Melatonin and its bioisosteres as potential therapeutic agents for the treatment of retinopathy of prematurity.

We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds 1-3) on the development of oxygen-induced retinopathy in newborn rats during a 21-day experiment. It was demonstrated that melatonin and its analogues 1-3 effectively reduce the total protein concentration in the vitreous body of rat pups, decrease concentration of VEGF-A, and lower the level of oxidative stress (as indicated by normalization of antioxidant activity in the vitreous body). Melatonin and its analogues 1-3 equally normalize the level of VEGF-A. Analogues 1 and 2 even exceed melatonin in their ability to reduce protein influx into the vitreous body. However, analogue 2 had no effect on antioxidant activity, while analogues 1 and 3 caused a significant increase in this parameter, with analogue 3 even slightly exceeding melatonin. Thus, it can be concluded that analogues 1-3 are comparable to melatonin and can be utilized as potential therapeutic agents for the treatment of retinopathy of prematurity.

[The role of endothelin-1 in the pathogenesis of familial exudative vitreoretinopathy]. / Rol' endotelina-1 v patogeneze semeinoi ekssudativnoi vitreoretinopatii.

Familial exudative vitreoretinopathy (FEVR) is a rare hereditary disease characterized by pathological retinal vascularization with a progressive and variable course. The mechanisms of disease progression remain unclear. One substance that plays an important role in the pathogenesis of retinal vascular diseases is endothelin (ET). It was found that tissue hypoxia enhances the expression of the gene encoding ET-1, and ET-1 can be locally produced in the eye. PURPOSE: The study evaluates the possible role of endothelin-1 in the pathogenesis of FEVR. MATERIAL AND METHODS: The study included 85 patients with FEVR aged from 1 months to 17 years who were examined in Helmholtz National Medical Research Center of Eye Diseases. The concentration of ET-1 was evaluated in 19 patients with FEVR in the blood serum (n=17), lacrimal fluid (n=18) and 16 patients from the control group. RESULTS: The median of ET-1 in the lacrimal fluid in patients with FEVR was 13.74 pg/mL, respectively, which exceeded the same indicator of the control group 4.66 pg/mL by 2.5 times (p<0.001). The median of ET-1 in the blood serum exceeded the control group by 2.4 times (21.61 pg/mL and 9.21 pg/mL, respectively, p<0.001). CONCLUSIONS: An increase in the concentration of ET-1 in the lacrimal fluid and blood serum of patients with FEVR in comparison with the control group indicates its involvement in the pathogenesis of the disease.

[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.

Enalaprilat as a new means of preventing the development of retinopathy of prematurity.

In a rat model of experimental retinopathy of prematurity (ROP), the safety of enalaprilat and its effect on the level of angiotensin-converting enzyme (ACE) and angiotensin-II (AT-II) in the vitreous body and retina were investigated. The study was performed on 136 newborn Wistar rat pups divided into 2 groups: group A - experimental (animals with ROP, n=64) and group B - control (n=72). Each group was further divided into 2 subgroups: A0 and B0 (n=32 and n=36, respectively) - animals that did not receive injections of enalaprilat, and A1 and B1 (n=32 and n=36, respectively) - animals treated with daily intraperitoneal (i.p.) injections of enalaprilat (0.6 mg/kg of body weight). This treatment started on day 2 and lasted either to day 7 or to day 14 in accordance with the therapeutic scheme. Animals were taken out of the experiment on day 7 and day 14. In samples of the vitreous body and retina, the content of ACE and AT-II was determined by enzyme immunoassay. On day 7 in subgroups A1 and B1 the levels of ACE and AT-II in the vitreous did not differ, while on day 14 were lower than in subgroups A0 and B0, respectively. Changes in the parameters studied in the retina were somewhat different from those found in the vitreous body. On the seventh day, the level of ACE in the retina of animals of subgroup B1 did not differ significantly from subgroup B0, and in subgroup A1 it was increased compared to subgroup A0. On day 14, its significant decrease was noted in subgroups A1 and B1 as compared with subgroups A0 and B0. At the same time, the level of AT-II in the retina of rat pups of subgroup B1 was lower than in subgroup B0, both on day 7 and day 14. On day 7, the concentration of AT-II, as well as the concentration of ACE, increased in subgroup A1 as compared to subgroup A0. On day 14, this parameter in subgroup A1 was significantly lower as compared to subgroup A0, but significantly higher than in subgroup B1. It should be noted that i.p. injections of enalaprilat, increased a death rate of animals of both groups. The use of enalaprilat, starting from the preclinical period of the ROP development, led to a decrease in the activity of the renin-angiotensin system (RAS) in ROP animals at the onset of retinopathy in the experimental model used. This opens up prospects for considering enalaprilat as a means of preventing the development of this pathology; however, the recognized high toxicity of the drug requires further studies and correction of the timing of its administration and dosage in order to achieve a balance of efficacy and safety of use in order to prevent the development of ROP in children.

