RU2297186C1 - Method for predicting tuberculosis etiology of chorioretinitis - Google Patents

Abstract

FIELD: medicine, ophthalmology.

SUBSTANCE: one should apply tuberculin samples for testing the picture of an eyeground through fixed time intervals. Ultrasound dopplerography should be used for detecting in central retinal artery (CRA) and posterior short ciliary arteries (PSCA) the values of circulation the alteration of which should be registered twice - before tuberculin samples and in 48 h. Moreover, one should register the alterations of maximal systolic velocity of circulation - Vs, minimal diastolic velocity of circulation - Vd and index of peripheral resistance - Ri; one should investigate initial state of systemic humoral immunity. Then, at the decrease of Vs threshold value by 25% and Ri increase - by 26% in CRA, and, also, Vs and Vd decrease by 35% and Ri increase by 40% in PSCA, moreover, at decreased quantity of CD22 lymphocytes by 26%, Immunoglobulins A and G by 13%, considerable increase of circulating immune complexes (CIC) ranged 64-87%, increased content of complement C3 and C4 components by 57% and 179%, correspondingly, the decrease of total hemolytic complement activity by 30%, increased content of immunoglobulin M ranged 9-27% it is possible to diagnose tuberculosis etiology of chorioretinitis. The innovation enables to state upon tuberculosis etiology of chorioretinitis at minimal manifestation of focal reaction in ocular tissues, it excludes pilot therapy and enables to shorten the terms of etiological diagnostics of tuberculosis chorioretinitis considerably.

EFFECT: higher accuracy and efficiency of diagnostics.

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Description

The invention relates to medicine, namely to ophthalmology, and can be used in the diagnosis of tuberculous etiology of chorioretinitis.

A known method for the diagnosis of active tuberculous uveitis, which consists in determining the magnitude of the change in the level of the biochemical indicator of blood serum with the introduction of tuberculin and comparing this value with a threshold value, in which the level of activity of blood serum adenosine deaminase (ADA) is used as the biochemical indicator of blood, determine the maximum value of the increase ADA activity twice at fixed time intervals after the introduction of tuberculin, reveal the maximum value of the increase in level I ADA activity baseline and a threshold value is exceeded, they diagnose active TB uveitis (Patent №2121688, RF. Publ. 10.11.1998).

However, the known method can be used only in the diagnosis of active tuberculous uveitis, while in half of the cases, uveitis is detected in the stage of calming and initial scarring. In addition, the known method is invasive, since in order to obtain results, it is necessary to examine the blood serum of patients three times, which poses a threat of infection with diseases such as hepatitis "B" and "C", AIDS.

A known method for the diagnosis of tuberculous uveitis, which consists of staging tuberculin samples for examination at fixed intervals of the fundus pattern, which use ultrasound dopplerography to determine the central artery of the retina (CAC) and posterior short ciliary arteries (CCCA) of blood flow, the change of which is recorded twice - before setting tuberculin samples and after 48 hours, while recording changes in the maximum systolic blood flow velocity - Vs, minimum diasto the personal blood flow velocity - Vd and the peripheral resistance index - Ri, and with a decrease in the threshold value of Vs by 25% and an increase in Ri by 26% in the CAC, as well as a decrease in Vs and Vd by 35% and an increase in Ri by 40%, they diagnose tuberculous etiology of uveitis (Patent No. 2231296, RF. Publ. June 27, 2004).

However, this method is used to diagnose the tuberculous etiology of uveitis of various localization (anterior, peripheral, posterior).

It is known to study systemic humoral immunity in eye tuberculosis, in which, as immunological parameters of blood serum, a decrease in the level of immunoglobulin A, an increase in circulating immune complexes, a decrease in complement activity, a decrease in the relative number of CD 22 lymphocytes, a tendency to an increase in the content of immunoglobulin M are used (Tarasova L.N. ., Panova I.E. Tuberculous eye lesions: pathogenesis, new ways to increase efficiency and treatment. Chelyabinsk, 2001. - 136 p.).

However, the results of a well-known study, based only on immunological parameters, cannot confirm that a specific tuberculous process is localized directly in the eye. In addition, the most significant changes in systemic indicators of humoral immunity are observed only with anterior localization of the tuberculous process, while posterior, generalized and intermediate uveitis of tuberculous etiology are quite common. In addition, to obtain the results, it is also necessary to study the blood serum of patients.

