[Angioarchitecture of small retinoblastomas: the role of optical coherence tomography angiography]. / Angioarkhitektonika malykh retinoblastom: rol' opticheskoi kogerentnoi tomografii-angiografii.

Optical coherence tomography angiography (OCTA) is a non-invasive diagnostic method used in children and adults. Features of angioarchitecture of small retinoblastoma are not sufficiently covered. PURPOSE: The study investigated the angioarchitecture of small retinoblastomas using OCTA. MATERIAL AND METHODS: The study included 10 children with binocular retinoblastoma aged 2.7±0.5 months with small tumors of central localization (10 foci). The tumors were divided into 3 groups: group 1 (n=4) - tumor thickness 0.8±0.2 mm; group 2 (n=3) - 1.6±0.5 mm; group 3 (n=3) - 2.4±0.8 mm. OCTA was performed on Spectralis HRA+OCT (2460 scans in total). Vessels were identified in the superficial, deep and outer layers of the tumor on En Face images. Their average number was estimated by visualization of yellow pixels in the superficial layers on 10 sagittal sections. Statistical analysis was done using Microsoft Excel, Statistica 8.0. The Kruskal-Wallis H test was used for comparative analysis of independent variables with more than two samples. RESULTS: Retinal vessels with feeding anastomoses connecting them to multiple small tortuous tumor vessels in the superficial layers were identified in group 1. Number of yellow pixels - 16.5±0.5. In the deep layers - single chaotic vascular arcades. In flat small retinoblastomas the vascular component was not evaluated. In group 2 in the superficial layers of the tumor we found multiple geniculate vessels of large and small caliber anastomosing between themselves and the retinal vessels. Number of yellow pixels was 21±0.8. A few vessels were identified in the deep and outer layers. In group 3 we identified single convoluted vessels in the superficial layers with glow and quantity increasing in the deep layers. In the deep layers - emergence of a small number of vessels. The maximum number of multiple own tumor vessels was determined in the outer layers. Number of yellow pixels - 10±0.8. CONCLUSION: The obtained results confirm the possibility to preclinically identify the angioarchitecture of small retinoblastomas in order to determine the activity of tumor growth and serve as a marker of neoplasm regression in the future, after organ-preserving treatment.

[The incidence of infection in tumor and eye fluid system, and specific humoral immunity to herpes viruses in patients with uveal melanoma].

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.

[The role of CXC and CC chemokines in patients with uveal melanoma]. / Rol' khemokinov klassov CXC i CC u bol'nykh s uveal'noi melanomoi.

Uveal melanoma is a malignant neoplasm with high metastatic potential; its pathogenesis is currently being studied. Chemokines play a key role not only in the inflammatory response, but also in enhancing angiogenesis, tumor invasiveness, increasing proliferative potential and metastasis. PURPOSE: To study the role of chemokines of classes CXC and CC in blood serum and tear fluid of patients with uveal melanoma. MATERIAL AND METHODS: The study included 118 people aged 53.7±12.2 years, among them 80 patients with uveal melanoma and 38 healthy donors. Group 1 included 32 patients with small tumors, group 2 (medium-sized tumors) - 26 patients; group 3 (large tumors) was comprised of 22 patients. Chemokines of classes CC (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL5/RANTES, CCL11/Eotaxin) and CXC (CXCL1/GRO-α, CXCL8/IL-8, CXCL10/IP-10, CXCL12/SDF-1α) were determined by multiplex analysis of the blood serum and tear fluid. Statistical processing: Student's t-test, Fisher criteria, and Pierson's chi-squared test (χ2), differences were considered significant at p<0.05. RESULTS: Significantly increased level of chemokines with pro-inflammatory (CCL5/RANTES), proliferative (CXCL10/IP-10) and pro-angiogenic (CXCL12/SDF-1α) effects was found in the blood serum of patients with small-sized uveal melanoma in comparison with healthy donors. Concentration of all studied pro-inflammatory, proliferative, and pro-angiogenic chemokines in the lacrimal fluid was found to be significantly elevated in both the affected and the paired "healthy" eyes in all 3 groups of patients, with the maximum content seen in the large tumor group. CONCLUSION: The obtained data indicates that early local and systemic immune imbalance can be observed in uveal melanoma, and detection of chemokines can serve as a good reason for developing targeted therapy for small uveal melanoma.

[Optical coherence tomography in diagnostics of small choroidal melanoma]. / Opticheskaia kogerentnaia tomografiia v diagnostike nachal'noi melanomy khorioidei.

