RU2644699C1 - Method for evaluation of efficiency of treatment of chronic blepharitis by laser doppler flowmetry - Google Patents

Method for evaluation of efficiency of treatment of chronic blepharitis by laser doppler flowmetry Download PDF

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RU2644699C1
RU2644699C1 RU2017112066A RU2017112066A RU2644699C1 RU 2644699 C1 RU2644699 C1 RU 2644699C1 RU 2017112066 A RU2017112066 A RU 2017112066A RU 2017112066 A RU2017112066 A RU 2017112066A RU 2644699 C1 RU2644699 C1 RU 2644699C1
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treatment
blood flow
chronic blepharitis
eyelids
neurogenic
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RU2017112066A
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Russian (ru)
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Татьяна Николаевна Сафонова
Наталия Павловна Кинтюхина
Виктор Васильевич Сидоров
Ольга Владимировна Гладкова
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Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт глазных болезней"
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/06Measuring blood flow

Abstract

FIELD: medicine.
SUBSTANCE: invention relates to medicine, specifically, to ophthalmology, and can be used to evaluate the effectiveness of treating chronic blepharitis. Doppler laser flowmetry of the eyelid is performed before and after the course of treatment. Neurogenic and myogenic oscillations of the microcirculation of blood flow and lymph flow are determined. With an increase of at least one of them by 3 % or more after the course of treatment, the treatment is evaluated as effective.
EFFECT: method provides objectification of the evaluation of the effectiveness of treatment of chronic blepharitis for the definition and correction of treatment tactics.
1 cl, 1 dwg, 2 ex

Description

The present invention relates to ophthalmology and is intended to assess the effectiveness of the treatment of chronic blepharitis by laser Doppler flowmetry (LDF). Chronic blepharitis is a general term that combines the inflammatory process on the skin of the eyelids, in the eyelash follicles and in the meibomian glands. This is usually a two-way, intermittent process that affects all age groups. The incidence of blepharitis is 37-47% of the total number of ophthalmic patients. A number of authors noted a high percentage (60-70%) of the development of dry eye syndrome in patients with chronic blepharitis [T.N. Safonova, N.P. Kintyukhina, A.E. Petrenko, O.V. Gladkova. Prevention of dry eye syndrome in chronic blepharitis of demodectic etiology. Breast cancer. Clinical Ophthalmology. 2016; 16 (2): 89-931. The treatment of blepharitis is long, requiring a local and systemic approach with the involvement of narrow specialists. However, subjective blepharitis symptoms may persist when a clinical evaluation of the signs indicates an improvement. The effectiveness of treatment is evaluated according to the results of clinical, functional tests, which is subjective. The severity of subjective symptoms, frequent relapses of the disease, the formation of dry eye syndrome, the need for multiple courses of therapy make us look for new methods of treatment for blepharitis, which is aimed at stopping the inflammatory process and preventing the development of dry eye syndrome [Sun XG, Zhou YM, Jiang C., Wang ZQ, Zhang Y. Study on the clinical manifestation of 438 cases with blepharitis. Chinese journal of ophthalmology. 2013; 49 (10): 878-83].

To assess the effectiveness of the treatment of chronic blepharitis, a biomicroscopic determination of clinical signs (the presence of an uneven edge of the eyelids, telangiectasia of the eyelid edge, scales, debris, "couplings" on the eyelashes) is used, a compression test is carried out, the number of functioning meibomian glands, the functional state of the meibomian glands, the Norne test are determined, Schirmer I test, Lipkof test, tests with vital dyes [T.N. Safonova, N.P. Kintyukhina, A.P. Petrenko, O.V. Gladkova. Prevention of dry eye syndrome in chronic blepharitis of demodectic etiology. Breast cancer. Clinical Ophthalmology. 2016; 16 (2): 89-93; Safonova T.N., Zabegailo A.O., Makarov I.A. A method for determining the degree of blepharoconjunctival form of dry eye syndrome. 2500 340. 2013 .; Avetisov S.E., Fedorov A.A., Polunin G.S., Pimenidi M.K. A method for determining the functional state of meibomian glands. 2,373,832. 2009; D. Korb. Methods for diagnosing meibomian gland dysfunction. A61B 3/10. 2010; Safonova T.N., Vasiliev V.P., Likhvantseva V.G. Sjogren's syndrome. M .: Publishing house of Moscow University; 2013].

