RU2766808C1 - Diagnostic method for the degenerative stage of retinal angiopathy in patients with hiv and tuberculosis co-infection - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely ophthalmology, and can be used to diagnose the pre-degenerative stage of retinal angiopathy in patients with HIV and TB co-infection. Spectral optical coherence tomography is performed. At the same time, by means of spectral optical coherence tomography, the caliber of retinal arteries and veins of the first order is measured twice with an interval of six months at a distance of 0.5-0.75 of the disc diameter from the edge of the optic nerve disc, and retinal arteries and veins of the second order are measured at the site of their first bifurcation, as well as retinal thickness measurement in the macular region. If a decrease in the caliber of vessels and a decrease in the thickness of the retina are recorded, while the difference in the average values of the corresponding retinal arteries of the first order is at least 12%, retinal arteries of the second order at least 11%, retinal veins of the first order at least 13%, retinal veins of the second order at least 15%, and the decrease in the thickness of the retina in the macular region occurs by 3.5-6.4% of the initially measured and reaches the indicators corresponding to the norm, then the pre-degenerative stage of retinopathy is diagnosed.

EFFECT: method provides the determination of the pre-degenerative stage of retinal angiopathy in patients with HIV and tuberculosis co-infection due to the prognostically significant characteristics of retinal vessels.

1 cl, 5 dwg, 1 ex

Description

The invention relates to medicine, namely to ophthalmology, and is intended for diagnosing the predegenerative stage of angioretinopathy in patients co-infected with HIV and tuberculosis.

In modern conditions, the incidence of HIV infection continues to grow, while tuberculosis of various localizations prevails among secondary diseases. Microcirculation disorders in the form of narrowing of arterioles and dilatation of venules in patients with co-infection with HIV and tuberculosis have a multiorgan character, including lesions of various structures of the eye. Against the background of the use of antiretroviral therapy (ART) in HIV-infected patients, the structure of the pathology of the organ of vision has changed. If in the era before ARVT the main disease leading to irreversible loss of vision in these patients was cytomegalovirus retinitis, now its proportion has slightly decreased, but a high level of eye damage and a decrease in visual functions in this group persist and are due to the development of HIV-associated retinopathy, cataracts, uveitis, macular edema, epiretinal membranes, retinal detachment and other pathological processes. Timely diagnosis of the state of the eye structures is a necessary condition for choosing an adequate management strategy and maintaining the quality of life of these patients.

A known method of dynamic calibrometry of retinal vessels (patent RU 2393755, 3.17.09.2008, op. 27.03.2010), including spectral optical coherence tomography.

A known method of calibrometry of retinal vessels of the first order using spectral optical coherence tomography (patent RU 2456909, 3.09.06.2011, op. 27.07.2012).

Both methods are not intended for diagnosing the predegenerative stage of angioretinopathy in patients co-infected with HIV and tuberculosis. They are carried out at the stage of clear clinical symptoms to determine indications for treatment, assess the dynamics and predict the course of various eye diseases.

The closest analogue, taken as a prototype, is a method for preclinical diagnosis of damage to the organ of vision, carried out by performing spectral optical coherence tomography (the article "Modern methods of preclinical diagnosis of damage to the organ of vision in sarcoidosis", published on the website of the breast cancer (Russian Medical Journal): No. 3 ( 1) dated March 30, 2018, pp. 9-11; authors: Skornyakov S.N., Sabadash E.V., Medvinsky I.D., Demin A.P. and others. branch of the Federal State Budgetary Institution NMIC FPI of the Ministry of Health of Russia, Yekaterinburg https://www.rmj.ru/articles/bolezni_dykhatelnykh_putey/Sovremennye_metody_doklinicheskoy_diagnostiki_poragheniya_organa_zreniya_pri_sarkoidoze/#ixzz5ZwCannFg). The known method is used for preclinical diagnosis of damage to the organ of vision in sarkidosis of the pulmonary and extrapulmonary localization. The disadvantage of this method is that it is not applicable for the diagnosis of the predegenerative stage of angioretinopathy in patients co-infected with HIV and tuberculosis.

The problem to be solved by the claimed invention is the development of a highly informative non-invasive method for the early diagnosis of angioretinopathy in patients with co-infection with HIV and tuberculosis based on accurate measurement of the diameter of the retinal vessels and the thickness of the retina in the macular region using optical coherence tomography.

