RU2528817C1 - Method for prediction of risk of progressing glaucomous optic neuropathy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: total visual field degrees, intraocular pressure and maximum visual acuity in a patient suffering glaucomous optic neuropathy, and a risk of progressing glaucomous optic neuropathy is predicted by formula: y=25.8+10.9x1-0.002x2-1.5x3, wherein y is a prognostic index, x1 is a maximum visual acuity, x2 is total visual field degrees, x3 is an intraocular pressure. If observing y=1.73 and less, a high risk of progressing glaucomous optic neuropathy, i.e. for 6-8 months following the examination is stated; if observing y=1.74-4.99, a moderate risk, i.e. for 9-12 months following the examination, is determined; the value y=5.00 and more shows a low risk of glaucomous optic neuropathy, i.e. the beginning of progressing for 13-24 months following the examination.

EFFECT: method enables predicting the risk of progressing glaucomous optic neuropathy to provide well-timed prescription of the neuroprotective treatment by the ophthalmological examination.

5 tbl, 2 ex

Description

The invention relates to medicine, namely to ophthalmology, and can be used to predict the degree of risk of progression of glaucoma optic neuropathy (GON).

Primary open-angle glaucoma (POAG) is characterized by the development of glaucoma optic neuropathy and a chronic slowly progressive course.

There are various clinical and laboratory methods for predicting the course of GON.

A known method for predicting the course of GON, based on a cluster analysis of crystallograms of the lacrimal fluid of patients with glaucoma. In the process of cluster analysis of crystallograms of the tear fluid of patients with glaucoma, an unfavorable prognosis of GON flow is determined in those cases when the length of the prevailing chains of crystallograms exceeds 13 pixels for the peripheral zone of the crystallogram and 12 for the central zone, and the difference in their light intensity is lower than 52 for the peripheral zone and 44 for the central zone [Patent RU 2281023, 2006].

Collecting tears in the amount necessary to study the level of protein is long and involves some inconvenience for patients.

In the method for predicting the risk of developing and progressing glaucoma, based on determining the corneal hysteresis and the central thickness of the cornea, the biomechanical coefficient of the cornea is calculated by the formula: K = KG / CTR · 50, where K is the biomechanical coefficient of the cornea, KG is the corneal hysteresis, and CTC is the central thickness cornea. When the value of K is less than 0.82, the risk of the development and progression of glaucoma is predicted [Patent RU 2354287, 2008]. However, this method uses devices that are not available in outpatient practice - an analyzer of biomechanical properties of the eye and an ultrasonic pachymeter.

A known method for assessing the dynamics of the visual functions of a patient with glaucoma by using static perimetry [Volkov V.V. Glaucoma with pseudo-normal pressure.-M.: Medicine, 2001]. According to this method, an increase in the central field of view of the number of cattle is an unfavorable sign of the development of the disease.

According to our own data, the disadvantage of this method is the need for its repetition in dynamics (at least with an interval of one month), and an increase in the number of cattle indicates an already existing deterioration in the condition of the optic nerve.

All of the above analogues do not predict the degree of risk of progression of GON, which is necessary for timely treatment that is started correctly.

Based on the closest technical essence, as a prototype, we have chosen a method for predicting the course of glaucoma optical neuropathy, based on the determination of the total concentration of albumin (OKA) and the effective concentration of albumin (ECA) in a patient with POAG in a tear, followed by calculation of the ECA / OKA ratio. When its value is lower than or equal to 0.3, the risk of GON progression is predicted in the coming year [Patent RU 2235503, 2003].

The method chosen by us as a prototype, as well as the above analogues, does not allow us to predict the degree of risk of progression of GON, which is necessary for timely treatment that has been started and correctly selected. The disadvantage of the prototype method should also include the availability of expensive fluorimeter equipment, which is available only in specialized centers.

The technical result of the invention is the development of an affordable and cheap clinical and laboratory method for predicting the degree of risk of progression of glaucoma optical neuropathy, which will ensure the timely appointment of neuroprotective treatment.

