RU2107480C1 - Method for treating endogenous and postoperative uveitis - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves applying Imunophan as immunocorrection means administered as subconjunctival injections in the cases of anterior uveitis or parabulbar injections in the cases of posterior uveitis at a dose of 0.5 ml of 0.005% solution once a day daily during the first five days and then each second day, the whole course consisting of 5-15 injections. EFFECT: enhanced effectiveness of treatment.

Description

 The invention relates to medicine, namely to ophthalmology, and is intended for the treatment of patients with endogenous and postoperative uveitis.

 Despite the wide arsenal of drugs, the treatment of endogenous, post-traumatic and postoperative uveitis remains one of the most difficult problems in ophthalmology. In recent years, immunocorrecting drugs obtained from animal thymus extracts or from the patient’s own blood have become more and more actively used in the treatment of these diseases (S. Mikuli. An experimental-clinical study of the action of T-activin in the presence of herpes virus infection of the eyes. Diss. Cand. Biol. Sciences.- M., 1985, 150 pp. Makarov P.V. Autolymphokinetherapy for penetrating injuries of the organ of vision.Dis. Cand. of Medical Sciences.- M., 1995, 125 pp.).

 Along with a positive therapeutic effect, the main disadvantages of the drugs used are also noted: difficulties in standardization and dosage, significant differences in the activity of the action due to the natural origin of the drugs, especially those obtained from autologous blood. These shortcomings significantly affect the effectiveness of treatment of patients.

 In this regard, the search and implementation of new drugs in ophthalmic practice is a very urgent task.

 The proposed method is based on the results of the successful use of the new peptide preparation "Imunofan" in the treatment of patients with various clinical forms of endogenous and postoperative uveitis.

 Under observation were 35 people (53 eyes), comprising two clinical groups.

 The first group included patients treated for exacerbation of chronic endogenous uveitis (36 eyes) or primary acute uveitis (4 eyes); Only 23 people, 40 eyes. The predominant lesion of the anterior eye was observed in 7 eyes (keratouveitis and anterior uveitis), posterior in 20 eyes (peripheral and posterior uveitis, chorioretinitis), generalized processes in 13 eyes.

 The second group included 12 patients (13 eyes) who underwent keratoplasty surgery (6 eyes) or cataract extraction (7 eyes), accompanied by severe inflammatory reactions (iridocyclitis, keratouveitis, panuveitis), which could not be stopped using traditional means (corticosteroids, desensitizing drugs, antibiotics, etc.).

 Treatment with Imunofan (subconjunctival injections for anterior uveitis, parabulbar injections for anterior processes) was prescribed after 1-2 weeks. after traditional therapy, which did not give a positive result (7 people, 12 eyes), or immediately (16 people, 18 eyes) in combination with symptomatic agents (mydriatics, heparin, glucose, diphenhydramine, etc.) and dexazone instillations; in some cases (6 people), systemic corticosteroids were used (pulse therapy).

 When evaluating the effectiveness of treatment, a traditional ophthalmological examination was performed (biomicroscopy, ophthalmoscopy, determination of the sensitivity of the cornea), EFI (sometimes electrical sensitivity of the retina; lability of the axial start of the optic nerve). The dynamics of the clinical symptoms of the disease and visual acuity were taken into account (on the day of discharge from the hospital and then in a more distant period with a follow-up period of 6-12 months).

 In parallel, immunological studies of lacrimal fluid and blood serum were carried out; terms: - before treatment; then on 8, 14 and 21 days and at the end of the course - after 1.5 - 2 months. Autoantibodies to tissue-specific S - retinal antigen were studied; antibodies to DNA and membrane antigens of the liver - as an indicator of autoimmunization with interorgan antigens (enzyme-linked immunosorbent assay); immunoglobulins (IgY, IgA, IgM; Mancini immunodiffusion); circulating immune complexes (CEC, PEG method).

 An analysis of the treatment results showed that the therapeutic effect was achieved with the vast majority of patients observed (50 of 53 treated eyes; 94.3%), including in patients in whom previously conducted traditional therapy was unsuccessful. The functional results of the treatment were slightly lower, which is explained by the previously developed post-inflammatory complications requiring surgical intervention (opacities of the lens and cornea, synechia, pupil deformity, fibrinous films in the vitreous body). High visual acuity (0.4-1.0) was obtained in 32 eyes (60.3%); tenth increase in visibility to 0.3 in 5 eyes (9.4%); a slight improvement in vision (per hundredths) to 0.1 - 0.2 in 8 eyes (15.1%) and below 0.1 in 8 eyes (15.1%).

