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In this age of technological advancement, an increasing number of people is being exposed to external risk factors of damaging their ocular surface (wearing contact lenses, electromagnetic radiation from computers, mobile devices, etc.). However, the presence of external factors does not lead to a 100% risk of developing the dry eye disease (DED). The trigger mechanism in the development of autoimmune lesions of the ocular environment in some systemic diseases is known to be associated with molecular genetic factors. The search for molecular genetic disorders is based on the analysis of polymorphic markers of a number of genes responsible for the state of the eye surface.To study the relationship of polymorphic markers rs7947461 of theThe study included 57 people with exogenous risk factors for DED development. The control group included volunteers without a history of ophthalmic pathologies (In the course of the study, 31 patients of the main group were diagnosed with DED and separated into the 1st subgroup; DED diagnosis was not confirmed in 26 patients, who were put into the 2nd subgroup. The 1st subgroup showed a significant increase in the frequency of predisposing genotypes of theThe revealed association of polymorphic markers rs7947461 of theВ эпоху развития технологий все большее число людей подвергается воздействию внешних факторов риска поражения глазной поверхности (ношение контактных линз, электромагнитное излучение компьютеров, мобильных устройств и прочее). Тем не менее наличие внешних факторов воздействия не приводит к 100% риску развития синдрома сухого глаза (ССГ). Известно, что пусковым механизмом в развитии аутоиммунного поражения глазной поверхности при ряде системных заболеваний являются ассоциированные с ним молекулярно-генетические факторы. В основе поиска молекулярно-генетических особенностей заболевания лежит анализ полиморфных маркеров ряда генов, ответственных за контроль состояния глазной поверхности.Определить взаимосвязь полиморфных маркеров rs7947461 генаВ исследование включены 57 человек, имеющих экзогенные факторы риска развития ССГ (основная группа). В группу контроля включены добровольцы без офтальмологической патологии в анамнезе (В ходе исследования у 31 пациента основной группы установлен диагноз ССГ, они выделены в 1-ю подгруппу, у 26 диагноз ССГ не подтвержден (2-я подгруппа). У пациентов 1-й подгруппы выявлено статистически значимое увеличение частоты предрасполагающих генотипов геновВыявленная ассоциация полиморфных маркеров rs7947461 гена

An association of polymorphic marker rs2228262 in the THBS1 gene with the risk of developing dry eye in Sjögren syndrome was revealed. Confocal microscopy data suggest that this polymorphic marker is responsible for the high probability of corneal nerve fiber lesion in Sjögren syndrome even in the absence of clinical and functional signs of dry eye syndrome. A significant correlation was established between polymorphic markers rs1478604, rs2228262 in THBS1 gene and the coefficients of anisotropy and orientation symmetry of corneal nerve fibers. These results allow considering these polymorphic markers as a genetic factor of predisposition to dry eye syndrome in patients with Sjögren syndrome.

to propose diagnostic algorithm of IgG4-related disease (IgG4-RD).One center retrospective research. 52 pts with IgG4-RD were included. The diagnosis was proved histologically and immunohistochemically. 48 out of 52 pts received treatment. Treatment included one of the following schemes (along with low oral glucocorticoids): rituximab monotherapy, cyclophosphamide monotherapy or their combination.The mean age was 47.4±5.9 years, the mean age of the disease onset was 43.9±16.0 years. Median time before the diagnosis was 24 months. The most often sites of IgG4-RD were lacrimal (63.5%), salivary (46.2%) glands, lungs (48%), lymph nodes (34.6%) and retroperitoneum (17.3%). In clinical picture the leading complain was organ enlargement, but not its dysfunction. Pain was characteristic for retroperitoneum localization. In 56.8% of pts with IgG4-related syalo - and/or dacryoadenitis there was association with ear - nose - throat organs affection. In 4 pts (7.7%) IgG4-RD was combined with some malignant disease, including MALT-lymphoma of lacrimal glands. Irreversible organ damage as an IgG4-RD outcome had 15.4% of pts. The main laboratory markers of IgG4-RD were ESR elevation (38.5%), blood eosinophilia (9.6%), immunological disturbances (serum total IgG and IgG4 elevation, IgE elevation, antinuclear antibodies, rheumatoid factor detection, hypocomplementemia). Serum IgG4 level1.35 g/l was elevated in 88% of pts and correlated with the number of affected organs (Spearman correlation coefficient 0.39, Student's test, р=0.0056). Monoclonal serum secretion and B-cell clonality in the tissue was detected in 4 (23.5%) out of 17 pts, but not all of them had both signs.Based on the analysis of clinical and laboratory characteristics of IgG4-RD a diagnostic algorithm was proposed that enhances the detection and examination of the patients with suspected IgG4-RD.Цель: предложить алгоритм диагностики IgG4-связанного заболевания (IgG4-СЗ). Материалы и методы. Одноцентровое ретроспективное исследование, в которое включено 52 пациента с IgG4-CЗ. Диагноз верифицирован гистологически и иммуногистохимически. Из 52 пациентов 48 лечились медикаментозно. Лечение проводилось по одной из схем (на фоне низких доз пероральных глюкокортикоидов): монотерапия ритуксимабом (РТМ); монотерапия циклофосфамидом (ЦФ); комбинированная терапия РТМ и ЦФ. Результаты. Средний возраст пациентов составил 47,4±15,9 года, средний возраст дебюта заболевания 43,9±16,0 лет. Медиана времени с момента дебюта до постановки диагноза - 24 мес. Наиболее часто поражались слезные (63,5%), слюнные (46,2%) железы, легкие (48%), лимфатические узлы (34,6%) и забрюшинное пространство (17,3%). В клинической картине преобладали жалобы на увеличение органов, а не на снижение их функции. Наличие болевого синдрома характерно для пациентов с ретроперитонеальным фиброзом. У 56,8% пациентов с IgG4-связанным сиало - и/или дакриоаденитом имелась ассоциация с поражением ЛОР-органов. У 4 (7,7%) пациентов IgG4-СЗ сочеталось с онкологическим заболеванием, в том числе с MALT-лимфомой слезных желез. Необратимые поражения органов как исход IgG4-СЗ были у 15,4% пациентов. Основными лабораторными отклонениями у пациентов с IgG4-СЗ были повышение скорости оседания эритроцитов (38,5 %), эозинофилия в крови (9,6%), иммунологические нарушения (повышение уровня общего IgG и IgG4 сыворотки, повышение IgE, выявление антинуклеарных антител, ревматоидного фактора и снижение уровня компонентов комплемента). Уровень IgG41,35 г/л повышен у 88% пациентов и положительно коррелировал с числом пораженных органов (коэффициент корреляции Спирмена 0,39, критерий Стьюдента, р=0,0056). Наличие моноклональной секреции в сыворотке крови и наличие В-клеточной клональности в ткани выявлено у 4 (23,5 %) из 17 исследованных, однако они не всегда сочеталась у одного пациента. Заключение. На основании анализа клинико - лабораторных проявлений IgG4-СЗ предложен алгоритм диагностики данного заболевания, который улучшит выявление и качество обследования пациентов с подозрением на IgG4-СЗ.

Anti-inflammatory therapy is a type of etiopathogenetic treatment of chronic mixed blepharitis. Nonsteroidal anti-inflammatory drugs (NSAIDs) have pronounced anti-inflammatory effect comparable to the action of corticosteroids.To assess of the effectiveness of a NSAID - 0.09% bromfenac - in the treatment of chronic blepharitis of non-infectious etiology.The study included 37 patients (74 eyes), 31 women (62 eyes) and 6 men (12 eyes) with chronic blepharitis. All patients underwent clinical, functional, instrumental and laboratory examination. The treatment of patients of the main group consisted of instillations of 0.09% bromfenac ('Broxinac', Sentiss, India) once per day and artificial tears with lipid component 3 times a day for 30 days. Patients in the control group only used artificial tears with lipid component 3 times a day for 30 days. The follow-up included examinations at one week, one and two months.The positive clinical and functional response after treatment corresponded to optimization of the state of microvasculature in both groups, however, the dynamics of changes in the control group were less pronounced.Elimination of microcirculatory disorders in the eyelids and signs of inflammation of the ocular surface determine the etiopathogenetic direction of using 0.09% bromfenac in the conservative treatment of chronic mixed blepharitis.Одним из направлений этиопатогенетического лечения хронического смешанного блефарита является противовоспалительная терапия. Выраженной противовоспалительной активностью, сопоставимой с действием кортикостероидов, обладают нестероидные противовоспалительные средства (НПВС). Цель исследования - оценка эффективности применения НПВС - 0,09% бромфенака - в терапии хронического блефарита неинфекционной этиологии. Материал и методы. В исследование включено 37 пациентов (74 глаза) - 31 женщина (62 глаза) и 6 мужчин (12 глаз) с хроническим блефаритом. Всем пациентам проводили клинико-функциональное, инструментальное и лабораторное обследование. Лечение пациентов основной группы заключалось в инстилляциях 0,09% бромфенака ('Броксинак', Sentiss, Индия) 1 раз в день и слезозаменителя с липидным компонентом 3 раза в день в течение 30 дней. Пациенты группы контроля применяли слезозаменитель с липидным компонентом 3 раза в день в течение 30 дней. Мониторинг эффективности лечения осуществляли через 1 нед, 1 и 2 мес. Результаты. Положительный клинико-функциональный ответ после лечения соответствовал оптимизации состояния микроциркуляторного русла в обеих группах, однако в группе контроля динамика изменений была выражена менее значительно. Заключение. Устранение микроциркуляторных нарушений в веках и признаков воспаления глазной поверхности определяет этиопатогенетическую направленность применения 0,09% бромфенака в консервативном лечении хронического смешанного блефарита.

