Репозиторий Университета

© 2019 Elsevier Ltd Four inhibitors of human carbonic anhydrase II (hCA II) were designed based on the previously reported subnanomolar 1,3-oxazole-based sulfonamide inhibitors of the enzyme to incorporate primary and secondary amine functionality in the carboxamide side chain. The new hydrophilic compounds were found to inhibit the target isoform in sub-nanomolar to low nanomolar range with a good degree of selectivity to several other hCA isoforms. The hydrophilic character of these compounds is advantageous for intraocular residence time but not for corneal permeability which generally requires that a drug be sufficiently lipophilic. Two of the four compounds investigated, however, were found to exert comparable efficacy as 1% eye drops in PBS to that of the clinically used 2% dorzolamide (Trusopt®) eye drops. This indicated that the absorption of the compounds may occur via alternative route across conjunctiva and sclera.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Changes in the biochemical composition of the tear film is a critical risk factor for the development of chronic perioperative dry eye syndrome, because increasing the duration of general anesthesia did not affect the dynamics of tear secretion recovery, but slowed down normalization of its structure and antioxidant activity in the post-anesthetic period.

© 2018, Media Sfera. All rights reserved. Condition of the ocular surface greatly depends on functional integrity of corneal nerve fibers. Improving the methods used to study corneal nerve fibers allows their condition to be timely evaluated and adequately interpreted. The article reviews the structure, function, chemical composition of corneal nerve fibers, specifics of their innervation, as well as application of modern methods of their evaluation in diagnostics of various pathological conditions.

© 2018 The Author(s). Background: Cornea protects the eye against natural and anthropogenic ultraviolet (UV) damage and mechanical injury. Corneal incisions produced by UV lasers in ophthalmic surgeries are often complicated by oxidative stress and inflammation, which delay wound healing and result in vision deterioration. This study trialed a novel approach to prevention and treatment of iatrogenic corneal injuries using SkQ1, a mitochondria-targeted antioxidant approved for therapy of polyethiological dry eye disease. Methods: Rabbit models of UV-induced and mechanical corneal damage were employed. The animals were premedicated or treated with conjunctival instillations of 7.5 μ M SkQ1. Corneal damage was assessed by fluorescein staining and histological analysis. Oxidative stress in cornea was monitored by measuring malondialdehyde (MDA) using thiobarbituric acid assay. Total antioxidant activity (AOA) was determined using hemoglobin/H2O2/luminol assay. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured using colorimetric assays. Results: In both models corneas exhibited fluorescein-stained lesions, histologically manifesting as basal membrane denudation, apoptosis of keratocytes, and stromal edema, which were accompanied by oxidative stress as indicated by increase in lipid peroxidation and decline in AOA. The UV-induced lesions were more severe and long healing as corneal endothelium was involved and GPx and SOD were downregulated. The treatment inhibited loss of keratocytes and other cells, facilitated re-epithelialization and stromal remodeling, and reduced inflammatory infiltrations and edema thereby accelerating corneal healing approximately 2-fold. Meanwhile the premedication almost completely prevented development of UV-induced lesions. Both therapies reduced oxidative stress, but only premedication inhibited downregulation of the innate antioxidant activity of the cornea. Conclusions: SkQ1 efficiently prevents UV-induced corneal damage and enhances corneal wound healing after UV and mechanical impacts common to ocular surgery. Its therapeutic action can be attributed to suppression of mitochondrial oxidative stress, which in the first case embraces all corneal cells including epitheliocytes, while in the second case affects residual endothelial cells and stromal keratocytes actively working in wound healing. We suggest SkQ1 premedication to be used in ocular surgery for preventing iatrogenic complications in the cornea.

Corneal transplantation is the most successful and frequently performed allotransplantation procedure. Benign outcome of penetrating and posterior keratoplasty depends on viability of the corneal tissue and presence of the proper endothelial layer, which retaining is one of the main objectives of preservation of donor material. Methods designed to reach this goal may be classified according to storage duration as short-term (storage in a moist chamber), medium-term (hypothermia), long-term (organ cultivation) and unlimited (cryopreservation). While there are reports of successful application of cryo-conserved corneas for penetrating keratoplasty, its use for this type of transplantation is limited due to complexity of the method and very high requirements for the quality of donor material. However, being a method of unlimited storage, it still attracts the attention of researchers. Taking into account the ongoing development of innovative keratoplasty technologies and the tendency for predominant use of layered grafts that in some cases do not need viable endothelium, methods of preservation of such material for anterior lamellar and intralamellar keratoplasties become relevant. In this context, cryopreservation without the use of cryoprotective agents is promising because it allows simple and fast accumulation of large amount of material with long storage time. Further research on the development of preservation methods of the corneal endothelial layer at sub-zero temperatures may allow storing the material by cryopreservation that will be suitable for penetrating and posterior keratoplasty.