 The most pronounced therapeutic effect was observed in newly ill patients with severe keratouveitis. Relief of inflammatory symptoms was noted after 4-5 injections of Imunofan. At the end of the course, there was a complete disappearance of edema and resorption of precipitates on the corneal endothelium, resorption of exudate in the anterior chamber of the eye. In 3 out of 4 eyes, the visus increased by 0.6 - 0.8 and reached 0.9 - 1.0.

 In the treatment of patients with chronic sluggish uveitis, the positive effect was manifested mainly by stopping the activity of the inflammatory process. The visual acuity in these patients, in connection with the previously developed post-vein complications, increased by as much (0.01 - 0.4 to 0.03 - 1.0) as in the first sick patients.

 In most patients with endogenous uveitis (17 out of 23), a stable remission was achieved (6-16 months).

 Imunofan also had a positive effect in the conservative treatment of operated patients (second group). In the subgroup of patients who did not undergo keratoplasty, the phenomena of photophobia, lacrimation, and corneal edema, which persisted despite the active traditional therapy, were managed to stop within a week using Imunofan. As a result, the eyes completely calmed down, the transplants took root and remained transparent for 4-6 months (observation period); 5 out of 6 operated eyes achieved satisfactory visual acuity (0.3 - 0.5).

 In the subgroup of patients who underwent cataract extraction, postoperative inflammation, which did not succumb to previously used therapy, with the help of Imunofan managed to stop in almost all eyes. In 3 cases, this required no more than 5 injections of the drug, on 4 eyes the phenomena of iridocyclitis persisted longer, which determined the duration of the course (up to 10-15 injections).

 The positive clinical effect obtained with the use of Imunofan was combined with immunocorrective action both at the local and systemic levels. The drug contributed to the normalization of the total content of T-lymphocytes, including activated, as well as the balance of T-helpers and T-suppressors of peripheral blood; levels of IgY, IgA, IgM in serum and especially in the lacrimal fluid; decrease in the initially increased concentration of CEC in the blood; the weakening of pathogonetically adverse shifts of local and systemic tissue-specific autoimmunity (autoantibodies to retinal S-AH) and a decrease in serum autoantibodies to native and denatured DNA.

 In general, the results of the use of Imunofan in the complex therapy of endogenous and postoperative uveitis indicate that the drug has a pronounced anti-inflammatory and immunorehabilitation effect, helping to optimize treatment and increase visual functions.

 Given the predominant localization of the inflammatory process, the drug is recommended to be administered subconjunctivally with anterior and parabulbar with posterior uveitis; with panuveitis, it is advisable to alternate subconjunctival and parabulbar injections.

 The technical result of the proposed method is to develop a treatment regimen for patients with endogenous and postoperative uveitis using the drug Imunofan.

 The method is as follows.

 Ophthalmic examination is carried out by generally accepted methods. If an active inflammatory process is detected in the eye (endogenous uveitis, postoperative reaction), an injection of 0.005% Imunofan solution of 0.5 ml is prescribed, subconjunctival - with a primary lesion of the anterior eye, parabulbar - in the posterior processes; the drug is administered once a day, every day for the first 5 days and then every other day with a general course of 5 to 10-15 injections.

 Clinical example 1. Patient P., female. 30 years. For two years, he suffers from front doppler OD, a chronic process, often recurring. Was admitted to the hospital in connection with acute inflammatory disease and decreased visual acuity (from 1.0 to 0.6) on OS; clinically: hyperemia of the conjunctiva of the eyeball, pericorneal injection, multiple precipitates on the corneal endothelium, serous exudate in the anterior chamber, Tyndall symptom 2+; pupil dilated, round; the diagnosis is acute serous anterior uveitis. OD - calm, old pigmented wide posterior synechiae; visual acuity 1.0; stage of unstable remission of chronic uveitis.

 An immunological examination before treatment (on the day of admission to the hospital) revealed a decrease in the percentage of active T-cells (up to 20%, at a norm of 27 - 32%), imbalance of immunoregulatory cells (increase in the concentration of T-suppressors, decrease in T-helpers ) with a decrease in the immunoregulatory index to 0.74 (with a norm of 1.0 - 2.5); in the lacrimal fluid, an increase in the level of IgA in OD (up to 0.32 g / l at the upper limit of the norm of 0.2 g / l) and a marked increase in the concentration of IgY in OI (up to 0.7 g / l and 0.5 g / l with a norm of up to 0.1 g / l). The patient underwent treatment: 0.5 ml immunofan in the form of subconjunctival injections once a day (N5 - daily, then N5 - every other day; total N 10) - 0; dexason in instillations of OI; desensitizing drugs.

 At the end of the course of therapy, OIs are calm; inflammatory symptoms are completely stopped; visual acuity 1.0 (without correction). Against the background of treatment, normalization of immunological parameters was noted. The duration of stable remission on OS is 16 months. (observation period).

 Clinical example 2. Patient G., husband. 48 years old. He was admitted to the hospital with a diagnosis of primary acute keratouveitis OS, severe, decreased vision to 0.3; clinically: severe hyperemia of the conjunctiva of the eyeball; injection of the perilimbal vasculature, cornea is swollen, deep infiltrates, sensitivity is reduced, fresh precipitates on the endothelium; in the moisture of the anterior chamber, serous exudate (Tyndall symptom 2+). The posterior segment of the eye is visible behind the fleur, without a pronounced pathology. The right eye is healthy, VIS 1.0.

An immunological examination prior to treatment showed shifts in T- and B immunity indicators: a decrease in the total percentage of T-lymphocytes to 34% (with a norm of 52 - 56%), activated T-cells to 12%; T-helpers up to 17% with a moderate increase in T suppressors up to 17%; as well as improving the sun _of lymphocytes to 32% (at a rate of 20 - 25%) and a moderate increase in the CEC - 186 USD

 Imunofan 0.5 ml subconjunctival was prescribed to the patient against the background of desensitizing drugs, without the active use of other medications. The total course of treatment with immunofan was 10 injections (daily for the first five days, then every other day). An improvement in the eye condition was noted after the 4th injection of the drug. The patient was discharged from the hospital after the eighth injection, while mild hyperemia of the conjunctiva, descemetitis, single deep infiltrates in the cornea persisted. Assigned two additional injections of Imunofan (outpatient). At the end of the course, the eye completely calmed down, single stromal opacities of the cornea remained; visual acuity increased by 0.6 and reached 0.9 without correction. An immunological examination after a month from the start of treatment did not reveal any significant deviations from the norm for any of the studied indicators. The duration of persistent remission is 10 months. (observation period).

 Clinical example 3. Patient B., husband 42 g. Diagnosis: chronic, sluggish bilateral panuveitis. The patient was admitted to the hospital in connection with the activation of the process in both eyes; artifact; Vision on OI - the count of fingers in the face. Clinically, OI: hyperemia of the conjunctiva of the eyeball and perilimbal zone. In the anterior chamber exudate (Tyndall symptom 2+), the anterior chamber angle is uneven, goniosynechia, the iris is atrophic, swollen, incomplete pupil fusion; in OD on the IOL, multiple precipitates, secondary membranous cataract. In the vitreous body OI opacities (4+); the fundus is not ophthalmoscopically.

 An immunological examination revealed pronounced changes in indicators of T and B immunity: a decrease in the percentage of total T-lymphocytes to 36%, activated T-cells to 14%, Helper cells to 18%, a moderate increase in Tsupressor to 18%; a decrease in BC3 - lymphocytes to 12% with a moderate increase in the content of serum IgY (18.03 g / l) and IgM (2.76 g / l), as well as IgY in the lacrimal fluid (OD-0.73 g / l; OS- 0.49 g / l); a significant increase in the level of CEC 267 at. e. The accumulation in the blood of antibodies to n-DNA (IN = 4.2) and S-AH of the retina (S-IgY 2.0; S-IgM = 3.4); the appearance of S-IgY and an increase in the level of S-IgM in the tear fluid of OI.

 A month before admission to the hospital, the patient was prescribed outpatient treatment, which included dexazone - parabulbar, gentamicin, mydriatics, desensitizing and absorbable drugs. Positive dynamics were not observed.

 Upon admission to the hospital, the patient was prescribed Imunofan subconjunctival and parabulbar (0.5 ml N 5 daily, then every other day; total N 15).

 Upon discharge from the hospital, at the end of the course of treatment, clinically OI: eyes are calm; incomplete secretion of the pupil, the contents of the anterior chamber are clean, the precipitates on the posterior lens capsule partially dissolve. Vision increased from counting fingers in the face to 0.1 on OD and 0.2 on OS.