The closest analogue of the proposed method is a method for evaluating the effectiveness of the treatment of chronic blepharitis, which consists in a compression test. Compression test is a method of screening diagnosis of the state of the meibomian glands and their secret. The test is carried out behind a slit lamp by means of a tapered compression of the eyelid with a fingertip near the front rib and the possibility of evacuation of the secret of meibomian glands along the entire length of the eyelid is determined. The condition of the ducts and the secretion of the meibomian glands is evaluated on a J. Shimazaki [J. Shimazaki, M. Sakata, K. Tsubota. Ocular surface changes and discomfort in patients with meibomian gland dysfunction. Archives of ophthalmology. 1995; 113 (10): 1266-70; Amano S., Clinic-based study on meibomian gland dysfunction in Japan. Investigative ophthalmology & visual science. 2017; 58 (2): 1283-1287].

This assessment method is mediated through the determination of the functional state of the meibomian glands. However, the condition of the eyelids before and after treatment is evaluated subjectively, while the structure of the eyelids is not taken into account in full, including the study of interstitial tissue and the determination of inflammation of the eyelids.

The task of the invention is to develop a new method for evaluating the treatment of chronic blepharitis.

The technical result of the invention is the objectification of evaluating the effectiveness of the treatment of chronic blepharitis to determine and correct treatment tactics.

The technical result is achieved by assessing the state of micro- and lymphocirculation of the skin of the eyelids using LDF.

It is known that one of the main components of eyelid inflammation is a change in microcirculation. Blood supply to the eyelids is characterized by a branched vascular network. The eyelids have an extensive lymphatic system. The mechanism of true inflammatory hyperemia includes: changes in the vascular wall (loss of vascular tone due to paralysis of the neuromuscular apparatus of blood vessels, decreased elasticity of the vascular wall, swelling of the endothelium) and surrounding tissues (compression of venules and lymph vessels by edematous tissue) [J. B. Holdsc. Basic and Clinical Science Course: Section 7: Orbit, Eyelids, and Lacrimal System (Basic and Clinical Science Course). American Academy of Ophthalmology. 2008].

To objectify the assessment of the state of microvessels, it is known to use the LDF method, which allows one to assess the state of blood flow in normal conditions and with pathological changes in the microvasculature. To record the movement of blood flow, the Doppler effect was used by probing the tissue with laser radiation [Laser Doppler flowmetry of blood microcirculation. Under. ed. Krupatkina A.I., Sidorova V.V. M .: Publishing house Medicine. 2005]. This method is quite simple to use, which allows it to be used in various pathological conditions. The LDF method is used as a way to assess the state of microcirculation to predict the course of pathological processes, diagnose and determine the effectiveness of treatment of various diseases. The first study of the blood flow of the skin of the upper and lower eyelids by the LDF method was conducted by Mannor G.E. et al. for comparison with other skin areas in healthy volunteers and in patients with basal cell carcinoma of the century [Mannor GE, Wardell K, Wolfley DE, Nilsson GE. Laser Doppler perfusion imaging of eyelid skin. Ophthalmic Plastic & Reconstructive Surgery. 1996; 12 (3): 178-85]. Subsequently, many papers were published on the use of LDF for assessing the condition of various parts of the eye. Despite successes in the study of microcirculation, the role of the lymph flow and its changes in the inflammatory process of the eyelids remains poorly studied.

With inflammation, a close relationship has been established between functional disorders of the internal environment in the tissues and the drainage lymphatic system [Ohhashi T, Kawai Y. Proposed new lymphology combined with lymphatic physiology, innate immunology, and oncology. Journal of Physiological Sciences. 2014; 65 (1): 51-66]. From the point of view of tissue homeostasis in the body, the blood and lymphatic microvessels, which form the basis of microcirculatory-tissue systems, should be considered in correlation. Lymphatic flow is an integral part of the microcirculatory system.

