RU2805940C1 - Method of assessing inflammatory process in children with endogenous uveitis - Google Patents

Abstract

FIELD: ophthalmology.

SUBSTANCE: invention is intended to assess the activity of the inflammatory process in children with endogenous uveitis. The content of urokinase plasminogen activator is determined in the tear fluid of the diseased eye. When its value is equal to or less than 46.5 pg/ml, the inflammatory process is assessed as inactive, when its value is equal to 46.6–80.6 pg/ml, the inflammatory process is assessed as sluggish, when its value is above 80.7 pg/ml, the inflammatory process is assessed as active.

EFFECT: invention provides the choice of adequate treatment tactics depending on the activity of endogenous uveitis.

1 cl, 4 ex

Description

The present invention relates to ophthalmology and is intended to assess the inflammatory process in children with endogenous uveitis.

Uveitis is a severe chronic disease that can manifest at any age. Despite the fact that this disease is less common in children than in adults [Kump, L. I., Cervantes-Castaneda, R. A., Androudi, S. N., & Foster, C. S. (2005). Analysis of Pediatric Uveitis Cases at a Tertiary Referral Center. Ophthalmology, 112(7), 1287-1292; Cunningham, E. T., Smith, J. R., Tugal-Tutkun, I., Rothova, A., & Zierhut, M. (2016). Uveitis in Children and Adolescents. Ocular Immunology and Inflammation, 24(4), 365-371], a more severe course and prognosis still attract the close attention of ophthalmologists and encourage the search for new ways of diagnosis and treatment.

Currently, there are various ways to determine the activity of uveitis. The fastest and most accessible is biomicroscopy of the anterior and posterior segments of the eye and ophthalmoscopy [Jabs D.A., Nussenblatt R.B., Rosenbaum J.T. Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop.Am J Ophthalmol. 2005;140(3):509-16; Nussenblatt R.B., Palestine A.G., Chan C.C., Roberge F. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92:467-471], however, the disadvantage of these methods is subjectivity.

High-tech instrumental examination methods are widely used, such as diagnostic ultrasound (US), optical coherence tomography (OCT), OCT with angiography (OCT-A), fluorescein angiography (FA), autofluorescence studies, electrophysiological studies, laser photometry [Ladas, J. G. , Wheeler, N. S., Morhun, P. J., Rimmer, S. O., Holland, G. N. (2005). Laser flare-cell photometry: methodology and clinical applications. Survey of Ophthalmology, 50(1), 27-47], which can also help determine the activity of the inflammatory process, however, these research methods are expensive, not always applicable, and each of them has narrowly limited diagnostic capabilities for uveitis.

The closest analogue of the proposed method is a method for the same purpose, in which to determine the activity of inflammation, counting the number of cells in the anterior chamber of the eye using biomicroscopy is used. However, the disadvantage of this method is subjectivity. In addition, the method does not allow assessing the activity of inflammation in the vitreous body and the posterior segment of the eye (Standardization of Uveitis Nomenclature for Reporting Clinical Data. Results of the First International Workshop. (2005). American Journal of Ophthalmology, 140(3), 509-516 doi:10.1016/j.ajo.2005.03.057).

The objective of the present invention is to create an objective method for determining the activity of uveitis of various localizations.

The technical result of the proposed invention is the choice of adequate treatment tactics depending on the activity of endogenous uveitis.

The technical result is achieved by determining the content of urokinase plasminogen activator (UPA) in the tear fluid (FL) of the diseased eye.

Proteolytic enzymes occupy an important place in the pathogenesis of the inflammatory process. UPA is a serine protease that is synthesized by leukocytes, vascular endothelial and smooth muscle cells, epithelial cells, fibroblasts, monocytes/macrophages, also involved in inflammation [Binder, B. R. (1995). Physiology and pathophysiology of the fibrinolytic system. Fibrinolysis, 9, 3-8]. During inflammation, along with the entry of leukocytes into the lesion, the components of the UPA system are released, which leads to the activation of neutrophils and the release of pro-inflammatory factors from monocytes [Mahmood N., Mihalcioiu S., Rabbani S.A. Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): diagnostic, prognostic, and therapeutic applications. Front. Oncol. 2018; 8:24; Blasi F. Urokinase and urokinase receptor: a paracrine/autocrine system regulating cell migration and invasiveness. Bioessays (1993) 15(2):105-11; Del Rosso M., Fibbi G., Pucci M., Margheri F., Serrati S. The plasminogen activation system in inflammation. Front. Biosci. 2008; 13:4667-4686]. This served as a theoretical prerequisite for determining the content of UPA to assess the activity of the inflammatory process in endogenous uveitis in children.

The pathogenetic justification for the proposed method was based on data obtained from an examination of 58 children (116 eyes) aged 7 to 17 years (on average 11.09±2.54 years) with endogenous uveitis.

All children underwent a biochemical examination - determination of the UPA content in the SF by enzyme-linked immunosorbent assay (ELISA) using the diagnostic kit ELISA kit for plasminogen activator, urokinase (Human). The UPA content was expressed in pg/ml.

Analysis of the data obtained and comparison with the clinical picture of uveitis revealed a correlation between the activity of the inflammatory process and the content of UPA in the SF of the diseased eye. Criterion indicators for the content of UPA in the SF were established, which were less than or equal to 46.5 pg/ml with an inactive inflammatory process, ranged from 46.6 to 80.6 pg/ml with low-grade inflammation, and were higher than 80.7 pg/ml ml for active uveitis.

