[The place of ciclosporin A cationic emulsion 0.1% in the therapy of xerophthalmia]. / Mesto kationnoi emul'sii tsiklosporina A 0,1% v terapii kseroftal'mii.

Dry eye disease (DED) is pathogenetically based on inflammation of the ocular surface. A step-by-step approach to DED treatment involves early initiation of anti-inflammatory therapy, including instillation of cyclosporine A (CsA). However, recommendations for the use of topical CsA in clinical practice are limited. This article presents an expert consensus on practical recommendations for the management of patients with DED, including indications, time of initiation and duration of CsA therapy, comparison of CsA forms currently registered in the Russian Federation, as well as issues of patient education.

[Adenocarcinoma of nonpigmented ciliary body epithelium (clinical cases)]. / Adenokartsinoma iz bespigmentnogo epiteliya tsiliarnogo tela (klinicheskie nablyudeniya).

The article presents two clinical cases of adenocarcinoma of nonpigmented epithelium of the ciliary body, which is a very rare malignant tumor of the organ of vision with distinctive features. Surgical treatment is necessary to verify this tumor and assess the degree of its aggressiveness in terms of the prognosis of the disease, with subsequent pathomorphological and immunohistochemical studies. The article also discusses the epidemiological aspects, morphological features, clinical manifestations of this pathological condition, as well as possible treatment options and features of follow-up monitoring of this group of patients.

[Doppler ultrasound in the assessment of blood supply to choroidal melanoma: parallels with contrast angiography and histography]. / Ul'trazvukovaya dopplerografiya v otsenke krovosnabzheniya melanomy khorioidei: paralleli s kontrastnoi angiografiei i gistografiei.

PURPOSE: Evaluation of blood supply to choroidal melanoma based on comparison of Doppler characteristics of blood flow with angiographic variant of angioarchitectonics and densitometric parameters of the tumor. MATERIAL AND METHODS: The study was performed in 135 patients (135 eyes) with choroidal melanoma. The initial prominence of the tumors varied from 0.6 to 15.2 mm (mean 5.07±3.58 mm), the diameter of the tumor base varied from 4.1 to 22 mm (mean 10.97±3.62 mm). Taking into account the biometric characteristics of choroidal melanoma, all patients were divided into 3 groups: «small¼ (n=49), «medium¼ (n=34) and «large¼ (n=52). In addition to standard diagnostic examination, the following instrumental methods for assessing the blood supply of choroidal melanoma were carried out: angiography with indocyanine green, optical coherence tomography angiography, ultrasound in color Doppler mapping mode, ultrasound histography. RESULTS: Comparative analysis of Doppler ultrasound and contrast angiography data in assessing the blood supply of choroidal melanoma established that the first angiographic type, presented by straight and parallel vessels (65%, p=0.037), is characteristic for hypovascular and avascular masses, the second type - for hypervascular choroidal melanomas, in which the new vessels can take the form of arches, loops and nets (68%, p=0.027). The study of densitometric characteristics in choroidal melanoma of various sizes indicates a natural decrease in the acoustic density of the tumor tissue with increase in the prominence of the mass, while there are significant differences in the acoustic density values in hypo/avascular (36.53±5.37 dB) and hypervascular variants (29.28±4.53 dB) of blood supply to tumor tissue. CONCLUSION: The obtained data on acoustic density of choroidal melanoma can be used in clinical practice for indirect assessment of the nature of blood supply to choroidal melanoma.

[Features of the course of lamellar macular holes with epiretinal proliferation]. / Osobennosti techeniya lamellyarnykh makulyarnykh razryvov, soprovozhdayushchikhsya razvitiem epiretinal'noi proliferatsii.