[Changes of a2-macroglobulin activity and endothelin-1 concentration in tears of rabbits after transplantation of retinal pigment epithelium cells derived from the induced pluripotent stem cells]. / Izmenenie urovnia a2-makroglobulina i éndotelina-1 v sleznoi zhidkosti krolikov posle transplantatsii kletok retinal'nogo pigmentnogo épiteliia, differentsirovannykh iz indutsirovannykh pliuripotentnykh stvolovykh kletok.

Retinal diseases accompanied with the dysfunction or death of the retinal pigment epithelial (RPE) cells are widespread, hard to treat, and appear to be a leading case of visual loss and blindness among the persons older than 55 years. Transplantation of RPE cells derived from the induced pluripotent stem cells (IPSC-RPE) is a promising method of therapy for these diseases. To ensure the transplant survival instant follow-up is required. It can be based on biochemical analyses of tear fluid that can be easily non-invasively collected. For the post-transplantation process monitoring we have choosen such polyfunctional bioregulators as α2-macroglobulin (α2-MG) and endothelin-1 (ET-1). RPE atrophy in New Zealand Albino rabbits was modeled via the subretinal injection of bevacizumab. IPSC-RPE in suspension or as a monolayer on the scaffold were transplanted subretinally 1 month after the injection. α2-MG activity and ET-1 concentration in tears were estimated during the first month and after 2, 3 and 7 months after transplantation. On the 7-14 days after transplantation α2-MG activity increased in tears of the both operated and controlateral eye probably as a reaction on the corticosteroid therapy. In 50% rabbits there was one more increase after 2-3 months that could be due to the immune inflammation. Concentration of ET-1 in tears decreased dramatically on the 7-14 days and 7 months after transplantation, and it could have an influence upon the retinal vassal tone. The data obtained show that estimation of bioregulators in tears can help monitoring local metabolic processes after RPE transplantation that is necessary for the opportune, reasonable and focused medicamental correction of post-transplantation process.

[Experimental stem cell replacement transplantation in retinal pigment epithelium atrophy]. / Zamestitel'naya transplantatsiya stvolovymi kletkami pri atrofii retinal'nogo pigmentnogo epiteliya v eksperimente.

PURPOSE: To develop and evaluate the results of the modified surgical technique for transplantation of retinal pigment epithelium (RPE) differentiated from human induced pluripotent stem cells (iPSC-RPE) in the form of a cell suspension into the subretinal space of rabbits with previously induced RPE atrophy. MATERIAL AND METHODS: The study was conducted on 10 New Zealand albino rabbits (20 eyes). One month after modeling RPE atrophy and retinal degeneration, rabbits were subjected to subretinal transplantation of iPSC-RPE cells in the form of a cell suspension. To prevent reflux of iPSC-RPE into the vitreal cavity, the injection site was sealed with 2-3 drops of autologous platelet-rich plasma (PRP). All rabbits underwent spectral optical coherence tomography (SOCT) and autofluorescence studies on the Heidelberg Spectralis system («Heidelberg Engineering¼, Germany). Enucleated animal eyes were studied with morphological and immunohistochemical methods. RESULTS: In this study we developed and evaluated a modified surgical technique of transplantation of iPSC-RPE in the form of a cell suspension into the subretinal space of rabbits with induced RPE atrophy. It was found that the use of PRP helps seal the defect and prevents cell suspension reflux into the vitreous cavity, effectively minimizing intra- and postoperative complications. Morphological in vivo study and examination of histological sections showed that implantable iPSC-RPEs were correctly integrated and adhered to the choroid in the surgery site. Immunohistochemical analysis involving fluorescence-marked antibodies confirmed the survival of iPSC-RPE integrated into the retina of model animals. CONCLUSION: This method improves the technology of iPSC-RPE transplantation on preclinical stages of the study, revealing new prospects in the treatment of degenerative diseases of the retina and the possibility of a personalized approach.