 An immunological examination showed a slight excess of the normal level of IgM in the blood serum (2.7 g / l). The remaining emitted indicators are within the age norm. Duration of remission 4 months. (observation period).

 Clinical example 4. Patient M., husband., 32 years. He was admitted to the hospital for surgical treatment due to clouding of the corneal transplant on OD; OS is healthy. An operation of end-to-end rekeratoplasty on OD was performed. In the postoperative period, against the background of instillations of dexason, glucose, use and desensitizing agents: photophobia, lacrimation, corneal transplant edema, iridocyclitis phenomena.

 An immunological examination revealed a decrease in the total percentage of T-lymphocytes to 30%, activated T-cells to 15%, Helper cells to 15%.

 The patient was prescribed Imunofan 0.5 ml subconjunctival daily. After a course of 5 injections, the eye calmed down; the graft has taken root, is transparent, visual acuity is 0.4, not core. An immunological examination showed no significant deviations from the age norm according to the studied parameters, a slight increase in the percentage of Tsupressor was noted (up to 22%), however, the immunoregulatory index was normal IM = 1.2.

 With a follow-up period of 10 months. after surgery, the graft is clear, the eye is calm.

p. i.c. Клинически на ОИ: радужка атрофична, зрачок среднего диаметра с задними синехиями; пигментные отложения на капсуле хрусталика; полная катаракта; глазное дно не офтальмоскопируется.Clinical example 5. Patient M., husband., 59 years old. Diagnosis: complicated cataract, chronic peripheral uveitis of both eyes, vision on

pic Clinically at OI: iris atrophic, pupil of medium diameter with posterior synechiae; pigment deposits on the lens capsule; complete cataract; the fundus is not ophthalmoscopically.

 He was admitted to the hospital for surgical treatment of complicated cataract of the right eye. Produced cataract extraction; the operation went without complications. In the postoperative period, against the background of active anti-inflammatory treatment (dexazone - subconjunctival and parabulbar, antibiotics, mydriatics, glucose), exacerbation of uveitis was observed. A week after surgery: aphakia; hyperthermia of the conjunctiva of the eyeball, the cornea is swollen, descemetitis, the anterior chamber is deep (Tyndall symptom 1+), the pupil is round, exudate in the pupil; fundus - pink reflex, details are poorly visible.

 An immunological examination revealed a pronounced increase in the concentration of CEC up to 251 c.u., serum IgM up to 2.76 g / l; and the level of IgY in the tear fluid OD (0.35 g / l); a significant increase in the levels of autoantibodies to n- and d-DNA in the blood (IN = 2.8 and 4.5, respectively), the accumulation of S - IgM in the tear fluid (IN = 2.4) and an increase in the level of S-IgM and S-IgY in blood.

 The patient was prescribed Imunofan parabulbarno (0.5 ml each, N 5 - daily; then every other day). After a course of 10 injections, the eyes calmed down, mild hyperemia of the conjunctiva of the eyeball, the anterior chamber is deep, the pupil is round, aphakia; fundus - pink reflex, chorioretinal foci at the extreme periphery with no signs of activity, pigmented foci in the flat part of the ciliary body.

 An immunological examination showed a significant drop in the concentration of the CEC to 146 cu; normalization of serum IgM and IgY levels in the tear; a drop in serum levels of anti-DNA antibodies and S-autoantibodies; disappearance of S - IgM in a tear. The remaining emitted immunological parameters remained within the age norm.

 When examined after 4 months. the eye is calm, with no signs of uveitis activity, visual acuity of 0.1 s core. (in connection with the formation of secondary cataract). With a follow-up period of 11 months, no exacerbations of uveitis were observed, the eye was calm, aphakia, secondary cataract, and visus 0.1.

 Thus, the local use of the immunocorrective drug Imunofan allows you to stop active endogenous and postoperative uveitis, including those that cannot be treated with traditional anti-inflammatory drugs. The therapeutic and functional effect when using Imunofan is combined with an immunorehabilitation action, which manifests itself both at the local and systemic levels. The terms of stable remission reach 10 - 16 months. (maximum observation time), at least 4 - 6 months.

Claims (1)

 A method of treating endogenous and postoperative uveitis by immunocorrective therapy, characterized in that Imunofan is used as immunocorrective agent, which is administered as subconjunctival injection for anterior uveitis or parabulbar injection for posterior uveitis at a dose of 0.5 ml of a 0.005% solution once a day, daily for the first five days and then every other day with a general course of 5 to 15 injections.