PURPOSE: To determine signs of small choroidal melanoma with different pigmentation using enhanced depth imaging optical coherence tomography (EDI-OCT). MATERIAL AND METHODS: The study included 344 patients with small choroidal melanoma with different pigmentation examined using EDI-OCT: 1st group - pigmented melanoma (228 eyes), 2nd group - low pigmented (65 eyes), and 3rd group - amelanotic (51 eyes). RESULTS: In pigmented small choroidal melanomas - elevation of choroidal profile towards vitreous, compression of choriocapillaries with a narrow even 'belt' and a 'shadow' effect; thinning, defects in Bruch's membrane; thickening of the retina above the tumor, lobulated photoreceptors; intra- and subretinal exudate (diffuse, cystic edema, neuroepithelial detachment); defects and detachment of pigment epithelium with hyperreflective foci, disorganization of the pigment with the formation of hyperreflective foci at different retinal levels. In low-pigmented small choroidal melanomas - elevation of choroidal profile towards vitreous, visualized inner surface of the sclera, 'excavation' of the choroid, enlarged choriocapillaries, contour of tumor; thickening of the retina, accumulation of intra- and subretinal exudate (local neuroepithelial detachments); disorganization of the pigment in pigment epithelium with hyperreflective foci in the outer retinal layers. In amelanotic small choroidal melanomas - elevation of choroidal profile towards vitreous, visualized inner surface of the sclera, 'excavation' of the choroid; contouring of choriocapillaries, longitudinal hyperreflective bands in the tumoral stroma, smoothness of the Bruch`s membrane, structural losses of photoreceptors; thickening of the retina (neuroepithelial detachment, diffuse edema); uneven thickening of pigment epithelium. CONCLUSION: EDI-OCT can help identify microstructural changes in the choroid and adjacent retina in small choroidal melanomas with different degrees of pigmentation, suggesting at the early stages a more aggressive course of the tumoral process affecting the prognosis of the disease. In addition, identification of the microstructure and degree of pigmentation of initial choroidal melanomas is necessary for planning an organ-preserving treatment.

[Mast cells in the microenvironment of uveal melanoma]. / Tuchnye kletki v mikrookruzhenii uveal'noi melanomy.

OBJECTIVE: To study the morphological features of the microenvironment of a tumor nodule in the eyes with uveal melanoma, focusing on mast cells. MATERIAL AND METHODS: A total of 43 enucleated eyes with uveal melanoma (260 histological specimens) were examined. The patients' age averaged 54±2.7 years. The morphopathological types of tumors were as follows: epithelioid-cell (n=9; 20.9%), spindle-cell type AB (n=15; 34.9%), and mixed-cell (n=19; 44.2%). The tumor prominence was 4.7±1.3 mm; the base diameter was 13.5±3.3 mm. Statistical methods, such as Microsoft Excel, Statistica 10.1, Spearman's rank correlation coefficient (rs), were applied. RESULTS: Mast cells in the microenvironment of uveal melanoma were present in 18 (41.9%) of the 43 eyes. There was a significantly higher correlation between the mixed-cell type of tumor and the accumulation of mast cells (rs=0.636). The correlation coefficient (rs) of the number of mast cells with the degree of tumor pigmentation in terms of densely and weakly pigmented forms was 0.571 and 0.717, respectively. Tumor invasion through the sclera was detected in 7 (16.3%) eyes with mast cells (rs=0.395). Tumor growth in the emissarium in the presence of mast cells was determined in 8 (18.6%) cases (rs=0.469). Comparison established a correlation between the number of mast cells and the sections of tumor blood vessels (rs=0.21). Granulated cells were noted in 15 (34.9%) cases; degranulated ones were seen in 3 (7%) cases of the 43 examined eyes. with an ejection of granules around the tumor cells, which may be evidence of their interaction. Granules were ascertained to be released around the tumor cells, which may be suggestive of their interaction. CONCLUSION: The study of the mast cell population as one of the components of the tumor microenvironment can be used to elaborate novel approaches for the targeted treatment of uveal melanoma, in particular for its impact on tumor angiogenesis, by using mast cell inhibitors. Therefore, it is relevant and promising to conduct further investigation of mast cells in uveal melanoma.

[Melanoma-associated vitelliform retinopathy (a clinical case study)]. / Melanoma-assotsiirovannaia vitelliformnaia retinopatiia (klinicheskoe nabliudenie).

Melanoma-associated vitelliform retinopathy is a manifestation of paraneoplastic syndrome in skin melanoma. Paraneoplastic syndrome, while not being a tumor or a metastatic disease, is regarded as a tumor-associated disease related to extraocular localization of neoplasm. In this clinical case, the diagnosis of melanoma-associated vitelliform retinopathy was based on a combination of clinical, angiographic, autofluorescence and morphometric signs of bilateral lesion. Analysis of the case showed that in common oncological diseases and complaints of visual impairment, examination of eye fundus is mandatory in order to timely diagnose the changes associated with tumor lesion. Detection of bilateral lesions with oval grey-yellow multiple foci at the level of retinal pigment epithelium may indicate melanoma-associated vitelliform retinopathy that requires diagnostic search for skin melanoma. A complex of instrumental studies including fluorescent angiography, optical coherence tomography and autofluorescence with feature identification allowed establishing the correct diagnosis in the particular case.