A known method for the diagnosis of active tuberculous choreoretinitis, in which the diagnosis of active tuberculous chorioretinitis is carried out by fluorescence fundus hagiography (FAGD). FAGD is performed on a television angiofluorimeter CO-2 (television standard) in the continuous video mode and video recording, which allows you to observe and record the distribution of fluorescein solution in the vascular system of the eye and the focus of a specific lesion. Television shooting and synchronous recording of time and circulating phases of the study can clearly identify the phenomena of hypo- and hyperfluorescence in the focus of a specific lesion. In the presence of the phenomenon of hypofluorescence in the choroidal, arterial and early venous phases, with initial marginal hyperfluorescence in the late venous or postvenous phase, followed by homogeneous accumulation of fluorescence from the periphery of the focus to the center and reaching a peak of hyperfluorescence no more than 10 min with a stable diagnosis tuberculous chorioretinitis (Patent No. 2143692 of the Russian Federation. Publish. 12/27/1999).

However, the known method provides for intravenous administration of a contrast agent, which causes a large number of contraindications to the use of the known method, in addition, the known method is not provided for the study of the initial indicators of humoral immunity.

The objective of the present invention is to increase the reliability of the diagnosis of tuberculous etiology of the inflammatory process localized in the posterior part of the eyeball due to registration of changes in hemodynamic parameters of blood flow amid provocative tests with tuberculin in combination with the initial state of systemic indicators of humoral immunity in tuberculous chorioretinitis.

The problem is solved in that in a method for the diagnosis of tuberculous etiology of chorioretinitis, including the staging of tuberculin samples for examination at fixed time intervals of the fundus pattern, ultrasound dopplerography is used to determine in the central retinal artery (CAC) and posterior short ciliary arteries (CCCA) blood flow parameters, the change of which is recorded twice - before setting tuberculin samples and after 48 hours, while the changes in the maximum systolic rate are recorded blood flow - Vs, minimum diastolic blood flow velocity - Vd and peripheral resistance index - Ri, examine the initial state of systemic humoral immunity, then with a decrease in the threshold value of Vs by 25% and an increase in Ri by 26% in CAC, as well as a decrease in Vs and Vd by 35% and an increase in Ri by 40% in SSCA, in addition, with a decrease in the number of CD 22 lymphocytes by 26%, immunoglobulins A and G by 13%, a significant increase in circulating immune complexes (CEC) from 64 to 87%, an increase in the content of complement components C3 and C4 57 and 179% respectively, bottom A decrease in the total hemolytic activity of complement by 30%, an increased content of immunoglobulin M from 9 to 27% is diagnosed with the tuberculous etiology of chorioretinitis.

The proposed method is illustrated by a detailed description and clinical examples.

The method is as follows.

Ultrasonic scanning of the vessels of the eyeball in three dimensions is carried out in the gray scale mode, color and energy Doppler mapping, working in real time. Scanning is performed, avoiding excessive pressure of the sensor on the eyeball, through the upper or lower eyelids of the closed eyeball in the standard horizontal position of the patient lying on his back without special devices.

Blood flow indices - maximum systolic blood flow velocity - Vs, minimum diastolic blood flow velocity - Vd and peripheral resistance index - Ri, are recorded in the CAC and SSCA using ultrasound dopplerography on a Medison 6000 instrument (ser. No. А34001642) before tuberculin is administered (initial values ) After the introduction of tuberculin, the same indicators are measured after a fixed period of time - 48 hours. Next, the level of changes in the value of blood flow parameters is calculated and correlated with the initial values of the indicators calculated on the basis of statistical processing of clinical trial data using the Statistica for Windous program version 5.1 of StatSoft company. A decrease in the threshold value of Vs through a fixed interval by 25% and an increase in Ri by 26% in CAC, as well as a decrease in Vs and Vd by 35% and an increase in Ri by 40% in CACA, favor the tuberculous etiology of chorioretinitis. The determination of indicators of humoral immunity in tuberculous chorioretinitis is carried out once - in the initial state. The content of immunoglobulins A, M, G, CEC, the total hemolytic activity of complement and its components in the peripheral blood is studied by a turbodimetric method. Decrease in the number of CD 22 lymphocytes by 26%, immunoglobulins A by 13%, immunoglobulins G by 13%, an increase in circulating immune complexes (CEC) from 64 to 87%, an increase in the content of complement components C3 and C4 by 57 and 179%, respectively, a decrease in the total hemolytic complement activity by 30% and an increase in the content of immunoglobulin M from 9 to 27% also suggests the presence of tuberculous chorioretinitis in the patient. But only with a combination of two signs, namely, a combination of changes in the parameters of humoral immunity with a threshold decrease in blood flow velocity in the vessels of the eye, it is possible to diagnose the tuberculous etiology of chorioretinitis.