The LDF method allows one to non-invasively evaluate not only the level of peripheral perfusion, but also to identify the features of blood flow regulation at the level of the microvasculature (ICR). Possessing high sensitivity to changes in the microhemodynamic situation in the vascular bed, the LDF method has an undeniable advantage over other research methods, since it allows one to assess the state of the functional mechanisms of microcirculation control. Analysis of the amplitude-frequency spectrum (ASF) of the reflected signal using the mathematical apparatus of the wavelet transform, which is currently widely used to analyze signals of a physiological nature, makes it possible to evaluate in isolation the contribution of each link in the microvascular bed that takes part in the modulation of blood flow [Nelson K.V. , Sergueef N., Lipinski S.M., Chapman AR, Glonek T. Granial rhythmic impulse related to the Trauble-Hering-Mayer oscillation: comparing laser-Doppler flowmetry and palpation. The Journal of the American Osteopathic Association, 2001; 101 (3): 163-73; Sidorov, V.V., Sakhno, Yu.F. The possibilities of laser Doppler flowmetry for assessing the state of blood microcirculation. Ultrasound and functional diagnostics. 2003; 2: 122-127]. By the values of the amplitudes of microcirculation oscillations in specific frequency ranges, it is possible to assess the state of functioning of certain perfusion control mechanisms. ASF LDF-gram is calculated in the frequency band from 0.005 to 3 Hz. In the frequency range under consideration, 5 non-overlapping regions are distinguished: 0.007-0.017 Hz — range of endothelial activity (E); 0.023-0.046 Hz - range of neurogenic activity (N); 0.07-0.12 Hz - the range of myogenic activity (M); 0.21-0.35 Hz - the range of the respiratory rhythm (D); 0.86-1.36 Hz - heart rate range (C). Blood flow oscillations with characteristic frequencies are determined by certain physiological processes: the influence of the cardiovascular and respiratory systems, the activity of smooth muscle cells of the vessel walls, neurogenic control and the functioning of the vascular endothelium [K.G. Sarkisov, G.V. Duzhak. Laser Doppler flowmetry as a method for assessing the state of microvasculature blood flow. The methodology of flowmetry. 1999: 9-14].

Factors determining the modulation of blood flow (according to A.I. Krupatkin, V.V. Sidorov): PM - microcirculation index, M - arithmetic mean value of the microcirculation index; And - the average fluctuation of perfusion relative to the value of the blood flow M; Kv is the coefficient of variation, SO2 is the relative saturation with blood oxygen of the microvasculature of the biological tissue; IT - neurogenic tone; MT - myogenic tone; Amax - maximum amplitude; (Amax / M) ⋅100% - reduced amplitude; E - fluctuations of endothelial nature; H - fluctuations of a neurogenic nature; M - fluctuations in myogenic nature; D - fluctuations in the respiratory nature; C - fluctuations of a heart nature; Sm is the perfusion oxygen saturation index; U is the parameter of specific oxygen consumption by the tissue (Fig. 1).

Microcirculation is under multilevel control, which is organized through a feedback system. In the process of blood flow self-organization, active perfusion control mechanisms (endothelial activity, neurogenic and myogenic components) and passive mechanisms (pulse and respiratory rhythms) are distinguished. Active and passive mechanisms form positive and negative feedbacks. Active mechanisms create lateral fluctuations in blood flow as a result of alternating contraction and relaxation of smooth muscle cells. Obviously, the work of active control mechanisms is determined by the local physiological needs of tissues. Passive mechanisms organize longitudinal fluctuations in blood flow, expressed in a periodic change in blood volume in the vessels. In arterioles, the nature of the volume change is determined by the pulse wave, and in the venules, by the working rhythm of the “breathing pump”. The recorded amplitudes of oscillations in the blood flow of endothelial, neurogenic and myogenic-endothelial independent origin are directly related to the values of the microvessel lumen and, consequently, to muscle tone. A decrease in the amplitude of oscillations is combined with an increase in the tone and stiffness of the vascular wall itself, and vice versa, an increase in amplitudes is a consequence of a decrease in vascular tone. With LDF, the Doppler frequency shift is filtered when registering back-reflected radiation from both red blood cells in the range of their velocities in microvessels and from diffusers of lymphogenesis in the lymphatic vessels in the range of speeds corresponding to their movement.