The technical result of the invention is achieved in that in patients with glaucoma optical neuropathy, the sum of the degrees of the field of view, intraocular pressure and maximum visual acuity are determined and the risk of progression of glaucoma optical neuropathy is predicted by the formula: y = 25.8 + 10.9x1-0.002x2-1.5x3 , where y is the prognostic index, x1 is the maximum visual acuity, x2 is the sum of the degrees of the field of view (CST), x3 is the intraocular pressure (IOP). With a value of y = 1.73 and less, a high degree of risk of progression of glaucoma optical neuropathy is predicted, that is, within 6-8 months after the examination, with a value of y = 1.74-4.99 - an average risk, that is, within 9 -12 months after the examination, with a value of y = 5.00 or more, a low degree of risk is predicted, that is, the onset of progression within 13-24 months after the examination.

The method is as follows.

To predict the risk of GON progression, it is necessary to conduct a standard examination of a patient with a diagnosis of glaucoma optic neuropathy, which includes: determining the maximum visual acuity, the sum of the degrees of the field of view, measuring the intraocular pressure.

The maximum visual acuity is determined using the Sivtsev Golovin table, using a spectacle set for maximum correction. The sum of the degrees of the field of view is determined on the kinetic perimeter by 8 meridians and these indicators are summarized. Intraocular pressure is determined using a Maklakov tonometer (10.0 g).

Next, substituting the obtained data in the formula, calculate the value of "y". The risk of progression of glaucoma optic neuropathy is predicted by the formula: y = 25.8 + 10.9x ₁ -0.002x ₂ -1.5x ₃ , where y is the prognostic index, x ₁ is the maximum visual acuity, x ₂ is the sum of the degrees of the field of view, x ₃ - intraocular pressure. With a value of y = 1.73 and less, a high degree of risk of progression of glaucoma optical neuropathy is predicted, that is, within 6-8 months after the examination, with a value of y = 1.74-4.99 - an average risk, that is, within 9 -12 months after the examination, with a value of y = 5.00 or more, a low degree of risk is predicted, that is, the onset of progression within 13-24 months after the examination.

When determining the risk of progression of glaucoma optic neuropathy, table 1 is used.

Table 1 Indicators for determining the degree of risk of GON progression Groups The value of "y" Risk degree one y = 1.73 and less High degree (progression within 6-8 months after examination) 2 y = 1.74-4.99 Medium (progression within 9-12 months after examination) 3 y = 5.00 or more Low degree (progression within 13-24 months after examination)

Salient features of the proposed method are:

- in patients with GON, the sum of the degrees of the fields of vision, intraocular pressure and maximum visual acuity are determined;

- predict the risk of progression of glaucoma optical neuropathy according to the formula: y = 25.8 + 10.9x1-0.002x2-1.5x3, where y is the prognostic index, x1 is the maximum visual acuity, x2 is the sum of the degrees of the field of view, x3 is the intraocular pressure . With a value of y = 1.73 and less, a high degree of risk of progression of glaucoma optical neuropathy is predicted, that is, within 6-8 months after the examination, with a value of y = 1.74-4.99 - an average risk, that is, within 9 -12 months after the examination, with a value of y = 5.00 or more, a low degree of risk is predicted, that is, the onset of progression within 13-24 months after the examination.

According to our data, the GON development process is unidirectional and, unfortunately, has a negative progression vector. Positive, of course, is the slow rate of progression of visual impairment. It manifests itself especially clearly during the first year of observation, when the slow progression of glaucoma optic neuropathy falls within the error of the research method. As a result, by the 12-15th month of observation, a statistically significant difference accumulates [Kulikova N.K., Alekseev V.N. Assessment of the stabilization of the process in patients with primary open-angle glaucoma who received conservative, laser or surgical treatment. // Glaucoma, 2009. - No. 2. - S.30-32].