The paper describes Russia's first diagnosed case of Erdheim--Chester disease (systemic histiocytosis) in a 65-year-old man who has been long treated for Ormond's disease (idiopathic retroperitoneal fibrosis). It also gives the data available in the literature on the pathogenetic components of these diseases and on the similarity of many clinical, laboratory, and morphological characteristics of these two immunoinflammatory diseases and covers the issues of their differential diagnosis. Invasive procedures with a careful morphological/immunomorphological examination of biopsy specimens obtained from affected tissues are shown to be necessary for accurate diagnosis.Описан первый случай диагностики в России системного гистиоцитоза - болезни Эрдгейма-Честера у 65-летнего мужчины, длительно получавшего терапию по поводу болезни Ормонда (идиопатического ретроперитонеального фиброза). Приведены данные литературы по патогенетическим звеньям, сходству многих клинических, лабораторных и морфологических характеристик этих двух иммуновоспалительных заболеваний, освещены вопросы дифференциальной диагностики. Показано, что проведение инвазивных процедур с тщательным морфологическим/иммуноморфологическим исследованием биоптатов пораженных тканей является необходимым условием для правильной постановки диагноза.

The expanding range of diagnostic instrumental methods allows an in-depth study of the morphological and functional state of the eyelids, which is the basis for determining the strategy for the treatment of chronic blepharitis and subsequent timely supplementation and altering of its algorithm.To substantiate the repeated courses of invasive treatment of chronic blepharitis based on morphological and functional studies.The study included 45 patients (90 eyes) with chronic mixed blepharitis. Instrumental research methods - laser Doppler flowmetry, laser scanning confocal microscopy (LSCM), tiascopy, and optical coherence tomography - were used to assess the morphological and functional state of the eyelids during meibomian gland probing (MGP) and eyelid massage course. The therapy effectiveness was evaluated after 1 week, 1, 3 and 6 months.Using a complex of diagnostic methods for assessing the morphological and functional state of the eyelids, surgical invasive treatment for mixed chronic blepharitis was proved to have a significant positive clinical effect compared with the eyelid massage traditionally used in polyclinic practice. After 6 months from the start of treatment, in the absence of changes in the clinical picture in both groups, functional changes in the control group were recorded that were expressed as a decrease in the values of the Norn test, confirmed by the data of tiascopy, and the number of functioning meibomian glands. The indicators of lacrimal meniscus depth in both groups corresponded to the values of the monitoring stage after 3 months. According to LSCM, the control group had higher inflammatory activity: the heterogeneity of the interstitium and the walls of the acini of the meibomian glands increased, the acinar area decreased in comparison with the main group. Deterioration of the blood flow microcirculation in both groups was manifested as a decrease in neurogenic rhythms. Additionally, a 3.05% decrease in myogenic rhythms was recorded in the main group. The study of the microcirculation of lymph flow showed a decrease in neurogenic rhythms in the main group by 4.79%.The analysis of the morphological and functional state of the eyelids after MGP has shown that its results persisted for 6 months, and repeated probing was justified, while the interval before repeated course of eyelid massage averaged 1.5 months.Расширяющийся спектр диагностических инструментальных методов позволяет проводить углубленное исследование морфофункционального состояния век, что является основой для определения стратегии лечения хронического блефарита с последующим своевременным дополнением и изменением его алгоритма.Обосновать проведение повторных курсов инвазивного лечения хронического блефарита на основе морфофункциональных исследований.Под наблюдением находилось 45 пациентов (90 глаз) с хроническим смешанным блефаритом. Для оценки морфофункционального состояния век при проведении зондирования мейбомиевых желез (ЗМЖ) и курса массажа век применяли инструментальные методы исследования: лазерную допплеровскую флоуметрию, лазерную сканирующую конфокальную микроскопию (ЛСКМ), тиаскопию, оптическую когерентную томографию. Мониторинг эффективности терапии осуществляли через 1 нед, 1, 3 и 6 мес.На основании комплекса диагностических методов оценки морфофункционального состояния век был доказан значимый положительный клинический эффект после проведения хирургического инвазивного лечения при смешанном хроническом блефарите по сравнению с традиционно используемым в поликлинической практике массажем век. Через 6 мес от начала лечения, при отсутствии изменений клинической картины в обеих группах, в контрольной группе были зафиксированы функциональные изменения, которые выражались в уменьшении значений пробы Норна, подтвержденных данными тиаскопии, числа функционирующих мейбомиевых желез. Показатели глубины слезного мениска в обеих группах соответствовали значениям этапа мониторинга через 3 мес. Более высокую воспалительную активность по данным ЛСКМ наблюдали в группе контроля: увеличилась гетерогенность интерстиция и стенок ацинусов мейбомиевых желез, уменьшилась ацинарная площадь. Ухудшение микроциркуляции кровотока в обеих группах проявлялось понижением нейрогенных ритмов. В основной группе зафиксировано снижение миогенных ритмов на 3,05%. Исследование микроциркуляции лимфотока показало понижение нейрогенных ритмов в основной группе на 4,79%.На основе анализа морфофункционального состояния век после ЗМЖ было показано сохранение результата воздействия на протяжении 6 мес и обосновано проведение повторного зондирования, в то время как сроки для повторного курса массажа век составили в среднем 1,5 мес.

Purpose of the study. To provide demographic, clinical, laboratory, ultrasound, radiological, morphological/ immunomorphological phenotype of IgG4-related ophthalmic diseases, which allowsmaking a differential diagnosis with granulomatous, autoimmune, inflammatory, endocrine and hematologic diseases affecting the eye and orbits. Materials and methods. From 2004 to 2016 108 (78.2%) of the 138 patients were diagnosed with non-tumoral lesions of eye and orbits. In 48 patients (35%) at admission and 5 patients in the follow were diagnosed IgG4-related ophthalmic disease. In the analysis of 82 (f-44, m-38) patients with IgG4-related disease, localization of lesions in orbit observed in 53 (f-36, m-17) and it was the most frequent involvement in patients with IgG4-related disease (64.5%). Only 7 patients had isolated IgG4-related ophthalmic disease, whereas 46 patients (87%) had involvement of 2-7 locations, as a manifestation of IgG4-related systemic disease.During the examination, the average age of patients with IgG4-related ophthalmic disease was 47.5 years (19-73 years). Median time to diagnosis was 52.8 months before 2004 and 36 months 2004-2016. Results. We noted the predominance of females in the ratio 2: 1 inthe group of patients with IgG4-related ophthalmic disease. Edema of the eyelids, nasal congestion (55-60%), tumor-like formations of the upper eyelids and increased lacrimation prevailed at the onset of the disease, whereas such functional impairment like limited mobility and pain in eyeballs, exophthalmos, ptosis and diplopia appeared later at 15-38% with a loss visual acuity in one case. Bilateral lesion (86%), mainly affecting the lacrimal glands (93.5%), infiltration of the extraocular muscles (83.5%) and retrobulbar tissue with a thickening of the optic nerve in one third of patients were the main localizations IgG4-related ophthalmic disease. Clinical symptoms were accompanied by the appearance of moderate inflammatory activity (38%), increased levels IgG (44%), IgG4(88%) and IgE (61%). Indicators of autoimmune disorders observed in 6-22% of patients, most often in patients with simultaneous involvement of the salivary glands. Significant lymphoplasmacytic infiltration (94%) with a ratio of plasma cells (IgG4/IgG) secreting IgG4> 40% (90%) with fibrosis formation (94%) and follicle formation (71%) with a moderate amount of eosinophils (34%) were the major morphological / immunomorphological manifestations of IgG4-related ophthalmic disease. Signs of vasculitis and obliterative phlebitis were found in a small amount of patients. Conclusion. Determination of elevated levels of IgG-4 / IgE in patients with edema, pseudotumor of the eyelid, sinusitis and increase of the palpebral lobe of the lacrimal gland suggests the presence of IgG4-related ophthalmic disease. Minimally invasive incisional biopsy of lacrimal glands and salivary glands followed by morphological / immunomorphological research is needed for the correct diagnosis. Diagnostic orbitotomy in ophthalmic hospitals in such cases is inexpedient, since it leads to the development of dry eye. Massive lymphoplasmacytic infiltration with IgG4 / IgG ratio more than 40%, advanced fibrosis in biopsiesof the orbits tissue or salivary glands when combined lesions are required for the making the diagnosis of IgG4-related ophthalmic disease.

The article reviews the literature on methods of evaluating the morphological and functional state of the eyelids in chronic blepharitis. Development of methods continues together with further research on the etiology and pathogenesis of the disease.В обзоре литературы представлены современные методы исследования морфофункционального состояния век при хроническом блефарите, разработка которых связана с продолжающимся изучением этиологии и патогенеза заболевания.

