[Study of the efficacy of cyclosporine used in patients at high risk of keratograft rejection. Communication 1. Results of clinical monitoring].

The paper presents the results of a long-term (up to 2-year) clinical monitoring of 30 patients operated on for leukomas of various etiology, who were a high risk group and received the oral cyclosporine HEXAL postoperatively. Three types of the course of a postoperative period were identified. These included: an absolutely favorable course in 33.3% of cases (Group 1), a relatively favorable one in 30% (Group 2), and an absolutely unfavorable course in 36.7% (Group 3). The studies demonstrated that cyclosporine diminished the degree of an inflammatory reaction and promotes its rapid relief and better functional results in the late postoperative period. Transparent and semi-transparent engraftment could be achieved in 63.3% of cases. The causes of poor outcomes (in 36.7%) may be the inadequate doses of the cyclosporine and the time of its administration (unsteady-state blood cyclosporine concentrations (TO), the inadequate efficiency or initial inefficiency of immunosuppressive therapy.

[Study of the efficacy of cyclosporine used in patients at high risk of keratograft rejection. Communication 2. Immunological treatment monitoring].

The paper presents the results of a long-term (up to 2-year) clinical and immunological monitoring of 25 patients operated on for leukomas of various etiology, who were a high risk group. The objective of the study was to clarify the causes of the inefficiency of treatment with cyclosporine (Cs) and to develop specific indications for its usage. The autoimmune reactions against the cornea (a cellular response) were studied. The levels of cytokines (interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-1beta, IL-2, IL-4, IL-8, and IL-10) and the markers of herpesvirus activation (IgM antibodies) were defined. Retrospectively, the patients were divided into groups according to the pattern of a postoperative period and to the type of immunograms: moderately reactive (n = 6 (24%)), hyperreactive (n = 6 (24%)), and areactive (n = 13 (52%)). The findings suggest that the inefficiency of treatment using the Cs dosage regimens may be due to the wide variability and specific features of immunological responsiveness in particularly critically ill patients. In the authors' opinion, areactive patients (most of them were the post-burnt) need the most careful approach. Overall, the findings suggest that it is necessary to strictly select a Cs dosage regimen on an individual basis and to correct it during clinical and immunological monitoring.

[Antibodies to retinal S antigen in the tear and serum as an indicator of the nature of a course of endogenous uveitis in children].

Antibodies (IgM and IgG) to retinal S antigen were studied by enzyme immunoassay in the tear (n = 135) and blood serum (n = 221) samples taken from 45 children with chronic endogenous uveitis during a follow-up (for 6 months to 5 years). The studies have confirmed the early evidence that detection of serum autoantibodies may be used for the diagnosis of autoimmune and infectious-and-autoimmune uveitis, the verification and prediction of renal alterations, risks for lesions in the second eye in unilateral uveitis and prerecurrence in bilateral uveitis. Criteria for detecting antibodies to lacrimal S antigen were developed. Its has been ascertained that it is expedient to use this procedure as a method for controlling the efficiency of treatment in uveitis involving the posterior parts of the eye, confirming, and predicting the risk for involvement of the retina into an inflammatory process, detecting trends for development of chronic forms of both bilateral and unilateral uveitis. Simultaneous accumulation of IgM and/or IgG antibodies in the lacrimal fluid and serum, as well as imbalance, i.e. a prolonged enhancement of only local or only systemic response to S antigen (of both classes), are prognostically unfavorable.

[Clinical variants and immunologic features of rheumatoid uveitis in children of different age]. / Klinicheskie varianty i immunologicheskie osobennosti revmatoidnykh uveitov u detei raznogo vozrasta.

Variability of clinical manifestations of rheumatoid uveitis, possibility of an atypical course (peripheral or panuveitis), and greater severity and specific features of the disease in case of its early (before the age of 3 years) manifestation are demonstrated on the basis of observations of 79 patients with rheumatoid uveitis. Despite systemic therapy with corticosteroids and cytostatics, no manifest post-steroid immunodeficiency was observed. Moderately expressed gammapathies were detected in 60% cases; hypoimmune states predominated, which were more often detected in children aged under 6 years. No cases of pronounced suppression of functional activity of lymphocytes were observed. Humoral and cellular response to persistent ophthalmotropic infections were observed more rarely than in children with uveitis of other etiology. Positive rheumatoid factor was detected in 9% cases, antinuclear antibodies in 60%. Antibodies to DNA were detected in the sera of 10% examinees, to native and denatured DNA in the lacrimal fluid of 21.2 and 16.7%, respectively. The causes of absence of obvious post-steroid immunodeficiency and relatively low rate of interorgan autosensitization in children with juvenile rheumatoid arthritis and uveitis are discussed. Further investigation of clinical and immunological correlations are needed for improving the prediction of the course of rheumatoid uveitis and development of treatment strategy.

[Comparative study of the role of cytokines in different forms of eye diseases. 1. Tumor necrosis factor-alpha]. / Sravnitel'noe issledovanie roli tsitokinov pri raznykh formakh glaznykh zabolevanii. Soobshchenie 1. Faktor nekroza opukholi al'fa.

Local and total-systems production of tumor necrosis factor-alpha (TNF) is studied in 214 patients with different clinical forms of inflammatory and other than inflammatory diseases of the eyes. Healthy donors were controls. A total of 265 blood sera, 335 lacrimal fluid samples, and 9 specimens of subretinal fluid were examined. The pathogenetic role of TNF was most persuasively confirmed for corneoscleral injuries, proliferative diabetic retinopathy, and total detachment of the retina. Local and systemic cytokine hyperproduction observed in these patients was associated with a grave course and unfavorable outcomes. One more manifestation of immunopathology was pronounced imbalance between the cytokine content in the lacrimal fluid and serum, which was observed in patients with active bilateral uveitis, extensive detachments of the retina, and complicated cataracts. The unfavorable impact of TNF deficiency during the development of a pathological process in the eye (early stages of diabetic retinopathy, burns, and contusions of the eye) is discussed. Clinical and immunological data validate the efficacy of TNF test for predicting the course of an eye disease, monitoring its treatment, and assessing the desirability of immunocorrection.

[Clinical and immunological features of peripheral uveitis in children and adolescents. Differentiated treatment strategy]. / Kliniko-immulogicheskie osobennosti perifericheskikh uveitov u deteí ipodrostkov. Differentsirovannaia taktika lecheniia.

Sixty-eight children with peripheral uveitis (PU) were examined, which is 11.5% of the total number of children with endogenous uveitis. In addition to the classical signs of PU, children often develop papillitis, corneal precipitations, and diffuse cataracts which are formed early. Clinical and immunological correlations were revealed, indicating a relationship between the clinical features and the disease etiology and pathogenesis: herpetic forms of PU (infectious and infectious-allergic) with immunopathological reactions to the retinal S-antigen only during late stages when the process takes a chronic course. Differentiated treatment strategy of PU with due consideration for the detected features is proposed.

[Study of antibodies to DNA in patients with bilateral and unilateral endogenous uveitis]. / Issledovanie antitel k DNK u bolnykh s dvustoronnimi i odnostoronnimi éndogennymi uveitami.

The study was aimed at elucidating the contribution of autoimmune factors to the development of bilateral uveitis in children and adults. Sera of 59 children (aged 3 to 15) and 34 adults (aged 18 to 60) with unilateral and bilateral endogenous uveitis were tested for antibodies to DNA in ELISA. In children aged 3 to 10 years with bilateral uveitis antibodies to n-DNA were detected more often than in those with unilateral involvement. This difference was most expressed during the active stage of the disease (p < 0.02). In adult patients the results were the contrary. Antibodies to d-DNA were more often found in subjects with unilateral uveitis (p < 0.05). Accumulation of anti-DNA antibodies in children may be an early sign of systemic immunity disorders, conducive to augmentation of ophthalmopathy and to the development of a bilateral process. A lower incidence of anti-DNA antibodies in adult patients with bilateral uveitis is probably due to the formation of specific circulating immune complexes but not to normalization of immunity. These findings permit us to hypothesize that DNA autoimmunization is one pathogenetic factor of bilateral development of uveitis.