The method is carried out as follows.

The content of urokinase plasminogen activator is determined in the tear fluid of the diseased eye. When its value is equal to or less than 46.5 pg/ml, the inflammatory process is assessed as inactive, 46.6-80.6 pg/ml - as sluggish, above 80.7 pg/ml - as active.

SF is collected, as is customary, using strips of sterile filter paper 5 mm wide, which are placed behind the lower eyelid for 5 minutes. The ELISA method using the diagnostic kit ELISA kit for plasminogen activator, urokinase (Human) determines the content of UPA in the fluid; it is also possible to use other methods to determine the content of UPA in biological fluids. The reaction is carried out in the traditional way, according to the instructions of the test system manufacturer.

The method is illustrated by the following examples.

Example 1. Patient Sh.E., 16 years old. Diagnosis of OU - inactive uveitis (?), corneal dystrophy, partial complicated cataract. Objectively: OU - band-shaped corneal dystrophy, the anterior chamber is of medium depth, uniform, transparent moisture. The iris is structural, the pupil is round, in the center, OD at 16 o'clock, posterior synechia, OS - initial opacification of the posterior capsule of the lens, there are a few cells in the vitreous body, the fundus of the eye: the central zone is poorly visible due to opacification of the cornea, the visible periphery is without pathology. The condition of the cornea made it difficult to examine the posterior segment of the eye. The content of UPA in the SF was determined, which was 31.2 pg/ml at OD, 41.2 pg/ml at OS, which is characteristic of the absence of activity of the inflammatory process. Scarification of the cornea was performed, which made it possible to examine the fundus in detail. No signs of inflammation were detected.

This example confirms the position that a UPA content in the SF less than or equal to 46.5 pg/ml characterizes an inactive inflammatory process in uveitis.

Example 2. Patient D.A., 12 years old. Diagnosis of OU - peripheral uveitis indolent (?), partial complicated cataract. Objectively: OU - dystrophic changes in the cornea paralimbally at 3 and 9 o'clock, the anterior chamber is of medium depth, transparent moisture, opacification of the posterior capsule of the lens, in the vitreous there are filmy opacities and small cells (determining the number of cells is difficult), examination of deeper structures is difficult. The content of UPA in the SF was OD - 56.4 pg/ml, OS - 80.6 pg/ml, the diagnosis of a low-grade inflammatory process was confirmed. Based on the data obtained, anti-inflammatory therapy was carried out, cells and exudation in the vitreous body decreased, visual acuity increased, ophthalmoscopy became possible, paravasal exudate in the periphery was detected in the fundus, anti-inflammatory therapy was continued.

This example confirms the position that the content of UPA in the SF in the range of values from 46.6 to 80.6 pg/ml characterizes sluggish uveitis and can be a criterion for anti-inflammatory therapy.

Example 3

Patient N.S., 13 years old. Diagnosis of OU - peripheral uveitis indolent (?), partial complicated cataract. Objectively: OU - dystrophic changes in the cornea paralimbally OD at 9 o'clock, OS at 3 o'clock, the anterior chamber is of medium depth, the moisture of the anterior chamber is transparent, opacification of the posterior capsule of the lens, in the vitreous - membranous opacities and small cells (determining the number of cells is difficult), examination fundus examination is difficult due to the condition of the vitreous body. The content of UPA in the SF is OD - 62.2 pg/ml, OS - 46.6 pg/ml, which is characteristic of a sluggish inflammatory process. Based on the data obtained, anti-inflammatory therapy was carried out; cells and exudation in the vitreous body decreased, visual acuity increased, ophthalmoscopy became possible, and anti-inflammatory therapy was continued.

This example also confirms the position that the content of UPA in the SF in the range of values from 46.6 to 80.6 pg/ml characterizes sluggish uveitis and can be a criterion for anti-inflammatory therapy.

Example 4. Patient A.M., 7 years old. Diagnosis of OS - active (exacerbation) of anterior uveitis (?)

Complaints of photophobia, lacrimation, redness of the left eye. Objectively OS - mixed injection of the conjunctiva, the anterior chamber is of medium depth, a detailed examination is difficult due to severe photophobia. The content of UPA in the SF OS is 283.8 pg/ml, which makes it possible to assume the activity of the inflammatory process. Taking into account this assumption, anti-inflammatory therapy was prescribed, which led to a decrease in photophobia and signs of eye irritation, allowing further examination of the OS: “sweating” of the corneal endothelium, anterior chamber of medium depth, cells in the IPC 2+, posterior synechiae at 5-7 o’clock, turbidity posterior capsule of the lens, multiple cells in the vitreous body, papillitis and macular edema were detected in the fundus.

This example confirms the position that the content of UPA in the SF in the range of values above 80.7 pg/ml characterizes active uveitis.

Thus, the proposed method makes it possible to determine the activity of the inflammatory process in children with endogenous uveitis, including those with insufficient transparency of optical media, based on determining the content of UPA in the fluid, which will contribute to a more accurate diagnosis, timely prescription (correction) of treatment, and will avoid the development of complications.

Claims (1)

A method for assessing the activity of the inflammatory process in children with endogenous uveitis, characterized in that the content of urokinase plasminogen activator is determined in the tear fluid of the diseased eye and, if its value is equal to or less than 46.5 pg/ml, the inflammatory process is assessed as inactive, 46.6- 80.6 pg/ml - as sluggish, above 80.7 pg/ml - as active.