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Purpose: to analyze the mutation frequency of the GNAQ/GNA11 gene in circulating tumor DNA and genotypes of the polymorphic marker C3435T of the ABCB1 gene in a large sample of patients with intraocular melanocytic neoplasms (IMN).Material and methods. In an open prospective study performed in 2015–2022, 272 IMN patients with intraocular melanocytic neoplasms aged 28 to 87 (ave. 58.3 ± 12.6), including 187 females (68.8 %) and 85 males (31.2 %), were divided into three groups depending on the nature of the tumor focus: Group I, n = 141, progressing choroidal melanomas; Group II, n = 67, stationary melanomas, and Group III, n = 64, choroidal nevi.Results. In Group I, at least one mutation in the GNAQ/GNA11 gene was detected in 134 patients (95.0 %). Of these, 35 patients (24.8 %) revealed two mutations, and 16 patients (11.3 %) had 3 mutations. In Group II, one mutation was detected in 49 patients (73.1 %), of which three patients (4.5 %) had two mutations. In Group III, one mutation in the GNAQ/GNA11 gene was detected in 13 patients (20.3 %). When comparing the overall frequency of mutations in the GNAQ/GNA11 genes in Groups I and II, significant differences were obtained (OR = 7.03 (2.77 to 17.86), F = 0.000015, ξ2 = 20.6), with Group I having mutations identified in 95 % of cases and Group II, in 73.1 %. Significant differences were also obtained when comparing the frequency of the studied mutations in Groups I and III (OR = 75.1 (28.36 to 198.86), F = 0.0000001, ξ2 = 121.15) with a frequency of 20.3 % in Group III. The frequency of mutations in the GNAQ/GNA11 genes was significantly higher in Group II than in Group III (OR = 10.68 (4.73 to 24.1), F = 0.0000001, ξ2 = 36.64). The frequencies of heterozygous mutations in all 4 exons were significantly higher in Group I than in Groups II and III, except for the GNAQ183 gene when comparing Groups I and II. Heterozygous mutations in all 4 exons were significantly more frequent in Group II than in Group III. Homozygous mutations were found only in Group I patients, but, in spite of this, no significant differences were detected when comparing them with other groups. The frequency of genotype CC of the polymorphic marker C3435T of ABCB1 gene was significantly lower in Group I as compared to Group II, whilst the frequency of genotype CT was significantly higher than in group II.Conclusion. The general analysis of molecular genetic studies of 272 patients with intraocular melanocytic neoplasms showed a direct correlation between the frequency of detection of mutations in genes and the size and source of the tumor. The obtained results substantiate both screening of patients from risk groups and differentiation of patients depending on the size and source of the tumor.

To assess the role of multifocal electroretinography (mf-ERG) in preclinical diagnosis of tumor-associated distant maculopathy in small choroidal melanoma (CM) of extramacular localization.Material and methods. 35 patients (35 affected and 35 fellow eyes) with small CM of extramacular localization and 23 healthy volunteers (46 eyes) aged 59.67 ± 14.2 years were given general ophthalmological examinations and mf-ERG. Density (nV/deg2), culmination time of the P1 component and amplitude (μV) of the N1 component were measured for 5 response rings (R1–R5) at different distances from the fixation point: central hexagon R1: 2.3° (fovea zone); R2: 2.3–6.9° (parafovea); R3: 6.9–14.3° (perifovea); R4: 14.3–20.8° and R5: 20.8–29.9° (middle periphery areas of the retina).Results. Eyes affected by CM showed a decrease in the density of the P1 component in the R1 hexagon by 25.7% of the normal values (p = 0.03). The fellow eyes showed an increase in the density of the P1 component in the R2 ring (p < 0.05). The peak latency of the P1 component in the R1–R5 rings in the affected and fellow eye was found to elongate by 30–45% (p < 0.05). The amplitude of the N1 component in the central hexagon of CM-affected eyes increased by 12.96%, whilst in the R4–R5 rings it decreased by 36–45% as compared with healthy individuals (p < 0.05). The fellow eye showed supernormal values of the N1 amplitude in R1 and its suppression in R4 and R5 rings (p < 0.05).Conclusion. The mf-ERG method is useful for preclinical diagnosis of tumor-associated distant maculopathy in small CM of extramacular localization. Changes in mf-ERG of the fellow eye in patients with small CM have been documented.

