Penetrating keratoplasty in children: results of surgical treatment

Penetrating keratoplasty (PK) in children is a complex and ultifacetedproblem that has been experiencing pediatric ophthalmology for several decades With all its radicality and with all its therapeutic potential, most surgeons prefer, nevertheless, to refuse to transplant the cornea in childhood, and transfer it to a later date, especially in infants (up to a year). In the absence of alternative interest in this operation did not fade, the practice of corneal transplantation in children continued and improved. The desirability of PK in corneal opacities (CO) in children is no longer discussed as such. On the agenda is another question: how to make this operation a truly effective way of treatment. This is not an easy task in itself, with many problems. Among them – the complexity of communication with a young patient, a special plasticity of the tissues of the child’s eye, heavy, as a rule, the combined nature of the pathology, predisposition to violent inflammatory reactions, etc. In many years of practice, for the most part, by trial and error, these problems are gradually finding their solution. An empirical experience always precedes the understanding of the problem and the search for its solution, no matter how unsuccessful it may seem at the very beginning. This work is devoted to generalization of such experience.Objective. To Evaluate the immediate and long-term results ofpenetrating keratoplasty in children. Material and methods. Retrospectively and prospectively analyzed the medical history and hospital records of children operated in the Department of pathology of eyes in children, Moscow Helmholtz Research Institute of Eye Diseases in the period from 1997 to 2017. The total sample consisted of 208 cases of the PK, was performed in 185 children on 208 eyes. By the nature of the disease, all observations were divided into congenital and acquired CO. Among the latter, turbidity of traumatic and non-traumatic nature was distinguished. Biological and functional results of PK were evaluated. The biological result of the operation was evaluated in terms of graft survival (Kaplan-Mayer model). The functional result was estimated approximately: by tracking the child’s toys from a certain distance and by the method of pr eferred gaze.Results. The first 6 months after the surgery, the transplants, with rare exceptions, remained transparent. By the end of the 1st year, 72% of transplants remained transparent, by the end of the 2nd year not less than 65%, by the end of the 3rd year-not less than 55%, by the end of the 5th year not less than 45% of transplants. In search of a more rigorous determination of the results, PK assessed the impact of particular clinical circumstances on the engraftment of transplants. It turned out that regardless of the etiology of the disease graft survival is significantly lower if keratoplasty is carried out in a vascularized couch, if simultaneously with corneal transplantation are other optical-reconstructive surgery: cataract extraction, vitrectomy, plastic iris, if the diameter of the transplant >8 mm, in the eyes with glaucoma in history. Transparency of transplants is significantly reduced in complicated postoperative course: recurrent rejection crises, increased IOP or the appearance of synechiae. In at least 80% of patients, corneal transplants have resulted in improved visual aquity (VA). In most of these cases, VA increased from light perception to 0.1-0.3. Satisfactory results, when VA after surgery reached 0.6-0.8, were in patients with keratoconus and congenital hereditary corneal  dystrophy. Among those who have measured hundredth of VA dominated children with severe congenital malformations of the cornea and anterior segment of the eye.Conclusion. PK in children today is a very successful surgical intervention, the therapeutic potential of which can be realized with proper consideration of risk factors, impeccable technique and careful postoperative monitoring

Predictive model of small choroidal melanoma progression after eye-saving treatment based on clinical, morphometric and immunological parameters