The question of the course of lamellar macular holes (LMH) - favorable or progressive - remains controversial to this day. It is important to study the features of the course of this pathology in patients with epiretinal proliferation (EP). PURPOSE: To establish the features of the course of lamellar macular holes with the presence of epiretinal proliferation. MATERIAL AND METHODS: Clinical and instrumental monitoring was carried out in 48 patients with LMH divided into two groups: with the presence of EP (n=27) and its absence (n=21). The follow-up period lasted 15.9±2.3 months. The following parameters were assessed: changes in best corrected visual acuity (BCVA), mean retinal sensitivity (MRS) of the retina in 2- and 4-degree zones, subjective complaints; the main morphometric and morphostructural parameters of the retina were evaluated using optical coherence tomography (OCT). RESULTS: Patients with LMH and EP had lower initial BCVA, as well as, according to OCT, disruption of the ellipsoid zone and the presence of a foveal bump (37% and 22.2% of patients, respectively). During the follow-up, patients with EP showed an increase in subjective complaints, a statistically significant decrease in MRS in the 2-degree zone, and a decrease of the minimal retinal thickness. CONCLUSION: LMH with EP are characterized by an unfavorable course, which is confirmed by a decrease in functional and anatomical parameters.

[Sarcoid granuloma of the iris (clinical cases and state of the problem)]. / Sarkoidoznaya granulema raduzhki (klinicheskie sluchai i sostoyanie problemy).

Granulomatous lesion of the iris has varying etiology, but in the differential diagnostic it should often be considered by sarcoidosis and tuberculosis damage. PURPOSE: To describe a clinical case of sarcoid lesion of the iris and provide an analysis of literature devoted to this problem in the context of its polyetiology. MATERIAL AND METHODS: The article describes one case of sarcoid granuloma of the iris in a young patient with a relapsing course of the disease. RESULTS: The presented clinical case demonstrates the need for differential diagnosis to clarify the causes of the disease and the possibility of recurrence involving appearance of a multifocal lesion. The article also reviews literature on this problem reflecting the polyetiological nature of granulomatous lesions of the iris, and argues the use of interventional diagnostic methods in the absence of extraocular pathology. CONCLUSION: Analysis of the clinical case and literature clearly demonstrates the need for differential diagnosis of granulomatous lesions of the iris.

[Protocol of intravitreal drug delivery. Consensus of the Expert Counsil of Retina and Optic Nerve Diseases of the All-Russian Public Organasation «Association of Ophthalmologists¼]. / Protokol vypolneniya intravitreal'nogo vvedeniya lekarstvennykh preparatov. Konsensus Ekspertnogo soveta po zabolevaniyam setchatki i zritel'nogo nerva Obshcherossiiskoi obshchestvennoi organizatsii «Assotsiatsiya vrachei-oftal'mologov¼.

Intravitreal drug administration is a procedure that has become widespread in modern ophthalmology. However, there is no global consensus on certain aspects of this manipulation, and practitioners feel the need for guidelines. In the Russian Federation, until now, such a document was not available. The expert council on diseases of the retina and optic nerve of All-Russian public organization «Association of Ophthalmologists¼, with participation of invited specialists, has studied and analyzed the existing foreign guidelines for performing intravitreal injections, as well as the regulatory framework in Russia. As a result, this Protocol was developed and approved for use in the healthcare system of the Russian Federation. The document regulates the requirements for specialists and organizations, the conditions for performing the procedure and the necessary material resources and presents an algorithm for performing intravitreal drug administration, a patient examination check-list for various conditions of the procedure, as well as parameters for evaluating and monitoring the quality of the procedure.

[Indocyanine green angiography in the diagnostics of choroidal tumors]. / Angiografiya s indotsianinom zelenym v diagnostike novoobrazovanii khorioidei.

PURPOSE: To study the use of ultrasound color Doppler imaging and indocyanine green (ICG) angiography for identification of malignant vasculature of choroidal tumors. MATERIAL AND METHODS: The study included 46 patients (46 eyes) with tumors of the choroid: 19 men and 26 women aged 22 to 89 years, average age 53.2±17.1 years. All patients underwent indocyanine green angiography and Doppler ultrasound imaging. At the time of examination, thickness of the tumors ranged from 1.1 mm to 3.0 mm, and the base diameter from 4.0 mm to 13.0 mm. Choroidal melanoma was diagnosed in 27 patients, choroidal nevus in 10, choroidal hemangioma in 5, and choroidal metastasis in 4 patients. RESULTS: The results of indocyanine green angiography demonstrate that the pathological malignant vasculature was determined: nevi was diagnosed in 7 out of 10 patients, choroidal melanoma in 16 out of 27, metastasis in 2 out of 4, and hemangioma in none of the 5 patients. Pathological malignant vasculature was determined in most patients with choroidal melanoma (77.8%), in all patients with choroidal hemangioma and in 3 patients with choroidal metastases. Ultrasound imaging revealed malignant vasculature in 15 of 27 (56%) patients with choroidal melanoma, it could be identified in all patients with hemangioma in 2 patients and with choroidal metastases, and in none patients with choroidal nevi. CONCLUSIONS: Indocyanine green angiography helps verify malignant vasculature in 77.8% of patients with small and medium sized choroidal melanomas. Angioarchitecture of choroidal tumors visualized with indocyanine green angiography is characterized by variability of patterns, which should be taken into account in the differential diagnosis of various pathological diseases.