Numerous studies have demonstrated the efficacy of anti-VEGF medications for exudative (wet) age-related macular degeneration (AMD). Significant IOP elevation is one of the side effects of anti-VEGF intravitreal injection. PURPOSE: To study the changes in the parameters of anterior segment of the eyeball against acute IOP elevation after repeated intravitreal injections (IVI) of anti-VEGF medication. MATERIAL AND METHODS: The study was conducted on a random sample of 45 patients (45 eyes) diagnosed with exudative (wet) form of AMD. All patients received two 0.05 ml intravitreal injections of ranibizumab with one-month interval. Measurements of IOP were performed with rebound tonometer Icare-Pro (ICare, Finland) before intravitreal injection, then one minute, 30 minutes and 3 hours after. The parameters of the ocular anterior segment, namely thickness and optical density of the cornea, volume and angle of the anterior chamber were evaluated by Scheimpflug imaging (Pentacam HR, Oculus, Germany) before IVI, and 15 minutes after. RESULTS: Statistically significant (p<0.05) elevation of IOP to 40 mm Hg (confidence interval 32-48 mm Hg) was recorded one minute after injecting 0.05 mL of ranibizumab solution into the vitreous cavity with IOP having the tendency for gradual normalization. When measured 15 minutes after IVI, the following parameters of the ocular anterior segment structures had reliably changed in the setting of elevated IOP: corneal thickness had increased to 27 µm (confidence interval 14-38 µm), corneal optical density - to 16.7 (confidence interval 10.4-19.5). No significant changes of either volume or angle of anterior chamber were revealed. Comparative analysis showed no significant changes of parameters after the 1st and the 2nd IVI. CONCLUSION: The revealed changes were transient in nature and did not require any corrections since all parameters returned to baseline after each injection.

PURPOSE: To evaluate various methods of stripping Descemet's membrane of a donor corneoscleral flap for Descemet's membrane endothelial keratoplasty (DMEK). MATERIAL AND METHODS: The study included 60 corneoscleral flaps (mean donor age was 62.9 years) from the eye bank of Research Institute of Eye Diseases, which were not suitable for clinical use due to positive serological results. Four alternative methods of donor material dissection in preparation for DMEK were compared: SCUBA (group A), our newly suggested method utilizing intracapsular ring (group B), 'liquid bubble' (group C), 'big bubble' (group D). Parameters under evaluation were mean transplant preparation time, density of endothelial cells before and after dissection, presence of complications during detachment of Descemet's membrane. RESULTS: Mean detachment time in group A was 8.5 min, in group B - 7 min, in group C - 8 min, and in group D - 5 min. Loss of endothelial cells as compared with baseline was in average 10.5% in group A, 9.3% in group B, 10.7% in group C, and 10.3% in group D. Group A had two cases with complications occurring during separation of Descemet's membrane, group B had one such case, group C - 2 cases, and group D - 3 cases. Histologic examination confirmed absence of stromal fibers on the detached Descemet's membrane in groups A, B and C. CONCLUSION: Among the described methods of preparing donor material for DMEK surgery, all except 'big bubble' proved equal in terms of resulting transplant quality. The 'big bubble' dissection technique requires more time to complete, while the resulting transplant has stromal fibers. Our newly suggested method of Descemet's membrane stripping that utilizes intracapsular ring proved safe and effective alternative for preparing donor material for DMEK.

The article describes a clinical case of Descemet's membrane detachment that occurred during cataract phacoemulsification with implantation of intraocular lens. Significant corneal edema developed in the early post-op period. Considering the ability of endothelium to close its own defects even with large injury area, the patient was followed-up for 2 years. Corneal edema was treated during 4 months and concluded with instillations of osmotic and anti-inflammatory drugs. At 1.5-2 months of therapy, the edema was gradually decreasing, and by the 4th month of the follow-up the cornea was practically transparent. Density of endothelial cells in central cornea, where the Descemet's membrane was absent, comprised 1000 cells/mm2. Further observation revealed cornea staying transparent for 2 years after the surgery. Complete optical recovery of patients with Descemet's membrane defect in this case study is supported by similar clinical cases briefly described in the article, and evidence that structural functional recovery of the corneal endothelial layer is possible even when it has large defects (more than 2.5 mm in diameter).

© 2018 Ismailova et al. Orbital decompression is a surgical procedure aimed at increasing the orbital volume and/or decreasing the volume of the orbital fat. The indications for orbital decompression are determined in the course of thorough eye examination. An important objective of examination of a patient with thyroid eye disease (TED) is determination of inflammation activity and severity. Orbital decompression is a surgical procedure that can be performed in both the active and non-active stages of the disease. However, the indications for the surgery in these cases are different. Optic neuropathy and severe corneal disease are threatening complications that may lead to permanent visual loss and generally occur in the presence of active orbital inflammation. If treatment with high-dose corticosteroids has proven ineffective, an urgent surgical procedure consisting of orbital decompression and, in case of involvement of the cornea, eyelid and corneal surgery has to be performed. Owing to significant progress in technology, improvement of methods and accumulated experience over the past decade, the indications for bone orbital decompression have extended compared to the time when this procedure was used only in patients with extremely severe TED. The most common complication of the orbital decompression is the development or deterioration of previously existing binocular diplopia and strabismus. In addition, other parameters may change as well, including the position of the globe, the eyelids, the angle of deviation of the eye, and intraocular pressure. Thus, bone orbital decompression is a major step of a comprehensive, often multistage, system of rehabilitation of patients with severe refractory TED.

© 2018, Media Sfera. All rights reserved. The article describes a newly developed and tested diffractive optical element (DOE) that converts non-uniform radiation of the laser output into a homogeneous ring. The Gerchberg-Saxton algorithm is shown to be well suited for achieving annular intensity distribution. Testing this ring transducer on threshold-plasticity cornea demonstrated the reversibility of axisymmetric changes in the cornea. Atomic-Force microscopy of the area of maximum stresses in the corneal periphery showed no significant changes in the structure of the cornea when irradiated in the selected mode. Measurement of Young’s modulus of the corneal surface areas after their irradiation also revealed no changes in the elastic properties, while examination of the corneal structure demonstrated the absence of significant structural changes in irradiated samples compared with intact ones.

© 2018 Media Sphera Publishing Group. All rights reserved. Cornea verticillata is the typical sign of ocular involvement in Fabry disease and manifests by the whorl-like, linear opacities in the inferior part of the cornea. Aim. To study the frequency of cornea verticillata in patients with Fabry disease and it’s relation to the severity of the disease and the types of mutation in the GLA gene. Materials and methods. We studied 69 adult (over 18 years) patients with a classic form of Fabry disease that was confirmed by enzymatic and molecular genetic studies. There were 39 males and 30 females. The median age was 39 years [30.0; 50.0]. The severity of Fabry disease was assessed using the Mainz Severity Score Index (MSSI) with a maximum value of 76 points. Depending on the MSSI score, patients were classified into mild (<20), moderate (20–40), and severe (>40) clinical categories. Results and discussion. At least one classic symptom of Fabry disease was present in 88.4% of patients. The majority of patients had the missense mutations of the GLA gene. Cornea verticillata was found in 65.2% of patients and occurred with a similar frequency in males (56.4%) and females (76.7%; p=0.07). Cornea verticillata was the single classic symptom of Fabry disease in only 4.9% of cases, while the rest of the patients presented with angiokeratoma, neuropathic pain and/or hypohidrosis. The frequency of classic symptoms of Fabry disease, as well as renal disease (with the exception of terminal chronic renal failure), brain and heart damage was similar in patients with and without cornea verticillata. Median MSSI scores were also similar in patienths with and without cornea verticillata (20.0 and 18.5 points, respectively; p=0.92). Similar results were obtained in males (26.5 and 30.0 points, p=0.97) and females (16.0 and 16.0 points, p=0.45). The frequency of cornea verticillata did not differ in patients with different types of mutations in the GLA gene. Conclusion. Cornea verticillata occured in 65% of adult patients with Fabry disease, was usually accompanied by the other classic symptoms of the disease, and was not associated with the severity of the disease.

© 2017 Astro Ltd. A two-photon laser femtosecond crosslinking process at the wavelength of 525 nm was studied in a human donor cornea in the presence of riboflavin using two-photon optical microscopy and nanoindentation. It was shown that such an approach results in efficient crosslinking of the corneal collagen and a significant (three-fold) increase in the Young's modulus of the corneal structure. Application of a femtosecond laser with the wavelength of 525 nm allows a drastic enhancement of efficiency in the presence of riboflavin on human corneas and a 50-fold reduction of the laser treatment duration in comparison with the use of a femtosecond laser with the wavelength of 760 nm. We relate this effect to a significant growth in the coefficient of two-photon absorption due to the laser wavelength falling within the edge of the photoinitiator (riboflavin) absorption band. Our studies on a donor human cornea demonstrate the good potential for the clinical application of a femtosecond laser with the wavelength of 525 nm for increasing the cornea rigidity using the two-photon laser femtosecond crosslinking technique.