Choroidal melanoma is a malignant tumor characterized by early metastasis and poor vital prognosis. Prognostic indexes for the tumor development are of importance, depending on various factors and making it possible to optimize therapeutic measures. Usage of present models for prediction of the uveal melanoma course enables optimal management of the patients with a malignant tumor upon primary admission, and to perform maximally efficient counseling. So far, however, a complex of clinical, morphometric and immunological indexes predictive for unfavorable course of initial choroidal melanoma following the eye-saving treatment remains not fully determined. Our purpose was to create a prognostic model for initial choroidal melanoma after eye-saving treatment, basing on clinical, morphometric and immunological parameters.We have performed examination and treatment of 31 patients with small choroidal melanoma (53.7 to 12.2 years old). To perform the analysis, we used clinical data (age, decreased vision, tumor localization, degree of pigmentation, presence of hemorrhages, orange pigmentation), morphometric indexes (intra- and subretinal exudate and disorganization of pigment of the retinal epithelium) and immunological parameters (serum levels of pro-inflammatory, pro-angiogenic, proliferative, metastasis-causing cytokines). Selection of variables for this model was based on assessment of significant differences between the groups with chorio-retinal scar (n = 14) and residual tumor and/or continued tumor growth (n = 17).Multivariate analysis with conditional exclusion of variables revealed prognostic significance with four markers: morphometric, i.e., disorganization of the pigment in retinal pigment epithelium – Z1 (rs = 0.455); immunological, increased blood serum concentration of hepatocyte growth factor (HGF) – Z2 (rs = 0.377); level of pro-inflammatory chemokine RANTES – Z3 (rs = 0.362), content of transforming growth factor (TGF-2â) – Z4 (rs = 0.431). A formula was calculated where P (z) is the value of the logistic function; Z, linear combination of symptoms; bo , intercept (free term), bi – regression coefficients for parameters Zi.P (z) = 1 : 1 + e – b0– b1z1– b2z2– b3z3– b4z4The logistic function increases monotonically and takes the values from 0 to 1 for any b and Z values [P∈ (0;1)]. If P (Z) is under the cutoff value, chorioretinal scar prognosis is predicted, at the higher values, a residual tumor or continued growth is expected. In ROC analysis, the area under the curve with this model was 0.891±0.11, thus providing good predictive quality.Usage of the predictive model is a possible solution for planning and correcting treatment strategy in the patients with small choroidal melanoma, in order to minimize complications and errors, and to ensure control of treatment

Efficacy of genetically engineered biological agents in the treatment of uveitis associated with rheumatic diseases in children

The efficiency of incorporating genetically engineered biological agents (GEBAs) into a combination treatment regimen for rheumatic diseases (RD) (juvenile idiopathic arthritis, Behcet's disease) in relation to associated uveitis of varying severity was studied in 92 children aged 2 to 17 years. The follow-up lasted 1.5 to 49 months. Twenty-three patients took consecutively 2 to 5 GEBAs. When infliximab was used, remission of uveitis occurred in 21% of 38 children and the disease activity and/or recurrence rates reduced in an additional 21%. These were in 45 and 38.6% of 44 patients on adalimumab (ADA) and in 27.8 and 27.8% of 18 patients on abatacept, respectively. There was an association of the efficiency of therapy with the severity of uveitis at the start of treatment. The use of ADA induced a steady remission of panuveitis resistant to therapy with glucocorticoids and cyclosporine in both patients with Behcet's disease. One of 4 rituximab-treated patients achieved a steady remission. Tocilizumab therapy caused an exacerbation of uveitis in 1 patient. The postoperative period showed no inflammatory complications in most cases (37 operations, 26 eyes, 20 patients). No local adverse reactions were seen; systemic reactions occurred in 14% of the patients, this caused GEBAs to be discontinued in 7%. There is evidence for a need for further investigations into the efficacy of GEBAs in RD-associated uveitis in children in order to define success criteria, differentiated indications, and therapy regimens

Оценка морфометрических параметров диска зрительного нерва и сетчатки при врожденной глаукоме у недоношенных детей

PURPOSE: To study the morphometric parameters of the optic nerve head and retina in premature infants with congenital glaucoma.METHODS: Children with congenital glaucoma (21 children) with favorable outcomes of 1-3 stages of retinopathy of prematurity (RP) aged from 6 months to 12 years were examined (group I). The control group consisted of 32 fullterm children with congenital glaucoma (group II). In addition to the standard methods of examination, Heidelberg retinal tomography (HRT) and optical coherence tomography (Spectralis-OCT) of optic nerve head (ONH) and retina were used.RESULTS: According to clinical manifestations of glaucoma, there were no significant differences between the groups. Both children with 1-2 stage of RP and congenital glaucoma and full-term infants with congenital glaucoma revealed the same pronounced morphometric changes in structures of the disk and peripapillary zone of the retina, which were characteristic for the development of glaucomatous optic neuropathy and intensified in the course of glaucoma progression. ONH changes interpretation in RP infants was hampered by traction deformation of the ONH and displacement of the central vessel trunk, especially in patients with stage 3 RP. We have not revealed a clear link between the changes in the optic nerve disk and IOP level.CONCLUSION: Morphometric parameters measurement and a number of pathognomonic symptoms of optic nerve and peripapillary retina damage in congenital glaucoma in premature infants identified in this paper are necessary for studying the pathogenesis of glaucomatous process in RP, clarifying the diagnosis, determining the disease prognosis, assessing glaucoma progression and developing treatment tacticsЦЕЛЬ. Изучить морфометрические особенности зрительного нерва и сетчатки у недоношенных детей с врожденной глаукомой.МЕТОДЫ. Обследованы дети с врожденной глаукомой (21 ребенок) с благоприятными исходами ретинопатии недоношенных (РН) 1-3 степени в возрасте от 6 мес до 12 лет (группа 1). Группу контроля составили 32 доношенных ребенка с врожденной глаукомой (группа 2).Помимо стандартных методов обследования применяли гейдельбергскую ретинальную томографию (НRТ) и оптическую когерентную томографию диска зрительного нерва (ДЗН) и сетчатки (Spectralis-OCT).РЕЗУЛЬТАТЫ. По клиническим проявлениям глаукомы существенных различий между группами не было. При врожденной глаукоме у детей с 1-2 степенью РН, как и у доношенных детей с врожденной глаукомой, выявлены одинаково выраженные морфометрические изменения структур всех зон ДЗН и зон перипиллярной сетчатки, характерные для развития глаукомной оптической нейропатии и усугубляющиеся по мере прогрессирования глаукоматозного процесса. При РН интерпретация изменений ДЗН затруднена вследствие тракционной деформации ДЗН и смещения сосудистых пучков, особенно при 3 степени РН. Четкой связи изменений ДЗН с показателями ВГД нами не выявлено.ЗАКЛЮЧЕНИЕ. Измерения морфометрических параметров и ряд выявленных в данной работе патогномоничных симптомов поражения зрительного нерва и перипапиллярной сетчатки при врожденной глаукоме у недоношенных детей необходимы для изучения патогенеза глаукоматозного процесса при РН, уточнения диагноза, определения прогноза заболевания, оценки стабилизации глаукоматозного процесса и выработки тактики лечения