In our studies, 30 patients with chronic blepharitis before and after treatment every day, week, month, 1.5, 3, 6, 12 months underwent LDF of the eyelid skin. Estimated mean values of changes in blood perfusion and lymph flow, and also analyzed the oscillations of blood flow and lymph flow. The mean values of perfusion of blood flow and lymph flow (M, σ, and K v ) were measured, and active (endothelial, neurogenic, myogee) and passive (respiratory, cardiac) oscillations were studied by analyzing their ASF. As a result of the treatment of chronic blepharitis, changes in the microcirculation of the skin of the eyelids were revealed. The analysis of the results showed that the most informative for assessing the effectiveness of treatment is the determination of the neurogenic and myogenic components of blood flow and lymph flow. It has been established that with the effective treatment of chronic blepharitis, at least one of the neurogenic, myogenic component of the blood flow, lymph flow of the eyelids increases by 3% or more. Endothelial, respiratory and cardiac blood flow oscillations were variable and individual and, therefore, uninformative to assess the effectiveness of the treatment of chronic blepharitis. Endothelial lymph flow oscillations were rarely recorded; their role needs further study. Respiratory and cardiac oscillations of the lymph flow were detected in single records; their presence is due to the transmission of respiratory and cardiac oscillations of adjacent arterioles and venules to thin-walled lymph vessels.

The method is as follows. Before treatment and after a course of treatment, patients with chronic blepharitis are treated with LDF of the eyelid skin, for example, using the LAZMA-MC-1 apparatus (LLC NPP Lazma, Russia). The sensor of the device is installed motionless sequentially in the medial, middle and lateral parts of the upper and lower eyelids, then the arithmetic mean value is determined. LDF is performed and neurogenic and myogenic oscillations of the microcirculation of blood flow and lymph flow are detected. With an increase of at least one of them by 3% or more after the course of treatment, the treatment is evaluated as effective.

Example 1

Patient X., born 1950 I turned to the Research Institute of Eye Diseases at the Federal State Budgetary Scientific Institution with complaints of discomfort and burning in the eyes. History: chronic gastritis. During the examination, clinical and functional data were within normal values: according to the Schirmer I test, basal secretion was 15 mm on both sides. The Norn test was 11 s on both sides. The compression test is positive (0 points) on both sides. The number of functioning meibomian glands was 17/18 on the right eye, 16/19 on the left eye. Diagnosis: chronic blepharitis in both eyes. Before the study, vasoactive drugs for 6 hours and smoking for 2 hours were excluded. During the study of blood flow and lymph flow by the LDF method, a deterioration in microcirculatory indices was revealed. The neurogenic and myogenic oscillations of blood flow and lymph flow in the upper and lower eyelids were 2.22 and 1.41, 2.02 and 2.11, 2.77 and 2.44, 2.78 and 2.91, respectively. The patient was prescribed blepharogel 1. The treatment duration was 45 days. After treatment, microcirculatory indices tended to improve. The patient noted a lack of discomfort and burning sensation. Clinical and functional data were not dynamic. Schirmer I test was 15 mm on both sides. The Norn test was 12 s on both sides. The compression test is positive (0 points) on both sides. The number of functioning meibomian glands in the right eye is 17/18, the left eye is 16/19). Clinical and functional tests were within normal values and did not provide the necessary information about the condition of the eyelids and the effectiveness of the treatment of chronic blepharitis. However, the positive dynamics of the state of the eyelids during treatment was identified using LDF. Neurogenic and myogenic oscillations of blood flow and lymph flow in the upper and lower eyelids were 5.31 and 3.94, 5.72 and 3.12, 5.83 and 3.5, 3.85 and 3.7, respectively. A 3% increase in the neurogenic and myogenic components of blood flow and the neurogenic component of lymphatic flow in the upper eyelid was revealed. Given the data of microcirculatory changes, the course of treatment was completed.

