Features of effector lymphocyte subsets in patients with uveal melanoma in recurrent and chronic herpesvirus infection

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

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

RADIOSURGICAL TREATMENT OF BENIGN SMALL EYELID TUMORS

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

Small choroidal melanoma and pseudomelanomas: methods of differential diagnostics (literature review). Part 3

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

Small choroidal melanoma and pseudomelanomas: methods of differential diagnostics. Part 1

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

OCT-Angiography in Early Choroidal Melanoma and Choroidal Nevi

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

Transpupillary thermotherapy efficiency in the combined treatment of small calcified retinoblastoma

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)

Transforming growth factor TGF-β in various small choroid melanoma clinical characteristics before and after eye-preserving treatment

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<0.05.Results. By analyzing the content of TGF-β1 and TGF-β2 in blood serum, significantly higher indices were noted in small choroidal melanoma with retinal exudate (19664.2±1708.7 and 4914.4±325.2 pkg/ml, respectively) compared with those without exudate (18778.7±1609.6 and 3857.3±275.1 pcg/ml, respectively). Comparing the dynamics of the content of TGF-β1 and TGF-β2 in blood serum in small stage of tumor (19902.2±1406 and 4220.7±277.8 pkg/ml, respectively) big tumor (23143.1±1984.5 and 4591.7±334.1 pcg/ml, respectively) we noted its significant increase with the growth of melanoma. The amount of TGF-β2 in the blood serum with bad course (presence of residual tumor or continued growth) of small choroidal melanoma after treatment was significantly higher (4864.1±1299.99 pcg / ml) compared with the good situation (3649.5±1216.5 pcg / ml).Conclusion. Our data may indicate the role of transforming growth factor (TGF-β) in the bad course of small choroidal melanoma and serve as an occasion for the development of targeted anti-TGF–β therapy in combination with radiation therapy