Introduction. Studies aimed at a direct research of human herpes viruses (HHVs) in the tumor material and eye media have not been carried out so far. Research goal to establish the frequency of detection HHVs DNA in the biomaterial of the eye and blood and to assess the specific humoral immunity to the causative agents of herpes virus infections in patients with uveal melanoma. Materials and methods. 38 patients with the uveal tract tumor were examined for the presence of DNA of HHV types 1 and 2 (HSV-1, 2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), EpsteinBarr virus (EBV) and herpes viruses 6 and 8 types (HHV-6, HHV-8) in tumor tissue, vitreous body, aqueous humour and blood plasma by real-time polymerase chain reaction; blood serum was studied by enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies to HHVs. Results. EBV DNA was present in tumor tissue in 20.6% of cases, in vitreous body in 4.2%, in blood plasma in 2.7%, and was not found in aqueous humor. Ig G antibodies to HSV-1, 2 and CMV were detected in 97.3% of cases, VZV 94.6%, HHV-6 32.4%, antibodies to HHV-8 were not detected. 20 patients (55.6%) had reactivation of chronic HSV-1, 2 infection, and 14 (38.9%) patients had reactivation of CMV infection. Markers of chronic EBV infection were found in all patients, its atypical reactivation was observed in 2 cases (5.4%). Conclusion. Our findings suggest the possible participation of EBV in the oncogenesis of the uveal tract and emphasize the need for further in-depth study of this problem.

Purpose. Conduct extended analysis of cytokine status and its role in inflammatory processes in uveal melanoma based on multiplex analysis of blood serum.Patients and methods. Immunological studies of blood serum and lacrimal fluid were performed in 80 patients with uveal melanoma and 38 healthy donors (control group). The average age of the surveyed was 53.7 ± 12.2 years. Group 1 included 32 patients with small-sized choroidal melanoma (T1NoMo), group 2 consisted of 26 patients with medium-sized tumors (T2NoMo), group 3 — 22 patients with large tumor size (T3NoMo). Cytokine content was determined in blood serum by the method of multiplex analysis on the xMAP platform in the Luminex xPONENT 3.1 program using 47 plex kits (ProcartaPlex, eBioscience, Austria).Results. In blood serum — increase of pro-inflammatory (LIF, RANTES, IP-10), anti-inflammatory (TGF-1β), proliferative (IL-15), pro-tumor (EGF), angiogenic (PIGF-1 and SDF-1α) cytokines compared with control group, p < 0.05.Conclusion. In response to the manifestation and growth of uveal melanoma, many chemoattractant mediators of proinflammatory, angiogenic, proliferative action are produced that promote metastasis. The study of cytokines at the systemic level in serum leads to a deeper understanding of the pathophysiology of carcinogenesis and to facilitate the development of targeted therapies for inhibiting tumor growth.

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.

Purpose. To assess the survival rate of patients with small and mediumsized uveal melanoma, depending on the clinical and pathomorphological picture and the cellular microenvironment. Material and methods. For a prospective study, 33 patients with T1-2N0M0 stage of the tumor were selected for the period from June 2005 to July 2018 at an average age of 54±2.7 years. In all cases, the enucleation of the affected eye was carried out with a morphological study of it and a study of the composition of the cellular microenvironment of the tumor node, which became the main criterion for compliance and inclusion in the study. Results. During the study period of observation after enucleation due to eye uveal tract melanoma, 9 (27.3%) of 33 patients died from metastatic disease. Of these, 2 with small and 7 with middle size of tumor. The timing of the appearance of metastases ranged from 15 to 96 (average 41.3±34.5) months. The median follow-up was 64.5 (95% confidence interval 29.3– 99.7) month. The 5-year survival rate of patients with small and medium sized uveal melanoma was 78.7%, and the 10-year survival rate was 72.7%. A significant dependence of the mortality of patients was revealed with the epithelioid cell type of melanoma, increase of tumor basal diameter, involvement of optic disc area and ciliary body, a significant degree of pigmentation, the presence of necrosis in tumor stroma, ingrowth into sclera emissarium and large number of tumor vessels. Survival decreases in patients with a large accumulation of lymphocytes around the tumor, the absence of macrophages, mast cells, fibroblasts on the one hand, and the presence of plasmocytes, myeloid-derived suppressor cells (promyelocytes, neutrophils, eosinophils) in tumor microenvironment.Conclusion. Studies have revealed a certain relationship between the life expectancy of patients and their mortality from metastatic disease with clinical and pathological signs and a specific composition of the cell microenvironment.