Эффективность композитного дренажа у детей с постувеальной глаукомой

PURPOSE: To evaluate the efficacy of trabeculectomy with Glautex drainage implantation in children with uveitic glaucoma (UG).METHODS: We analyzed the results of trabeculectomy with Glautex drainage implantation in 11 children with UG aged 4-15 years, including 4 children who already previously underwent glaucoma surgery.RESULTS: Qualified success rate 3, 12 and 24 months after the surgery (with and without hypotensive medications) amounted to 72.7, 54.5 and 45.4% respectively, absolute success — to 36.4, 27.3 and 27.3%. IOP decompensation in all cases was caused by excessive wound healing in the filtering bleb area. All patients with long-term glaucoma compensation Glautex drainage implantation was the first glaucoma surgery they underwent, and the efficiency of repeated operations was lower than that of primary ones. There were no significant differences in the efficacy of operations in phakic eyes and in cases of artiphakia or aphakia. The results also showed no clear dependence on systemic immunosuppressive therapy or lack thereof, and on uveitis etiology (rheumatoid, idiopathic). Postoperative adverse effects included 1 case of drainage eruption through the conjunctiva 3.5 weeks after the operation with conjunctival healing after the removal of the exposed drainage fragment followed by topical medical treatment, and 1 case of flat ciliochoroidal detachment, which reversed after medical treatment.CONCLUSION: Trabeculectomy with Glautex drainage implantation, especially if performed as a repeated hypotensive surgical intervention, is not effective enough in children with UG due to extremely intense excessive scarring in extrascleral and scleral areas of the surgical site. Further research is needed to find effective methods of surgical treatment and excessive proliferation prevention in children with UG.ЦЕЛЬ. Оценить эффективность синустрабекулэктомии (СТЭ) с имплантацией дренажа Глаутекс у детей с постувеальной глаукомой (ПУГ).МЕТОДЫ. Проведен анализ результатов СТЭ с имплантацией дренажа Глаутекс у 11 детей в возрасте от 4 до 15 лет с ПУГ, из них у 4 антиглаукоматозная операция была повторной.РЕЗУЛЬТАТЫ. Относительная эффективность операции (на фоне и без гипотензивных медикаментов) составила 72,7, 54,5 и 45,4%, абсолютная — 36,4, 27,3 и 27,3% в сроки 3, 12 и 24 месяца после вмешательства соответственно. Некомпенсация глаукомы во всех случаях была обусловлена рубцеванием в области фильтрационной подушки (ФП). У всех пациентов с длительной компенсацией глаукомы операция с дренажом Глаутекс была первым гипотензивным вмешательством, а эффективность повторных операций была меньше, чем первичных. Существенной разницы в эффективности операции в факичных глазах и в случаях артифакии или афакии у пациентов, получавших и не получавших системную иммуносупрессивную терапию, а также в зависимости от этиологии увеита (ревматоидный, неясной этиологии) выявлено не было. Нежелательными явлениями были: в 1 случае — прорезывание дренажа через конъюнктиву через 3,5 недели после операции с заживлением конъюнктивы на фоне медикаментозного лечения после удаления обнажившегося фрагмента дренажа, в 1 случае — плоская цилиохориоидальная отслойка, которая прилегла на фоне медикаментозной терапии.ЗАКЛЮЧЕНИЕ. СТЭ с имплантацией дренажа Глаутекс, особенно проведенная в качестве повторного гипотензивного вмешательства, недостаточно эффективна у детей с ПУГ в силу чрезвычайно интенсивного избыточного рубцевания в экстрасклеральной и склеральной зонах операции при данной форме глаукомы. Необходимы дальнейшие исследования с целью поиска эффективных методов хирургического лечения и профилактики избыточной пролиферации при ПУГ у детей