The problem to be solved by the claimed invention is to increase the efficiency of diagnosis and treatment of severe eye lesions in patients with HIV/tuberculosis co-infection, reduce the risk of complications leading to irreversible loss of visual function and disability of patients.

The technical result of the claimed invention is the identification of prognostically significant characteristics of the vessels of the retina, allowing the most accurate diagnosis of the predegenerative stage of angioretinopathy in patients with co-infection with HIV and tuberculosis. Also, the technical result is to increase the efficiency of diagnosis and treatment of severe eye lesions in patients with co-infection with HIV and tuberculosis, to reduce the risk of complications leading to irreversible loss of visual function and disability of patients.

To achieve the claimed technical result in a method for diagnosing the predegenerative stage of angioretinopathy in patients with co-infection with HIV and tuberculosis, including spectral optical coherence tomography, according to the invention, by means of spectral optical coherence tomography, twice with an interval of six months, the measurement of the caliber of the retinal arteries and veins of the first order at a distance of 0.5-0.75 disc diameter from the edge of the optic disc, and retinal arteries and veins of the second order - at the site of their first bifurcation, as well as measuring the thickness of the retina in the macular region, and if a decrease in the caliber of the vessels and a decrease in the thickness are recorded the retina, while the difference in the average values of the indicators of the corresponding retinal arteries of the first order is at least 12%, the retinal arteries of the second order - at least 11%, the retinal veins of the first order - at least 13%, the retinal veins of the second order - at least 15%, and reduction in retinal thickness macular region occurs at 3.5-6.4% of the initially measured and reaches normal values, then the pre-degenerative stage of angioretinopathy is diagnosed. The invention is illustrated by drawings.

In FIG. 1 shows a method for diagnosing the predegenerative stage of angioretinopathy in patients with co-infection with HIV and tuberculosis, Nerve Fiber 3D Disc map in SLO mode, search for a measurement point for the caliber of retinal vessels.

In FIG. 2 - the same, Nerve Fiber 3D Disc map in En Face mode, measuring the caliber of retinal vessels at the selected point.

In FIG. 3 the same, a table with the average values of the retinal vessel diameter according to calibermetry in the group of patients with co-infection with HIV and tuberculosis (μm).

In FIG. 4 - the same, a table with average values of the thickness of the entire retina in the macular zone (µm M±m) in patients with co-infection with HIV and TB.

In FIG. 5 - the same, initial degenerative changes: thinning of the retina in the fovea, vitreoretinal traction.

The inventive method is carried out as follows.

Initially, a standard ophthalmological examination was performed, as well as OCT using the iVue-100 Version 3.3 device (Optovue, USA). Then carry out the measurement of the caliber of the retinal arteries and veins of the first and second order. To do this, after searching for the studied vessel and the measurement point of its caliber in the SLO mode on the tomogram (Fig. 1), the height of its shadow is measured using the En Face measurement option. All measurements of the vessels of the first order are carried out at a distance of 0.5-0.75 of the diameter of the disk from the edge of the optic disc, the vessels of the second order - at the site of their first bifurcation. The slider is moved from the top wall of the vessel to the bottom. The length of the perpendicular between the walls corresponds to the diameter of the vessel (Fig. 2). The results are displayed in absolute values, in micrometers. The calibers of 8 vessels of the 1st order of each eye are measured: upper temporal and nasal arteries and veins, lower temporal and nasal arteries and veins, and 8 vessels of the 2nd order: upper temporal and nasal arteries and veins, lower temporal and nasal arteries and veins.

To assess the state of the retina, patients measure the thickness of the entire retina in the macular area using the Retina Map option on the iVue-100 Version 3.3 device (Optovue, USA).

The examination is carried out initially upon inclusion in the study, then every month for six months with data recording after 3 and 6 months.

For statistical data processing, the program "Statistica 6" is used.

On the basis of the clinic of the Ural Research Institute of Phthisiopulmonology - a branch of the Federal State Budgetary Institution "National Medical Research Center for Phthisiopulmonology and Infectious Diseases" of the Ministry of Health of Russia, studies were carried out according to the claimed method.

