Introduction. Standard eye enucleation (EE) may not always guarantee a sufficient length of resection of the optic nerve (ON) so that the tumor cells do not spread along the optic nerve at the intersection line. Surgical access and the scope of surgical intervention are determined by the spread and localization of the tumor, as well as the qualification of the operating team.Purpose— to evaluate the role of extended surgical interventions in the spread of extraocular tumors on the ON.Materials and methods. The study included 9 patients with retinoblastoma (RB) and macroinvasion of the ON during primary magnetic resonance imaging (MRI) and/or micromorphological invasion of the ON resection line after EE. 4 of the 9 patients were treated with primary/secondary EE, induction chemotherapy (CT) and high-dose CT (HDCT), radiation therapy (RT). 5 out of 9 patients underwent secondary extended surgical interventions: exenteration of the orbit (n = 1), osteoplastic lateral orbitotomy with precanal resection of the ON (n = 2) in combination with EE in one case, subfrontal craniotomy (n = 1) and orbitozygomatic craniotomy (n = 1) with prechiasmal resection of the ON and EE with adjuvant RT (excluding the latter case) and CT, without HDCT.Results. It should be noted that the overall survival (OS) of 5 patients with complete microscopic resection (R0) after extended secondary operations was 75 ± 0.217 % with an average follow-up period of 77.25 ± 18.8 months, while in 4 patients with R1 (n = 4) without secondary extended operations with HDCT reached only 50 ± 0.25 % with an average follow-up period of 57 ± 24.8 months.Conclusion. MRI is mandatory for the primary diagnosis of RB, especially when there is a risk of the tumor spreading through the ON. Secondary surgery with R0-resection has a positive effect on survival. The need for adjuvant RT and CT after surgery should be discussed.

Introduction: Selective ophthalmic arterial injection (SOAI) therapy for intraocular retinoblastoma is currently recognized by the world ophthalmic-oncological communities and this method is used in leading specialized institutions. However, the using of this type of treatment can lead to complications. Side effects can be both systemic, affecting the course of the procedure itself, and local in nature, associated with intraocular changes.Purpose: Conduct an analysis of complications during SOAI in children with intraocular retinoblastoma.Material and methods: The study includes the results of treatment of 110 children (129 eyes) with unilateral and bilateral retinoblastoma who received SOAI both with insufficient efficacy of previous treatment for resistant and recurrent forms of RB (99 children / 116 eyes), and as primary local chemotherapy without previous treatment (11 patients / 13 eyes). 313 procedures were performed, of which the treatment stage was completed in 303 cases. Depending on the hemodynamic characteristics of the blood supply to the eye and the orbital region, 2 methods of delivering of the chemotherapy were used: 1) microcatheter technique (245 procedures performed; 81.0 %) 2) microballoon technique (58 procedures performed; 19.0 %).Results: The structure of the complications was as follows. 1. The group of intraoperative complications included: spasm of the ICA, cerebral arteries — 4 cases (1.3 %), acute cardio-respiratory manifestations and hemodynamic instability — 93 (29.7 %). 2. Group of general complications: cerebrovascular accident — 3 cases (0.9 %), hematological toxicity — 14 (4.5 %). 3. Group of local complications. A) External extraocular manifestations: transient eyelid edema — 49 (15.7 %), frontal arteritis — 2 (0.6 %), ptosis of the upper eyelid — 11 (3.5 %), ptosis and deviation of the eyeball — 2 ( 0.6 %), soft tissue necrosis — 1 (0.3 %). B) Intraocular manifestations: retinal detachment — 13 (4.2 %), chorioretinal atrophy — 4 (1.2 %), edema of the optic nerve head — 2 (0.6 %), atrophy of the optic nerve head — 1 (0.3 %), hemophthalmia — 3 (0.9 %).Conclusion: Modern interventional endovascular methods allow to carry out the SOAI safety and reduce the number of possible complications.