Purpose. Conduct an extended analysis of the cytokine status and its role in inflammatory processes in uveal melanoma based on multiplex analysis of the tear fluid.Patients and methods. Immunological studies of blood serum and lacrimal fluid were performed in 80 patients with uveal melanoma and 38 healthy donors (control group). The average age of the surveyed was 53.7 ± 12.2 years. Group 1 included 32 patients with small-sized choroidal melanoma (T1NoMo), group 2 consisted of 26 patients with medium-sized lesions (T2NoMo), group 3 — 22 patients with large tumor sizes (T3NoMo). The cytokine content in the tear fluid was determined by the method of multiplex analysis on the xMAP platform in the Luminex xPONENT 3.1 software using 47 plex kits (ProcartaPlex, eBioscience, Austria).Results. In the lacrimal fluid of the patient and the paired eye — an increase in pro-inflammatory (IL-1α, IL-2, IL-6, IL-17A, IL-18, TNF-α, MCP-1, MIP-1α, RANTES, GRO-α, IL-8, IP-10), anti-inflammatory (IL-1RA, IL-4, IL-10, IL-5, TGF-1β), proliferative (FGF-2, HGF, IL-15, PDGF-BB, Eotaxin), pro-tumor (NGF-β, IL-7), antitumor (IL-21), angiogenic (VEGF-A, SDF-1α) cytokines in the initial stage of uveal melanoma compared with the control group, p < 0.05.Conclusion. In response to the manifestation and growth of uveal melanoma, many chemoattractant mediators are produced, including pro-inflammatory and angiogenic effects, which promote tumor progression and affect the body’s immune response. The study of the lacrimal fluid proved the imbalance of the local immunity not only of the patient, but also of the paired «healthy eye». Research into cytokines leads to a deeper understanding of the pathophysiology of carcinogenesis and may contribute to the development of targeted therapies for inhibiting tumor growth.

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.

The aim of the study is to conduct a comparative analysis of percentages for peripheral blood effector lymphocyte subsets in patients with uveal melanoma manifested by recurrent and chronic herpesvirus infection. There were 141 subjects enrolled: 70 patients with uveal melanoma, 38 patients with corneal ulcers and involvement of the uveal tract as well as 33 healthy donors. Immunophenotyping was performed by using laser flow cytometry with panel of monoclonal antibodies to differentiate lymphocyte subpopulations. IgM and IgG antibodies to herpesvirus infections were determined by using enzyme-linked immunosorbent assay on an automatic ELISA analyzer Lazurit (USA) with diagnostic kits of CJSC “Vector-Best” (Koltsovo). The data obtained showed that the absolute number of blood lymphocytes (CD45+) in patients with uveal melanoma did not differ from those in healthy donors. In contrast, patients with corneal ulcers and involvement of the uveal tract had this parameter increased. A decreased relative and absolute count of T cells (CD3+) in uveal melanoma, but increased absolute CD3+ number in inflammation was observed. No difference in relative and absolute content of the CD3+CD4+ helper/inducer subpopulation in patients with recurrent herpesvirus infections was found. Corneal ulcers in cancer patients revealed significantly increased absolute level of CD3+CD4+ helpers/inductor cells. Chronic herpesvirus infection in uveal melanoma patients showed increased relative and absolute number of cytotoxic T lymphocytes (CD3+CD8+). Recurrent herpesvirus infection was featured with decreased relative number of T lymphocytes (CD3+CD8+), upon inflammation, there was noted increased absolute and decreased relative number compared with healthy subjects. Double positive T cells increased in tumor and inflammation. B lymphocytes (CD19+) increased in melanoma and inflammation. The relative number of blood natural killer cells (CD16+CD56+) in uveal melanoma increased upon recurrent infection. Inflammation was coupled to decreased relative level of natural killer cells (CD16+CD56+). Melanoma showed no changes in CD4+/ CD8+ ratio; upon inflammation, its increase was noted in acute and chronic herpesvirus infections (p < 0.05). The suppression of the immune system in uveal melanoma, restricting antiviral defense, was revealed. The data obtained seem to be important for development of personalized approaches to prognosis and treatment of patients with uveal melanoma.