Иммуногистохимическое исследование увеальной меланомы и ее клеточного микроокружения

Introduction. Uveal melanoma pathogenesis is determined by a number of factors, including the tumor molecular genetics, the organism’s immune response, and other ones. One of the approaches to studying the peculiarities of pathogenesis of this cancer is to determine the local subpopulations of lymphocytes and macrophages in combination with the study of the proliferative activity of tumor cells.Objective – to study the immunohistochemical features of uveal melanoma and its cellular microenvironment.Materials and methods. 24 enucleated eyes with uveal melanoma (144 histological and 216 immunohistochemicalpreparations) without previous treatment were analyzed. Cells of the immune microenvironment were analyzed: lymphocyte subpopulations and CD 68+ and CD 163+ antigens expressed by macrophages in the melanoma stroma and 2–3 mm from it. The tumor cell proliferation index Ki-67 was diagnosed.Results. All tissue samples of uveal melanoma revealed the presence of lymphocytes in the microenvironment of tumor cells. A large proportion of the studied subpopulations of lymphocytes were T-cytotoxic CD28+ lymphocytes (absolute content: 607.3 ± 431.2, relative: 18.84 % ± 12.12 %) (p = 0.018). A smaller proportion, but in equal proportions, were  T-helpers CD4+, T-cytotoxic CD8+ and CD25+ lymphocytes (p = 0.6). The absolute number of natural killer cells subpopulation CD16+ was lower compared to CD56+ (p = 0.05). However, an almost equal relative content of the studied subpopulations was noted (p = 0.9). Histological examination revealed the presence of uveal melanoma macrophages in the microenvironment of the tissue. The immunohistochemical study of CD68+ and CD163+ antigens expressed by anti-inflammatory and pro-tumor macrophages showed that their absolute and relative content in the uveal melanoma tissue is almost the same with a slight predominance of CD163+ (p = 0.7). Immunohistochemical analysis showed that the nuclei of melanoma cells contain, on average, 575.2 ± 388.5 significant cells of the Ki-67 proliferation protein. This protein was found in 16.69 ± 10.88 % of tumor cells.Conclusion. Immunohistochemical study allows to identify subpopulations of lymphocytes infiltrating the tumor, to determine the subtypes of macrophages and to estimate the Ki-67 index of tumor cell proliferation. The data obtained will make it possible to further evaluate the significance of individual immune cells (in particular, T-cytotoxic CD28+ lymphocytes) in the pathogenesis of uveal melanoma in order to develop targeted effects, substantiate new immunotherapeutic approaches to the treatment of primary tumors and reprogramming altered immune cells.Введение. Патогенез увеальной меланомы определяется целым рядом факторов, включая молекулярно-генетические, иммунологические и др. Одним из подходов к изучению особенностей патогенеза опухолей данного типа является определение локального содержания в них отдельных субпопуляций лимфоцитов и макрофагов в сочетании с анализом пролиферативной активности опухолевых клеток.Цель исследования – изучить иммуногистохимические особенности увеальной меланомы и ее клеточного микроокружения.Материалы и методы. Проанализированы 24 энуклеированных глаза с увеальной меланомой (144 гистологических и 216 иммуногистохимических препаратов) без предшествующего лечения. Изучены клетки иммунного микроокружения: субпопуляции лимфоцитов и экспрессируемые макрофагами антигены CD68+ и CD163+ в строме меланомы и в 2–3 мм от нее. Определен индекс пролиферации опухолевых клеток Ki-67.Результаты. Во всех образцах ткани увеальной меланомы выявлено наличие лимфоцитов в микроокружении опухолевых клеток. Большую часть исследуемых популяций лимфоцитов составили Т-цитотоксические CD28+-лимфоциты (абсолютное количество положительно окрашенных клеток – 607,3 ± 431,2; относительное – 18,84 ± 12,12 %) (p = 0,018), меньшую часть (практически в равном соотношении) – Т-хелперы CD4+, T-цитотоксические CD8+ и CD25+ лимфоциты (p = 0,6). Абсолютное количество натуральных киллеров субпопуляции CD16+ оказалось ниже по сравнению с субпопуляцией CD56+ (р = 0,05). Однако отмечено практически равное относительное количество изучаемых субпопуляций (р = 0,9). Гистологическое исследование выявило наличие в микроокружении ткани увеальной меланомы макрофагов. При иммуногистохимическом исследовании экспрессируемых противовоспалительными и проопухолевыми макрофагами антигенов CD68+ и CD163+ отмечено, что их абсолютное и относительное количество в ткани данной опухоли практически одинаковое, с небольшим преобладанием CD163+ (p = 0,7). Иммуногистохимический анализ показал, что в ядрах клеток меланомы в среднем содержится 575,2 ± 388,5 значимых клеток белка пролиферации Ki-67. Этот белок обнаружен в 16,69 ± 10,88 % опухолевых клеток.Заключение. Иммуногистохимическое исследование позволяет выявить субпопуляции инфильтрирующих опухоль лимфоцитов, определить подтипы макрофагов и оценить индекс Ki-67 пролиферации опухолевых клеток. Полученные данные в дальнейшем дают возможность оценить значимость обнаружения отдельных субпопуляций иммунных клеток (в частности, Т-цитотоксических CD28+-лимфоцитов) в патогенезе увеальной меланомы в целях разработки таргетного воздействия, обоснования новых иммунотерапевтических подходов к лечению первичной опухоли и перепрограммирования измененных иммунных клеток