[The effects of a trehalose-based drug used after laser keratorefractive surgeries]. / Rezul'taty primeneniya preparata na osnove Tregalozy posle lazernykh keratorefraktsionnykh operatsii.

PURPOSE: To analyze the effectiveness of artificial tear drops Thealoz (trehalose 3%) in the correction of dry eye syndrome (DES) after ReLEx SMILE and FEMTO LASIK keratorefractive surgeries. MATERIAL AND METHODS: The study included 20 patients (40 eyes) who underwent a keratorefractive surgery and were prescribed instillations of Thealoz artificial tear drops for the correction of dry eye syndrome. Patients were divided into 2 group: the 1st group consisted of 10 patients who underwent ReLEx SMILE surgery, the 2nd group - 10 patients after FEMTO LASIK. The effectiveness of the treatment was evaluated at 1 and 3 months after the surgery using Ocular Surface Disease Index (OSDI), changes in the anterior corneal epithelium (Oxford scale), and tear break-up time (Norn's test). RESULTS: It was found that the use of artificial tear drops Thealoz regardless of the type of keratorefractive surgery helps reduce discomfort based on the OSDI questionnaire from 10.90±4.55 to 10.20±4.07 and 8.89±3.26 points by 1 and 3 months of the follow-up, respectively (p≤0.05). The degree of epitheliopathy according to the Oxford scale decreases from 0.73±0.75 to 0.25±0.43 points 3 months after the surgery (p≤0.05), which is accompanied by a significant increase in tear break-up time (Norn's test) from 11.18±1.19 to 12.43±1.03 and 12.45±1.03 seconds 1 and 3 months after treatment, respectively (p≤0,05). CONCLUSION: Complex evaluation of the ocular surface has proved that artificial tear drops Thealoz is effective in reducing DES manifestations after keratorefractive surgery. The results clearly demonstrate that the drug helps increase stability of the tear break-up time, as well as contributes to the decrease in epitheliopathy and subjective discomfort sensations, giving grounds to widen its use in clinical practice.

[Artificial tear drops Thealoz in the correction of dry eye syndrome after keratorefractive surgery]. / Primenenie preparata Tealoz v korrektsii sindroma sukhogo glaza posle keratorefraktsionnykh operatsii.

PURPOSE: To analyze the effectiveness of artificial tear drops Thealoz (trehalose 3%) in the correction of dry eye syndrome (DES) after keratorefractive surgery based on instrumental monitoring of the condition of eye surface. MATERIAL AND METHODS: The study included 20 patients (40 eyes) who underwent a keratorefractive surgery and were prescribed instillations of Thealoz artificial tear drops for the correction of dry eye syndrome. Patients were divided into 2 groups: the 1st group consisted of 10 patients who underwent ReLEx SMILE surgery, the 2nd group - 10 patients after FEMTO LASIK. The effectiveness of the treatment was evaluated at 1 and 3 months after the surgery using conventional instrumental monitoring: tear break-up time (Norn's test), tear film osmolarity test and OCT-meniscometry. RESULTS: Regardless of the type of surgery, tear film break-up time has significantly increased from 11.16±0.38 sec to 12.95±0.24 (p≤0.05) and 13.85±0.03 (p≤0.05) by months 1 and 3, respectively; it correlated with progressive decrease of tear film osmolarity from 317.29±1.39 to 308.00±0.79 mOsm/L (p≤0.05) at one month, and by the 3rd month - to 301.75±0.27 mOsm/L (p≤0.05). An improvement in OCT-meniscometry parameters was also observed in the form of a significant increase of the height and depth after 1 and 3 months. CONCLUSION: The use of artificial tear drops Thealoz contributes to the reduction of DES manifestations after keratorefractive surgery: increased stability of the tear film, restoration of the tear meniscus parameters and tear film osmolarity. The use of trehalose ophthalmic solution is advisable in patients after keratorefractive surgery.

[Ocular sarcoidosis as a clinical manifestation of multiorgan involvement]. / Sarkoidoz organa zreniia kak klinicheskoe proiavlenie mul'tiorgannogo porazheniia.

Eye lesion in sarcoidosis is often the first and only sign of a disorder, which suggests a possible systemic disease. Currently sarcoidosis is considered a multisystemic granulomatous disease that requires multidisciplinary approach. PURPOSE: To study the prevalence and clinical aspects of sarcoidosis eyes based on the representative sample of patients diagnosed with extraocular nonspecific granulomatous disease. MATERIAL AND METHODS: The study included 417 patients with multi-organ sarcoidosis. Females prevailed in the study population (259 patients - 62.11%); average patient age was 43.5±3.5 years. RESULTS: Patients with systemic signs of sarcoidosis had an eye lesion in 7.7% of cases. Females (71.87%) at the age of 48.5±2.5 were diagnosed with sarcoidosis more often. Among the clinical forms of sarcoidosic eye lesion, anterior uveitis prevailed (59.37%), affection of the posterior uveal tract was observed less often (31.25%); the disease had chronically recurrent course in 53.12% of patients. Among rare disease forms, orbital granuloma was found in two patients, and one patient had sarcoidosis of the skin of the medial angle of the eye. CONCLUSION: Analysis of the clinical material revealed the occurrence rate of eye lesion in patients with systemic manifestations of sarcoidosis, and gave insight on the polymorphism of clinical signs of organ lesion in multiorgan and isolated granulomatous inflammation.

[Effect of medicinal treatment on epithelial wound healing after phacoemulsification]. / . Vliianie medikamentoznoi terapii na épitelizatsiiu rogovichnogo razreza posle fakoémul'sifikatsii.

AIM: to compare the dynamics of epithelial wound healing under two different post-op treatments in patients after uncomplicated phacoemulsification. MATERIAL AND METHODS: This prospective randomized clinical trial included 40 eyes of 40 patients aged 66.4±8.2 years who underwent uncomplicated phacoemulsification with flexible intraocular lens implantation through a 2.2-mm corneal incision. Patients were randomized to receive either dexamethasone 0.1% and diclofenac 0.1% (n=20 eyes, Group I), or bromfenac 0.09% (n=20 eyes, Group II). Also, all patients instilled levofloxacin 0.5%. The dynamics of epithelial wound healing was assessed with the RTVue-100 spectral domain optical coherence tomograph with CAM-L corneal module in the 3D CORNEA mode 2 hours after surgery and on days 1, 3, 5, and 10. RESULTS: The postoperative period was uneventful in all cases. Two hours after surgery, epithelial defects were found in all eyes and their length did not differ statistically p=0.47. On the first day after surgery, complete epithelization was observed in 30% of cases from Group I and 60% of cases from Group II. The average length of epithelial defects was reliably smaller in Group II than in Group I (p=0.04 respectively). On postoperative day 3, 20% eyes from Group I still had epithelial defects with the average length of 0.45±0.13 mm, while there was only one eye with a 0.2-mm epithelial defect in Group II. Finally, on postoperative day 5, there was a single 0.3-mm epithelial defect in one eye from Group I. On day 10, none of the patients had epithelial defects in either group. CONCLUSION: Epithelial wound healing at the site of corneal incision after non-complicated phacoemulsification was found to be faster in patients instilled with bromfenac twice daily than in patients receiving dexamethasone and diclofenac four times daily as anti-inflammatory therapy and given topical fluoroquinolones for antibacterial purpose.

[OCT-morphometric and angiographic parallels between different variants of central serous chorioretinopathy]. / Morfometricheskie i angiograficheskie paralleli pri razlichnykh variantakh techeniia tsentral'noĭ seroznoĭ khorioretinopatii.

