Cystatin C and cystatin SN as possible soluble tumor markers in malignant uveal melanoma

Background The aim of the study was to determine the concentration of endogenous cystatin C and cystatin SN, as potential tumor biomarkers, in the serum and biological fluids of the eye in both healthy controls and patients with uveal melanoma. Patients and methods The concentration of both cystatins was determined in the intraocular fluid (IOF), tear fluid, and serum of patients with uveal melanoma and compared to baseline measurements in IOF, tears, serum, cerebral spinal fluid, saliva and urine of healthy controls. Results The concentration of cystatin C in all the biological matrices obtained from healthy controls significantly exceeded the concentration of cystatin SN and was independent of gender. Cystatin C concentrations in the tear fluid of patients with uveal melanoma (both the eye with the malignancy, as well as the contralateral, non-affected eye), were significantly greater than cystatin C concentrations in the tear fluid of healthy controls and was independent of tumor size. The concentration of cystatin SN in IOF of patients with uveal melanoma was significantly less than the corresponding concentration of cystatin SN in healthy controls. Conclusions The ratio of cystatins (CysC:CysSN) in both the serum and tear fluid, as well as the concentration of cystatin SN in IOF, would appear to strongly suggest the presence of uveal melanoma. It is further suggested that multiple diagnostic criteria be utilized if a patient is suspected of having uveal melanoma, such as determination of the cystatin C and cystatin SN concentrations in serum, tears, and IOF, ocular fundus and ultrasound imaging, and biopsy with histopathological evaluation.

The Diagnostic Value of Genetic Mutation Analysis and Mutation Profiling of cfDNA in Intraocular Fluid for VRL

Vitreoretinal lymphoma (VRL) is a rare but aggressive masquerade syndrome, which would be easily confused with uveitis. The diagnostic gold standard remains the pathologic examination of ocular specimen with invasiveness and low sensitivity. To improve the safety and accuracy of VRL diagnosis, alternative techniques using intraocular fluid (IOF) samples are emerging. In this study, we aimed to test the diagnostic value of genetic mutation analysis of circulating cell-free DNA (cfDNA) in IOF for VRL and exhibit the mutation profile for revealing the molecular characteristics of VRL. Twenty-three suspected VRL patients were selected as the training group, who had genetic mutation analysis using a panel containing 446 tumor-related genes. Another external cohort including 5 VRL patients and 5 uveitis patients was selected for further validation. In training group, all of VRL patients had obtained 23 (IQR 13.5, 36.0) cfDNA mutations in IOF (sensitivity 100%), and 2 out of 6 uveitis patients had one and four mutations respectively (specificity 67%). The latter were identified as clonal hematopoiesis mutations. In validation group, all of VRL patients were positive and all of uveitis patients were negative for mutation analysis (sensitivity and specificity 100%). VRL patients from the two groups were characterized by the high mutation frequencies of PIM1 (21/22, 90.91%), MYD88 (17/22, 77.27%), CD79B (11/22, 50.00%), ETV6 (11/22, 50.00%) and IRF4 (11/22, 50.00%), and 77.27% were MCD subtype with PI3K-Akt signaling pathway alternation. In conclusion, it demonstrated a new mini-invasive and feasible method for VRL diagnosis using a panel of 466 tumor-related genes.

Structural and biomechanical properties and trace elements composition of the corneoscleral eye shell in normal tension glaucoma

The results of comparative studies of the structural and biomechanical features of the corneoscleral eye shell in various clinical forms of glaucoma are presented. The article discusses how the systemic and local imbalance of trace elements that regulate collagen biosynthesis, the formation of cross-links in the connective tissue structures of the sclera, and the hydrodynamics of the intraocular fluid, affect the intraocular pressure level, and thereby the character of the development of glaucomatous lesions in normal tension glaucoma. Modern literature is shown to indicate the prospects for further research in this direction.

The role of intraocular f luid polymerase chain reaction in the diagnosis, treatment and monitoring of cytomegalovirus retinitis

Purpose. To study the possibilities of a new method of CMRR treatment in the prevention of irreversible blindness. Material and methods. 74 patients with cytomegalovirus retinitis, frolicking after hematopoietic stem cell transplantation. The first group (9 people, 15 eyes) consisted of children, whose treatment was carried out under ophthalmoscopic control. The second group (65 people, 114 eyes) consisted of children in whom the control of the effectiveness of treatment was carried out using PCR of aqueous humor in real time. Results. In the first group, retinal detachment was diagnosed in three out of fifteen eyes, accounting for 20%. In the second group, the incidence of retinal detachment was 3.5% of 114 eyes. Among patients receiving treatment under ophthalmoscopic control, CMRR relapses were detected in 5 cases, which amounted to 33.3%. In children, whose treatment was controlled by intraocular fluid PCR, relapses were diagnosed in 22 cases, which amounted to 19.29%. Conclusions. Intravitreal administration of antiviral drugs under the control of polymerase chain reaction is a more effective method of treating cytomegalovirus retinitis than intravitreal administration under ophthalmoscopic control. Key words: cytomegalovirus retinitis, intraocular fluid polymerase chain reaction.

