[The role of lipid metabolism and antioxidant system changes in the development of retinal vein occlusion].

PURPOSE: To compare changes in lipid metabolism and antioxidant status in patients with retinal vein occlusion (RVO) with that in patients with a history of ischemic stroke and in patients with no clinical manifestations of atherosclerosis. MATERIAL AND METHODS: A total of 111 patients were enrolled in the study. Group 1 included 80 patients with RVO and grade 2-3 stage II-III essential hypertension, group 2-11 patients with grade 3 stage III essential hypertension, high cardiovascular risk and a history of ischemic stroke. The control group included 20 patients with no clinical manifestations of atherosclerosis. All patients underwent a standard ophthalmic examination, fluorescent retinal angiography, lipid metabolism and redox system assessment. RESULTS: The levels of low-density lipoproteins (LDL) and cholinesterase were higher in study groups than in controls regardless the type of RVO. A statistically proven increase in oxidized LDL (oxLDL) was found in patients with complicated hypertension and ischemic RVO. A direct correlation was determined between the level of anti-oxLDL IgG and lipid peroxidation activity (LP) (R = 0.376; p = 0.136) as well as the levels of glutathione peroxidase (GPx) (R = 0.529; p = 0.029) and GPx per gram of hemoglobin (R = 0.543; p = 0.024) in patients with branch RVO. Redox system assessment showed a decrease of thiols and an increase of LP metabolites. CONCLUSION: The results demonstrated that retinal vein occlusions develop under disorders of lipid metabolism similar to those in patients with a history of ischemic stroke. The correlation between the level of anti-oxLDL IgG and LP points to the redox system involvement in the intricate pathogenesis of RVO.

[Intraocular pressure and ocular blood flow features intravitreal infection of anti-vascular endothelial growth factor agents].

OBJECTIVE: to investigate intraocular pressure (IOP) and ocular blood flow (OBF) changes as well as the individual normal range of IOP in patients with age-related macular degeneration (AMD) with or without concomitant glaucoma after intravitreal anti-vascular endothelial growth factor (VEGF) therapy. MATERIAL AND METHODS: Group 1 included 34 patients (34 eyes) with AMD and no glaucoma, group 2-34 patients (34 eyes) with both AMD and glaucoma. In all patients the IOP and OBF were measured (with Ocular Blood Flow Analyzer) and the individual normal range of lOP calculated before the treatment, on the third day after the injection and at the 1-month follow-up visit. Statistical analysis was performed by STATISTICA 10. RESULTS: In group 1 there were no significant changes in ocular blood flow at different times after ranibizumab injection. In group 2 a considerable decrease in OBF was detected 1 month after the injection (p<0.001). In group 1 the intraocular pressure was at the same level before and after the treatment. In group 2 the IOP significantly decreased on the third day after the anti-VEGF injection (p=0.03) but was back to the initial level in 1 month. The individual normal range of lOP, when calculated on the third day after the injection, appeared to be much lower than before due to a moderate decrease in both IOP and OBF. At the 1-month follow-up the individual normal range of IOP was back to initial values in non-glaucoma patients but remained low in the glaucoma group due to reduced OBF. CONCLUSION: The established decrease in the individual normal range of IOP in the late period after an anti-VEGF injection should be taken into account when managing patients with both AMD and glaucoma.

[Age-related macular degeneration].

The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.

[Contemporary pharmacogenetic approaches to the treatment of age-related macular degeneration].

A study on the role of CFH, HTRA and IL-8 gene polymorphism in age-related macular degeneration (AMD) development has been conducted. At the first stage of the study genetic testing was done in 69 patients with exudative AMD and 370 random Moscow citizens without the disease. The goal of the second stage was to determine the influence of gene polymorphism on patient's response to endovitreal ranibizumab treatment. For that, visual acuity and foveal thickness were assessed before and after ranibizumab injections in 120 patients with wet AMD. All patients were genotyped for the genes of interest. The results showed that the presence of homozygous 402H polymorphism in CFH gene, as well as homozygous (-625)A mutation in HTRA1 gene, determines certain clinical presentations. Moreover, visual acuity below 0.1 and presence of 402H, (-625)A and (-251)A alleles in both copies of all three genes (CFH, HTRA and IL-8) are negative predictors of disease severity and antiangiogenic treatment response.

[Morphological manifestations of systemic atherosclerosis found in fundus (experimental study)].

Results of angiography and morphology of 32 eyes (16 chinchilla rabbits) with experimental atherosclerosis are presented. N.N. Anichkov and S.S. Khalatova experimental hypercholesterolemia model (1912) was used. The animals were divided into the following groups: initial and advanced atherosclerosis, control group, follow-up 3 and 6 months. After 3 months progressive reduction of perfused retinal vessels and early degenerative changes of neurons and photoreceptors were found. In 6 months these changes became more significant and generalized. Due to ongoing small vessel reduction blood flow went to the major vessels and changed its distribution followed by ischemia of adjacent retina. No changes in choriocapillary layer and retinal pigment epithelium were found in any of groups studied.