Exclusion criteria: presence of vascular pathology proven by instrumental methods, previously diagnosed retinal angiopathy, diabetes mellitus of the first or second type, clouding of the eyes (for example, the presence of cataracts), the presence of nystagmus, the presence of any pathology excluding the possibility of fixing the gaze during the examination.

Two groups were formed.

The first group (19 people (38 eyes)) consisted of patients of both sexes, aged 33-35 years, co-infected with HIV and tuberculosis. The stage of HIV infection was characterized by the number of CD4+ cells from 200 to 400, the viral load was not more than 5 thousand copies. All patients received ART (three drugs, no intolerance reactions) for no more than two years. The secondary disease in patients of this group is tuberculosis of pulmonary or extrapulmonary localization, detected no more than a year ago, of which 12 people (63%) were bacterial excretors, 7 (37%) were multidrug resistant. All patients received continuous chemotherapy with specific antibiotics in accordance with the spectrum of drug sensitivity, without intolerance reactions.

The control group (20 people (40 eyes)) consisted of healthy volunteers of both sexes aged 25 to 45 years.

In all groups, a standard ophthalmological examination was performed, as well as an examination according to the claimed method.

During a standard ophthalmological examination, no pathological changes were detected in patients of the control group at all stages, and in patients with co-infection with HIV and tuberculosis until the sixth month of the examination.

The results of calibrometry of retinal vessels in patients with co-infection with HIV and tuberculosis and healthy volunteers are presented in the table of Fig. 3. Mean vessel caliber values are presented at initial examination, after three (second appointment) and six (third appointment) months. Calibration data in patients of the control group did not have significant differences over the entire observation period.

The data obtained indicate a decrease in the average value of the caliber of arteries of the first order in patients with co-infection with HIV and tuberculosis during the initial examination by 15.2% from the corresponding indicators in healthy volunteers. At the same time, the caliber of arteries of the II order and veins of the I order slightly (by 3%), and the veins of the II order more significantly (by 10.8%) exceed the data of the control group. During the examination after three months, we noted the following dynamics in the state of the retinal vessels: narrowing of the caliber of arteries of the I and II order by 12% and 11%, respectively, veins of the I and II order by 13% and 15%, respectively, from the initial examination. The results of the examination after six months indicate the continuation of this trend: narrowing of the caliber of arteries of the I and II order by 19% and 17.6%, respectively, veins of the I and II order by 25% and 27.2%, respectively, from the initial examination.

The average values of the thickness of the entire retina in the macular area according to the results of OCT with the Retina Map option in patients with co-infection with HIV and tuberculosis and in the control group are presented in the table in Fig. 4 shows the indicators recorded during the initial visit, after three (second visit) and six (third visit) months. In the control group, retinal thickness indicators remained stable throughout the entire examination period.

The results obtained indicate an increase in the thickness of the retina in all areas of the macular area in patients with co-infection with HIV and tuberculosis at the initial examination. The average values of the thickness of the entire retina exceed those of the control group: in the fovea zone - by 4%, parafovea - by 6.6%, perifovea - by 7.5%. An examination conducted after three months demonstrates a gradual decrease in the thickness of the entire retina: in the fovea by 3.5%; parafovea - an average of 5.5%; perifovea - 6.4% of the original data. At the same time, the retinal thickness indicators at this stage began to correspond to the limits of the norm and were comparable with the control group, which could be erroneously interpreted as the normal state of the retina. Examination data after 6 months record a further decrease in the thickness of the retina: in the fovea by 12.8%, parafovea - by 12.2%, perifovea - by 14.1%. Dynamic observation demonstrates an obvious tendency towards a gradual thinning of the retina in the macular zone in this group of patients, which indicates the progression of the degenerative process.

Thus, when observing patients with co-infection with HIV and tuberculosis, an ophthalmological examination using the OCT method and taking into account the previously presented prognostically significant characteristics allowed us to pay attention to the following stages in the state of the retina of these patients: angioretinopathy in the edema stage (first appointment) without clinical manifestations is accompanied by an increase in the caliber of the retinal veins in relation to the indicators of the caliber of the veins in the control group and the thickness of the retina in the macular region; the pre-degenerative stage of angioretinopathy (pseudonorma), also without clinical manifestations, is characterized by a narrowing of the caliber of the retinal vessels and a decrease in the thickness of the retina in the macular zone almost to the values corresponding to the limits of the norm, which can be mistaken for a normal state; and angioretinopathy in the stage of degeneration with a progressive decrease in the caliber of the retinal vessels and further thinning of the retina in the macular zone, which in some cases is accompanied by patient complaints of visual dysfunctions (distortions, decreased vision) and the appearance of clinical symptoms (violation of the retinal profile in the macular zone, vitreoretinal traction) fixed by OCT (Fig. 2).