To compile a multivariate linear model, we conducted a study of 3-year (36 months) dynamics of visual functions in 182 patients with POAG with an interval of 3 months. There were no statistically significant differences between patients by gender and age. So, with long-term follow-up of patients with GON, the first statistically significant changes in visual acuity become noticeable within 12-15 months from the start of the observation, and then a slow but constantly negative dynamics remains. So during the first year of observation, visual acuity decreases by 0.06 (by about 9%), after two years by 0.16 (25% of the initial level) and, finally, after 3 years by 0.23 (35%), an average of about 10% per year.

The same negative dynamics of the glaucoma process can be seen in the analysis of the results of the kinetic perimetry of patients with POAG. In the study of CPS during the first year, the boundaries of the field of view along the 8 meridians narrowed from 361 ° ± 6 to 356 ° ± 6, that is, by 2%. After 2 years, the GPA decreased from 361 ° ± 6 to 316 ° ± 7. 12% narrowing. And finally, by the end of the third year, the sum of the degrees of the field of view decreased by 35%, from 361 ° ± 6 to 236 ° ± 9. Thus, if the deterioration of visual acuity is distributed fairly evenly over the years of observation, then the narrowing of the field of view tends to accelerate from 2% in the first year, 12% in the second and 35% in the third [Kulikova N.K., Alekseev V.N. Assessment of the stabilization of the process in patients with primary open-angle glaucoma who received conservative, laser or surgical treatment. // Glaucoma, 2009. - No. 2. - S.30-32].

Based on multivariate correlation and regression analysis, the most significant criteria for determining the risk of GON progression were determined. The result was the identification of the most significant criteria (Table 2): maximum visual acuity (x1), the sum of the degrees of the field of view (x2), intraocular pressure (x3). All coefficients of the equations are significant (p = 0.000001), and the factors taken into account have a high contribution and account for 93.3% (R ² = 0.9328) of the variation of the dependent variables, respectively. In assessing the independence of residuals for the model, the coefficient D (Darbin-Watson statistics) was 1.9. The significance of the constructed mathematical model and statistical reliability were determined by the Fisher criterion.

table 2 Source data Y (x) Observation period Y X1 X2 X3 1 month 5 0.62 373.67 18.79 2 month 4.99 0.70 391.00 18.8 3 month 4.97 0.67 354.00 18.81 4 month 4.96 0.66 355.00 18.83 5 months 4.95 0.66 351.33 18.85 6 months 4.93 0.64 352.00 18.89 7 month 4,58 0.63 348.00 18.91 8 month 4.69 0.62 349.00 18.93 9 months 4,53 0.61 347.00 18.95 10 months 3,55 0.61 349.33 18.96 11 months 3,51 0.60 347.00 18.97 12 months 3,5 0.59 347.00 18,99 13 months 2.93 0.58 346.33 19.01 14 months 2.91 0.57 344.00 19.12 15 months 2.75 0.57 343.67 19.15 16 months 2.68 0.56 341.00 19.25 17 months 2,56 0.56 342.33 19.35 18 months 2,53 0.55 341.67 19.38 19 month 2.49 0.55 340.67 19.43 20 months 2.41 0.54 340.67 19.43 21 months 1.97 0.53 340.33 19.45 22 months 1.96 0.52 339.00 19.47 23 months 1.93 0.52 336.33 19.49 24 months 1.89 0.52 335.67 19.51 25 months 1.73 0.51 336.00 19.53 26 months 1.68 0.50 335.33 19.56 27 month 1,61 0.50 334.67 19.59 28 month 1,53 0.49 334.00 19.63 29 month 1.45 0.48 332.00 19.68 30 month 1.43 0.47 329.67 19.78 31 months 1.41 0.47 330.00 19.79 32 months 1.35 0.46 328.67 19.83 33 months 1.31 0.46 327.33 19.85 34 month 1.21 0.43 322.67 19.87 35 month 1,11 0.42 321.33 19.89 36 months one 0.41 320.67 19.9