The article reviews the results of Russian and foreign studies concerning the search of susceptibility genes for widespread multifactorial diseases: Sjogren's syndrome and rheumatoid arthritis. Studying regularity patterns of genome changes in autoimmune processes with ophthalmic manifestations and their correlation with the severity of dry keratoconjunctivitis will contribute to a better understanding of the etiology and pathogenesis of eye manifestations of the diseases, and will also allow the development of new effective methods of diagnosis and targeted therapy.В обзоре обобщены результаты отечественных и зарубежных исследований, посвященных поиску генов предрасположенности к распространенным мультифакториальным заболеваниям: синдрому Шегрена и ревматоидному артриту. Изучение закономерности изменений генома аутоиммунных процессов при их офтальмологической манифестации и корреляции со степенью тяжести сухого кератоконъюнктивита будет способствовать лучшему пониманию этиологии и патогенеза глазных проявлений заболеваний, а также позволит разработать новые эффективные методы диагностики и целенаправленной терапии.

The authors have described the world's first case of necrotizing sarcoid granulomatosis (NSG) in a 22-year-old woman with the clinical presentations of acute abdomen, which are associated with abdominal lymph nodal infiltration and necrosis, obvious constitutional disturbances (fever, nocturnal sweats, and significant weight loss), high inflammatory activity (anemia, leukocytosis, high erythrocyte sedimentation rates and C-reactive protein levels), the gradual appearance of splenic and hepatic necrotic foci, and infiltration into the lung and lacrimal glands with the development of unilateral uveitis. The patient underwent five surgical interventions, several needle biopsies for recurrent abdominal syndrome, and long-term antibiotic treatment for presumed sepsis, which had caused drug-induced hepatitis. Bacteriological examination of blood, puncture samples, and removed abdominal cavity tissues, serological tests, and immunomorphogical study of biopsy samples and removed tissues yielded negative results for the presence of bacterial, fungal, and tuberculosis infections. NSG was diagnosed on the basis of the systemic nature of the lesion, the presence of granulomas with severe abdominal lymph nodal necrosis and necrotizing granulomatous/lymphocytic vasculitis in the mesentery and removed spleen, as well as the absence of granulomas in the spleen, appendix, and biopsy materials of the liver, colonic mucosa, and parotid gland. Fludarabine therapy was first used in world practice due to the inefficient treatment with high-dose glucocorticoids and cyclophosphamide and to a disease relapse when reducing their doses. The paper gives a detailed review of the literature on the clinical, laboratory, radiological, and morphological manifestations of the disease, which allow the differential diagnosis of NSG with different variants of granulomatous lesions. Based on the 5-year follow-up of the patient and on the analysis of clinical, laboratory, radiological, and morphological changes, the authors uphold the concept that the disease is an independent nosological entity: necrotizing angiitis with sarcoid reactions, rather than the entity of nodular or classic sarcoidosis.Описан первый в литературе случай дебюта некротизирующего саркоидного гранулематоза (НСГ) у 22-летней женщины с клинической картины 'острого живота', связанной с инфильтрацией и некрозом лимфатических узлов брюшной полости, выраженными конституциональными нарушениями (лихорадка, ночные поты, значительное снижение массы тела), высокой воспалительной активностью (анемия, лейкоцитоз, высокие СОЭ и уровень С-реактивного белка), постепенным появлением очагов некроза в селезенке, печени, инфильтрации легких и слезных желез с развитием одностороннего увеита. Больная перенесла 5 хирургических вмешательств, несколько пункционных биопсий в связи с рецидивами абдоминального синдрома, длительное лечение антибактериальными препаратами с развитием лекарственного гепатита в связи с предполагаемым септическим состоянием. Бактериологическое исследование крови, пунктатов и удаленных тканей брюшной полости, серологическое исследование крови, иммуноморфологическое изучение биоптатов и удаленных тканей дали отрицательные результаты на наличие бактериальной, грибковой и туберкулезной инфекции. Учитывая системный характер поражения, наличие гранулем с мощным некрозом лимфатических узлов брюшной полости и некротизирующего гранулематозного/лимфоцитарного васкулита в брыжейке, удаленной селезенке, а также отсутствие гранулем в селезенке, червеобразном отростке, биоптатах печени, слизистой оболочке толстой кишки и околоушной железы, диагностирован НСГ. Впервые в мировой практике использована терапия флударабином в связи с недостаточной эффективностью терапии высокими дозами глюкокортикостероидов и циклофосфамида, а также обострением заболевания при снижении доз. Приведен подробный обзор литературы по клинико-лабораторным, рентгенорадиологическим и морфологическим проявлениям заболевания, позволяющим провести дифференциальную диагностику НСГ с различными вариантами гранулематозных поражений. На основании 5-летнего наблюдения за больной, анализа клинико-лабораторных, рентгенорадиологических и морфологических изменений авторы отстаивают концепцию, согласно которой заболевание представляет собой самостоятельную нозологическую единицу: некротизирующий ангиит с саркоидной реакций, а не форму узловатого или классического саркоидоза.

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), various eye diseases are detected in 30-60% of patients, with chronic graft-versus-host reaction - in 50-90% of patients. Among the complications, the most frequent is damage to the eye surface and eyelids. The article presents a clinical case of successful minimally invasive treatment of chronic posterior blepharitis in a patient who has undergone allogeneic hematopoietic stem cell transplantation. Normalization of the outflow of meibomian gland secretion after the medical procedure was a prerequisite for improving the quantitative and qualitative composition of the lipid layer of the tear film and a factor contributing to a decrease in the amplitude of inflammation, which is reflected in the clinical and functional results.После аллогенной трансплантации гематопоэтических стволовых клеток (алло-ТГСК) различные глазные заболевания выявляют у 30—60% пациентов, при хронической реакции трансплантата против хозяина — у 50—90% пациентов. Среди данных осложнений наиболее частым является поражение глазной поверхности и век. В статье представлен клинический случай успешного малоинвазивного лечения хронического заднего блефарита у пациента, перенесшего алло-ТГСК. Нормализация оттока секрета мейбомиевых желез после проведения лечебной процедуры стала предпосылкой улучшения количественного и качественного состава липидного слоя слезной пленки и фактором, способствующим уменьшению амплитуды воспаления, что нашло отражение в клинико-функциональных результатах.

To study the effectiveness of soft contact lenses in severe keratoconjunctivitis sicca (KCS) treated with local immunosuppressive therapy.We have examined 41 patients (60 eyes) with severe KCS, including 3 men (4 eyes) and 38 women (56 eyes) aged from 27 to 76 years. Group 1 consisted of 22 persons (30 eyes) who were prescribed cyclosporine А 0.05% instillations 2 times daily, artificial tears, and soft contact lenses. Group 2 consisted of 19 patients (30 eyes) who received instillations of cyclosporine А 0.05% 2 times daily for no less than 6 months and artificial tears. Apart from the standard ophthalmic examination, the assessment included Schirmer's test, tear break-up time test, fluorescein eye stain test, tear osmometry, Heidelberg tomography of the cornea, optical coherence tomography of the anterior segment with meniscometry, impression cytology of the conjunctiva, tear pH measurement, plating of the content of the conjunctival cavity for its microflora, measurement of the width of the palpebral fissure, and calculation of the ocular surface disease index (OSDI). Treatment outcomes were evaluated at 1, 3, 6, and 12 months.In group 1, complete re-epithelialization of the cornea (confirmed by all the methods used) was achieved rather shortly, in 1-3 months, while in group 2 - in 6 months.The use of soft contact lenses in addition to cyclosporine A instillation therapy promotes restoration of corneal and conjunctival epithelium, reduces treatment time, and improves quality of life for patients, thus, proving itself a safe and effective treatment of autoimmune KCS.Цель - изучить эффективность применения лечебных мягких контактных линз (МКЛ) на фоне местной иммуносупрессивной терапии сухого кератоконъюнктивита (СКК) тяжелой степени. Материал и методы. Обследован 41 человек (60 глаз) с тяжелой степенью СКК: 3 мужчин (4 глаза) и 38 женщин (56 глаз) в возрасте от 27 до 76 лет. В 1-ю группу вошли 22 человека (30 глаз), носивших лечебную МКЛ на фоне инстилляций Циклоспорина А 2 раза в сутки не менее 6 мес и слезозаменительной терапии; 2-ю группу составили 19 пациентов (30 глаз), получавших инстилляции Циклоспорина А 2 раза в сутки не менее 6 мес и слезозаменительную терапию. Кроме стандартного офтальмологического обследования, проводили тест Ширмера, пробу Норна, тесты с витальными красителями, осмометрию слезы, Гейдельбергскую томографию (HRT) роговицы, оптическую когерентную томографию (ОКТ) переднего отрезка с менискометрией, импрессионно-цитологическое исследование конъюнктивы, pH-метрию слезы, посев содержимого конъюнктивальной полости на микрофлору, измеряли ширину глазной щели, определяли индекс поражения глазной поверхности (OSDI). Мониторинг результатов лечения осуществляли через 1, 3, 6 и 12 мес. Результаты. В 1-й группе полная эпителизация роговицы достигнута в короткие сроки (1-3 мес), во 2-й группе - через 6 мес, что подтверждено всеми методами исследования. Заключение. Применение лечебной МКЛ на фоне инстилляций Циклоспорина А ускоряет репарацию эпителия роговицы и конъюнктивы, сокращает сроки лечения и повышает качество жизни пациентов, являясь безопасным и эффективным методом лечения СКК аутоиммунного генеза.Цель - изучить эффективность применения лечебных мягких контактных линз (МКЛ) на фоне местной иммуносупрессивной терапии сухого кератоконъюнктивита (СКК) тяжелой степени. Материал и методы. Обследован 41 человек (60 глаз) с тяжелой степенью СКК: 3 мужчин (4 глаза) и 38 женщин (56 глаз) в возрасте от 27 до 76 лет. В 1-ю группу вошли 22 человека (30 глаз), носивших лечебную МКЛ на фоне инстилляций Циклоспорина А 2 раза в сутки не менее 6 мес и слезозаменительной терапии; 2-ю группу составили 19 пациентов (30 глаз), получавших инстилляции Циклоспорина А 2 раза в сутки не менее 6 мес и слезозаменительную терапию. Кроме стандартного офтальмологического обследования, проводили тест Ширмера, пробу Норна, тесты с витальными красителями, осмометрию слезы, Гейдельбергскую томографию (HRT) роговицы, оптическую когерентную томографию (ОКТ) переднего отрезка с менискометрией, импрессионно-цитологическое исследование конъюнктивы, pH-метрию слезы, посев содержимого конъюнктивальной полости на микрофлору, измеряли ширину глазной щели, определяли индекс поражения глазной поверхности (OSDI). Мониторинг результатов лечения осуществляли через 1, 3, 6 и 12 мес. Результаты. В 1-й группе полная эпителизация роговицы достигнута в короткие сроки (1-3 мес), во 2-й группе - через 6 мес, что подтверждено всеми методами исследования. Заключение. Применение лечебной МКЛ на фоне инстилляций Циклоспорина А ускоряет репарацию эпителия роговицы и конъюнктивы, сокращает сроки лечения и повышает качество жизни пациентов, являясь безопасным и эффективным методом лечения СКК аутоиммунного генеза.