Purpose. To reveal predictors of small choroidal melanoma transpupillary thermotherapy efficiency using optical coherence tomography-angiography.Patients and methods. 34 patients with small choroidal melanoma at an average age of 55.0 ± 2.9 years were examined. Optical coherence tomography-angiography was performed on an OCT-Angiography Software for RS-3000 Advance Optical Coherent Tomograph, Nidek, Japan, before and 4 months after 1 session of transpupillary thermotherapy. Transpupillary thermotherapy (TTT) was performed with a Nidec DC 3300 diode laser.Results. Prior to TTT — a loop-shaped, cranked-convoluted with an uneven lumen heterogeneous nature of the vasculature of the tumor with numerous bends and interlacing, located under the vessels of the retina in the central zone; the area of neovascular vasculature is 32.82 mm2, the density is 12.42 %. The limiting avascular zone is on the periphery. Around melanoma is a homogeneous hyperreflective rim of dilated choriocapillaries. 4 months after 1 session of TTT in 24 (70.6 %) of 34 cases — occlusion of the choriocapillaries in the central and peripheral zone of the tumor (avascular regions), expansion of the large and medium vessels of the choroid around the focus — predictors of complete tumor devitalization (chorioretinal scar). In 6 (17.6 %) of 34 patients, occlusion of the choriocapillaries in the central zone, expansion of large and medium vessels of the choroid around the tumor, along its periphery and in the paracentral region, retinochoroidal anastamoses along the periphery and in the paracentral zone, heterogeneous neovascularization of the choriocapillaries around; decrease in the area of vasculature — 12.44 mm2, density — 6.15 %, (p < 0.05) — predictors of partial devitalization of small choroidal melanoma (residual tumor). In 4 (11.8 %) of 34 cases, tumor vessels in the tumor area, large and medium vessels of the choroid around, along its periphery and in the central zone, occlusion of the choriocapillaries in the central zone, retinochoroidal anastamoses in the periphery and in the central zone, heterogeneous neovascularization choriocapillaries around; vascular network area — 29.13 mm2, density — 10.17 %, (p > 0.05), lack of devitalization (continued growth).Conclusion. The introduction of optical coherence tomography-angiography revealed the predictors of the effectiveness of transpupillary thermotherapy of the initial melanoma of the choroid, which are various types of tumor vascularization, indicating its about complete, partial or absence devitalization after treatment.

The third part of literature review (see first part in ROJ 2019; 12 (4): 99–108, second part in ROJ 2020; 13 (2): 88–98) discusses the features characteristic of small uveal melanoma and pseudomelanomas (choroidal nevus, circumscribed choroidal hemangioma, melanocytoma, choroidal metastatic carcinoma, congenital hypertrophy of retinal pigment epithelium, late-stage age-related macular degeneration, focal retinochoroiditis, organized subretinal hemorrhage, retinal hemangioma) which were revealed by optical coherence tomography and optical coherence tomography-angiography. The need for further comparative studies aimed at defining differential diagnostic is emphasized.