Central serous chorioretinopathy (CSCR) is a frequent cause of vision deterioration. Often it is associated with type 1 neovascularization under the pigment retinal epithelium (RPE). Optical coherence tomography angiography (OCT-angiography) enables non-invasive and contrast-free detection of neovessels in any retinal layer, which makes the method appropriate for diagnostics in CSCR. AIM: to investigate OCT-morphometric and angiographic parallels between different CSCR courses. MATERIAL AND METHODS: The study included 37 patients with CSCR. All the patients underwent standard ophthalmic examination, measurement of the axial eye length (AL) (Lenstar 900, 'Haag-Streit', Switzerland), spectral OCT and OCT-angiography with SSADA algorithm (RTVue xR Avanti, 'Optovue', USA) as well as fundus imaging and fluorescein angiography (FA) (VISUCAM 500, 'Zeiss', Germany). Judging from the results of spectral OCT and intravenous FA, the patients were divided into 2 groups: group 1 - 20 patients with pigment epithelium detachment (PED) and group 2 - 17 patients without PED. AL averaged 23.75±0.27 mm in group 1 and 23.55±0.40 mm in group 2. RESULTS: Comparative analysis of morphometric parameters in the two groups showed that those patients, whose CSCR manifested with only neurosensory retinal detachment (group 2), demonstrated greater choroidal thickness in the projection of the fovea, central retinal thickness as well as the height and extent of neurosensory retinal detachment. Neovasculature was identified in 11 eyes from group 1 (with PED). Structurally, the neovascular network was either loop-like (7 eyes), or tree-like (4 eyes). In loop-like networks, the maximum neovessel diameter averaged 35.474±4.967 µm and the total area of the neovascular complex was 0.581±0.380 µm2. Tree-like complexes were notable for the generally greater maximum neovessel diameter (65.626±17.316 µm) and area (0.225±0.133 µm2). CONCLUSION: Non-PED patients show pronounced transudative symptoms and significantly greater subfoveal retinal thicknesses. According to OCT-angiography findings, half of those CSCR patients, with PED, present neovascular networks of either loop-like, or tree-like structure.

[Macular choroidal blood flow in concurrent age-related macular degeneration and primary open-angle glaucoma]. / Sostoyanie khorioidal'nogo krovotoka v makulyarnoi zone pri sochetanii vozrastnoi makulyarnoi degeneratsii i pervichnoi otkrytougol'noi glaukomy.

UNLABELLED: Ocular circulation disorders are an important factor in the development of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). To date, however, there have been no studies on choroidal blood flow peculiarities in case of concurrent AMD and POAG. AIM: to determine distinctive features of choroidal blood flow characteristic of concurrent AMD and POAG and to assess their role in disease pathogenesis. MATERIAL AND METHODS: Macular choroidal blood flow, including blood supply, was assessed in 54 patients (102 eyes) by means of Doppler ultrasound. Three groups were formed: group 1 - 38 eyes with both AMD and POAG; group 2 - 41 eyes with AMD and no signs of optic nerve pathology; and group 3 - 23 eyes with POAG and no signs of AMD. Groups 1 and 2 were subdivided into two subgroups each: А - atrophic AMD and B - macular drusen. The mean patient age was 78.7±8.4 years. The following parameters of choroidal blood flow were of interest: peak systolic velocity (Vps), end diastolic velocity (Ved), time-averaged maximum velocity (Vtamax), and resistance index (RI). RESULTS: Groups 1, 3, and 2A had an evident choroidal hypoperfusion in the macular area (decreased Vtamax) with uncompensated perfusion deficit, despite autoregulation efforts (decreased Vps, Ved, decreased or normal RI). Group 2B demonstrated a significantly higher rate of choroidal hyperperfusion (increased Vps, Ved, Vtamax, and RI). CONCLUSION: Concurrent AMD and POAG are notable for choroidal hypoperfusion in the macular area that leads to inadequate trophism of the neurosensory retina and can aggravate the course of AMD contributing to progression of its atrophic form.

[Optical coherence tomography angiography in the diagnosis of neovascular age-related macular degeneration].