The rationale for the claimed method is the data from clinical trials when comparing two groups of patients with tuberculosis and non-tuberculous chorioretinitis. The main group included 27 patients with tuberculous chorioretinitis in the stage of maximum activity and initial remission. The control group included 21 patients with chorioretinitis of nonspecific etiology. The etiology of tuberculosis in patients of the main group was established on the basis of three main diagnostic criteria, namely: the characteristic clinical picture, the presence of a focal reaction in response to the introduction of tuberculin, and the therapeutic effect of the trial treatment with tuberculostatics. In the control group, similar studies were carried out, however, focal reactions were negative or doubtful, and trial treatment did not give a positive result, which was the basis for the exclusion of the tuberculous etiology of chorioretinitis.

In the main group, in all patients, a decrease in the threshold value of Vs through a fixed interval by 25% and an increase in Ri by 26% in CAC, as well as a decrease in Vs and Vd by 35% and an increase in Ri by 40% in CCCA, were noted. In addition, a decrease in the number of CD 22 lymphocytes by 26%, immunoglobulins A by 13%, immunoglobulins G by 13%, an increase in circulating immune complexes (CEC) from 64 to 87%, an increase in the content of complement components C3 and C4 by 57 and 179% were recorded accordingly, a decrease in the total hemolytic activity of complement by 30% and an increased content of immunoglobulin M from 9 to 27%.

In the control group, a decrease in Vs and an increase in Ri in CAC, a decrease in Vs and Vd, and an increase in Ri in SCCA did not reach the threshold level in 100% of cases, as well as indicators of systemic humoral immunity in blood serum.

The data obtained indicate a high diagnostic significance of the totality of the proposed indicators: their sensitivity and specificity when the threshold level is exceeded is 95.7 and 97.8%, respectively.

Example 1 implementation of the proposed method.

Patient D., medical history No. 13246, 33 years old, was admitted to the Department of Eye Microsurgery (MHG) of the Kurgan Regional Hospital on May 14, 2005 due to peripheral focal chorioretinitis of the left eye, visual acuity of the right eye is 1.0, and the left eye is 0.2 not corrected. The field of vision of both eyes is not changed. Pathology in the right eye was not detected. On the periphery of the fundus of the left eye in the lower section, an active focus of a round shape with fuzzy boundaries was determined, which mediated into the vitreous body, with pronounced exudation over its surface. Due to pronounced exudative changes in the vitreous, it was not possible to determine the etiology of chorioretinitis reliably from the clinical picture. After achieving stabilization of inflammation and performing clinical, x-ray and laboratory examinations and ultrasound dopplerography, on May 26, 2005, the patient was given a Mantoux test of 2 TE. After 48 hours, the exudation into the vitreous body sharply increased, which did not allow us to assess the condition of the chorioretinal focus. Therefore, the focal reaction was recorded as doubtful. Dopplerography revealed a decrease in V max and an increase in Ri in CAC, as well as a decrease in Vs and Vd and an increase in Ri in SCCA, reaching a threshold level. Given the pronounced exudative component of inflammation, further tuberculin diagnostics of the patient was contraindicated, in connection with which she was prescribed trial treatment (6.0 ml of a 10% solution of isoniazid intramuscularly, pyrazinamide 1.0 g by mouth, 0.5 ml of a 5% solution of saluside parabulbar ) After 18 days, a distinct positive dynamics was noted: the focus was flattened, the boundaries of the inflammatory focus improved, exudation on the surface of the focus and in the vitreous body significantly resolved, due to which visual acuity increased to 0.5. In the study of systemic humoral immunity in this patient, a decrease in the number of CD 22 lymphocytes by 26%, immunoglobulins A by 13%, immunoglobulins G by 13%, an increase in circulating immune complexes (CEC) from 64 to 87%, an increase in the content of complement components C3 and C4 by 57 and 179%, respectively, a decrease in the total hemolytic activity of complement by 30% and an increased content of immunoglobulin M from 9 to 27%.

Thus, the tuberculous etiology of chorioretinitis was established taking into account the clinical picture, focal response to 2 TE and the therapeutic effect of the trial treatment for five weeks. Based on a change in the threshold level of blood flow parameters against the background of provocative tests with tuberculin in combination with the threshold level of indicators of systemic humoral immunity, it is possible not to conduct trial therapy (three weeks), but to begin complex anti-tuberculosis therapy immediately, which is very important in this severe case of tuberculosis chorioretinitis and can reduce the time of diagnosis by half.