Purpose: to analyze the frequency and possible associations of GNAQ and GNA11 oncogenes in peripheral blood ctDNA, as well as the relationship of the ABCB1/MDR1 rs1045642 polymorphic marker gene with the clinical and instrumental characteristics of nevi and initial choroidal melanoma. Material and methods. A prospective study of 81 previously untreated patients (84 eyes, mean age 57.8 ± 13.8 years) included general ophthalmological examinations and special instrumental diagnostics: ultrasound checkups, spectral optical coherent tomography (SOCT), OCT angiography. Depending on the nature of the pathology, the patients were divided into three groups: I — with benign choroidal nevus (23 eyes, 28 %; mean age 61.1 ± 13.6 years); II — with suspicious choroidal nevus (24 eyes, 29 %; mean age 54.8 ± 13.0 years); III — small choroidal melanoma (37 eyes, 43 %; mean age 56.2 ± 14.8 years). Genotyping was performed by melting curve analysis. Results. A significant association was revealed between the presence of ctDNA (GNAQ/GNA11 oncogenes) and the CC genotype of the ABCB1 gene with the risk of developing a small melanoma of the choroid and choroidal nevi. In patients with suspicious choroidal nevus, there is an unfavorable significance of mutations in the GNAQ/GNA11 genes (ctDNA). A relative unfavorable predictive significance of the presence of mutations in the GNAQ/GNA11 genes in peripheral blood ctDNA of patients with a benign choroidal nevus was suggested. No significant associations between GNAQ/GNA11 mutations, ABCB1 gene polymorphism and clinical/instrumental tumor features were found. Conclusion. The revealed features can be used for screening the patients with melanocytic intraocular tumors and for developing modern approaches to predicting the course of UM in the early preclinical period.

Purpose. To study the role of transforming growth factor TGF-β in various small choroidal melanoma clinical characteristics before and after eye-preserving treatment.Material and methods. In total, the study included 111 people with an average age of 53.7±12.2 years with choroidal melanoma (n=78) and healthy donors (n=33). Group 1 (n=32) included patients with small choroidal melanoma; group 2 (n=25) included patients with medium-sized tumors; group 3 (n=21) included patients with large melanomas. All patients with choroid melanoma were treated by laser coagulation, transpupillary thermotherapy, brachytherapy, observation after 7±1.2months. A study of transforming growth factor (TGF-β1 and TGF-β2) was performed on a BD FACS Canto II flow cytometer. Statistical processing: Student’s t-test, Fisher criteria and χ2, p

Purpose: To study the features of small choroidal melanoma and choroidal nevi angioarchitectonics using the optical coherence tomography angiography (OCTA).Patients and methods. We examined 128 patients with small choroidal neoplasms: 41 — with small choroidal melanoma (group 1), 42 — with suspicious nevi (group 2) and 45 — with benign nevi (group 3). All patients underwent general ophthalmic examinations and special instrumental diagnostic methods (ultrasound examination (US), fluorescence angiography (FA), spectral optical coherence tomography (SOCT), OCTA).Results. OCTA in all patients with small choroidal melanoma showed neovascular network under retinal pigment epithelium. We found a looped, cranked-twisted, heterogeneous vascular network with uneven clearance and with numerous bends and weaves, located under the vessels of retina. The limiting avascular zone corresponding to the tumor slope was determined in 19 (46.3 %) of 41 cases. There was a rim of dilated hyperreflective choriocapillaries on the periphery of the tumor. We identified hyperreflective homogeneous enlarged choriocapillaries in the focus area with a brighter glow than the surrounding choriocapillaries in 39 (92.9 %) of 42 patients with suspicious choroidal nevus. We detected an avascular zone with surrounding extended hyperreflective choriocapillaries in the center of the nevus in 3 (7.1 %) of 42 cases. We diagnosed homogeneous isoreflective choriocapillaries similar in brightness to the surrounding vessels in all 45 patients with benign nevi.Conclusions. Thus, the complex of clinical and instrumental methods, including OCTA, makes it possible to establish the diagnosis of malignant tumor of the choroid in early stages. At the same time, OCTA: 1) allows to visualize of the tumor vessels in the choroidal layer in 100 % of cases of in small choroidal melanoma; 2) makes it possible to distinguish the newly formed tumor vessels from the choriocapillaries in case of small choroidal melanoma; 3) provides an opportunity to establish the correct diagnosis and provide timely assistance to patients with benign and malignant choroidal tumors.

Purpose: to describe a clinical case of ocular complications of gastric stromal tumor treatment with imatinib mesylate.Material and methods. A patient aged 78 was examined by general ophthalmologic and instrumental methods, including ultrasound and spectral optical coherence tomography (SOCT).Results. Ophthalmoscopy helped diagnose a blunted foveal reflex of the right eye. In the left eye, fuzzy boundaries of the optic disc edema and the macular reflex, the presence of gray-yellow foci of an irregular shape with even distinct boundaries in the paramacular zone were revealed. In the lower part of the left eye fundus, a weakly pigmented gray-yellow focus with uneven indistinct boundaries and an uneven surface was to be seen. SOCT showed in the right eye a retinal edema in the macula and paramacular zones and an epiretinal membrane. In the left eye, SOCT showed vitreoretinal tractions and retinal edema on the edges of the optic nerve; in the paramacular zone and in the inner parts of the fundus, vitreoretinal tractions, epiretinal fibrosis, retinal edema was observed whilst in the lower parts of the fundus complete destruction of all retinal layers due to the hyperreflective focus with a small-shaped inner contour, an even choroidal profile with thinning of the choroid, vitreoretinal tractions, and epiretinal membrane in the left eye could be seen.Conclusions. The clinical case of eye complications of imatinib mesylate in the treatment of gastric stromal tumor necessitates an interdisciplinary integrated approach (involving an oncologist and an ocular oncologist) in the diagnosis and treatment of eye tumors. A complex of instrumental methods of diagnostics of eye fundus diseases involving additional refinement methods (SOCT) ensures differential diagnosis of retinopathy during the chemotherapy, secondary metastatic involvement, and vitreoretinal pathology of a different pathogenetic etiology. Early diagnosis facilitates providing adequate treatment aimed at preserving the patient’s vision, the eye, and life.

Conjunctival lymphomas are predominantly extranodal B-cell non-Hodgkin’s lymphomas (NHL), most of them are MALT-lymphomas originating from the mucosa-associated lymphoid tissue. Manifestations of the conjunctival NHL are very diverse, and often imitate the appearance of other ocular diseases, which makes their clinical diagnosis difficult and significantly lengthens the time from the first visit to the ophthalmologist until the diagnosis is verified. The article presents the case histories of two young patients who were treated for a long time at the place of residence as acute chlamydial conjunctivitis (in one case — 3, in the other — almost 5 months). A comprehensive laboratory study to detect specific blood antibodies, DNA of the pathogen in conjunctival scrapings and the cytological picture of the conjunctiva did not confirm the chlamydial etiology of the process. A pronounced lymphoid reaction mainly due to small lymphoid cells was found in both patients in scrapings from the conjunctiva of the eyelid, which was the basis for referring patients for consultation to oncologist. Histological examination of conjunctival biopsy specimens also revealed proliferation of lymphoid tissue: patients with suspected MALT lymphoma were referred to onco-hematologists. A PCR analysis of the biopsy material revealed HHV-8 DNA in one patient and Epstein-Barr (EBV) DNA in another, although no pathogen genomes were detected in the conjunctiva scrapings. Immunohistochemical analysis in one patient confirmed the conjunctival MALT-lymphoma, in another one diagnosed hyperplasia of the conjunctival mucous-associated lymphoid tissue, caused by prolonged antigenic stimulation (EBV DNA was detected in the biopsy). The follicular appearance of the lymphocyte hyperplasia in conjunctiva may imitate the clinical picture of infectious diseases. For differential diagnosis of chlamydial conjunctivitis and MALTlymphoma, especially in young patients with refractory follicular conjunctivitis, it is advisable to include a set of serological, molecular biology and cytological methods.

Purpose. Using optical coherence tomography (OCT), determine the preclinical changes in optic nerve head (ONH) after chemotherapy in children with retinoblastoma (RB). Material and methods. 38 patients (76 eyes) were examined and treated: 15 girls, 23 boys with RB averagely aged 21.0 ± 1.5 months. Of these, 58 affected eyes before treatment belonged to groups А (3), В (16), С (33), D (3), and Е (3). All tumor nodes were located on the fundus outside the optic disk. The examination of these eyes was carried out on an optical coherent tomograph SOCT Copernicus 4.2 (Poland). The 58 eyes were first tested before treatment, then after 3 or 4 courses of systemic chemotherapy (CT), once again after 6 courses of systemic CT and 1–3 courses of superselective intraarterial CT and 4–9 courses of intravitreal CT. 15 healthy children (30 eyes) of the corresponding age were examined as a control. Results. After 3 courses of systemic CT, OCT determined optic neuropathy with edema in 46.6 %. Morphometric data included parapapillary retinal cystic cavities, elevation of the contour of the optic disc towards the vitreous, increased rim volume (to 0.87 ± 0.12 mm3) and average thickness of the nerve fiber layer increased to 0.39 ± 0.06 mm (p < 0.01). After combined chemotherapy we revealed the thinning of the peripapillary choroid (to 80.0 ± 3.2 μm) with no retinal edema in 34.5 %, a reduction of rim volume to 0.34 ± 0.2 mm3 and the layer of nerve fibers to 0.02 ± 0.01 mm (p < 0.01). These changes are evidences of optic nerve disc atrophy. Conclusion. OCT is an informative method of examining the optic disc in children with RB at different stages of treatment, which identifies signs of edema and symptoms of atrophy more often (respectively, by 15.6 % and 17.3 %). Preclinical diagnostics of optic disc pathology with the help of OCT allows predicting visual functions in children with RB at its early stages and developing a differentiated approach to the choice of RB treatment.

The first part of the literature review described the ophthalmoscopic picture of the small choroidal melanoma and pseudomelanomas [ROJ, 2019; 12 (4): 99–108]. This is the second part of the review, which describes the features characteristic of small uveal melanoma and pseudomelanomas, revealed by fluorescence angiography and autofluorescence. Typical properties of fluorescence and autofluorescence are presented for every disease of the eye fundus studied: small choroidal melanoma, choroidal nevus, circumscribed choroidal hemangioma, melanocytoma, choroidal metastatic carcinoma, congenital hypertrophy of the retinal pigment epithelium, late-stage age-related macular degeneration, focal retinochoroiditis of the posterior pole, organized subretinal hemorrhage, retinal hemangioma. The attention was focused on the similarity of angiographic and autofluorescence symptoms of the diseases under study. The need for new differential diagnostic criteria was emphasized.

Choroidal melanoma is a malignant tumor prone to early metastasis. Its clinical picture is polymorphic, as a result of which it can simulate many diseases of the fundus, which are referred to in the literature as pseudomelanomas. Among these are: choroidal nevus, localized choroidal hemangioma, melanocytomas, choroidal metastatic carcinoma, congenital hypertrophy of retinal pigment epithelium, late stage of age-related macular degeneration, focal retinal choroiditis, organized subretinal hemorrhage, retinal hemangiomas. However, studies comparing the clinical signs of all listed pseudomelanomas and small choroidal melanoma are few. The first part of the review describes the ophthalmoscopic picture of the small choroidal melanoma and pseudomelanomas.