The results of multivariate regression analysis are given in table 3.

table 3 Results of multivariate regression analysis Regression statistics Multiple R 0.965857499 R-squared 0.932880708 Normalized R-squared 0.926588274 Standard error 0.37446173 Observations 36 Analysis of variance df SS Ms F
Significance F Regression 3 62,3653842 20,7884614 148,2543579
7.58357E-19 The remainder 32 4.487090796 0.140221587 Total 35 66.852475 Odds Standard error t-statistic P-value Y intersection 25,7563789 15.97958796 1,611829977 0.116819774

X1 10,94585904 4,106229725 2,665671375 0.011942934 X2 -0.001915418 0,010277053 -0.186378126 0.853324781 X3 -1,466356898 0.724865897 -2.022935421 0,051501869

To build the model, the following names were adopted: R - coefficient of multiple correlation; R ² is the coefficient of determination; adR ² is the adjusted coefficient of determination; F is the Fisher test; Df is the number of degrees of freedom for the F - criterion; t are the criteria for the coefficients of the regression equation; SS is the sum of the squared deviations; MS is the sum of mathematical expectations (Tables 4, 5).

Table 4 Accepted names for building a model No. Name in EXCEL report Accepted Items Formula one Multiple R Multiple correlation coefficient, correlation index

$$R=\sqrt{R^2}$$

2 R-squared The coefficient of determination, R ² $$R^2=\mathrm{one}-\frac{{\displaystyle \sum e{(t)}^2}}{{\displaystyle \sum {(y-\overline{y})}^2}}=\frac{{\displaystyle \sum {(y_t-\overline{y})}^2}}{{\displaystyle \sum {(y_t-\overline{y})}^2}}$$

3 Normalized R-squared Adjusted ad R ² $$\overline{R^2}=\mathrm{one}-(\mathrm{one}-R^2)\frac{n-\mathrm{one}}{n-k-\mathrm{one}}$$

four Standard error Standard error of estimation $$S_e=\sqrt{\frac{{\displaystyle \sum e{(t)}^2}}{n-k-\mathrm{one}}}$$

5 Observations The number of observations, n N

Table 5 Items for analysis of variance Df - number of degrees of freedom SS - sum of squares Ms F - Fisher test Regression k = 3

$${\displaystyle \sum {(y_t-\overline{y})}^2}$$

$${\displaystyle \sum {({\overline{y}}_t-\overline{y})}^2/k}$$

$$F=\frac{R^2/k}{(\mathrm{one}-R^2)/(n-k-\mathrm{one})}$$

The remainder n-k-1 = 32 Σe (t) ² Σe (t) ² / nk-1 Total n-1 = 31 $${\displaystyle \sum (y_t-\overline{y{)}^2}}$$

We give examples from clinical practice.

Example 1. A / c No. 2782. Patient S., 68 years old. Diagnosis: left eye - POAG developed stage compensated, glaucoma optic neuropathy. Instills antihypertensive eye drops daily once a day at night. Twice a year, she undergoes outpatient therapy. The maximum visual acuity of the left eye is 0.6. In the central field of view with static perimetry, absolute and relative scotomas are observed. The total boundaries of the peripheral fields of view along the eight meridians are 361 degrees. Tonometric pressure 19 mm Hg according to Maklakov. Electrotonographic indicators: outflow velocity coefficient C = 0.23; minute volume of chamber moisture F = 1.32. On the fundus - excavation of the optic disc 8/10 in the lower-outer segment blanching of the optic nerve disc. Using the formula y = 25.8 + 10.9x1-0.002x2-1.5x3, the value y = 3.00 was determined, based on a comparison of the obtained value with the data given in table 1, the average risk of progression of glaucoma optical neuropathy during 9 months after this examination. Taking into account normal ophthalmotonus, the patient refused to conduct neuroprotective treatment. Upon repeated examination after 6 months, against the background of normal IOP, a decrease in visual acuity to 0.5 n / k, an increase in the number of absolute cattle in the central field of vision to 9 due to a decrease in the number of relative ones was noted. The total boundaries of the peripheral fields of vision decreased by 15 °. Tonometric pressure 19 mm Hg according to Maklakov. Electrotonographic indicators: outflow velocity coefficient C = 0.22; minute volume of chamber moisture F = 1.23. The blanching of the optic disc was intensified, spreading to the upper segments. The value y = 1.70, based on a comparison of the obtained value with the data given in table 1, a high degree of risk of progression of glaucoma optical neuropathy was predicted, which required the appointment of neuroprotective and additional antihypertensive therapy.