Drainage surgery for primary open-angle glaucoma: past, present, future

Relevance. Despite many techniques for reducing intraocular pressure, surgical treatment of glaucoma has limited effectiveness. First, due to excessive scarring of new intraocular fluid outflow pathways and second, antifibrotics medicaments are unable to effectively control wound healing. The use of drainages reduces the risk of excessive scarring in the area of the filtration pad and forms several ways of outflow of intraocular fluid. The review presents the following sections: development history, advantages, disadvantages, surgical technique and promising directions of glaucoma drainage surgery. Purpose. Summarizing data on the possibility of drainage surgery, historical aspects, causes of scarring and methods of dealing with them. Provide data on various modern drainage devices that are used not only in Russia and their effectiveness. Material and methods. To perform the review, we searched for literature sources on the abstract databases E-library, PubMed and Scopus for the period up to and including 2018, using the keywords «glaucoma drainage surgery» (in the E-library database), «anti-glaucoma drainage» and «anti-glaucoma drainage device» (in the PubMed and Scopus databases). Abstracts of conferences were excluded from the review. A total of 40 articles related to the review topic were identified. The beginning of publications on this issue in domestic sources dates back to 1970, and in foreign sources to 1987. Results. The review presents the history of development, advantages, disadvantages of surgical techniques and promising areas of glaucoma drainage surgery. Various models of drainage devices, as well as their specific and non-specific complications are described. The effectivenes of various valves were 70%, with an average decrease in the level of IOP by at least 50% from the preoperative values. At the same time, the risk of an increase in the level of IOP above the target values is about 10% per year, which leads to the fact that after 5 years only in 50% of cases drainage devices function effectively. Therefore, studies of biomaterials, forms and techniques of drainage implantation surgery, new controlled-release antifibrotic drugs can positively affect the long-term effectiveness of glaucoma surgery. Conclusion. The data presented in the literature review allow us to identify the most effective models of drainage devices, their effectiveness, implantation techniques and possible complications. Key words: glaucoma, refractory glaucoma, glaucoma drainage surgery, drainages.

The role of intraocular hydrodynamics in inducing posterior hyaloid membrane detachment (preliminary report)

At present, it is believed that the detachment of the vitreous body occurs due to the contraction and liquefaction of the vitreous body, while the exit of the liquid part of the vitreum into the retrovitreal space passes passively through the formed prepapillary opening, after which the vitreous body collapses, however, more precise mechanisms have not been described. Purpose. Substantiate a hypothesis of influence of intravitreal hydrodynamics in inducing detachment of the posterior hyaloid membrane based on the analysis of OCT data. Material and methods. An OCT study was performed in 30 patients with initial detachment of the posterior hyaloid membrane (PHM) with macular adhesion, macular traction, and macular hole. The features of the location of the PHM in the region of the macula, foveola and the place of attachment of the PHM to the optic nerve were studied. Results and discussion. As a result of the analysis of OCT images, it was found that with macular holes, macular adhesion and macular traction, a closed space is formed between the posterior hyaloid membrane and the retina (subbursal space) in the form of a dome, which indirectly indicates an increase in pressure within this space. In 28 patients, the zone of dissection or thinning of the PHM was found parapapillary, through which the intraocular fluid is likely to be injected into the subbursal space. Conclusions: This study suggests the leading role of intravitreal hydrodynamics and the formation of an area of increased pressure in the subbursal space in the induction of the detachment of the PHM, the pathogenesis of vitreomacular adhesion, vitreomacular traction and macular hole. The topic requires more detailed study. Key words: posterior hyaloid membrane, OCT, vitreous body, macular hole.

Differential diagnosis of active and inactive forms of cytomegalovirus retinitis

Purpose. Present the results of a study on the differential diagnosis of active and inactive forms of cytomegalovirus retinitis. Material and methods. 29 patients with cytomegalovirus retinitis, who underwent weekly fundus fluorescence angiography and intraocular fluid polymerase chain reaction during treatment. Results. Residual contrast fluorescence in the zone of cytomegalovirus retinitis foci was assessed on a scale from 0 to 4. The correlation between the intensity of contrast fluorescence in the fundus and the number of virus copies in the moisture of the anterior chamber was determined. The median of Spearman's criteria for the studied group of patients was 0.49. Conclusion. A positive relationship was revealed between the residual luminescence of CMR foci on PAH in the delayed phase of the study and the PCR values of the intraocular fluid, which makes it possible to rely on angiography data for the differential diagnosis of active and inactive CMRR. Key words: cytomegalovirus retinitis, fluorescein angiography.