Introduction. Retinoblastoma (RB) is a malignant tumor of the retina, the survival rate for the intraocular form reaches 99 %. According to the researchers, the risk factors for the occurrence of refractory or recurrent forms of RB are the size of the tumor at primary diagnosis (more than 15 mm), the child's age at the onset of the disease (up to one year), bilateral RB, and the presence of subretinal and vitreal screenings. If methods of local destruction of the tumor are not applicable for the successful treatment of intraocular refractory or recurrent RB, then they resort to the second line of polychemotherapy as an alternative to enucleation. New versions of local chemotherapy and radiation therapy (gamma knife) are being developed and applied. Nowadays, researchers have a negative attitude towards traditional radiation therapy (EBRT) as a method of organ-preserving treatment due to serious consequences (asymmetry of the facial skeleton and second radio-induced tumors).Aim of the study — to increase the effectiveness of organ-preserving treatment in patients with refractory or recurrent intraocular RB.Materials and methods. In the period from 10.2018 to 12.2019 at the N.N. Blokhin National Medical Research Centre of Oncology it was received three-component selective intra-arterial chemotherapy (SIAC) in 15 patients (15 eyes) aged 11 to 52 months. Eyes initially affected by RB (n = 15), according to the IIRC (Murphree) classification, had the following groups: group B in 1 case, group C in 3, group D in 7, and group E in 4 eyes. It should be noted that all patients initially received intensive combined conservative therapy: in 11 (73 %) of 15 cases — systemic chemotherapy VEC; in 13 (86 %) of 15 — SIAC with melphalan, in all cases, additionally, two-component SIAC was used in combination with melphalan with topotecan. In some cases, local therapy in the form of intravitreal chemotherapy (IVIC) was added to the treatment of 6 (40 %) of 15 patients in the form of melphalan monotherapy and in one case (6 %) a doublet was used in combination with melphalan and topotecan. Also, in some patients, additional local ophthalmic therapy was used: transpupillary thermotherapy (TTT) in 6 out of 15 patients, including in combination with cryotherapy (CT) in 1 patient and in combination with brachytherapy (BT) in one case. At the same time, incomplete tumor regression (refractory form of the disease) was noted in 7 out of 15, and a recurrent course of the disease — in 8 out of 15 patients. Incomplete tumor regression and recurrent RB were the reasons for the appointment of a three-component SIAC using carboplatin, melphalan and topotecan, in combination with IVIC with pronounced endophytic growth of RB, as an alternative to irradiation and enucleation of the eye.Results. The average number of three-component SIAC courses was 1.46 ± 0.63 (rang 1—3). The combination of SIAHT with IVHT was performed in 3 out of 15 patients. All children (n = 15) are alive with a median period of follow-up of23.92 ± 15.68 (10—64) months. One in 15 patients was lost from observation due to their parents’ desire to be treated abroad. It is known that the child is alive, but there is no data on the condition of his eyes. 9 out of 14 patients needed additional treatment after SIAC intensification. To consolidate the resulting effect as a full regression in 2 cases, the final IVIC courses were conducted (n = 2). In connection with the presence of residual tumor and/or intraocular progression and/or appearance of new lesions in 1 of 9 patients were IVIC and TTT, 2 of 9 — IVIC, SIAC, CT, TTT. In 4 out of 9 cases, enucleation was performed, and in 2 out of 4 — the operation was performed after continuing the attempt of organ-preserving treatment: after CT and TTT (n = 1) and IVIC, CT, TTT and BT (n = 1). No child was given ERBT. There were no cases of stroke after SIAC. We managed to save 10 (71.4 %) of 14 eyes with visual acuity: object vision in 4 (40 %) out of 10, eye fixation in 3 (30 %) out of 10, and light perception in 3 (30 %) out of 10 cases. The average follow-up period from the end of three-component SIAC in 14 patients was 13.57 ± 5.27 (6—22) months.Conclusion. Thus, the three-component SIAC is effective and safe for patients with refractory and recurrent retinoblastoma, as evidenced by a high percentage of retained eyes and the presence of visual functions from light perception to object vision.

Introduction . Standard eye enucleation (EE) may not always guarantee a sufficient length of resection of the optic nerve (ON) so that the tumor cells do not spread along the optic nerve at the intersection line. Surgical access and the scope of surgical intervention are determined by the spread and localization of the tumor, as well as the qualification of the operating team. Purpose — to evaluate the role of extended surgical interventions in the spread of extraocular tumors on the ON. Materials and methods . The study included 9 patients with retinoblastoma (RB) and macroinvasion of the ON during primary magnetic resonance imaging (MRI) and/or micromorphological invasion of the ON resection line after EE. 4 of the 9 patients were treated with primary/secondary EE, induction chemotherapy (CT) and high-dose CT (HDCT), radiation therapy (RT). 5 out of 9 patients underwent secondary extended surgical interventions: exenteration of the orbit (n = 1), osteoplastic lateral orbitotomy with precanal resection of the ON (n = 2) in combination with EE in one case, subfrontal craniotomy (n = 1) and orbitozygomatic craniotomy (n = 1) with prechiasmal resection of the ON and EE with adjuvant RT (excluding the latter case) and CT, without HDCT. Results . It should be noted that the overall survival (OS) of 5 patients with complete microscopic resection (R0) after extended secondary operations was 75 ± 0.217 % with an average follow-up period of 77.25 ± 18.8 months, while in 4 patients with R1 (n = 4) without secondary extended operations with HDCT reached only 50 ± 0.25 % with an average follow-up period of 57 ± 24.8 months. Conclusion . MRI is mandatory for the primary diagnosis of RB, especially when there is a risk of the tumor spreading through the ON. Secondary surgery with R0-resection has a positive effect on survival. The need for adjuvant RT and CT after surgery should be discussed.

Т.Л. Ушакова , А.С. Волкова, Т.В. Горбунова, О.В. Горовцова, И.С. Долгополов, Е.В. Михайлова, Т.Р. Панфёрова, И.В. Глеков , В.Г. Поляков 2 ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России; Россия, 115478, Москва, Каширское шоссе, 23; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России; Россия, 125993, Москва, ул. Баррикадная, 2/1, стр. 1; ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; Россия, 117997, Москва, ул. Островитянова, 1

Introduction. The main reason for enucleation of the eye when attempting organ-preserving treatment are intraocular tumors that do not respond well to chemotherapy.Purpose. The aim of the study was to find new effective and safe organ-preserving methods of treatment of intraocular refractory and recurrent retinoblastoma (RB).Materials and methods. The study included female chinchilla rabbits. The cell line of human RB was intravitreally inserted into the right eye of each animal. The left eye was a control. After obtaining a stable intraocular growth of RB and prolongation of the growth of RB, human cytotoxic lymphocytes (CTL) were intravitreally injected into the affected and control eye K1 at a concentration of 1 × 106 in 0.1 ml suspension and K2 – 5 × 106 in 0.1 ml, respectively.Results. Histological examination of the removed right eyes in animals confirmed the presence of nodal growth of malignant small-cell tumor on the border of the vascular and retinal membranes (epicenter in the choroid) on the posterior wall of the eye. There was scant lymphoid infiltration, without signs of therapeutic pathomorphosis. In the removed animal»s left eyes there is a preservation of histological structures of the eyeball, without dystrophic changes in the cells of the retina and vascular membranes. In the area of limb unit microcap lymphohistiocytic infiltration (with no elements of the tumor). In the choroid single scattered lymphocytes.Conclusion. A short period of observation of the tumor did not allow conclusions about the effectiveness of CTL, but the concentrations of CTL used in the experiment did not lead to dystrophic changes in retinal cells and the choroid of the eye, which is an important factor in overcoming the toxicity of the proposed adoptive immunotherapy. At the next stage of the experiment, in our opinion, it is necessary to study in more detail the cytotoxic effect on healthy structures of the eye and the effectiveness of CTL in a larger number of affected rabbit eyes, using their different concentrations and multiplicity of administration.

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Retinoblastoma is one of highly curable diseases; today the total 5-year survival rate in patients with retinoblastoma exceeds 95%. The article summarizes the current world experience on treatment of patients with intraocular retinoblastoma. The treating skills of intraocular malignant tumor in children are a balance between the patient’s life and the preservation of an eye and its visual functions. The complex and challenging task is the treatment of common intraocular retinoblastoma groups «C», «D», «E» when the large size or localization of the tumor does not allow performing the local (focal) destruction of the tumor. As a rule, in such cases neoadjuvant chemotherapy (CT) is performed at the first stage in order to reduce the size of the tumor for further focal therapy. However, the analysed data on the effectiveness of neoadjuvant CT in combination with focal or radiotherapy demonstrated the limited possibilities of the proposed therapy. Local drug delivery in cancer therapy became a real breakthrough in the organ-preserving treatment of children with large intraocular retinoblastoma. The most widely used current methods of local drug delivery are intravitreal (IVitC) and selective intra-arterial chemotherapy (SIAC) as monotherapy or in combination with neoadjuvant CT and focal therapy which significantly increased the percentage of preserved eyes without radiotherapy administration or damage to the patient survival. The review discusses the different IVitC and SIAC techniques, chemotherapy schemes, dosages of chemotherapy, immediate and long-term complications of treatment.