Babesia spp. in ticks and wildlife in different habitat types of Slovakia

Background: Babesiosis is an emerging and potentially zoonotic disease caused by tick-borne piroplasmids of the Babesia genus. New genetic variants of piroplasmids with unknown associations to vectors and hosts are recognized. Data on the occurrence of Babesia spp. in ticks and wildlife widen the knowledge on the geographical distribution and circulation of piroplasmids in natural foci. Questing and rodent-attached ticks, rodents, and birds were screened for the presence of Babesia-specific DNA using molecular methods. Spatial and temporal differences of Babesia spp. prevalence in ticks and rodents from two contrasting habitats of Slovakia with sympatric occurrence of Ixodes ricinus and Haemaphysalis concinna ticks and co-infections of Candidatus N. mikurensis and Anaplasma phagocytophilum were investigated. Results: Babesia spp. were detected in 1.5 % and 6.6 % of questing I. ricinus and H. concinna, respectively. Prevalence of Babesia-infected I. ricinus was higher in a natural than an urban/suburban habitat. Phylogenetic analysis showed that Babesia spp. from I. ricinus clustered with Babesia microti, Babesia venatorum, Babesia canis, Babesia capreoli/Babesia divergens, and Babesia odocoilei. Babesia spp. amplified from H. concinna segregated into two monophyletic clades, designated Babesia sp. 1 (Eurasia) and Babesia sp. 2 (Eurasia), each of which represents a yet undescribed novel species. The prevalence of infection in rodents (with Apodemus flavicollis and Myodes glareolus prevailing) with B. microti was 1.3 % in an urban/suburban and 4.2 % in a natural habitat. The majority of infected rodents (81.3 %) were positive for spleen and blood and the remaining for lungs and/or skin. Rodent-attached I. ricinus (accounting for 96.3 %) and H. concinna were infected with B. microti, B. venatorum, B. capreoli/B. divergens, Babesia sp. 1 (Eurasia), and Babesia sp. 2 (Eurasia). All B. microti and B. venatorum isolates were identical to known zoonotic strains from Europe. Less than 1.0 % of Babesia-positive ticks and rodents carried Candidatus N. mikurensis or A. phagocytophilum.Inst. de PatobiologíaFil: Hamsikova, Zuzana. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Kazimirová, Mária. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Harustiakova, Danka. Masaryk University. Faculty of Medicine and Faculty of Science, Institute of Biostatistics and Analyses; República ChecaFil: Mahrikova, Lenka. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Slovak, Mirko. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Berthova, Lenka. Slovak Academy of Sciences. Biomedical Research Center. Institute of Virology; EslovaquiaFil: Kocianova, Elena. Slovak Academy of Sciences. Biomedical Research Center. Institute of Virology; EslovaquiaFil: Schnittger, Leonhard. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin