RU2669735C1 - Method for predicting the risk of progression of glaucoma - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology, and can be used to predict the risk of progression of glaucoma. Determine the velocity of the pulse wave (PWV) in the arteries of the upper and lower extremities, flow-dependent vasodilation (HDV) of the brachial artery in a sample with reactive hyperemia, the total antioxidant capacity of blood serum (AOS), the level of depression (Ud) on the depression scale AT. Beka. In this case, the speed of propagation of the pulse wave is determined with the help of sphygmomanometry. Regression value F is calculated using the mathematical formula: F = 0.152 + 1.053 × PWV_worse – 2.007 × HDV - 0.075 × AOC + 0.891 × Ud, where PWV_worse is the worst of the pulse wave velocity from the right and left sides. Then calculate the risk factor for the progression of glaucoma Krp:Krp = 1/(1 + e^(-F)), where e is a mathematical constant equal to 2.718. At a value of the risk factor for the progression of Krp≤0.5 predict a low risk of glaucoma progression. If the risk factor for progression is known, Krp>0.5 predict a high risk of glaucoma progression.

EFFECT: method provides data with high sensitivity and specificity for monitoring the patient's condition and determining the need for optimization of treatment tactics by calculating the regression value F using a mathematical formula.

1 cl, 1 dwg, 1 tbl, 3 ex

Description

The invention relates to ophthalmology and is intended to predict the risk of progression of glaucoma optic neuropathy, taking into account comorbid pathology.

A known method for predicting the risk of developing and progressing glaucoma (See Patent RU No. 2610565, IPC A61F 3/00 publ. February 13, 2017) in which bi-directional corneal pneumoplasty is performed, determines the internal pressure according to Goldman, CH (corneal hysteresis) - corneal hysteresis, CRF (corneal resistance factor) is the corneal resistance factor and the coefficient of biomechanical stress of the fibrous membrane of the eye is calculated by the formula:

Kbs = IOPg / CH + CRF.

With a Kbs value of 1.1 or more, the risk of developing and progressing glaucoma is predicted.

The disadvantage of this method is the unidirectional study of only local factors of GON progression without taking into account systemic risk factors.

This drawback is due to the choice of only one mechanical pathogenetic factor for the progression of glaucoma - IOP, taking into account the biomechanical parameters of the cornea. As you know, glaucoma is a multifactorial disease and elimination of local risk factors for progression without correction of systemic factors will not stop the progression of GON.

There is also a method of determining the risk of progression of glaucoma, described in patent RU No. 2599208, IPC A61F 3/00 publ. 10.10.2016) in which, using the assessment of the elastic properties of the cornea and sclera, the eyes determine the elasto-lifting coefficient for Schiotz differential tonometry (γ _S ) and for Maklakov elastotonometry (γ _M ). Their ratio is calculated by the formula K = γ _S / γ _M then, when its K value is more than 2.4, the risk of glaucoma progression is determined.

The disadvantage of this method is the high probability of damage to the cornea and ocular surface, which in the case of glaucoma is extremely undesirable, because due to the constant instillations of antihypertensive drops in 89% of patients with POAG, an ocular surface disease is initially observed.

This disadvantage is due to the fact that with the known method, a long-term effect on the cornea is carried out when performing elastotonometry according to two methods without interruption on the same eye, i.e. contact method of performing the methods: differential tonometry according to Schiotz and elastotonometry according to Maklakov with loads of different weights under local anesthesia, the absence of a GlauTest 60 tonograph in many institutions. In addition, with the known method, only the biomechanical component, the elastic-elastic properties of the cornea and sclera, is contributed to the progression of glaucoma. .

A known method for predicting the course of glaucomatous optic neuropathy by laboratory research, which is based on the determination of the patient with POAG in a tear, the total concentration of albumin (OKA) and the effective concentration of albumin (ECA), which then calculates the level of ECA / OKA and if its value is lower or equal 0.3 predict the risk of progression of glaucomatous optic neuropathy over the coming year (see patent RU No. 2235503, IPC A61B 5/145, G01N 33/68, publ. 10.09.2004).

The disadvantage of this method is the complexity, inaccessibility and low accuracy of determining the level of ECA / OKA.

This drawback is due to the need to use expensive equipment - a fluorimeter, which is available only in a few specialized centers and the complexity of the tear collection technique.

Closest to the claimed invention is adopted as a prototype method for predicting the risk of progression of glaucoma optical neuropathy, described in patent RU No. 2530588 IPC G01N 33/50, publ. 07/30/2013, in which the level of lactate in the blood of patients with glaucoma is determined and the relationship between the level of lactate and the progression of glaucoma optical neuropathy (GON) is proved. If the lactate level is higher than 4.33 mmol / l, the risk of GON progression is predicted within 1 year after the examination.

The disadvantage of this method is the lack of data with high sensitivity and specificity for subsequent monitoring of the patient's condition and determine the need for optimization of treatment tactics.

This drawback is due to the fact that only the severity of oxidative stress, namely lactate, is taken into account to identify the risk of glaucoma progression, but oxidative stress is a universal damage mechanism characteristic of many age-related diseases: hypertension, coronary heart disease, diabetes mellitus, etc., but not may act in isolation as a predictor of GON progression without taking into account other pathogenetic mechanisms, especially in conditions of concomitant comorbid pathology in a patient Comrade POAG.

The technical task of the invention “Method for predicting the risk of glaucoma progression" is to obtain data with high sensitivity and specificity for subsequent monitoring of the patient's condition and determine the need for optimization of treatment tactics.

The technical result of the claimed invention "A method for predicting the risk of glaucoma progression" is to determine the risk of progression of primary open-angle glaucoma based on a combination of systemic factors of comorbid pathology that increase the risk of glaucoma progression: increased stiffness (rigidity) of the arteries of the upper and lower extremities, characterizing atherosclerotic lesions of the vascular system; endothelial dysfunction, which determines vasoregulatory and vasomodulating vascular function; a decrease in antioxidant protection of blood serum and an increase in oxidative damage; unstable psycho-emotional state of patients, leading to the development of depression.

The technical result is achieved by the fact that in the known method for predicting the risk of glaucoma progression, according to the invention, the pulse wave propagation speed (PWV) in the arteries of the upper and lower extremities is determined using sphygmomanometry, the flow-dependent vasodilation (PZVD) of the brachial artery is determined in a sample with reactive hyperemia, determine the total antioxidant ability of blood serum (AOS), the severity of depression (UD) is determined on a scale of depression A.T. Beck and calculate the value of the regression F using a mathematical formula:

F = 0.152 + 1.053 × PWV_worse-2.007 × PZVD - 0.075 × AOC + 0.891 × Ud,

where PWV_worse is the worst of the pulse wave velocity indicators on the right and left sides;

then calculate the risk factor for the progression of glaucoma CRP:

Krp = 1 / (1 + e ^(-F) ),

where e is the mathematical constant equal to 2.718;

and with a risk factor for progression of CRP ≤0.5, a low risk of glaucoma progression is predicted, with a CRP value> 0.5, a high risk of glaucoma progression is predicted.

Between the distinguishing features and the achieved technical result, there is the following causal relationship.

Unlike analogs and prototypes, determining the value of regression using a mathematical formula based on a set of independent indicators characterizing the stiffness (rigidity) of limb arteries, vascular endothelial function, antioxidant ability of blood serum and the severity of depression in patients with primary open-angle glaucoma allows to determine the risk of primary progression open-angle glaucoma based on a combination of systemic factors of comorbid pathology that increase the risk of prog glaucoma testing. The determination of the pulse wave propagation velocity (PWV_worse) in the arteries of the upper and lower extremities allows us to evaluate the stiffness (rigidity) of the vascular wall and obtain information on the general condition of the vascular system, the risk of developing atherosclerotic damage. Determination of flow-dependent vasodilation (PVDV) allows you to evaluate the functional vasoregulatory ability of the vascular endothelium, and a study of the state of the antioxidant system in the blood serum (AOS) makes it possible to identify the severity of oxidative damage. Determination of the level of severity of depression (UD) on the scale of depression A.T. Beck allows you to determine the assessment of the contribution of disorders of the psycho-emotional sphere to the progression of the disease. The set of all independent indicators characterizing the comorbid pathology makes it possible to calculate the regression value according to the formula:

F = 0.152 + 1.053 × PWV_worse-2.007 × PZVD - 0.075 × AOC + 0.891 × Ud,

PWV_worse - the worst of the pulse speed indicators on the right and left sides.

Having obtained the regression value, after the logit transformation, the risk factor for the progression of glaucoma is calculated using the mathematical formula:

Krp = 1 / (1 + e ^(F) ),

where e is the mathematical constant equal to 2.718;

Further determination of the membership in a subgroup of persons with a low or high risk of glaucoma progression is carried out by a certain risk factor for progression, namely: with a value of CRP ≤0.5, a low risk of glaucoma progression is predicted with a value of CRP> 0.5, a high risk of glaucoma progression is predicted. Thus, the combination of essential features allows us to determine the risk of progression of primary open-angle glaucoma based on a combination of systemic factors of comorbid pathology that increase the risk of glaucoma progression, namely: increased stiffness (rigidity) of the arteries of the upper and lower extremities, which characterizes atherosclerotic lesion of the vascular system; endothelial dysfunction, which determines vasoregulatory and vasomodulating vascular function; a decrease in antioxidant protection of blood serum and an increase in oxidative damage; unstable psycho-emotional state of patients, leading to the development of depression.

An analysis of the prior art by the applicant, including a search by patent and scientific and technical sources of information and identification of sources containing information about analogues of the claimed invention, “A method for predicting the risk of glaucoma progression,” allowed us to establish that the applicant did not find a source characterized by signs that are identical to all essential features of the claimed technical solution. According to the information available to the applicant, the totality of all the essential features of the claimed invention "Method for predicting the risk of glaucoma progression" is not known from the prior art, which allows us to conclude that the claimed invention "Method for predicting the risk of glaucoma progression" meets the criterion of "novelty".

The definition from the list of identified analogues of the prototype, as the closest in the totality of the characteristics of the analogue, allowed us to identify a set of significant, relative to the perceived by the applicant technical result, distinctive features in the claimed invention "Method for predicting the risk of progression of glaucoma" set forth in the claims. Therefore, the claimed invention "A method for predicting the risk of progression of glaucoma" meets the criterion of "novelty."

To verify the conformity of the claimed invention "Method for predicting the risk of progression of glaucoma" to the criterion of "inventive step", the applicant conducted an additional search for known solutions to identify a set of features that match the distinctive features of the claimed invention "Method for predicting the risk of progression of glaucoma". The search results showed that the claimed invention "A method for predicting the risk of glaucoma progression" does not follow explicitly from the prior art, since the effects identified by the combination of essential features of the claimed invention and transformations to achieve a technical result are not revealed from the prior art. Therefore, the claimed invention "Method for predicting the risk of progression of glaucoma" meets the criterion of "inventive step".

Thus, the above information indicates the receipt, when using the claimed invention "Method for predicting the risk of glaucoma progression," of data with high sensitivity and specificity for subsequent monitoring of the patient's condition and determine the need for optimization of treatment tactics, as well as additional technical results in the form of improving other technical and operational of possibilities, therefore, the claimed invention "A method for predicting the risk of progression Ucomy ”meets the criterion of“ industrial applicability ”.

The set of essential features characterizing the essence of the invention can be repeatedly used in a highly technological and, at the same time, relatively inexpensive process for predicting the risk of glaucoma progression with obtaining a technical result consisting in the possibility of predicting the risk of glaucoma progression with determining the worst of the pulse wave velocity indicators on the right and left side, flow-dependent vasodilation, total antioxidant ability of serum cr vi, the level of depression and receiving data at a high sensitivity and specificity for the subsequent monitoring of the patient's condition and determine whether to optimize the treatment strategy.

The essence of the claimed invention "Method for predicting the risk of progression of glaucoma" is illustrated by the description of the method, Fig. 1 - which shows the ROC-curve of the method for predicting the risk of glaucoma progression and examples of specific performance, as well as the Appendix “DEPRESSION SCALE A.T. BEKA "(Adult version)

The claimed "Method for predicting the risk of progression of glaucoma" was carried out as follows.

The regression value was determined using a mathematical formula, based on a set of independent indicators characterizing the stiffness (rigidity) of limb arteries: the functions of the vascular endothelium, the antioxidant ability of blood serum and the severity of the depressed state in patients with primary open-angle glaucoma, for which the pulse wave propagation velocity (PWV_worse) was determined and assessment of stiffness (rigidity) of the vascular wall, allowing to obtain information about the general condition of the vascular system, the risk of development atherosclerotic damage, characterizing the stiffness (rigidity) of the arteries of the extremities, while initially assessing the stiffness of the vascular wall, for which the pulse wave velocity - Pulse Wave Velocity (PWV) was determined using sphygmomanometry, taking into account the fact that high speed is directly proportional to high stiffness. The increased stiffness (rigidity) of the arteries of the limbs provides direct information about the damage to the vessels of the organs of the target and has predictive value for assessing the progression of the disease. The pulse wave propagation velocity, as the value used to detect earlier atherosclerosis, makes it possible to suggest the progression of the atherosclerotic process and evaluate the effectiveness of the therapy. The study was carried out using a VaSera VS-1000 Fukuda Denshi sphygmomanometer, using the main patient examination mode, maintaining the required temperature and humidity in the room. Before the start of the study, time was given to the patient to relax and calm down, for this he was laid on his back and kept in this position for minutes, after which, without changing the patient's position, they put on cuffs marked with a color:

- on the shoulders, put on color-cuffed cuffs so that the center of the shoulder cuff (the junction with the duct) is above the center of the inner surface of the shoulder, and the lower edge is directly above the elbow bend;

- the cuffs marked in color were put on the shins so that the lower edge of the ankle cuff was 1 cm higher than the ankle joint, and the connection with the air duct was fixed above the inner ankle, then the electrodes for recording the electrocardiogram (ECG) and the FKG microphone for recording acoustic FCG signal.

After that, the pulse wave propagation velocity (PWV), ankle-brachial index (ABI), blood pressure (BP) on the shoulders and legs were measured non-invasively, and the CAVI (Cardio-Ankle Vascular Index - cardio-ankle vascular index) was determined by recording plethysmograms on 4 limbs (using cuffs), electrocardiogram (ECG), phonocardiogram (FCG). Measurements were performed sequentially, first on the right shoulder and lower leg, then on the left shoulder and lower leg. For the model, the worst value of the indicators was chosen to demonstrate the general manifestations of the systemic pathological process. Next, the assessment of the vasoreactive function of the brachial artery endothelium was determined, and a test with reactive hyperemia was performed. To study the degree of endothelial dysfunction (ED), a sample with reactive hyperemia was performed on an En Visor ultrasound device from Philips. After determining the vasoreactive function of the brachial artery endothelium, flow-dependent vasodilation (PASV) was determined with an ultrasound vascular probe (7 MHz) from the change in brachial artery diameter. Reactive hyperemia was modeled by cuff occlusion of the brachial artery for 8 minutes, while the brachial artery was subjected to temporary compression, after which the response of the vessel to the elimination of occlusion was evaluated. In the B-mode, the right brachial artery was located at the level of the distal segment of the shoulder, after which a pressure of 50 mmHg was pumped in the pneumatic cuff of the tonometer, located proximal to the location. exceeding systolic blood pressure. After 8 min, occlusion was stopped, the brachial artery was re-located from the 30th to the 90th second from the moment of cuff decompression, the diameter of the brachial artery was measured manually according to the boundaries of the media intima of the near wall and the lumen-intima of the far wall of the vessel, and the initial diameter of the artery (ID) and the diameter of the artery at 30, 60 and 90 seconds from the moment of decompression of the cuff. Normally, the brachial artery expands by 0.2-0.5 mm. The calculation of flow-dependent vasodilation (PZVD) was carried out according to the formula:

PZVD (%) = (DRG - ID) / ID⋅100,

where DRG is the maximum diameter against a background of reactive hyperemia.

Normally, after decompression, the artery should expand by 0.2-0.5 mm and increase in blood flow velocity due to the accumulation of tissue metabolites during occlusion (mainly adenosine, a powerful vasodilator of tissue origin), as well as the direct tonogenic effect of the blood flow itself or, more precisely, the shear stress of the PZVD. In conditions of endothelial dysfunction, as a rule, a "perverted" response is observed. Moreover, the more pronounced endothelial dysfunction (ED) of the studied artery, the less will be its dilatation (up to a paradoxical reaction). The degree of dilatation of the brachial artery against the background of the sample with reactive hyperemia by more than 10% of the initial diameter was recognized as normal. A lower value or detection of vasoconstriction was regarded as a pathological reaction. The severity of endothelial dysfunction (ED) was assessed by the results of tests with reactive hyperemia. According to experts, the average error of the method was 0.04 mm, and the maximum error did not exceed 0.1 mm. The variability of the results is not more than 1%. In clinical trials in large cohorts of patients, an increase in arterial diameter by 2% as a result of treatment is sufficient to judge an improvement in endothelial function. The method is very useful for assessing early changes in arterial tone disorders and their reversibility and has been widely used both in Russia and abroad.

To assess the state of the antioxidant system in blood serum, the total antioxidant ability of blood serum (AOC) was determined using the ImAnO × (TAS / TAC) Kit reagent kit from lmmundiagnostik (Germany). AOS was expressed in micromoles of peroxide decomposed by antioxidants per liter of serum and was determined by the formula using the standard. To evaluate AOS, the data recommended by the manufacturers of the kits were used: less than 280 μmol / l - low AOS; from 280-320 μmol / l - average AOS, more than 320 μmol / l - high AOS.

Next, the severity of depression (Ud) was determined. To identify the level of severity of depression (depressive state), a survey was conducted on a scale (test questionnaire) of depression A.T. Beck.

DEPRESSION SCALE A.T. BEKA

Adult option

The questionnaire contains assertion groups. Read each group of statements carefully. Then, identify in each group one statement that best matches how you felt THIS WEEK AND TODAY. Check the box next to the selected statement. If several statements from the same group seem equally suitable for you, then check the boxes next to each of them. Before making your choice, make sure you read All the statements in each group »

one.

- 0 I do not feel upset, sad.

- 1 I'm upset.

- 2 I’m upset all the time and I can’t disconnect from it.

- 3 I am so upset and unhappy that I can not stand it.

2.

- 0 I do not worry about my future.

- 1 I feel puzzled by the future.

- 2 I feel that nothing expects me in the future.

- 3 My future is hopeless, and nothing can change for the better.

3.

- 0 I do not feel like a failure.

- 1 I feel that I have suffered more failures than other people.

- 2 When I look back at my life, I see many failures in it.

- 3 I feel that as a person I am a complete loser.

four.

- 0 I get as much satisfaction from life as before.

- 1 I do not get as much satisfaction from life as before.

- 2 I no longer receive satisfaction from anything.

- 3 I am not completely satisfied with my life, and I'm tired of everything.

5.

- 0 I do not feel guilty of anything.

- 1 Quite often, I feel guilty.

- 2 Most of the time I feel guilty.

- 3 I constantly feel guilty.

6.

- 0 I do not feel that I can be punished for anything.

- 1 I feel that I can be punished.

- 2 I expect to be punished.

- 3 I feel already punished.

7.

- 0 I was not disappointed in myself.

- 1 I was disappointed in myself.

- 2 I am disgusted with myself.

- 3 I hate myself.

8.

- 0 I know that I am no worse than others.

- 1 I criticize myself for mistakes and weaknesses.

- 2 I always blame myself for my actions.

- 3 I blame myself for all the bad things that are happening.

9.

- 0 I never thought to commit suicide.

- 1 Thoughts come to me to commit suicide, but I will not carry them out.

- 2 I would like to commit suicide.

- 3 I would kill myself if I had the chance.

10.

- 0 I pay no more than usual.

- 1 Now I pay more often than before.

- 2 Now I cry all the time.

- 3 I used to be able to cry, but now I can’t, even if I want to.

eleven.

- 0 Now I am no more irritable than usual.

- 1 I'm more easily annoyed than before.

- 2 Now I constantly feel annoyed.

- 3 I became indifferent to things that annoyed me before.

12.

- 0 I have not lost interest in other people.

- 1 I am less interested in other people than before.

- 2 I almost lost interest in other people.

- 3 I completely lost interest in other people.

13.

- 0 I put off making decisions sometimes, as before.

- 1 More often than before, I put off making a decision.

- 2 It’s more difficult for me to make decisions than before.

- 3 I can no longer make decisions.

fourteen.

- 0 I do not feel that I look worse than usual.

- 1 It worries me that I look old and unattractive.

- 2 I know that there have been significant changes in my appearance that make me unattractive.

- 3 I know that I look ugly.

fifteen.

- 0 I can work as well as before.

- 1 I need to make an extra effort to start doing something.

- 2 I hardly force myself to do anything.

- 3 I can not do any work at all.

16.

- 0 I sleep as well as before.

- 1 Now I sleep worse than before.

- 2 I wake up 1-2 hours earlier, and it is difficult for me to fall asleep again.

- 3 I wake up a few hours earlier than usual and can no longer fall asleep.

17.

- 0 I get tired no more than usual.

- 1 Now I get tired faster than before.

- 2 I get tired of almost everything I do.

- 3 I cannot do anything because of fatigue.

eighteen.

- 0 My appetite is not worse than usual.

- 1 My appetite has become worse than before.

- 2 My appetite is now much worse.

- 3 I have no appetite at all.

19.

- 0 Recently, I have not lost weight or weight loss was negligible.

- 1 Recently, I have lost more than 2 kg.

- 2 I lost more than 5 kg.

- 3 I lost more than 7 kg.

I intentionally try to lose weight and eat less (cross-check).

WELL NO_

twenty.

- 0 I am not worried about my health more than usual.

- 1 I am worried about my physical health problems, such as pain, indigestion, constipation, etc.

- 2 I am very concerned about my physical condition, and it is difficult for me to think about anything else.

- 3 I am so concerned about my physical condition that I can’t think of anything else.

21.

- 0 Recently, I did not notice a change in my interest in sex.

- 1 I’m less concerned about sex than before.

- 2 Now I am much less interested in sexual problems than before.

- 3 I completely lost my sexual interest.

Total score

- 0-9 - lack of depressive symptoms

- 10-15 - mild depression (subdepression)

- 16-19 - moderate depression

- 20-29 - severe depression (moderate)

- 30-63 - severe depression

Subscales

- Paragraphs 1-13 - cognitive-affective subscale (SA)

- Paragraphs 14-21 - subscale of somatic manifestations of depression (S-P)

Individual symptoms

It is also possible to evaluate separately the severity of 21 symptoms of depression:

1. Mood

2. Pessimism

3. Feeling of bankruptcy

4. Dissatisfaction

5. Guilt

6. The feeling that I will be punished

7. Self-loathing

8. Ideas of self-incrimination

9. Suicidal thoughts

10. Tearfulness

11. Irritability

12. Violation of social ties

13. Indecision

14. Body image

15. Loss of performance

16. Sleep disturbance

17. Fatigue

18. Loss of appetite

19. Weight Loss

20. Body Coverage

21. Loss of libido

The depression test questionnaire included 21 question-approval of the most common symptoms and complaints. Paragraphs 1–13 included questions of the cognitive-affective subscale (C-A), paragraphs 14–21 included questions related to somatic manifestations of depression (S-P). The patient was asked to carefully read each group of statements. Then the patient determined one statement in each group that best corresponded to how he felt this week and today, after which the patient ticked the selected statement. If several statements from one group seemed to the patient the same, well suited, he chose all the answers.

For each category, each point on the scale was evaluated from 0 to 3 in accordance with the increase in the severity of the symptom. The total score ranged from 0 to 62 and decreased in accordance with the improvement. The test results were interpreted as follows: 0-9 - no depressive symptoms, 10-15 - mild depression (subdepression), 16-19 - moderate depression, 20-29 - severe depression (moderate), 30-63 - severe depression. After determining the level of severity of depression (UD) on a scale (test questionnaire) of depression A.T. Beck, the regression value (F) was determined using the mathematical formula:

F = 0.152 + 1,053 × PWV_worse - 2,007 × PZVD - 0,075 × AOS + 0,891 × Ud,

where PWV_worse is the worst of the pulse wave velocity indicators on the right and left sides,

Following this, after the logit transformation with the calculation of the separation point, the risk factor for the progression of glaucoma was calculated:

Krp = 1 / (1 + e ^(-F) ),

where CRP is the risk factor for progression;

e is a mathematical constant equal to 2.718,

after that, membership in a subgroup of people with a low or high risk of glaucoma progression was determined: with a risk factor for progression of CRP ≤ 0.5, a low risk of glaucoma progression was predicted with a CRP value> 0.5, a high risk of glaucoma progression was predicted.

The specificity of this model was 97.3% sensitivity -98.0%; on average, 97.6% of the initial grouped observations presented in table No. 1 were correctly classified. The indicator of the forecast accuracy for the risk of glaucoma progression was the area under the ROC curve - for the developed model it was 0.998 (p <0.001), which corresponds to the very good quality of the model shown in Fig. 1 - ROC-curve of the method for predicting the risk of glaucoma progression and testified to the high informative value of the proposed markers for predicting the risk of glaucoma progression: the worst of the pulse wave velocity indicators on the right and left sides, flow-dependent vasodilation, total serum antioxidant ability, depression level.

The claimed method was implemented in examples of specific performance.

EXAMPLE 1. Patient N., 65 years old. Diagnosis: POAG of the initial stage, the right eye, IOP is normalized by hypotonics; POAG of the advanced stage, IOP is normalized by surgery and hypotonics. Concomitant diseases: GB, IHD, COPD. The CIRS-G scale comorbidity index was 21 points (max 56 bps), the CIRS-G scale general severity index was 2.67 units (max 4 units). The patient addressed to identify the risk of GON progression of the right eye. Tonometric pressure 19/17 mm Hg according to Maklakov, which corresponds to the average norm. Electrotonographic and hemodynamic parameters within the age norm. Maximum visual acuity with a correction of 0.8 / 0.4. The total field of view along the 8 meridians is 519/140. Static perimetry revealed a general decrease in retinal photosensitivity (threshold strategy KP-30), relative and absolute scotomas, the mD index was -1.40 dB for the right eye and -20.2 dB for the left eye. With ophthalmoscopy, ed. on the right 5/10, the configuration of the neuroretinal girdle is preserved, on the left 9/10, marginal excavation of the optic nerve head. Structural changes in the retina were noted on OCT: the layer of retinal nerve fibers (START) for the right and left eyes was 79/56, the average retinal ganglion cell complex (CGC cf.) was 78/57, respectively, the volume of focal loss of retinal ganglion cells (GCS) was 6 , 1 / 16.6, the volume of diffuse losses - 13.2 / 28.1. When sphygmomanometry revealed an increase in the propagation speed of the pulse wave in the arteries of the upper and lower extremities to 15.6 m / s, which indicated an increased stiffness of the arteries. Next, flow-dependent vasodilation (PVDV) was calculated in a sample with reactive hyperemia, a result of 4.5% was obtained, which corresponded to moderate endothelial dysfunction. The study of the state of the antioxidant system revealed a decrease in the total antioxidant ability of blood serum (AOS) to 204.7 μmol / L, which meant an extreme degree of severity of oxidative stress in this patient. Questioning revealed mild depression (18 points). When calculating the integral risk coefficient of progression, a result of 0.99 was obtained.