Example 2. A / C No. 10164. Patient N., 66 years old. Diagnosis: right eye - POAG far advanced stage of compensated, glaucoma optical neuropathy. A year ago, a hypotensive operation was performed for glaucoma in order to reduce IOP. Antihypertensive drops does not apply. Neuroprotective therapy was carried out in a hospital setting. The maximum visual acuity of the right eye is 0.6. Tonometric pressure 18 mmHg according to Maklakov. Electrotonographic indicators: outflow velocity coefficient C = 0.22; minute volume of chamber moisture F = 1.30. When conducting static perimetry in the central field of view, a lot of relative cattle and several absolute ones are found. The total boundaries of the peripheral fields of view along the eight meridians are 270 degrees. Using the formula y = 25.8 + 10.9x1-0.002x2-1.5x3, the value y = 4.80 was determined, based on a comparison of the obtained value with the data given in table 1, the average risk of progression of glaucoma optical neuropathy was determined during 9 months after this examination. Considering that the neuroprotective treatment was just completed, IOP was compensated, the patient did not receive any treatment after this examination. When re-contacted after 6 months, the ophthalmological parameters changed slightly: the maximum visual acuity of 0.6; SGPZ was 270 degrees., And IOP amounted to 19 mm Hg. Using the formula y = 25.8 + 10.9x1-0.002x2-1.5x3, we determined the value y = 3.30 and compared with the data shown in table 1, which determined the average risk of progression of glaucoma optical neuropathy due to an increase in IOP . The patient was prescribed neuroprotective and additional antihypertensive therapy.

These examples indicate that determining the value of "y" according to the formula y = 25.8 + 10.9x1-0.002x2-1.5x3 can provide prognostic information that allows you to predict the degree of risk of progression of GON and prescribe neuroprotective treatment in a timely manner.

The claimed method was calculated the value of "y" according to the survey in 54 patients with POAG with glaucoma optic neuropathy. In 23 patients, a low risk of progression of glaucoma optical neuropathy was predicted, in 15 patients - medium and in 16 patients - high.

Thus, an affordable and cheap clinical and laboratory method for predicting a high, medium, and low risk of progression of glaucoma optical neuropathy has been developed, which allows us to predict the risk of GON progression within 6-8, 9-12, and 13-24 months after the examination, which in turn, provides timely appointment of neuroprotective treatment.

Claims (1)

A method for predicting the risk of progression of glaucoma optic neuropathy, consisting of a clinical laboratory study, characterized in that in a patient with glaucoma optic neuropathy, the sum of the degrees of field of view, intraocular pressure and maximum visual acuity are determined and the risk of progression of glaucoma optic neuropathy is predicted by the formula: y = 25, 8 + 10.9x ₁ -0.002x ₂ -1.5x ₃ , where y is the prognostic index, x ₁ is the maximum visual acuity, x ₂ is the sum of the degrees of the field of view, x ₃ is the intraocular pressure, and with the value y = 1, 73 and less predict a high risk of progression of glaucoma optical neuropathy, that is, within 6-8 months after the examination, with a value of y = 1.74-4.99 - an average risk, that is, within 9-12 months after the examination, with a value of y = 5.00 or more predict a low degree of risk, that is, the onset of progression within 13-24 months after the examination.