Example 2

Patient U., born in 1960 first contacted the FSBI “Research Institute of Eye Diseases”. Constantly complained of heaviness, burning of the eyelids, eye fatigue. On examination: according to the Schirmer I test, basal secretion was 10 mm on both sides. The Norn test was 10 s on both sides. The compression test is negative (2 points) on both sides. The test with fluorescein showed a decrease in the number of functioning meibomian glands (right eye 6/4, left eye 4/4). In the acarogram, 7 adult Demodex speciei (spp.) Were found in both eyes. Diagnosis: chronic blepharitis in both eyes. The patient was examined for blood flow and lymph flow using the LDF method. Before treatment, neurogenic and myogenic oscillations in blood flow and lymph flow in the upper and lower eyelids were 2.17 and 1.61, 1.98 and 1.98, 3.58 and 3.64, 2.59 and 2.78, respectively. The patient was prescribed dexodem phyto cream gel. The duration of treatment was 45 days. 1.5 months after treatment, complaints of fatigue and heaviness of the eyelids were identified, Schirmer I test was 10 mm on both sides. The Norn test was 10 s on both sides. The compression test is negative (2 points) on both sides. The test with fluorescein showed the number of functioning meibomian glands in the right eye 6/4, in the left eye - 4/4. The acarogram contains 7 adult Demodex spp. in both eyes. There was no dynamics in the clinical picture and functional tests, which did not provide the necessary information on the effectiveness of the treatment of chronic blepharitis. However, there was a positive tendency to change the condition of the eyelids on the basis of an increase in microcirculatory indicators. Neurogenic and myogenic oscillations of blood flow and lymph flow of the upper and lower eyelids amounted to 5.5 and 2.7, 2.56 and 2.41, 7.14 and 4.06, 2.83 and 3.35, respectively. A 3% increase in neurogenic oscillations of blood flow and lymph flow in the upper eyelid was revealed. The course of treatment has been completed. The patient was transferred to maintenance therapy, including treatment of the edges of the eyelids with medical wipes.

The LDF method objectively determines the state of microcirculation of the skin of the eyelids and allows us to study the neurogenic and myogenic oscillations of the blood flow and lymph flow of the skin of the eyelids, which serves as a criterion for evaluating the results of treatment effectiveness.

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  1. A method for evaluating the effectiveness of the treatment of chronic blepharitis, characterized in that they perform laser Doppler flowmetry of the skin of the eyelids before and after the course of treatment and determine neurogenic and myogenic oscillations of the microcirculation of blood flow and lymph flow, and if at least one of them increases by 3% or more after the course of treatment, the treatment is evaluated how effective.
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US20080273171A1 (en) * 2007-05-04 2008-11-06 Advanced Medical Optics, Inc. Methods and devices for measuring tear film and diagnosing tear disorders
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RU2500340C1 (en) * 2012-11-22 2013-12-10 Федеральное государственное бюджетное учреждение "Научно-исследовательский институт глазных болезней" Российской академии медицинских наук (ФГБУ "НИИГБ" РАМН) Method of determining degree of blepharoconjunctival form of dry eye syndrome

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Publication number Priority date Publication date Assignee Title
US20080273171A1 (en) * 2007-05-04 2008-11-06 Advanced Medical Optics, Inc. Methods and devices for measuring tear film and diagnosing tear disorders
RU2373832C1 (en) * 2008-07-11 2009-11-27 Государственное учреждение Научно-исследовательский институт глазных болезней Российской академии медицинских наук (ГУ НИИГБ РАМН) Method of determining functional state of tarsal glands
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