(F = 0.152 + (1.053 × 15.6) - (2.007 × 4.5) - (0.075 × 204.7) + (0.891 × 18) = 8.252)

After the logit transformation with the calculation of the separation point, we obtained the value of the risk coefficient of progression:

Krp = 1 / (1 + 2.718 ^(8.252) ) = 0.99

Thus, the value of the CRP progression risk coefficient is> 0.5, therefore, it is possible to predict a high risk of GON progression in both eyes in this patient, although according to the results of all studies (morphometric, functional), convincing data for the progression of glaucoma in the right eye were not found. The patient remained on the previous antihypertensive treatment, refused the proposed consultation of related specialists for the correction of lipid metabolism, metabolic disorders, supporting antioxidant therapy and psychocorrection in the glaucoma school of patients.

However, after 1 year of observation, morphometric and functional studies revealed signs of glaucoma progression in the right eye, the mD index was -3.44 for the right eye and -24.2 dB for the left eye, which confirms the legitimacy of using the proposed coefficient to predict glaucoma progression and treatment correction.

EXAMPLE 2. Patient C, 66 years old, Diagnosis: POAG of the developed stage of both eyes, IOP is normalized by hypotonics. Concomitant diseases: GB, apnea, DEP. The comorbidity index on the CIRS-G scale was 10 points (max 56 b.), The index of general severity on the CIRS-G scale was 1.52 units (max 4 units). The patient turned to the next dispensary appointment. No complaints. Tonometric pressure 18/18 mm Hg according to Maklakov, which corresponds to the average norm. Electrotonographic and hemodynamic parameters within the age norm. Maximum visual acuity with a correction of 0.9 / 1.0. The total field of view along the 8 meridians is 490/490. Static perimetry revealed a general decrease in photosensitivity of the retina (threshold strategy KP-30), paracentral relative scotomas, the mD index was -5.23 dB for the right eye and -4.26 dB for the left. With ophthalmoscopy, ed. both eyes 6/10. On OCT: the layer of retinal nerve fibers (START) for the right and left eyes was 75/67, the average retinal ganglion cell complex (CPG cf.) was 72/69, respectively, the volume of focal loss of retinal ganglion cells (GCS) was 7.1 / 6 , 9, the volume of diffuse losses is 14.2 / 13.6. With sphygmomanometry, a pronounced increase in the propagation velocity of the pulse wave in the arteries of the upper and lower extremities 16.8 m / s was revealed. When calculating the flow-dependent vasodilation (PZVD) in the sample with reactive hyperemia, the result was 5.9%, which corresponds to moderate endothelial dysfunction. The total antioxidant ability of blood serum (AOS) was within the age norm of 378 μmol / L. Questionnaire on the test - questionnaire Beck showed that the patient is in a state of severe depression (29 points). When calculating the integral risk coefficient of progression, the result is 0.97.

(F = 0.152 + (1.053 × 16.8) - (2.007 × 5.9) - (0.075 × 378.0) + (0.891 × 29) = 3.502)

After the logit transformation, with the calculation of the separation point, we obtained the value of the risk coefficient of progression:

Krp = 1 / (1 + 2.718 ^(3.502) ) = 0.97

Thus, the value of the risk factor for the progression of CRP> 0.5, therefore, it is possible to predict a high risk of glaucoma progression in this patient. The patient was recommended the supervision of a cardiologist and therapist with the correction of endothelial dysfunction, revealed changes in lipid metabolism, metabolic disorders. In parallel with the treatment by a cardiologist and therapist, the patient underwent a course of psychocorrectional treatment with a psychotherapist, attended classes at the School of Patients with Glaucoma. After 1 year of observation, morphometric and functional studies revealed stabilization of the glaucoma process, the mD index was -4.21 for the right eye and -2.76 dB for the left eye, the pulse wave propagation velocity improved, the function of the vascular endothelium, the manifestations of depressive moods decreased, improved psycho-emotional state of the patient. This confirms the possibility of the claimed method not only to predict the risk of disease progression, but purposefully and in a timely manner to influence the identified disorders characterizing the psycho-somatic comorbid background, thereby increasing the effectiveness of personalized therapy and rehabilitation.