Laser confocal tomography of the cornea enables studying ultrathin sections of corneal layers, which provides additional reliable information on tissue changes in keratoconjunctivitis sicca (KCS).To assess the significance of laser confocal tomography of the cornea in the diagnosis and monitoring of KCS.We investigated 38 eyes of 30 patients with severe KCS. The patients were divided into two groups. Group 1 (15 patients, 19 eyes) was prescribed cyclosporine А 0.05% instillations 2 times daily, artificial tears, and soft contact lenses. Group 2 (15 patients, 19 eyes) received only instillations of cyclosporine А 0.05% 2 times daily and artificial tears. Besides standard ophthalmic examination, additional tests were performed, namely Schirmer's test, tear break-up time test, fluorescein eye stain test, tear osmolarity test (TearLab System, USA), and Heidelberg retinal tomography of the cornea (HRT, Heidelberg Engineering GmbH, Germany).HRT findings revealed a 3 times shorter epithelization period and faster recovery of corneal transparency in group 1 as compared to group 2 (1.5 and 4.5 months, respectively). There was also an evident reduction in the number of immune cells in the cornea, most pronounced in group 1 at 3 months, which is indicative of inflammation termination.The use of HRT of the cornea in KCS patients allows real-time cellular level observation of corneal changes, which together with clinical findings and diagnostic tests not only confirms the diagnosis but also determines treatment effectiveness. It has been also found that soft contact lenses accelerate epithelization of the cornea and relieve inflammation of the ocular surface in KCS patients under cyclosporine A 0.05% instillation therapy. Transparency of financial activity: the authors have no financial interest in the submitted materials and methods.Лазерная конфокальная томография (НRT) роговицы позволяет получить ультратонкие послойные срезы роговицы, что дает дополнительную достоверную информацию об изменениях роговицы при сухом кератоконъюнктивите (СКК). Цель - оценить значение HRT роговицы в диагностике и мониторинге СКК. Материал и методы. Под нашим наблюдением находились 30 человек (38 глаз) с СКК тяжелой степени тяжести. Больные были разделены на 2 группы: 1-я группа - 15 человек (19 глаз) - применяла лечебную мягкую контактную линзу (МКЛ) на фоне инстилляций 0,05% Циклоспорина А 2 раза в сутки и слезозаменительную терапию; 2-я группа - 15 человек (19 глаз) - получала инстилляции 0,05% Циклоспорина А 2 раза в сутки и слезозаменительную терапию. Проводили стандартное и дополнительное офтальмологическое обследование: тест Ширмера, пробу Норна, тесты с витальными красителями, определение уровня осмолярности слезы ('TearLab System', США), HRT роговицы ('Heidelberg Engineering GmbH', Германия). Результаты. По данным HRT роговицы установили, что сроки эпителизации и восстановления прозрачности роговицы в 1-й группе в 3 раза короче, чем во 2-й, и составляли в среднем 1,5 и 4,5 мес соответственно. Отмечали уменьшение количества иммунных клеток в роговице, которое было наиболее выражено в 1-й группе через 3 мес от начала лечения, что свидетельствовало о купировании воспалительного процесса. Выводы. Применение HRT роговицы у больных с СКК дает возможность определить изменения роговицы на клеточном уровне в режиме реального времени, что совместно с клинико-диагностическими тестами позволяет не только правильно верифицировать диагноз, но и оценивать эффективность лечения. Использование лечебных МКЛ на фоне инстилляций 0,05% Циклоспорина А у больных с СКК ускоряет эпителизацию роговицы и купирует воспаление на глазной поверхности.

IgG4-related disease (IgG4-RD) is a systemic immune-related disease that may involve the pancreas, liver, retroperitoneal space, biliary tract, salivary and lacrimal glands, eye socket, lung, and kidney. In term of pathomorphogenesis, it is a fibroinflammatory disease manifesting as a tumor-like lesion of organs, elevated serum IgG4 levels, and a morphofunctional substrate - the development of marked fibrosis and lymphoplasmacytic infiltration in the tissues with the high content of IgG4-positive plasma cells. The detection of a tumor-like nodule frequently leads to that the patients with IgG4-RD undergo major traumatic surgery for presumed cancer. At the same time, a number of investigations show the association of IgG4-RD with the development of cancer and lymphoproliferative diseases. The paper describes two clinical cases: Russia's first diagnosis of MALT lymphoma of the lacrimal gland, IgG4-positive and IgG4-RD with a rare onset with a destruction focus in the cervical vertebrae, multiple organ dysfunction, B-cell clonality in salivary gland tissue and PIgMκ secretion. It also reviews world literature on the development of lymphoproliferative diseases in the presence of IgG4-RD.Связанное с IgG4 заболевание (IgG4-СЗ) - системное иммуноопосредованное заболевание, которое может вовлекать поджелудочную железу, печень, забрюшинное пространство, желчевыводящие пути, слюнные и слезные железы, глазницу, легкие, почки. С учетом патоморфогенеза это фибровоспалительное заболевание, проявляющееся опухолеподобным поражением органов, повышением уровня IgG4 в сыворотке крови и морфологическим субстратом - формированием выраженного фиброза и лимфоплазмоцитарного инфильтрата в тканях с высоким содержанием IgG4-позитивных плазматических клеток. Обнаружение опухолеподобного узла зачастую приводит к тому, что пациенты с IgG4-СЗ подвергаются обширным травматичным операциям по поводу предполагаемых онкологических заболеваний. В то же время в ряде исследований показана ассоциация IgG4-СЗ с развитием онкологических и лимфопролиферативных заболеваний процессов. В статье авторы приводят описание двух клинических случаев: первой в России диагностики MALT-лимфомы слезной железы, IgG4-позитивной и IgG4-СЗ с редким дебютом с очага деструкции в шейных позвонках, мультиорганным поражением, наличием В-клеточной клональности в ткани слюнной железы и секрецией PIgMκ. Приведен обзор мировой литературы о развитии лимфопролиферативных заболеваний на фоне IgG4-СЗ.

The article reviews literature on relationships between polymorphic variants of the genes THBS1, GTF2I, MUC1, TRIM21, STAT4, PTPN22 with clinical features of dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's syndrome. The development and implementation of a method for analyzing polymorphic gene variants used to diagnose dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's syndrome will allow assessment of the possibility of developing dry keratoconjunctivitis and/or its progression in patients with autoimmune diseases or in people at risk. Determination of clinical and morphological regularities of dry keratoconjunctivitis in accordance with the revealed molecular and genetic changes will contribute to better understanding of the etiology and pathogenesis of ophthalmological manifestations of autoimmune diseases, and will also help improve the diagnostics and prognosis of dry keratoconjunctivitis.В обзоре проведен анализ литературных данных о взаимосвязи полиморфных вариантов генов THBS1, GTF2I, MUC1, TRIM21, STAT4, PTPN22 с клиническими особенностями сухого кератоконъюнктивита при ревматоидном артрите и синдроме Шегрена. Разработка и внедрение в практику методов анализа полиморфных вариантов генов, используемых для диагностики сухого кератоконъюнктивита при ревматоидном артрите и синдроме Шегрена, позволят выявить возможность развития сухого кератоконъюнктивита и/или его прогрессирование у пациентов с аутоиммунными заболеваниями или у людей, находящихся в группе риска. Определение клинико-морфологических закономерностей течения сухого кератоконъюнктивита в соответствии с выявленными молекулярно-генетическими изменениями будет способствовать лучшему пониманию этиологии и патогенеза офтальмологической манифестации аутоиммунных заболеваний, а также позволит усовершенствовать диагностику и прогноз сухого кератоконъюнктивита.