[Role of optical coherence tomography angiography in diagnostics of early choroidal melanoma and circumscribed choroidal hemangioma]. / Opticheskaia kogerentnaia tomografiia-angiografiia v diagnostike nachal'noi melanomy i otgranichennoi gemangiomy khorioidei.

Small choroidal melanoma is a malignant tumor that is prone to early metastasis, its amelanotic form is often similar to circumscribed choroidal hemangioma. The main attribute for tumor identification is its vascularization, which is the target of various examination methods. Optical coherence tomography angiography (OCTA) has not been previously used in complex diagnostics of early choroidal melanoma and circumscribed choroidal hemangioma for detection of tumor vessels and the nature of their branching, as well as for vessel caliber comparison. Purpose to examine vascularization of early uveal melanoma and circumscribed choroidal hemangioma by optical coherence tomography angiography. MATERIAL AND METHODS: The study included 23 patients with early choroidal melanoma (13 subjects) and circumscribed choroidal hemangioma (10 subjects) that were examined by optical coherence tomography angiography. According to ultrasound investigation, mean tumor prominence was 1.1±0.3 mm, mean base diameter - 8.1±0.6 mm. RESULTS: Optical coherence tomography angiography in 13 patients with small choroidal melanoma revealed presence of a neovascular component localized under retinal pigment epithelium (RPE) that had marginal avascular zone corresponding to the tumor slope. The loop-like shape of tumor vessels with numerous twists and interweaving was noted under retinal vessels. A tree-shaped neovascular component with large-caliber vessels in the form of a tree trunk with multiple branches extending from it was seen under RPE in 4 cases with circumscribed choroidal hemangioma; diffuse vascularization in the form of numerous tiny tortuous vascular branches was seen in 6 patients. CONCLUSION: Optical coherence tomography angiography allows detection of tumor`s own vessels with characteristics of their vascularization in early choroidal melanoma and circumscribed choroidal hemangioma. Increasing the frequency of detection of tumor`s own vessels will make possible early differential diagnostics of a malignant or benign tumor and will help establish adequate conserving therapy.

[Specific immunoglobulins G and M in blood serum in retinoblastoma and 'pseudoretinoblastoma']. / Spetsificheskie immunoglobuliny G i M v syvorotke krovi pri retinoblastome i 'psevdoretinoblastomakh'.

Perinatal inflammatory retinal diseases and intrauterine retinal maldevelopments are mistaken for retinoblastoma as often as in 8-16% of cases. AIM: To analyze the infectious status in children with retinoblastoma and pseudoretinoblastoma at different ages. MATERIAL AND METHODS: A total of 47 retinoblastoma suspects aged 4-69 months were enrolled. Pseudoretinoblastoma (inflammatory retinal diseases and intrauterine maldevelopments of the retina) was detected in 14 children (group 1), retinoblastoma - in 33 children (group 2). In each group, two subgroups were identified: 'a' - children under 12 months of age (1a - 5 patients, 2a - 10 patients) and 'b'- children over 12 months of age (1b - 9 patients, 2b - 23 patients). Their blood sera were examined for antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, toxoplasma, toxocara, chlamydia, and mycoplasma (enzyme-linked immunosorbent assay). RESULTS: According to serological screening, all patients from group 1a (children under 12 months of age with pseudoretinoblastoma), in contrast to other groups, were infected perinatally with cytomegalovirus infection. All 47 patients were seronegative to toxoplasma. Toxocara infection was identified in children over 12 months of age: in 3 out of 9 patients with pseudoretinoblastoma and in 2 out of 23 patients with retinoblastoma (p>0.05). Markers of Epstein-Barr viral activity were detected only in 3 retinoblastoma children over 12 months of age. CONCLUSION: The results suggest that cytomegalovirus infection plays the leading role in the development of perinatal eye pathology, which, in infants, is clinically similar to retinoblastoma. In children over 12 months of age we found no serological signs that could be regarded as specific of either retinoblastoma, or pseudoretinoblastoma. The only thing worth paying attention to is the activation of Epstein-Barr virus infection in children over 12 months of age with retinoblastoma.

[Iridal lymphoma (clinical case)]. / Limfoma raduzhki (klinicheskoe nablyudenie).

This is a case report of rare iridal involvement in intraocular lymphoma confirmed by the full range of diagnostic measures, including ultrasound biomicroscopy, optical coherence tomography of the anterior segment of the eye, iridectomy with biopsy and further cytological and histopathological examination of the obtained material.

Testing patients with uveal melanoma for herpesvirus infections.

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.