[Electroretinographic signs of retinal remodeling after experimental induction of retinal pigment epithelium atrophy]. / Elektroretinograficheskie priznaki remodelirovaniya setchatki posle induktsii atrofii retinal'nogo pigmentnogo epiteliya v eksperimente.

Various animal models of atrophy of retinal pigment epithelium (RPE) are created in order to study certain aspects of geographical atrophy in humans. To study the effects of new methods of therapy, it is necessary to determine the objective functional markers of structural changes in the retina. PURPOSE: To determine the alterations in activity of the retina that characterize its remodeling in induction of RPE atrophy. MATERIAL AND METHODS: Full-field electroretinograms (ERG), pattern ERG, and multifocal ERG were recorded according to the ISCEV standards from the right eyes of twenty rabbits of the New Zealand albino breed 6-7 weeks after induction of RPE atrophy by subretinal administration of 0.9% sodium chloride or bevacizumab solution. RESULTS: Characteristic electroretinographic signs of RPE atrophy and retinal remodeling are described. Changes in ERG indicate a predominant inhibition of the functional activity of photoreceptors compared with bipolar cells, which objectively reflects an impairment of their metabolism associated with RPE pathology. With the injection of bevacizumab, a sharp weakening of the functional symbiosis of Mueller cells with bipolar cells was observed. According to pattern ERG, the function of the retinal ganglion cells was reduced. The reaction of the paired eyes after induction of RPE atrophy included a moderate decrease in the amplitude of b-wave of photopic ERG and activation of glia-neuronal relationships. CONCLUSION: Subretinal injections of 0.9% sodium chloride and bevacizumab trigger changes in the retina that reflect specific remodeling of retinal neurons of the second and third orders, which characterizes the used models of RPE atrophy.

[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.

[Pathogenetically oriented approach to prevention of retinopathy of prematurity (experimental study)]. / Patogeneticheski orientirovannaya profilaktika retinopatii nedonoshennykh (eksperimental'noe issledovanie).

Intraperitoneal injections of exogenous melatonin during the development of the retinal vascular system in experimental rats has been shown in a number of experimental studies on the model of EROP to prevent the appearance of histological signs of the development of experimental retinopathy of prematurity (EROP), stabilize the blood-retinal barrier and have a pronounced antioxidant effect, but pathogenetic basis for these phenomena hasn't been studied. PURPOSE: To study the influence mechanism of melatonin and its analogues on the development of EROP at the preclinical stage of the pathological process to substantiate new approaches to prevention of ROP. MATERIAL AND METHODS: The study included 42 Wistar rat pups (84 eyes) divided into 6 groups: control group, experimental group (rat pups with EROP), experimental groups who underwent injections of melatonin and its analogues K-148, AL-3, K-096. The pups were euthanized on day 7 (4-5 pups from each group at each study period), binocular enucleation was performed, and the content of hypoxia-induced factor1α (HIF-1α) and VEGF-A was determined in retinal samples. RESULTS: The intraperitoneal injections of melatonin and its analogs led to a significant decrease in the level of HIF-1α and VEGF-A in the retina of the rat pups of the experimental group until the beginning of pathological vasoproliferation. CONCLUSION: Melatonin and its analogues are able to prevent the development of EROP by reducing the level of angiogenic factors in the retina of rat pups at the stage of existing avascular zones, which allows for them to be considered as a new promising approach to preventing the development of ROP.

[Long-term functional outcomes after congenital cataract extraction with intraocular lens implantation in children of the first year of life]. / Otdalennye funktsional'nye rezul'taty posle ekstraktsii vrozhdennoi katarakty s implantatsiei intraokulyarnykh linz detyam pervogo goda zhizni.

PURPOSE: To study best corrected visual acuity (BCVA) and identify its relationship with various factors in eyes with pseudophakia in long-term periods after removal of congenital cataract (CC) in the first year of life. MATERIAL AND METHODS: The study included 54 children (72 eyes) aged 4 to 12 years who had undergone CC removal with intraocular lens (IOL) implantation at the age of 2-11 months. Examination included: visual acuity testing, Flicker ERG 30 Hz electroretinography (MBN, Russia), optical coherence tomography (HRT-OCT) on the Heidelberg Spectralis (Heidelberg Engineering, Germany) platform. RESULTS: The best results were obtained after removal of bilateral congenital cataract (BCC): BCVA in 58.0% of cases was 0.15-0.3, and in 12.0% of cases - 0.4-0.8. BCVA was 0.1 or less in 95.5% of cases and only one child had 0.2 after removal of unilateral congenital cataract (UCC). The best BCVA was achieved in children operated on the 2-5 month of age (BCVA more than 0.3 in 68.7%; only children from that group had 0.5-0.8), without any concomitant pathology and with normal indicators of ERG Flicker 30 Hz. Deviations from physiological formation of the macula were revealed using OCT. The direct relationship was shown between BCVA, and the maximal retinal thickness in parafovea and choroidal thickness in the subfoveal area. CONCLUSION: BCVA significantly varies after CC removal with IOL implantation in infancy: 0.02-0.8. The main factors influencing BCVA in that case are: laterality of cataract, child age at the time of operation, duration of visual deprivation, concomitant eye pathology and refractive amblyopia accompanying incomplete correction of aphakia.

[Results of long-term observation of extremely premature babies with retinopathy]. / Rezul'taty dlitel'nogo nablyudeniya gluboko nedonoshennykh detei s retinopatiei.

PURPOSE: To study the long-term clinical and functional outcomes of retinopathy in extremely premature infants. MATERIAL AND METHODS: The study included 42 patients (84 eyes) with retinopathy of prematurity (ROP) at the age of 9-18 years. All patients underwent comprehensive ophthalmological examination, including morphometric (OCT), functional (ERG) and psycho-physical (computer perimetry) methods. RESULTS: A high occurrence of low vision (67%) was revealed in extremely premature children with ROP during school years and adolescence, which depended on the severity of active ROP and the formation of pronounced residual changes in the fundus during the cicatricial phase of the disease, a high occurrence of refractive errors (92%), including high degree myopia (46%), late complications that develop with ROP of any degree (68%), impaired retinal electrogenesis - due to both ROP and deep morphological and functional immaturity of the retina. CONCLUSION: Patients with any degree of cicatricial ROP born in the early stages of gestation and with extremely low body weight need regular complex ophthalmologic examination and lifelong follow-up.

[Viral and non-viral infections in the etiopathogenesis of uveitis]. / Virusnye i drugie infektsii v étiopatogeneze uveitov.

The article reviews literature and proprietary data on the role of pathogens in the etiology of infectious and non-infectious uveitis. Infectious uveitis is caused by active intraocular replication of the virus (herpesvirus, acute stage of enterovirus), or by long-term persistence of the viruses in eye tissues (Fuchs syndrome associated with rubella virus, late complications of enterovirus uveitis). Clinical picture, severity, outcomes of infectious uveitis depend on the pathogen, adequacy of the immune response and genetic characteristics of the patient. Infections trigger the development of non-infectious uveitis, including autoimmune. Their trigger mechanisms involve antigenic mimicry, bystander activation, epitope spreading, presence of superantigens, intestinal microbiota. An uncontrolled, excessive host immune response contributes to cell destruction even after removal of the infection.

[Refraction in pseudophakic eyes after surgical treatment of congenital cataracts]. / Refraktsiia pri artifakii posle khirurgicheskogo lecheniia vrozhdennykh katarakt.