Example 2 implementation of the proposed method.

Patient L., medical history No. 16593, 45 years old, was admitted to the Department of Eye Microsurgery (MHG) of the Kurgan Regional Hospital on August 5, 2005 due to chronic, recurrent central chorioretinitis of the left eye. Visual acuity of the left eye of 0.3 is not corrected, the right eye of 1.0. Field of vision of both eyes without pathology. In the left eye, a weakly expressed mixed injection of the conjunctiva was noted, in the front and middle layers of the vitreous body inflammatory cellular elements (++) were detected. On the fundus in the posterior pole region there is a rough chorioretinal focus 1.5 PD with fuzzy borders and abundant pigment deposition. There are no changes registered in the right eye. The clinical picture in this patient was characteristic of tuberculous chorioretinitis, and the recurrent course of the disease necessitated the exclusion of tuberculous etiology of the disease. On August 8, 2005, the Mantoux 2TE reaction was delivered after a clinical minimum of the examination and ultrasound dopplerography. After 48 hours, the patient had a general reaction in the form of subfebrile condition, general weakness, joint pain. Papule 18 mm with vesicles (hyperergic reaction). No focal reaction was observed. The introduction of a larger dose of tuberculin was contraindicated by a TB doctor due to a hyperergic skin reaction. Dopplerography performed after 48 hours showed a slight decrease in Vs and an increase in Ri in CAC, as well as a decrease in Vs and Vd and an increase in Ri in CSCA, which did not reach the threshold level. In the study of systemic humoral immunity, the registered indicators in this patient also did not reach the threshold level. On the recommendation of the phthisiatrician, a trial treatment was carried out (6.0 ml of a 10% solution of isoniazid intramuscularly, pyrazinamide 1.0 g by mouth, 0.5 ml of a 3% solution of isoniazid parabulbarno). Against the background of the trial treatment, no improvement in the clinical picture was noted, in addition, after 34 days the inflammatory infiltration of the vitreous body intensified, which was the reason for its cancellation.

Thus, despite the Mantoux hyperergic reaction, the tuberculous etiology of chorioretinitis in this patient was excluded on the basis of the lack of a focal reaction and the ineffectiveness of trial therapy. Unregistered decrease in blood flow by the threshold level 48 hours after tuberculin administration and the studied indicators of systemic humoral immunity, also not reaching the threshold level, confirm the results of the survey.

The proposed method allows to ascertain the tuberculous etiology of chorioretinitis with minimal severity of the focal reaction in the tissues of the eye, thereby reducing the risk of visual impairment, eliminates trial treatment and significantly reduces the time for the etiological diagnosis of tuberculous chorioretinitis.

In addition, the proposed method is non-invasive and does not pose a threat of infection with serious diseases (hepatitis, AIDS). It can be used for the posterior localization of the tuberculosis process in the choroid and various degrees of inflammatory activity. It has no contraindications for its use in patients, it can be used on an outpatient basis, basic diagnostic equipment is used for its implementation.

The proposed method is used in the state regional institution Kurgan Regional Clinical Hospital.

Claims (1)

A method for the diagnosis of tuberculous etiology of chorioretinitis, including staging tuberculin samples for examination at fixed time intervals of the fundus pattern, characterized in that ultrasound dopplerography is used to determine the central retinal artery (CAC) and posterior short ciliary arteries (CCCA) of blood flow parameters, the change of which is recorded twice - before setting tuberculin samples and after 48 hours, while recording changes in the maximum systolic blood flow velocity - Vs, minimum diastolic blood flow velocity - Vd and peripheral resistance index - Ri, examine the initial state of systemic humoral immunity, then with a decrease in the threshold value of Vs by 25% and an increase in Ri - by 26% in CAC, as well as a decrease in Vs and Vd by 35% and increase Ri by 40% in SCCA, in addition, with a decrease in the number of CD 22 lymphocytes by 26%, immunoglobulins A and G by 13%, a significant increase in circulating immune complexes (CIC) from 64 to 87%, an increase in the content of complement components C3 and C4 by 57% and 179%, respectively, a decrease in total hemoliti eskoy compliment activity by 30%, the increased content of immunoglobulin M from 9 to 27% diagnose the etiology of tuberculosis chorioretinitis.