Background.Retinoblastoma (RB) is a life threatening cancer disease. A breakthrough in the treatment of children with RB is associated with the improvement of conservative treatment that was administered in at least one of the two tumor-affected eyes in most bilateral cases, that was chemotherapy both systemic and local (selective intra-arterial and intravitreal) in most cases combined with laser therapy, cryotherapy, or brachytherapy. The development of such techniques as local chemotherapy is focused on preservation of visual functions, reducing the number of enucleations and radiotherapy (RT) course. The success of the healing of RB is closely associated with a multidisciplinary approach to diagnosis and treatment, as well as specialized longterm follow-up clinical examination.Objective.eye and vision preservation against large intraocular tumors with different growth types and localization without the course of remote radiation therapy was the main purpose.Methods.In the period from September 2012 to January 2016, the study enrolled 45 patients with RB when at least one eye had intraocular tumor spread corresponding to the group C or D. According to the ABC international classification, patients have a relatively good prognosis for organ-preserving treatment. 4 of 18 children with bilateral RB had undergone primary enucleation of worse eye the worst eye, group E; 49 (77.8%) of the 63 affected eyes had features for groups C and D. In this study, no patient received local chemotherapy initially, only after prior systemic chemotherapy. Selective intra-arterial chemotherapy (SIAC) was applied to 41 patients (45 eyes; mean course number was 2), and 32 patients (34 eyes) had undergone intravitreal chemo therapy (IViC) (mean course number was 2). Focal therapy and local chemotherapy were the main methods of treatment for progression (new lesions on the retina) in 8 (16.3%) of 49 eyes with tumors of group C (n=1) and D (n=7); the relapse in 14 of 49 (new lesions on the retina) in eyes with tumors of group C (n=5) and D (n=6) and (new lesions on the retina and the vitreous) in eyes with tumors of group D (n=3) (28.5%), and stabilization of disease n=23 (46.9%). We should note that 2 patients underwent repeated course of in case of systemic chemotherapy, 1 patient — a Gamma Knife procedure due to registered disease stabilization, progression or relapse.Results.10 (20.4%) of 49 eyes saved due to the combined chemotherapy. In 45 patients diseasefree survival rate was 56.1±8.9 % (with mean follow-up period 26.9±2.5 months). 1 of 45 patients died from leukemia. 44 of 45 patients are alive without metastasis. The mean follow-up was 20 months (3 to 43 months). Eye salvage rate in group C — 14 (93.3%) of 15, in group D — 31 (91.2%) of 34.Conclusion.These methods: second line of systemic chemotherapy, RT, and a Gamma Knife procedure should be considered as a failure of primary treatment. Our study demonstrated a high efficacy of local chemotherapy with promissing techniques of conservation therapy, which safety increases due to experience.

PURPOSE:To illustrate the successful outcome of pars plana vitrectomy (PPV) with melphalan irrigation for vitreous hemorrhage (VH) with suspected viable retinoblastoma. Despite the high risk of intraocular surgery, it was performed to preserve the only potentially seeing eye with treated retinoblastoma.METHODS:Vitreous hemorrhage occurred in the only eye of a 4-year-old boy after treatment for recurrent multifocal group C retinoblastoma with systemic chemotherapy (carboplatin, etoposide, and cyclophosphamide; and vincristine, cyclophosphamide, and doxorubicin), ruthenium brachytherapy with plaque repositioning, cryotherapy, and external radiotherapy. The VH developed 8 months after repeated brachytherapy with subsequent intravitreal melphalan chemotherapy. The patient's parents refused to remove the eye. The fellow eye was enucleated earlier because of VH and secondary glaucoma, without histologic signs of a viable tumor. Pars plana lensectomy, 25-G vitrectomy with melphalan irrigation (5 μg/mL), and silicone oil tamponade were performed.RESULTS:No ophthalmoscopic or morphologic signs of a viable tumor were detected. Four months later, the silicone oil was removed. Visual acuity was 20/200 with aphakic correction. Follow-up for 34 months revealed no signs of tumor recurrence or dissemination.CONCLUSIONS:Despite the high risk of intraocular surgery, the need to preserve the only potentially seeing eye with treated retinoblastoma may require PPV. Thus, in unclear cases of VH with suspected viable tumor, PPV with intraocular melphalan irrigation, with caution, may be a reasonable procedure.