation of the optic nerve and retina) showed that patients with POAG have a statistically significant (p <0.05) decrease in some indicators of blood circulation of the optic nerve and retina: MBR in the temporal sector of the optic disc and peripapillary retina is less than 20 ,30 USD, BW less than 14.50 USD, and PSV in the lateral CCCA below 11.39±1.78 cm/s. A retrospective analysis of volume and velocity parameters of LSFG and ultrasound in patients with POAG confirmed that the values of these parameters make it possible to assess blood circulation as impaired.

According to the results of the study, when comparing the blood flow parameters of the optic nerve and retina of the control group with groups with the initial and advanced stages of POAG, a statistically significant (p <0.05) decrease in MBR in the temporal sector, MT and PSV in the lateral CCCA was revealed. In terms of MV, MA, EDV in the lateral CCCA, PSV and EDV in the medial CCCA, no statistically significant changes were detected (Table - Parameters of blood flow of the optic nerve and retina in the studied groups).

Clinical example 1.

Patient B., 59 years old, complained of worsening vision in the right eye, which appeared 3 months ago. History of arterial hypertension, compensated by taking antihypertensive drugs. During a standard ophthalmological examination, the best corrected visual acuity (BCVA) was 0.8 on the right and 1.0 on the left, in the right eye, during ophthalmoscopy, the optic disc is pale, the boundaries are clear, the vascular bundle is slightly shifted to the nose, E/D glaucomatous 0.6, according to static MD perimetry , dB - 2.20, early stage POAG was detected in the right eye.

When conducting a comprehensive study of the blood circulation of the optic disc and retina using LSFG and ultrasound, the following parameters were determined: MBR in the temporal sector of the optic disc and peripapillary retina - 19.57 USD, MT - 14.23 USD, PSV in the lat. 10.39 cm/s, which indicates a violation of blood circulation in the studied area.

Based on the study data, the patient was recommended to receive additional conservative therapy in the form of agents that improve peripheral circulation.

Clinical example 2.

Patient B., 63 years old, complained of blurred vision and defects in the visual field of the right eye, which appeared 4 months ago. History of arterial hypertension, compensated by taking antihypertensive drugs, on OD - POAG, compensated by local antihypertensive drugs, initial stage. During a standard ophthalmological examination, the best corrected visual acuity (BCVA) was 0.7 on the right and 1.0 on the left, in the right eye, during ophthalmoscopy, the optic disc is pale, the boundaries are clear, the vascular bundle is shifted to the nose, E/D glaucomatous 0.4, according to static MD perimetry, dB - 4.20 in the right eye, compensated POAG of an advanced stage was revealed.

When conducting a comprehensive study of the blood circulation of the optic disc and retina, the following parameters were determined: MBR in the temporal sector of the optic disc and peripapillary retina - 17.57 USD, MT - 10.83 USD, PSV in the lat. s, indicating a circulatory disorder.

Based on the data obtained as a result of the study, the patient was recommended to undergo an examination of the optic nerve (OCT) in order to assess morphometric changes, prescribe conservative therapy in the form of agents that improve peripheral circulation and locally - additional hypotensive therapy in the form of installations.

Thus, the proposed method makes it possible to assess the state of the blood circulation of the optic nerve and retina in patients with POAG and accordingly adjust the management and treatment tactics of patients with POAG.

Claims (1)

A method for assessing the blood circulation of the optic nerve and the peripapillary region of the retina in primary open-angle glaucoma, characterized in that laser speckle flowgraphy (LSFG) and ultrasound examination (US) are performed in color Doppler mapping and pulsed Doppler mode and at the value of the average blurriness index (MBR) in the temporal sector of the optic disc and peripapillary retina is less than 20.30 a.u., the image blur index of the microvasculature (MT) of the optic disc and peripapillary retina is less than 14.50 a.u. and maximum systolic blood flow velocity (PSV) in the lateral posterior short ciliary artery of the retina according to ultrasound data below 11.00 cm/s, blood circulation is assessed as impaired.