Dry eye syndrome (DES) is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles. The clinical manifestations of DES can be highly variable, so its diagnosing is typically based on a combination of symptoms, signs, and clinical tests. Majority of the techniques involved in the diagnosis of this disease has a large degree of subjectivity. The present article reviews current dry eye diagnostic tests and presents a new tear film stability assessment technique that may potentially become the objective method for establishing DES diagnosis.Синдром 'сухого глаза' (ССГ) представляет собой многофакторное заболевание глазной поверхности, характеризующееся снижением гомеостаза слезной пленки и сопровождающееся глазными симптомами, в развитии которых этиологическую роль играют нестабильность слезной пленки, гиперосмолярность, воспаление и повреждение глазной поверхности и нейросенсорные нарушения. Клиническая манифестация ССГ достаточно вариабельна, поэтому при установлении диагноза необходимо в совокупности оценивать выраженность симптомов заболевания, данные клинического осмотра и диагностических тестов. Оценка большинства методов диагностики ССГ (особенно на ранних стадиях заболевания) имеет преимущественно субъективный характер. В данном обзоре литературы представлены современные методы диагностики синдрома 'сухого глаза', а также новый метод анализа состояния слезной пленки, который потенциально можно рассматривать в качестве объективного диагностического критерия при ССГ.

The interplay of different structures belonging to either the anterior segment of the eye or its accessory visual apparatus, which all share common embryological, anatomical, functional, and physiological features, is discussed. Explanation of such terms, as ocular surface, lacrimal functional unit, and ocular surface system, is provided.Рассмотрен вопрос о взаимосвязи различных структурных элементов переднего отрезка глаза и его придаточного аппарата, объединенных эмбриологически, анатомически, функционально и физиологически. Раскрыты понятия 'глазная поверхность', 'функциональная слезная единица' и 'система глазной поверхности'.

to identify the role of laser scanning confocal microscopy (LSCM) in diagnostic and to assess the effectiveness of involutional blepharitis treatment.The study involved 32 patients (64 eyes) with chronic blepharitis aged in average 75.21±3.56 years. All patients completed questionnaire (SPEED), underwent Schirmer I, Norn tear break-up time and compression tests, had the number of functioning meibomian glands (NFMG) calculated. The patients' eyelids were examined with LSCM, and the condition of conjunctiva was evaluated by microbiological study. The patients were also tested for Demodex spp. Based on the results of LSCM the patients were divided into two groups: atrophic and obstructive. The first group (13 patients, 26 eyes) was prescribed treatment of eyelid margins with 'Blephaclean' tissues 3 times a day and artificial tears 'Thealoz' 4 times a day. The second group (19 patients, 38 eyes) was recommended therapy with warm compress 2 times a day, application of eyelid gel 'Theagel' 3 times a day and instillations of 'Thealoz' 4 times a day. The follow-up began 2 months after therapy start.Clinical-functional, morphological parameters and laboratory findings had a tendency for improvements after the treatment. The application of tissues, eyelid gel and artificial tears contributed to increase of NFMG, improvement of tear film stability and tear production. The treatment resulted in decreased secretion reflectivity of the lacrimal canal orifice and lower degree of heterogeneity of acinar and interstitial walls according to LSCM readings.The data acquired on the discriminate application of eyelid hygiene products based on LSCM and clinical-functional examination allows the recommendation of such therapy for the treatment of various forms of involutional blepharitis.Цель - определить роль лазерной сканирующей конфокальной микроскопии (ЛСКМ) в диагностике и оценке эффективности терапии инволюционного блефарита. Материал и методы. В исследование включены 32 пациента (64 глаза) с хроническим блефаритом, средний возраст которых составил 75,21±3,56 года. Всем пациентам проводили анкетирование (SPEED), тест Ширмера I, пробу Норна, определение числа функционирующих мейбомиевых желез (ЧФМЖ), компрессионную пробу, ЛСКМ век, микробиологическое исследование состояния конъюнктивы, Demodex spp. По результатам ЛСКМ пациенты были разделены на 2 группы: атрофическую и обструктивную. Пациентам 1-й группы (13 человек, 26 глаз) назначали обработку краев век салфетками для век 'Блефаклин' 3 раза в день и слезозаменитель 'Теалоз' 4 раза в день. Пациентам 2-й группы (19 человек, 38 глаз) рекомендовали применение тепловых компрессов 2 раза в день, нанесение геля для век 'Теагель' 3 раза в день и инстилляции 'Теалоза' 4 раза в день. Мониторинг эффективности лечения осуществляли через 2 мес от начала терапии. Результаты. После лечения клинико-функциональные, морфологические и лабораторные показатели имели тенденцию к улучшению. Применение салфеток, гелей для век, слезозаменителей способствует увеличению ЧФМЖ, повышению стабильности слезной пленки и объема слезопродукции. В результате лечения выявлено понижение секреторной рефлективности устья, степени гетерогенности стенки ацинуса и интерстиция по данным ЛСКМ. Заключение. Полученные данные по избирательному применению средств для гигиены век, основанные на проведении ЛСКМ и клинико-функционального обследования, позволяют рекомендовать их для лечения различных форм инволюционного блефарита.

As any mucous membrane the conjunctiva is characterized by a definite pH value which guarantees-physiological functioning of the ocular surface. The most commonly used method of assessment is potentiometric pH measurement with ion-specific glass microelectrodes. The results, however, can be affected by such factors, as conjunctival sac zoning, tissue acidity, epithelial trauma, and reflex tear secretion. Few data and hypotheses are available on mechanisms of maintaining the acid-base balance of the conjunctival sac (bicarbonate buffering system in particular).to study spatial variability of conjunctival tear fluid pH and possible mechanisms of its maintenance using original methods of acidity measurement and mineral content assessment.Tear pH was determined in 42 healthy participants (84 eyes) by means of litmus test strips and computer- aided colorimetry. Electron probe microanalysis in combination with energy dispersive spectrometry was performed in 8 healthy participants (8 eyes, 8 samples).In the group of 42 healthy participants (84 eyes) the pH value of conjunctival tear fluid varied from 6.30 to 7.23 with the average of 6.76 and pH mode 6.74. The pH value of conjunctival mucous discharge was measured in 25 healthy participants (28 eyes) and varied from 7.00 to 8.00 with the average of 7.26 and pH mode 7.30. The main mineral components of tear fluid are chlorine, sodium, potassium, and boron. Borate buffer is regarded as a mechanism of maintaining the acid-base balance of the ocular surface.The developed method of pH measurement ensuresreliable determination of conjunctival sac acidity in accordance with zoning and heterogeneity of its media as well as the complex structure of the tear film. In a healthy population, the acidity of tear significantly differs from that of conjunctival mucous discharge. Soluble chlorine, sodium, potassium, and boron compounds are the prevailing mineral components of tear fluid. Borate buffer appears to be the most stable of all mechanisms of maintaining the acid-base status of tear fluid.

Uridine phosphorylase (UP; EC 2.4.2.3), a key enzyme in the pyrimidine-salvage pathway, catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate. Expression of UP fromShewanella oneidensisMR-1 (SoUP) was performed inEscherichia coli. The high-resolution X-ray structure of SoUP was solved in the free form and in complex with uridine. A crystal of SoUP in the free form was grown under microgravity and diffracted to ultrahigh resolution. Both forms of SoUP contained sulfate instead of phosphate in the active site owing to the presence of ammonium sulfate in the crystallization solution. The latter can be considered as a good mimic of phosphate. In the complex, uridine adopts a high-synconformation with a nearly planar ribose ring and is present only in one subunit of the hexamer. A comparison of the structures of SoUP in the free form and in complex with the natural substrate uridine showed that the subunits of the hexamer are not identical, with the active sites having either an open or a closed conformation. In the monomers with the closed conformation, the active sites in which uridine is absent contain a glycerol molecule mimicking the ribose moiety of uridine.