Aim of the study – to evaluate the long-term results of the radiosurgical method using microsurgical techniques for the treatment of small benign eyelid tumors. Material and methods. In Ocular Oncology Centre of Helmholtz Moscow Research Institute of Eye Diseases for the period from 2012 to 2018 year 248 patients were examined and treated (108 children aged 12 ± 1.2 years and 140 adults aged 46 ± 8.1 years) with benign eyelid tumors: pigmented (nevus), vascular (capillary hemangiomas), epithelial (follicular keratosis, keratopapilloma). The Surgitron EMC radiosurgery device was used as surgical aids. All patients used microsurgical technique. The longitudinal size of the tumors was 3.4 ± 0.5 mm, transverse – 6 ± 0.8 mm. All patients after surgical treatment underwent histopathological study. The observation period is on average 6 ± 1.4 years. Results. In 133 (53.6 %) of 248 patients, nevi were detected, in 76 (30.7 %) – keratopapilloma and inverted follicular keratosis, in 39 (15.7 %) – capillary hemangioma. Various modifications of radiosurgical treatment were used depending on the location of the tumor, its size, the degree of activity using different modes and powers from 1 to 4 Wt. Intraoperative complications were not noted. The early postoperative period was accompanied by the presence of signs of mild inflammation, which was stopped by local therapy. The formation of a tender scar was observed on average after 7 ± 2 days. Two cases (0.8 %) of recurrence of keratopapilloma were noted 2 years after the first operation. Tumors were removed by radio excision. Conclusion. Benign eyelid tumors, especially of melanocytic origin, are subject to obligatory dynamic observation, and if minimal signs of their progression are detected, their surgical removal is indicated. Radiosurgical treatment using microsurgical techniques is the method of choice in the treatment of small benign eyelid tumors and depends on the size of the tumor, its localization and the nature of the tumor process. The use of the radiosurgical method with obligatory microsurgical technique for treating benign tumors of small sizes with the observance of the rules of radicalness and antiblasticity allows maintaining visual functions with simultaneous surgical treatment, providing normal anatomical and topographic correlations of the anterior segment of the eye and high quality of life of the patient.

Purpose: to evaluate the effectiveness of transpupillary thermotherapy (TTT) of small calcified retinoblastomas (SR) having various calcification degrees. Material and methods. The results of treatment of 111 children (92 eyes, 198 tumors) with small calcified retinoblastomas by TTT were analyzed. All tumor foci were divided into 3 groups: Group 1, with tumor size of 1.0 mm or less with a low degree of calcification in the form of small specks of single grains (69 tumors); group 2, with tumor sizes between 1.1 and 2.0 mm and calcination degrees varying from small singular inclusions to a third of tumor volume (61 tumors), and group 3, with tumor sizes between 2.1 and 3.0 with calcifications claiming from one third to three fourths of tumor volume (68 tumors). Results. TTT proved effective after one application in 82.6 % of Group 1 cases, 70.5 % of Group 2 cases, and in 38.2 % of Group 3 cases. The presence of calcinates in the tumor stroma is no contraindication for TTT. Conclusion. TTT used in combined eye preserving RB treatment destroys in most cases calcified tumor foci, and allows for an extended list of indications to eye preserving treatment, which enables the preservation of the eye not only as a cosmetic but as a functional organ. For citations: Saakyan S.V., Tatskov R.A., Myakoshina E.B., et al. Transpupillary thermotherapy efficiency in the combined treatment of small calcified retinoblastoma. Russian ophthalmological journal. 2017; 10 (3): 71-77. doi: 10.21516/2072-0076-2017-10-3-71-77 (in Russian).

Results of comprehensive ELISA tests of blood serum for the presence of IgM-, IgA-, and IgG-antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, human herpes virus 8 type, Chlamydia trachomatis in 38 patients with uveal melanoma are presented. The polymerase chain reaction was used to detect DNA of these pathogens in tumor biopsies, vitreous body of 10 enucleated eyes, as well as in plasma IgG-antibodies to HHV 6 were revealed in 50% of patients; IgG-antibodies to HHV 8, in 5.3% of patients. Among the 16 patients with uveal melanoma at advanced stages, 6 patients had antibodies indicative of EBV reactivation (1.2-3.3). Chlamydia trachomatis genome was detected in both biopsies; in one of them, in conjunction with EBV and CMV DNA . Tissue samples from the identified infectious agents were related only to the spindle-cell histologic type AB of uveal melanoma. In plasma, genomes of pathogens were not determined. The results indicate the presence of infectious agents in patients with uveal melanoma and require further study of the pathogenetic role of infections in the pathogenesis of uveal melanoma.