Thus, it has been established that the dynamics of the parameters of the caliber of the retinal vessels and its thickness in the macular zone in patients with co-infection with HIV and tuberculosis, as well as their ratio, are diagnostically significant indicators for determining the prognosis of further visual functions in this group of patients.

Identification of prognostically significant characteristics of the caliber of retinal vessels in relation to the thickness of the retina in the macular area makes it possible to diagnose preclinical pathology of the posterior segment of the eye in patients with co-infection with HIV and tuberculosis. Dynamic monitoring of these indicators makes it possible to timely determine the pre-degenerative stage of angioretinopathy even before the patient complains of impaired visual functions and pathological changes in the state of the eye structures, recorded during a standard ophthalmological examination. The proposed method allows to increase the efficiency of diagnosis and treatment of eye lesions in patients with co-infection with HIV and tuberculosis, to reduce the risk of severe complications leading to a decrease in visual function and disability.

The implementation of the claimed method is illustrated by an example from clinical practice.

Patient A., 40 years old. IB No. 3247. On August 6, 2018, he was admitted to the FGBU UNIIF in the department of osteoarticular tuberculosis with a diagnosis of Combined tuberculosis. Tuberculous spondylitis Th6-L1,L3 spondylitis stage, peak phase, complicated by paravertebral swell abscess. Tuberculosis of the bones of the left foot. Fistulous form. PCR(+). Tuberculosis of the soft tissues of the chest wall. Infiltrative tuberculosis of the upper zone of the left lung with bilateral seeding. MBT (-). B20 4 B stage, ARVT. Chronic viral hepatitis C. No complaints about the organs of vision.

Initially, the patient underwent a standard ophthalmological examination: Vis OD=1.0; VisOS=1.0. OU - The pattern of the iris is not changed, the pigment border is preserved, the photoreaction is alive. The lens is transparent. The optic disc is pale pink, the boundaries are clear. The caliber of vessels is compared. The macular area is not changed. Intraocular pressure OD=21 mm Hg. Art., IOP OS=21 mm Hg. Art.

Fundus photography with calibrometric analysis using the iVue-100 Version 3.3 device (Optovue, USA): using the previously described method, we measured the diameters of arteries and veins of the I and II orders in different quadrants. After analyzing the diameters of the retinal arteries of the 1st order (84 μm, 85 μm, 78 μm, 76 μm) and the retinal arteries of the 2nd order (72 μm, 74 μm, 69 μm, 67 μm), when assessing the diameters of the retinal veins of the 1st order (126 μm, 133 µm, 128 µm, 127 µm) and II order (119 µm, 123 µm, 120 µm, 118 µm). Measurement of the thickness of the entire retina was carried out using the Retina Map option (273 µm, 346 µm, 337 µm, 333 µm, 335 µm, 326 µm, 306 µm, 315 µm, 324 µm.).

Diagnosis: Angiopathy of the retina in both eyes. OCT revealed: an increase in the thickness of the retina (retinal edema) in the macular zone using the Retina Map program.

Three months later, patient A. underwent a follow-up examination. A standard ophthalmological examination, OCT of the anterior and posterior segment of the eye, and vascular calibrometry were performed. The patient did not complain about the organ of vision. Ophthalmological examination: VOD=1.0, VOS=1.0, OD OS is calm. The cornea OD OS is transparent, PC OD OS is of medium depth. Moisture PC OD OS transparent. Iris OD OS - structural. The pigment border is preserved. Lens OD OS - initial opacities in the cortical layers. Fundus OU: ONH-pale pink. The contours are clear. Prominence - no. Macular area - without pathological foci. Edema - no. Break - no. Arteries-N. Vienna-N. Diagnosis: Hypermetropia 1 degree in both eyes. OCT revealed:

Fundus photography with calibrometric analysis using the iVue-100 Version 3.3 device (Optovue, USA): using the previously described method, we measured the diameters of arteries and veins of the I and II orders in 4 quadrants. After analyzing the diameters of the retinal arteries of the 1st order (70 µm, 75 µm, 69 µm, 70 µm) and the retinal arteries of the 2nd order (64 µm, 62 µm, 61 µm, 62 µm), we revealed a decrease in the average diameter value relative to the patient’s initial data of at least than by 12 and 11%, respectively; when assessing the diameters of the retinal veins of the 1st order (111 µm, 116 µm, 109 µm, 108 µm) and the 2nd order (101 µm, 101 µm, 103 µm, 99 µm), a decrease in the average value of the caliber of the retinal veins by at least 13 and 15% respectively.

Measurement of the thickness of the entire retina was carried out using the Retina Map option: 265 µm, 327 µm, 319 µm, 311 µm, 316 µm, 298 µm, 292 µm, 305 µm, 294 µm.

OCT revealed: a decrease in the thickness of the retina in the macular zone using the Retina Map program by 4% relative to the initial data, the indicators correspond to the norm.

The data obtained indicate the presence of a pre-degenerative stage of angioretinopathy in patients with co-infection with HIV and tuberculosis, taking into account further negative dynamics during the control examination six months later, at which, after a standard ophthalmological examination, OCT of the anterior and posterior segment of the eye and vascular calibrometry were performed. The patient did not complain about the organ of vision. Ophthalmological examination: VOD=1.0, VOS=1.0, OD OS is calm. The cornea OD OS is transparent, PC OD OS is of medium depth. Moisture PC OD OS transparent. Iris OD OS - structural. The pigment border is preserved. Lens OD OS - initial opacities in the cortical layers. Fundus OU: ONH-pale pink. The contours are clear. Promotion - no. The macular area is without pathological lesions. Edema - no. Rupture - no. Artery-N. Vienna-N. Diagnosis: Hypermetropia 1 degree in both eyes. OCT revealed:

Fundus photography with calibrometric analysis using the iVue-100 Version 3.3 device (Optovue, USA): using the previously described method, we measured the diameters of arteries and veins of the I and II orders in different quadrants. After analyzing the diameters of the retinal arteries of the 1st order (61 μm, 65 μm, 68 μm, 60 μm) and the retinal arteries of the 2nd order (56 μm, 54 μm, 58 μm, 53 μm), we revealed a decrease in the diameter of the average value by at least 21 and 22%, respectively, relative to the initial data (at least 32 and 16%, respectively, relative to the control group); when assessing the diameters of the retinal veins of the 1st order (96 μm, 102 μm, 103 μm, 101 μm) and the 2nd order (98 μm, 96 μm, 99 μm, 89 μm), a decrease in the average value of the caliber of the retinal veins by at least 19 and 22%, respectively, from the initial data (at least 18 and 6%, respectively, relative to the control group).

Measurement of the thickness of the entire retina was carried out using the Retina Map option: 239 µm, 302 µm, 297 µm, 291 µm, 294 µm, 280 µm, 277 µm, 276 µm, 265 µm.

OCT revealed: a decrease in the thickness of the retina in the macular zone using the Retina Map program by 11% relative to the initial examination and by 8% relative to the norm.

Thus, there was a negative dynamics in the state of the retina in the absence of patient complaints and the preservation of visual functions.

Claims (1)

A method for diagnosing the pre-degenerative stage of angioretinopathy in patients with co-infection with HIV and tuberculosis, including spectral optical coherence tomography, characterized in that, by means of spectral optical coherence tomography, the caliber of retinal arteries and veins of the first order is measured twice with an interval of six months at a distance of 0 .5-0.75 of the disc diameter from the edge of the optic disc, and of the retinal arteries and veins of the second order - at the site of their first bifurcation, as well as measuring the thickness of the retina in the macular region, and if a decrease in the caliber of the vessels and a decrease in the thickness of the retina are recorded, while the difference in the average values of the indicators of the corresponding retinal arteries of the first order is at least 12%, the retinal arteries of the second order - at least 11%, the retinal veins of the first order - at least 13%, the retinal veins of the second order - at least 15%, and the decrease in the thickness of the retina in macular area occurs at 3.5-6.4% of the original measured and reaches normal values, then the pre-degenerative stage of retinopathy is diagnosed.

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