To provide the clinical, laboratory, radiological, morphological, and immunomorphological signs that permit the differential diagnosis to be made in patients with involvement of the nasal cavity and accessory sinuses (NCAS).In the period 2009 to 2013, the Laboratory for Intensive Therapy for Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, associated the disease onset with NCAS involvement in 39 (7.6%) of 512 examinees. NCAS involvement was present at disease onset in 100% of the patients with natural killer (NK) cell lymphoma (NK/T lymphoma), in 84.5% of those with Wegener granulomatosis (WG), in 29.5% of those with IgG4-related disease (IgG4-RD), and in 17.5% of those with sarcoidosis. Such an onset could be extremely rarely observed in histiocytosis.Despite the similar clinical manifestations, NCAS involvements in NK/T lymphoma of nasal type and WG at disease onset show clear differences in the laboratory and systemic manifestations of these diseases. The patients with lymphoma have no characteristic laboratory abnormalities at disease onset, except the 100% presence of Epstein-Barr virus (EBV) DNA in blood and, only as a tumor grows, fever appears and there are elevated C-reactive protein and lactate dehydrogenase levels and pronounced destructive changes in the facial bones with mandatory hard palate destruction; at the same time the signs of systemic involvement are virtually absent. The patients with WG at disease onset have fever, high erythrocyte sedimentation rate, elevated C-reactive level, significant anemia, leukocytosis and 90% are found to have anti-neutrophil cytoplasmic antibodies with the rapid development of systemic manifestations: involvements of the lung, kidney, and peripheral nervous system. Destructive changes in the facial bones are minimal and hard palate destructions are absent. The patients with IgG4-RD, sarcoidosis, and juvenile xanthogranuloma have similar clinical and laboratory manifestations in the absence of hemorrhagic nasal discharge, nasal septal perforation, and facial bone destruction, with the practically involvement of the salivary/lacrimal glands and orbital regions. A third of the patients are observed to have different allergic manifestations, moderate eosinophilia, and signs of autoimmune disorders (the presence of rheumatoid and antinuclear factors, hypergammaglobulinemia). Elevated serum IgG4 levels are characteristic of IgG4-RD.Blood anti-neutrophil cytoplasmic antibodies, EBV DNA, and IgG4 levels should be determined in all patients with NCAS involvement. Mini-invasive incision biopsies of the nasal mucosa, orbital regions, and major salivary glands should be done, by morphologically verifying the diagnosis of sarcoidosis, histiocytosis, and WG and by making an immunomorphological examination to diagnose NK/T lymphoma and IgG4-RD.

Analysis of functional tear production indices in patients with Grave's disease and thyroid eye disease confirmed lacrimal gland involvement in inflammatory autoimmune process. Close direct correlation was found between tear production and main disease characteristics - severity and activity.

86 patients with verified diagnosis of sarcoidosis with globe, adnexa and orbit manifestations were observed. The age of the patients ranged from 21 to 43 years old (average 35,1+/-1,2 years), among them 25 males and 61 females with disease duration from 1 month till 12 years and 15 years follow-up. The study is based on different variants of globe, adnexal and orbital sarcoidosis. In our practice we observed sarcoidosis as a combination of several manifestations simultaneously. In 32 patients of 38 patients examined HLA-B-7, B-8, DR-2, DR-3, DR-15 were detected, that confirms genetic predisposition to sarcoidosis and determines the course of the disease. In 27 patients cellular and humoral immunity disbalance was found, that confirms the immune etiology of sarcoidosis as well. However the treatment of patients was pathogenic as the etiology of sarcoidosis is still unknown.

To characterize a group of patients with IgG4-related disease (IgG4-RD) in a Russian population and to evaluate the efficiency of rituximab therapy.In 2009 to 2011, at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, 30 patients (16 men and 14 women; mean age 44 years) were diagnosed with IgG4-RD that was confirmed by determination of serum IgG4 levels and immunohistochemical study of biopsy samples stained for IgG4-positive plasma cells. Seven patients received rituximab therapy.It was assumed at baseline that there were different types of neoplasias in 12 (40%), non-Hodgkin's and Hodgkin's lymphomas in 10 (33.3%), Sjögren's syndrome in 5 (16.7%), and Wegener's granulomatosis in 3 (10%). When 2 or more locations were involved, the condition was regarded as multifocal fibrosclerosis (33.3%). Localized forms were revealed in 20 (66.7%) patients. Among them, the largest number of patients was those who had orbital pseudotumor, Mikulicz's disease, or retroperitoneal fibrosclerosis. The most common sites of involvement were orbits (66.7%), salivary glands (70%) and lymph nodes (36.7%). Comparison of serum IgG4 levels in 28 patients with IgG4-RD, 22 patients with Sjögren's disease, salivary and lacrimal gland lymphomas, and 10 healthy controls showed that the concentration of IgG4 was significantly higher in Group 1 (median 2.6 g/I; IQR 1.22-4.65 (p0.001). Tissue IgG4/IgG ratio varied from 25 to 50% and averaged 38%. A moiré-like pattern of varying fibrosis was noted in 83% of cases. Analysis of laboratory data revealed elevated C-reactive protein concentrations (46.7% with a mean of 39.5 mg/l; normal values5.0 mg/l), increased erythrocyte sedimentation rate (60% with a mean of 37.6 mm/h), hypergammaglobulinemia (30% with a mean of 29.4%; normal range 13-22%), and rheumatoid factor (23.3%). After rituximab therapy, all the patients showed a decrease of IgG4 levels to the normal levels and positive changes evidenced by visualization techniques (computed tomography, magnetic resonance imaging).IgG4-RD is a novel problem in modern medicine, which requires a multidisciplinary approach and further study. Rituximab therapy is a promising treatment.

Clinical changes of lacrimal gland (LG) in sarcoidosis are studied. 33 patients (66 orbits) with verified systemic sarcoidosis were examined using digital ultrasound. Different varieties of LG structural changes in sarcoidosis are studied. Different types of LG structural changes were determined in patients with sarcoidosis defined as pseudoedematous and combined forms. Analysis of the results let us reveal characteristic local acoustic changes. Obtained results may be useful for diagnosis of LG changes in patients with sarcoidosis.

To evaluate the efficacy of rituximab (RT) in cryoglobulinemic vasculitis (CGV) and MALT lymphomas of the parotid gland (PG) in patients with Sjögren's disease (SD).RT therapy was performed in 13 patients with SD and CGV and in 17 with SD and PC MALT lymphoma. Eleven patients with SD received RT monotherapy and 19 with this disease had combined therapy with RT and cyclophosphan (CP). RT was used intravenously dropwise at a dose of 500 mg weekly or once every two weeks in combination with intravenous dropwise CP 1000 mg the next day with 4-6 per course. For the diagnosis of MALT lymphomas, all the patients with SD underwent incisional PG biopsy under local anesthesia at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. PG biopsy specimens were histologically and immunohistochemically studied at the Russian Cancer Research Center, Russian Academy of Medical Sciences. In 11 cases, B-cell clonality was identified from immunoglobulin (Ig) heavy chain genes rearrangements, by using polymerase chain reaction at the Hematology Research Center, Ministry of Health and Social Development of the Russian Federation.Cutaneous manifestations of vasculitis disappeared in 75% of cases after monotherapy with RT and in 100% of cases after combination therapy with RT and CP. At 6-month follow-up, a complete response to therapy remained in 25% of the patients after a course of monotherapy and in 83% after combined therapy. Serum monoclonal Ig cryoglobulins and their urinary light chains ceased to be detectable in 75% of the patients in both groups at 3 months. At 6 months, a recurrence of mixed monoclonal cryoglobulinemia was seen in 50 and 43% of cases after monotherapy and combined therapy, respectively. The clinical and laboratory response of cryoglobunemic glomerulonephritis to combined therapy with RT and CP was complete in 60% of cases at 6-month follow-up. After RT monotherapy, the patients with SD and PG MALT lymphoma achieved a complete clinical response in 88%, of whom histological and immunohistochemical reexaminations of PG biopsy specimens revealed no signs of MALT lymphoma in 71% of cases. B-cell clonality remained in the PG biopsy specimens following RT monotherapy. After the combination of RT and CP, a complete clinical response to therapy was observed in 100% of the patients, a complete histological response and a complete molecular one were seen in 83 and 60%, respectively.RT showed its efficacy in treating SD patients with CGV and PG MALT lymphomas.

Increase of lacrimal gland (LG) volume was revealed in 1/3 of patients with thyroid eye disease (TED) using visualization methods. Authors show morphological data confirming development of autoimmune process in LG in TED, biopsy samples were studied within 6 hours after exitus. Specific histomorphological characteristics were analysed considering dystrophic and degenerative changes in LG tissue. Quantitative assessment of fibrosis and vascularization extent is determined using fibrosis and vascularization index.

Sarcoidosis is a chronic idiopathic multisystem granulomatous inflammatory disease of unknown etiology. Prevalence of this condition is approximately 3-5: 100 000 with the highest incidence at the age of 25-40 years old and no gender predomination. Early morbidity, disability and severe prognosis worsen patient's condition and make them socially limited. In some cases ocular involvement and vision loss aggravate general condition of the patients. Ocular involvement in sarcoidosis occurs in 10-75% patients. At the same time some data confirm the fact that in 7% of patients ocular damage is the presenting sign making them come to an ophthalmologist whereas orbital involvement may present in systemic disease only. Unclear etiology and clinical similarity with other conditions cause difficulties in early diagnosis and monitoring of patients with sarcoidosis.