[Clinical and immunological criteria of the activity of inflammatory reaction and autolymphokine therapy in penetrating wounds of the eye]. / Kliniko-immunologicheskie kriterii aktivnosti vospalitelnoi reaktsii i autolimfokinoterapiia pri pronikaiushchikh raneniiakh glaza.

Clinical and immunological criteria of an unfavorable course of posttraumatic process were defined and the efficacy of autolymphokine therapy in the postoperative treatment of patients with penetrating wounds to the eye assessed. A total of 119 patients were examined. Autolymphokine therapy supplemented the traditional postoperative treatment in 38 of them. An unfavorable course of the posttraumatic period was associated with high levels of tumor necrosis factor-alpha and interleukin-1-beta in the blood serum and lacrimal fluid, with accumulation and long persistence of high titers of antibodies to lens antigens and retinal S-antigen in the lacrimal fluid, with intensive cellular immune response to these antigens in the leukocyte migration inhibition test, and with a deficit of tissue-specific anticorneal antibodies in the lacrimal fluid during the first 3-4 weeks after the injury. In the event of a favorable outcome the cytokines were detected in the minimal amounts, and antibody titers were moderate. Autolymphokine therapy 2 to 3 times decreased the concentration of cytokines in the lacrimal fluid, maintained the moderate level of autoantibodies in the lacrimal fluid, decreased the incidence of the leukocyte migration inhibition and the duration of its detection, and shortened the period of autoantibody detection in the blood serum.

[The clinico-immunological validation of a differentiated approach to the use of corticosteroids in treating S-dependent uveoretinitis]. / Kliniko-immunologicheskoe obosnovanie differentsirovannogo podkhoda k primeneniiu kortikosteroidov pri lechenii S-zavisimykh uveoretinitov.

A total of 630 patients with uveitis of different etiology aged 5 to 70 were examined. Signs of autoimmunization with retinal S-antigens (mol. weight 48 kD) associated with retinal involvement were detected in more than half of them. A moderate level of S-antigen in the tears was found to promote a favorable outcome of uveoretinitis. Deficit or a drastic increase of S-antigen titers in the tears, accumulation of S-antibodies and circulating S-antigen-antibody complexes in the serum, and blood leukocyte migration inhibition in response to S-antigen were observed in chronic and complicated cases. As many as 75% focal chorioretinitis and panuveitis cases, 50% of posterior and 37% of peripheral uveitis were referred to S-related forms. The authors validate a differentiated approach to the treatment of S-uveoretinitis. If S-antibodies are accumulated only in the tears, local corticosteroids are effective; if both local and total-systems reactions are boosted, the maximal effect may be achieved by local and systemic corticosteroids and cytostatics. In case of a deficiency of S-antibodies in the tears immunodepressive therapy was of no avail, and good results could be attained only by immunomodulating therapy: corticosteroids+hemoperfusion in adults and corticosteroids+thymus preparations and/or interferonogens in children.

[Specific immune complexes formed by retinal S antigens and S antibodies in infectious-allergic and post-traumatic uveitis]. / Issledovanie spetsificheskikh immunnykh kompleksov, obrazovannykh S-antigenom setchatki i S-antitelami, pri infektsionno-allergicheskikh i posttravmaticheskikh uveitakh.

A method for the detection in the blood of specific circulating immune complexes (S-CIC) formed by the retinal S antigen and S antibodies. S-CICs were disintegrated by ultrasonic treatment of blood serum samples, passive hemagglutination test and specific inhibition of passive hemagglutination were used in identification of S antigen and S antibodies. S-CICs were detectable in bilateral uveoretinitis and in suspected sympathetic ophthalmia and undetectable in unilateral processes, including those involving the retina.