The optimal method of correcting aphakia in infants with congenital cataract (CC) is intraocular correction. Considering the growth of the eyes, most authors implant an IOL with lower dioptric power to try to anticipate the refractive indices after the growth, which in some cases do not match the prediction. PURPOSE: To evaluate the achieved refraction and its relation to the anterior-posterior axis of pseudophakic eyes after extraction of CC in children of up to one year of age. MATERIAL AND METHODS: The study included 115 children (159 eyes) examined 1 to 11 years after the extraction of bilateral or unilateral CC at the age of 2-11 months. Optical power of the implanted IOL had been calculated using SRKII formula for hypercorrection to result in emmetropic or weak myopic refraction by the time the eye growth finishes. The subjects underwent autorefractometry on Retinomax K-Plus 3 device and ultrasonic biometry on Humphrey 835 A/B-scan system. RESULTS: The incidence of unplanned refraction in children aged 1 to 3 years was 61.2%, aged 3 years to 5 years 11 months - 24.4%, and in children of 6-11 years - 50.0%; it was associated with pronounced unplanned eye growth in 48.6% of cases with bilateral CC and in 27.3% of cases with unilateral CC. CONCLUSION: The main cause of unplanned refraction in pseudophakic eyes in children with CC is unpredictable increase of the length of anterior-posterior axis after surgery.

The Role of Catecholamines in the Development of Pathological Retina Neovascularization in an Experimental Model of Retinopathy of Prematurity in Rats.

This work is dedicated to proving our hypothesis that catecholamines and their metabolites play a crucial role in the development of retinopathy of prematurity, which leads to progressive uncontrollable vascularization in the retina, leading to blindness. The study was performed in an animal model of retinopathy of prematurity, which was achieved by hyperoxygenation in rats on postnatal days 7, 14, 21, and 30. The content of catecholamines and their metabolites in the retina of rats was determined by high performance liquid chromatography with electrochemical detection. It was shown that, in the rats with retinopathy, the content of L-DOPA on days 21 and 30 was decreased as compared to the control, whereas the content of noradrenaline on day 14 life increased compared to the control. However, we did not observe changes in the content of dopamine in the experimental animals relative to the control in any period studied. Given the published data on the involvement of catecholamines in the regulation of vasculogenesis in the retina in normal state, our data on the changes in the catecholamine metabolism in the retina in the model of retinopathy of prematurity can be regarded as evidence of the important role of catecholamines in the pathogenesis of this severe disease.

Biochemical and Functional Changes in the Eye As a Manifestation of Systemic Degeneration of the Nervous System in Parkinsonism.

Parkinson's disease (PD) is a systemic neurodegenerative condition caused by the death of dopaminergic neurons of the nigrostriatal system of the brain. This disease is diagnosed after most neurons have already been lost, which explains the low efficiency of treatment. Hope for increasing treatment efficiency rests in the development of new strategies for early diagnosis of PD based on a search for peripheral markers that appear as early changes in non-motor functions. Since impairment of the visual function is one of the manifestations of PD, the purpose of our work was to identify biochemical and physiological changes in a mouse's eye and eyelid in models of preclinical (presymptomatic) and clinical (symptomatic) stages of PD. We found that the norepinephrine, dopamine, and serotonin levels in the mouse eye reduced not only in the model of the early clinical stage, but also in the model of preclinical stage, an indication that pathological changes in the monoaminergic systems of the brain had affected the eye even before the motor disorders emerged. Moreover, in both models of PD, mice had increased intraocular pressure, indicating the development of both metabolic and functional impairments, which can be used as diagnostic markers. Unlike in the eye, the serotonin level in the eyelid was increased in mice at both parkinsonism stages and in presymptomatic mice to a much higher extent than in symptomatic ones. Given that serotonin is involved in the regulation of lacrimal glands of the eyelid, an increase in its level in parkinsonian mice should alter the composition of tear fluid, which could serve as a diagnostic marker of early stage of PD. Thus, the changes in the metabolism of monoamines in the eye and eyelid observed in mice at the early stage of parkinsonism are accompanied by changes in the function of these structures and, therefore, can be used as diagnostic markers of the early stage of PD.

[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.

[Melatonin as a new promising agent for the treatment and prevention of retinopathy of prematurity]. / Eksperimental'noe issledovanie vozmozhnosti primeneniya melatonina v lechenii i profilaktike retinopatii nedonoshennykh.