A complex of measures for lid hygiene in ocular surface disease is developed. These measures together with tear substitution and antibacterial treatment were revealed to result in elimination of blepharoconjunctivitis and dry eye signs, recovery of tear film and long-time remission, that significantly improved patient's life quality. When using this complex of measures meibomian glands are not damaged and their anatomy and functions are completely preserved. Lid hygiene affects all glands, there is no pain and no local anesthesia needed, normal tear film is formed

For the first time vital morphological structure of lacrimal gland was investigated based on spatial ultrasound digital examination. Structural characteristics of lacrimal gland are described considering anatomic topography and blood supply. These characteristics are analyzed based on planar and volumetric sonography depending on the patient age and pattern of changes. Their correlation is studied. The results of lacrimal gland examination allowed us to analyze a number of ultrasound diagnostic signs and compare them with changes in acute dacryoadenitis, MALT-lymphoma, Sjogren disease, sarcoidosis and thyroid eye disease. Revealed features may be useful for understanding of nature of clinical presentation. The results of the study may help to interpret diagnostic signs and follow up their evolution in a clinical course of a disease.

Clinical methods of functional and morphological examination of lacrimal glands, ocular surface and precorneal tear film are presented. The importance of adnexa complex examination for accurate diagnosis and choice of treatment option is emphasized.

This article reviews ethiology and pathogenesis of dry eye syndrome due to meibomian gland disfunction (MDG). It is showed that blink rate influences meibomian gland functioning and computer vision syndrome development. Current diagnosis and treatment options of MDG are presented.

The current methods widely used in ophthalmology to examine patients to diagnose the dry eye syndrome and to trace the course of a process are invasive. Both the Norn test using stains and the Schirmer test with the filter paper strips being inserted are stimuli that affect the rate of tear generation, which misrepresents the data obtainable. The developed procedures for examining the eye in polarized light permit one to considerably reduce the invasiveness of patient examination. The study indicated the high efficiency and diagnostic value of the proposed procedures in the examination of patients with the dry eye syndrome. Polarization filters available in the standard kit of up-to-date slit lamps make it possible to use the proposed procedures without any modification of ophthalmological equipment in wide clinical practice.

The paper touches upon the specific features of the structure of orbital formations, by considering their anatomic topography and biophysical properties. By studying the results of investigations of the morphological and biophysical studies of orbital tissues, the authors analyze their features and compare their relationships. These results unraveling each of the considered orbital anatomic elements from the acoustic profile ranges may be useful in understanding the nature of clinical changes, which will be able to interpret these or those diagnostic signs--guides and to trace their evolution. In addition, this approach can help interpret the texture of an ultrasound digital image of eye socket soft tissue and permit one to look at pathological clinical manifestations from the so-called biophysical essence. This will allow additional information to be gleaned, by analyzing the usual signs.

The paper describes a case of Mikulicz's disease (MD) in a young woman (aged 19 years) with symmetrical large salivary gland lesion concurrent with the enlarged lacrimal glands. Immunomorphological and molecular studies of parotid gland biopsy specimens revealed the formation of MALT tissue without signs of B-cell clonality of an infiltrate. The diagnosis of lacrimal sac lymphoma was ruled out. MD was diagnosed. The use of rituximab in therapy for MD has first demonstrated a positive result in Russian and worldwide practice.

Fifty-three patients with eye diseases caused by autoimmune disorders received complex treatment involving extracorporeal techniques, such as hemosorption, plasmapheresis, and double cascade plasma filtration in combination with pulse therapy. Clinical, laboratory, morphometric, and biochemical studies show the efficacy of hemosorption in relieving acute manifestations of an inflammatory process and the stabilizing action of these methods on ocular epithelial tissue, immunological activity, and systemic manifestations of the underlying disease.

To investigate the incidence of MALT-lymphoma in Sjogren's disease by means of biopsy of the enlarged parotid glands.The incisional parotid biopsy was performed in 57 primary Sjogren's syndrome (pSS) patients with existing parotid enlargement. The median age was 54 years (range 19-75 years). The median pSS duration was 7 years (range 1-30 years). The palpable parotid enlargement was defined as grade 1 and massive (visional) enlargement of the parotid glands was defined as grade 2. Histologic and immunohistochemical examinations for diagnosis of lymphoma were made. High resolution electrophoresis and immunofixation were performed for detection of monoclonal immunoglobulins in the serum and their free light chains in the urine.Biopsy of the enlarged parotid glands identified MALT-lymphoma in 37 of 57 (64.9%) pSS patients. Of 37 pSS patients with parotid enlargement of grade 2, diagnosis of MALT-lymphoma was made in 89.2%. Of 20 pSS patients who had parotid enlargement of grade 1, MALT-lymphoma was diagnosed in 20%. In patients with grade 1 enlarged parotid glands MALT-lymphoma was identified only in cases with the presence of monoclonal immunoglobulins in the serum and their free light chains in the urine (3 of 4 patients) or in case of disseminated disease (lymphoma involved regional lymph nodes and soft tissues of the face)--1 of 4 patients. In patients with grade 2 enlargement of parotid glands MALT-lymphoma located most frequently in affected parotid glands (69.6%).The incisional biopsy of enlarged parotid glands is necessary for detection of MALT lymphoma in pSS patients.

The paper analyzes the diagnostic capacities of two studies (the routine Schirmer test and lacrimal meniscus biometry). It indicates the basic limitations of the Schirmer test and describes a procedure for lacrimal meniscus biometry. Based on the results of studying the lacrimal meniscus in healthy individuals from a control group, the authors revealed a relationship of the height of the lacrimal meniscus to the area and horizontal size of the palpebral fissure. Comparison of the results of studies of basal lacrimal secretion in the presence of dry keratoconjunctivitis and dry eye syndrome in the study patients with hypolacrimation defined the latter as mild, moderate, and severe. There was discordance between the values in 33.85% of cases. The Schirmer test has not shown to be the method of choice in examining basal lacrimal production; erroneous results may be obtained in a third of patients. Lacrimal meniscus biometry makes it possible to identify the degree of significant hypolacrimation more exactly and to minimize the indices of preserved basal secretion.

The paper presents the results of three-dimensional combined tear ultrasound analysis in various diseases accompanied by the dry eye syndrome. Sixty-five patients with clinical manifestations of the dry eye syndrome were examined. Of them, there were 20 patients with Sjogren's syndrome and disease, 25 with dry eye syndrome of unknown genesis, 5 with lachrymal gland tumorous lesion, 5 with cystic lacrimal gland changes (dacryops), and 10 persons above 65 years of age (a risk group). In each of the study group the study determined the mean sizes of a ultrasound section of the lacrimal gland, its mean volume, and densitometric indices, such as density and vasculogenicity index, as well as the mean values of hemodynamic parameters in the lacrimal artery. The characteristic echographic signs of lacrimal gland structural changes and vascularization are described in Sjogren's disease and syndrome, dry eye syndrome of unknown genesis, dacryops, neoplastic processes involving the lacrimal gland. The proposed algorithm of lacrimal gland ultrasound study can enhance the accuracy and validity of results of the differential diagnosis of various lacrimal gland diseases with the clinical manifestations of the dry eye syndrome. The findings may be further used for the monitoring and detection of three-dimensional and structural changes in the lacrimal gland, which result from various pathological processes with the clinical manifestations of the dry eye syndrome.

The paper presents an algorithm of ultrasound spatial analysis of the unaltered lacrimal gland. The algorithm has been used to define its shape, size, density, structural features and the pattern of blood supply, as well as the anatomic and topographic position in the orbit. The study was conducted in the B- and 3D-modes of color and energy Doppler mapping on both sides. The procedure was based on the clinical examination of 40 healthy individuals aged 20 to 75 years who had no systemic vascular and lymphoid tissue lesions or functional impairments of the lacrimal gland itself. The study defined the mean values of the ultrasound section of the lacrimal gland: 1-1.8 and 0.5-0.8 cm for vertical and horizontal ones, respectively; the mean volume of the lacrimal gland of 0.66 to 1 cm(3) and the densitometric parameters (density and vasculogenicity index); three types of structural manifestations of the unaltered lacrimal gland were identified. The proposed algorithm of ultrasound study of the lacrimal gland may enhance the accuracy and validity of results in the differential diagnosis of various orbital diseases.

The paper presents two classifications of the dry eye syndrome: the Madrid and Russian classifications. The creation of its classification is required for the elaboration of treatment policy for this category of patients. The classifications are based on the scientific data on the epidemiology, etiology, and pathogenesis of the dry eye syndrome. Each classification identifies different forms of the dry eye. The classifications virtually published at the same time do not greatly differ from each other and they reflect the current approach to systematizing different forms of the dry eye. The paper analyzes the Madrid versus Russian classifications.