AIM: to determine optical coherence tomography (OCT) angiography signs of classic and occult choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) and evaluate their information value in monitoring the effect of anti-VEGF therapy. MATERIAL AND METHODS: The study enrolled 76 patients (87 eyes), including 68 patients (72 eyes) with wet AMD and 8 patients (15 eyes) with no signs of neovascularization. All patients underwent spectral-domain OCT, OCT angiography, and fluorescein angiography (FA). OCT angiography was used to evaluate neovascular networks in terms of their location, shape, size, and extent of visualization. Sensitivity and specificity of the method were assessed separately in a group of 37 CNV eyes and 15 unsuspicious eyes, specific findings at FA being the main diagnostic criteria. To determine the information value of OCT angiography in monitoring the effect of intravitreal ranibizumab therapy, 9 patients (9 eyes) were selected, in whom the exam was performed the day before the injection and then at days 3, 10, 17, 24, and 31. RESULTS: The patients were divided into two groups. Group 1 consisted of 43 eyes with occult CNV, group 2--of 29 eyes with classic CNV. Neovascular loops underneath the retinal pigment epithelium were found in 76.74% of occult CNV cases. In patients with classic CNV, the neovasculature was clearly visible in 82.76% of eyes, loop-like and tree-like networks occurring with similar frequency (51.72% and 42.28% respectively). OCT angiography results obtained prior to and following ranibizumab injection revealed a change in not only the size of neovascularization, but also the density, thickness, and branching pattern of newly formed blood vessels. Sensitivity and specificity of OCT angiography has been shown to be 89.2% and 93.3% respectively. CONCLUSION: OCT angiography enables diagnosis of both classic and occult choroidal neovascularization in patients with AMD as well as dynamic assessment of the size of the neovascular complex during anti-VEGF treatment. The method has high sensitivity and specificity.

[Ophthalmic oncology: achievements over the last two decades].

The article describes current trends in scientific research, especially those that concern treatment of the most common cancers. The latter include malignant eyelid and conjunctiva tumors, retinoblastoma and choroidal melanoma. Relevant publications in Russian and foreign journals demonstrate a progressive advance in treatment approaches: from radical methods associated with surrounding tissue damage to local tumor destruction. Comparative analysis of the methods and their effectiveness suggest that Russian ophthalmic oncology meets state-of-the-art international criteria.

[Complications of transpupillary thermotherapy for choroidal melanomas and possibilities for their prevention].

The authors analyze cases of complications occurring in patients with choroidal melanoma after transpupillary thermotherapy (TTT) (72 cases). The frequency of complications (31.94%) is consistent with those given in the literature (22-32%). The bulk is due to vascular disorders that mainly appear as vasculopathy (23.6%). Their frequency with the unique treatment procedure is shown to depend on the degree of pigmentation of a tumor and its thickness. Previous brachytherapy for melanoma increases the likelihood of retinal neovascularization with preretinal hemorrhages. The frequency of such events can be reduced by TTT for small choroidal melanomas during maximum mydriasis.

[Clinical aspects of ocular tuberculosis of different localization]. / Osobennosti klinicheskoi kartiny tuberkuleza glaz razlichnoi lokalizatsii.

Detailed study of a representative clinical sample and monitoring of 410 patients with ocular tuberculosis enabled the authors disclose the pathomorphosis and describe the clinical features of the disease. Tuberculosis of anterior location is observed at middle age and is characterized by frequent relapses, monolateral involvement, predominance of mixed and exudative inflammation, and high incidence of complications. Posterior tuberculous uveitis more often occurs in young people and is characterized by involvement of one or both eyes, productive inflammation, long remissions, and lesser incidence of complications.

[Immunological aspects of tuberculosis uveitis pathogenesis]. / Immunologicheskie aspekty patogeneza tuberkuleznogo uveita.

Based on clinical and immunological examinations of 251 patients with tuberculous uveitis (TU), 3 types of its course (productive, exudative, and mixed) were identified. The immunopathologic pattern of each type was found to be different: the productive type was characterized by delayed hypersensitivity, the exudative one had immediate hypersensitivity, and the mixed one had both. The immunogenetic markers of mixed TU were defined. These included HLA antigens, such as A2, B7, B21, and B27.

[Clinical immunological classification of tuberculous uveitis]. / Kliniko-immunologicheskaia klassifikatsiia tuberkuleznogo uveita.

Clinical and immunological studies carried out in 251 patients with tuberculous uveitis (TU) revealed three types of inflammatory reactions in the uveal tract in this patient population: productive, exudative, and productive-exudative (mixed), differing by the type of immune disorders. The findings helped develop a clinical immunological classification of TU, taking account of the clinical form of uveitis, type of inflammatory reaction of the uveal tract, disease pattern, involvement of one or both eyes, complications, and the immunopathological variants of TU course.