EXAMPLE 3. Patient T., 83 years old. Diagnosis: POAG of the initial stage of both eyes, IOP is normalized by hypotonics. It has been observed for 6 years, the condition is stable. Concomitant diseases: GB, IHD. The comorbidity index on the CIRS-G scale was 7 points (max 56 b.), The index of general severity on the CIRS-G scale was 1.22 units (max 4 units). The tonometric pressure is 20/21 mm Hg according to Maklakov, which corresponds to the average norm. An age-related decrease in the rate of outflow of intraocular fluid to C = 0.14 / 0.12, hemodynamic parameters within the age norm is determined electrotonographically. Maximum visual acuity with a correction of 0.6 / 0.6, decreased vision due to age-related cataracts and AMD. The total field of view along the 8 meridians is 510/510. Static perimetry revealed a general decrease in retinal photosensitivity (threshold strategy KP-30), the mD index was 5.19 for the right eye and 2.32 dB for the left. With ophthalmoscopy, ed. both eyes 5/10. On the OST: the layer of retinal nerve fibers (RNF) for the right and left eyes was 73/68, the average retinal ganglion cell complex (KGC cf.) was 70/66, respectively, the volume of focal loss of retinal ganglion cells (GCS) was 5.1 / 5 , 4, the volume of diffuse losses is 10.2 / 12.6, which corresponds to the functional loss of retinal ganglion cells, taking into account old age. With sphygmomanometry, an increase in the propagation velocity of the pulse wave in the arteries of the upper and lower extremities to 16.4 m / s was revealed. Flow-dependent vasodilation (PVDV) in the sample with reactive hyperemia was 7.4%, which corresponds to mild endothelial dysfunction. The total antioxidant ability of blood serum (AOS) was within the age norm and amounted to 306 μmol / L. Questioning on the Beck scale revealed moderate depression (20 points). When calculating the integral risk coefficient of progression, the result is 0.08.

(F = 0.152 + (1.053 × 16.4) - (2.007 × 7.4) - (0.075 × 306.0) + (0.891 × 20) = - 2.578)

After the logit transformation with the calculation of the separation point: the value of the risk coefficient of progression

Krp = 1 / (1 + 2.718 ^(2.578) ) = 0.08.

Thus, the value of the risk factor for progression of CRP is <0.5, therefore, it is possible to predict a low risk of glaucoma progression in this patient. The patient was recommended to continue to instill hypotensive drops, to attend classes of the School of patients with glaucoma. Conducting courses of neuroprotective therapy is impractical, the frequency of visits to an ophthalmologist 1 time per year. After 2 years of observation, morphometric and functional studies revealed stable visual functions, the mD index was 5.81 for the right eye and -3.14 dB for the left. On the fundus without negative dynamics. Thus, the claimed Method for predicting the risk of glaucoma progression allows to optimize the management and treatment tactics based on an individual approach to each patient. With a risk factor for progression of CRP ≤0.5, a low risk of glaucoma progression is predicted, with a CRP value> 0.5, a high risk of glaucoma progression is predicted.

The alleged invention "A method for predicting the risk of glaucoma progression" improves the accuracy of early diagnosis of glaucoma progression, since it provides the ability to predict the risk of glaucoma progression by determining the severity of stiffness (rigidity) of the arterial wall, endothelial dysfunction, oxidative stress and depressive disorders and obtaining data with high sensitivity and specificity for subsequent monitoring of the patient's condition and determination the need to optimize treatment tactics.

Claims (8)

1. A method for predicting the risk of glaucoma progression, characterized in that they determine the pulse wave propagation speed (PWV) in the arteries of the upper and lower extremities, the flow-dependent vasodilation of the brachial artery in a sample with reactive hyperemia, and the total antioxidant ability of blood serum (AOS) , the level of severity of depression (UD) on the scale of depression A.T. Beck and calculate the value of the regression F using a mathematical formula: F = 0.152 + 1,053 × PWV_worse - 2,007 × PZVD - 0,075 × AOS + 0,891 × Ud, where PWV_worse is the worst of the pulse wave velocity indicators on the right and left sides, then calculate the risk factor for the progression of glaucoma CRP: Krp = 1 / (1 + e ^(-F) ), where e is the mathematical constant equal to 2.718, and with a risk factor for progression of CRP ≤0.5, a low risk of progression of glaucoma is predicted, with a value of CRP> 0.5, a high risk of progression of glaucoma is predicted. 2. The method according to p. 1, characterized in that the propagation velocity of the pulse wave is determined using sphygmomanometry.

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