To develop algorithm of early diagnosis of extranodal lymphoma arising in patients with Sjorgen's disease (SD).SD diagnosis was made in 457 patients treated in Rheumatology Institute clinic in 1999-2004, 38 (8.3%) females aged 19-82 had lymphoproliferative diseases. MALT-lymphomas were diagnosed in 15 (42.2%) patients. All the patients have undergone morphological, immunomorphological investigations of the salivary glands, postoperative material was analysed in some patients. In addition, the following investigations were made: ultrasonography of the salivary glands, lymph nodes, viscera; scintigraphy; trephine biopsy of the bone marrow; myelograms; CT of the chest, abdomena and brain; tests for monoclonal immunoglobulins in the serum and light chains in urine; biopsy of the parotid gland. Clinical, morphological and immunophenotypical characteristics of MALT-lymphomas were assessed by WHO classification. Lymphoma stages were classified according to Ann Arbor.Parotid glands were affected with MALT-lymphoma most frequently. Predominant were extranodal lymphomas of the parotid submandibular, minor salivary glands of the lip and lacrimal glands of stage I E-II E. Extranodal lymphoma with nodal lesion of stage IV occurred less frequently. Untreated long existing MALT-lymphomas of the parotid glands may transform into B-large cell lymphomas deteriorating SD prognosis. The presence of long-term (12 months) massive enlargement of parotid/submandibular salivary and lacrimal glands, massive infiltration, monoclonal immunoglobulins in blood serum and their light chains in the urine predict development of MALT-lymphoma in SD.In SD, MALT-lymphomas develop primarily in target organs--salivary and lacrimal glands. SD patients with persistent enlargement of the parotid glands need biopsy for early detection of malignant lymphoproliferation.

To present differential-diagnostic signs of sarcoidosis with affection of the salivary and lacrymal glands and Sjogren's disease.The examination of 620 patients with affection of the salivary and lacrymal glands revealed sarcoidosis in 19 of them. The diagnosis was verified histologically. Clinical, serological and histological characteristics of sarcoidosis patients were compared to those of 200 patients with Sjogren's disease (SD) detected among the examinees.Sarcoidosis patients vs those with SD (p0.001) had massive enlargement of the salivary glands (84.3%) with severe xerostomy which appeared rather early (78.9%), affection of the lacrymal glands manifesting with enlargement of the palpebral region, edema of the upper eyelids (57.9%), pulmonary lesion (78.9%), cranial nerves (47.4%), skin (42%), enlargement of the intrathoracic lymph nodes (100%).In spite of the presence of mucosal dryness simulating SD, sarcoidosis of the lacrymal and salivary glands has some specific features allowing differentiation of sarcoidosis.

To specify the risk of severe systemic manifestations and transformation into malignant lymphoma in Sjogren's disease (SD) patients with monoclonal mixed cryoglobulinemia (MMC).A prospective study performed in 1985-1990 included 248 SD patients followed up after the initial detection of monoclonal immunoglobulins (Ig) with serum active rheumatoid factor (RF). The patients' cryoglobulins (CG) were examined. The type of CG was determined by electrophoresis in agarose gel combined with immunofixation and immunoelectrophoresis with mono-specific antisera to heavy and light Ig chains. Biopsies of the lower lip salivary glands and skin were made in all the patients with MMC and 40 patients without CG. The biopsies were studied histologically, histochemically and immunomorphologically. Clinical symptoms and prognosis were studied in all the patients observed in 1985-2000 after the initial diagnosis of MMC. In suspected lymphoma development, histological and immunophenotypical studies of lymph node, bone marrow biopsies, trephine biopsies were made as well as myelograms, Ga-67 scintigraphy, CT of the thoracic and abdominal cavities. The total of clinical, morphological, immunophenotypical and cytogenetic characteristics of lymphoma was estimated by REAL classification.CG at first examination was detected in 50 (20.2%) of 248 patients with SD. 20 (40%) of 50 patients were diagnosed to have MMC with monoclonal IgMchi (19) and IgA (1) in the serum with RF activity. Ten (50%) patients with MMC developed lymphoma after 10.9 +/- 3.3 years, on the average. In the absence of CG lymphoma developed in 5.5% (p0.001). B-cell intoxication in patients with diffuse lymphadenopathy, foci of lymphoid infiltration in the lungs, ulcers of the crus and such indices as stab neutrophilic shift, monocytosis, hypoproteinemia with hypogammaglobulinemia, disappearance of the RF, CG, low CIC level, immunodeficiency of monoclonal Ig and appearance of the protein BJ in the urine are markers of developing large B-cell immunosecreting lymphomas. Highly aggressive diffuse LCL resulted in death of 70% SD patients with MMC; 30% died of immunocomplex cryoglobulinemic vasculitis. 10-15-year survival of SD patients after detection of MMC was 50%, free of CG - 97% (p0.001).MMC is a definite serological marker of developing lymphoma and ulcerative-necrotic vasculitis in SD. In detection of MMC in SD patients it is necessary to prescribe early pathogenetically validated treatment before development of life threatening manifestations.

The trial enrolled 38 patients with chronic HCV-infection and Sjogren's syndrome (mean age 44.3 +/- 13.7 years). Biopsy of the minor salivary glands (MSG) was made in 20 patients. Polymerase chain reaction was used to study 20 MSG biopsies, 38 samples of native saliva for HCV-RNA. Saliva samples were also studied for Herpes virus DNA (EBV, CMV, HHV-VI type). All the patients with VHC appeared to have signs of xerostomia, 24 (63.2%) patients had xerophthalmia. MSG pathohistological changes were found in 19 (95%) patients. In the majority of cases (86.9%) they were characterized by mild infiltration and advanced fibrosis. HCV-RNA was found in the saliva of 23 (57.5%) patients, in MSG tissue--in 9 (39.1%) patients. HCV-RNA detection in the saliva did not depend on the degree of viremia, viral RNA in MSG correlated with viral load. EBV and HHV-VI, HHV-VI only and EBV were detected only in 7 (18.4%), 10 (26.3%) and 6 (15.8%) patients, respectively. Xerostomia occurred with the same rate (26.1 and 31.3%) in patients with and without herpes viruses in the saliva. Detection rate for HCV-RNA in the saliva was not related with viremia degree. Sjogren's disease symptoms in CHC patients did not depend on the presence or absence of DNA of herpes viruses in the saliva.

To examine clinical features of Sjogren's syndrome (SS) and morphological picture of the lesser salivary glands (LSG) in chronic hepatitis C (CHC).The examination of 42 patients with SS and chronic HCV infection (mean age 44.3 +/- 13.7 years) has detected signs of chronic hepatitis and hepatic cirrhosis, respectively, in 31 (71.4%) and 11 (26.2%) patients. "Dry syndrome" was diagnosed by criteria of European SS Study Group. LSG biopsy of the lower lip was conducted in 23 (54.7%) of 42 patients.The "dry" syndrome in CHC ran subclinically in 73.8% patients. Apparent symptoms of SS were seen primarily in middle-aged and aged women with CHC history over 10 years. The first signs of SS occurred in 25 (59.5%) patients 2.9 +/- 3.1 years prior to diagnosis of hepatic disease. All the patients had xerostomy. Xerophthalmia was recorded 1.5 times less frequently. In 16 (47.1%) patients with CHC "dry eye" and in 6 (17.6%) patients dry keratoconjunctivitis were detected. Pathohistological changes of LSG were diagnosed in 21 (91.3%) of 23 patients with CHC. In the majority of cases (86.9%) the glands exhibited insignificant inflammatory infiltration and advanced fibrosis. LSG in CHC is characterized by fibrosis prevalence over cell infiltration. 83.3% CHC patients had SS and other extrahepatic lesions. SS was most evident in 28.6% CHC patients with cryoglobulinemia.Registration of SS symptoms in CHC patients depends on targeted examination of patients with chronic HCV infection. The severity of the symptoms correlates directly with the infection duration and age of the patient. LSG lesions in CHC patients with SS are characterized by fibrosis pre-domination over cell infiltration.

Characterization of Sjogren's disease (SD) with onset at early age basing on the comparison of two patient groups--with the disease onset at the age under 30 and over 50.Clinical, ophthalmological and stomatological examinations were performed in 31 SD patients who developed the disease at the age under 30 (group 1) and over 50 (group 2).In group 1 the disease started with parotitis in 42.8% of cases, dysfunction of secreting epithelial glands was rare, functional activity of exocrine glands was normal, dysproteinemia (high total protein levels, hypergammaglobulinemia, hypoalbuminemia) and immunological defects (high levels of circulating immune complexes, rheumatoid factor, antinuclear factor) were more pronounced. At retrospective analysis not only a decline of functional activity of the salivary and lacrimal glands but also appearance of systemic symptoms were registered.Development of systemic SD symptoms at young age necessitates early pathogenetic therapy employing corticosteroid, cytostatic and other drugs.

Six protein components were detected in the tears by exclusive high-pressure liquid chromatography. By their molecular weight, these components were identified as lacrimal prealbumin, human serum albumin, lactoferin, IgG, and IgA. The relative content of these proteins in tears correlates with the clinical picture of kerato-conjunctivitis sicca. Correlation coefficients (ci) were -0.66 for lysozyme, -0.58 for prealbumin, 0.70 for serum albumin, -0.63 for lactoferrin, and 0.65 for IgA. Linear regression analysis showed that the relative content of IgA and serum albumin rapidly increased in the course of disease. The relative content of lysozyme, lactoferrin, and prealbumin dropped, but two times slower. The authors propose assessing the quantitative changes in the lacrimal protein composition by a special diagnostic parameter: P = sigma(dni-di)ci/C, where dni and di are the mean relative levels of the protein component in health and disease, C the sum of absolute values of correlation coefficients for all components (C = sigma[ci]). The (dni-di) value reflects the effect of disease on changes in the relative content of each protein component and the ci/C value the intensity of this effect. This parameter can be used for assessing the involvement of the eyes in Sjogren's syndrome and monitoring the efficacy of treatment.