AIM: To evaluate the effect of exogenous melatonin on the blood-retinal barrier and oxidative status of the vitreous in rats with oxygen-induced retinopathy (OIR) and analyze its prospects in the treatment and prevention of retinopathy of prematurity (ROP). MATERIAL AND METHODS: The study was performed on 48 Wistar rat pups (96 eyes) divided into 4 groups 12 animals each: OIR group, melatonin group and two control groups. In order to induce retinopathy, rat pups and does were placed in an incubator for 14 days after birth. Oxygen concentration in the incubator changed from 60 to 15% every 12 hours. The controls for this experiment were rats that grew under normoxic conditions (21%). The two other groups of rats were injected with 30 ml intraperitoneal melatonin (Sigma-Aldrich) in sterile 0.05 M phosphate buffer (pH 7.4) at a dose of 10 mg/kg for 14 days starting on day 1. The pups were killed on days 7 (n=16), 14 (n=16), and 18 (n=16). Binocular enucleation was performed in all cases. The total protein level and antioxidative activity (AOA) were then measured in vitreous samples. RESULTS: Oxygen-induced retinopathy had two phases and was accompanied by a sharp increase in the vitreal AOA and total protein. After intraperitoneal melatonin injections made during the period of early OIR-associated vascular changes, the said parameters were decreased down to near-control values at any times during the follow-up period. CONCLUSION: Exogenous melatonin, due to its strong antiangiogenic and antioxidant activity, helps stabilize the blood-retinal barrier in OIR.

[Modern perspective on the problem of retinopathy of prematurity].

The article contains an analysis of the current state of the problem of retinopathy of prematurity (RP). Advances of international and Russian ophthalmology in understanding the pathogenesis, clinical presentation of both active and regressive RP, results of multicentre studies on RP treatment and prognosis were taken into consideration. There is a tendency towards a considerable change in the range of survived premature newborns and a growing need for development of new treatment approaches on the basis of pathogenetic studies. A wide range of RP outcomes, late complications, and concomitant pathology, which determine functional prognosis and quality of life in patients who have had RP, is discussed.

[Clinical course and results of treatment of zone I retinopathy of prematurity].

23 infants (46 eyes) with zone I retinopathy of prematurity (ROP) were examined. Zone I ROP is characterized with distinctive clinical presentation, course, prognosis and treatment results. Coagulation of retina in active I zone ROP showed efficacy in 70%: in posterior ROP - 56,3%, in anterior ROP - 79%. Surgery was performed in 12 eyes with stage 4a-5 ROP. Lens-sparing vitrectomy at gestational age of 44-45 weeks resulted in partial or total reattachment of retina that was achieved in 5 eyes with 4a-4b stage ROP. In the other cases the surgery played an eye preserving role. Late functional results are indicative of multifactorial pathogenesis of visual function impairment in infants with I zone ROP.

[Depth of retinal vessels and electroretinogram changes in stage 3 and 4 cicatricial retinopathy of prematurity].

The article presents the results of a study on retinal vessels in stage 3 and 4 cicatricial retinopathy of prematurity (ROP) by means of spectral-domain optical coherence tomography (SD OCT). The study comprised 29 children (40 eyes) aged from 6 month to 12 years with stage 3 and 4 cicatricial ROP, of which 17 children (21 eyes) under 6 and 12 children (19 eyes) over 6 years of age. SD OCT was used to approach the depth of retinal vessels and the caliber of the first-order vessels. Only in 8 eyes (20%) proper retinal vessels were located in the ganglion cell layer. In 12 eyes (30%) the vessels occurred in the nerve fiber layer and in other 20 eyes (50%) they appeared to have extraretinal growth. Thus, physiological depth of retinal vessels (i.e. in the ganglion cell layer) was seen in only 20% of cases. A relationship between the degree of retinal vascular system displacement and the presence of extraretinal tissue was established (p < 0.01). No correlation was found between gestational age and birth weight and the location of retinal vessels (p > 0.05). Location of retinal vessels can serve as a severity criterion, an important test to reveal preclinical negative changes, and a risk factor for late complications (tractional retinoschisis, detachment and tears). A tendency to smaller diameter of retinal vessels and higher artheriovenous index in children with ROP in comparison with healthy full-term children of the same age might indicate a decrease of retinal blood filling which might later cause development of retinal dystrophies.