[Ocular changes in systemic atherosclerosis].

Up-to-date aspects of ocular changes in systemic atherosclerosis are reviewed. At the present time despite of wide use of current methods of ocular blood circulation and retina examination there are no papers that allow to estimate dynamics of impairment of visual functions from different viewpoints (clinical, functional, blood flow, morphological etc.) in initial isolated ocular atherosclerosis. Etiology, pathogenesis and ideas about potential effect of systemic atherosclerosis on the eye are discussed. Features of blood flow in optic nerve head compared to retinal vessels are described. According to the last data correlation between the degree of reduction of a-wave of scotopic electroretinogram and deterioration of haemodynamic parameters exists.

[Experimental and morphological study of the effect of antiangiogenic therapy on corneal neovessels].

The article presents the results of an experimental and morphological study of combined antiangiogenic effect of photodynamic therapy with Photosens photosensitizer and Avastin (bevacizumab) on neovascularization process in corneal stroma. The combined approach has demonstrated an advantage over separate application of these methods, what, however, has to be proved clinically.

[Age-related macular degeneration and glaucoma: intraocular pressure monitoring after intravitreal injections].

In recent decades the problem of low vision and blindness in elderly people became major and socially significant issue. The number of patients having age-related macular degeneration (AMD) in association with glaucoma grows all over the world that attaches medical and social value to this problem. 102 patients with AMD were under follow-up, 7 of them had primary open-angle glaucoma (POAG). Three consecutive injections of ranibizumab resulted in visual acuity increase from 0.21 +/- 0.17 till 0.37 +/- 0.12. The mean retinal thickness in foveal zone decreased from 289.36 +/- 88.73 till 230.47 +/- 88.02 microm. Ocular hypertension within 12 hours after procedure was observed in 13 (12.7%) of 102 patients. In all cases intraocular pressure (IOP) returned to preoperative values in 3 days after hypotensive medical treatment. In one case trabeculectomy was performed simultaneously with ranibizumab intravitreal injection, the next two injections were performed in a month intervals. So the problem of IOP increase after intravitreal injections remains unsolved. Glaucoma is not an absolute contraindication to intravitreal injections in treatment of exudative AMD although patients with associated conditions need individual approach in terms of both IOP compensation and number of ranibizumab injections.

[The value of autofluorescence imaging in diagnosis of retinal diseases].

Results of fundus autofluorescence imaging using confocal scanning laser ophthalmoscope HRA II ("Heidelberg Engeneering", Heidelberg, Germany) are presented. 106 patients with various retinal and optic nerve conditions were examined. The following conditions were diagnosed using autofluorescence imaging: early stage of age-related macular degeneration, macular hard and soft drusen, signs of retinitis pigmentosa, senile macular hole, central serous chorioretinopathy and optic disc drusen.

[Influence of genetic mutations on clinical presentation of subretinal neovascularization. Report 2: The impact of HTRA and VEGF genes polymorphism].

A detailed analysis of influence of HTRA (serine peptidase) and VEGF (vascular endothelial growth factor) genes mutations is presented. The presence of one gene copy with allele of A- polymorphism rs1120638 of HTRA1 gen, T- polymorphism rs10490924 and de11443in54 of ARMS2 gene increases the risk of CNV in patients with AMD. The feature of clinical presentation in patients with CNV associated with (-625) A mutation of promoter region of HTRA1 gene in two chromosomes was fulminant course of the disease from exudative to scarring processes with fibrous tissue formation not just with sub-, but also intra- and preretinal localization. Genetic screening showed that combination of studied mutations (402H, (-625) A and (-251) A in both gene copies of CFH, HTRA and IL-8) results in the most severe and rapidly progressing form of the disease. Two new mutations were revealed in promoter region of VEGF gene: G > A replacement in position of (-72) nucleotide from transcription start and G > A replacement in 5'-nontranslated region of the 1st gene exon in position of (+31) nucleotide from transcription start.

[Influence of genetic mutations on clinical presentation of subretinal neovascularization. Report 1: The impact of CFH and IL-8 genes polymorphism].

Genetic analysis was performed in patients with subretinal neovascularization (CNV). The results showed significant association of CFH (compliment factor H) gene polymorphism with increase (rs1061170, rs514943 and rs380390) or decrease (rs529825, rs7524776, rs1831281, rs2274700, rs1576340, rs12144939, rs7540032) of CNV development risk. The incidence of IL-8 gene mutation was significantly (p = 0.008) higher in patients after chorioretinitis. Apparently -125 > A polymorphism in patients with chorioretinitis increases risk of CNV development, thus promoting raise of proangiogenic factors concentration in eyes with inflammatory background. The clinical presentation in patients with AMD and myopic disease associated with (-125) A mutation of promoter region of IL-8 gene was similar to that of patients with chorioretinitis. The features are the following: focal pattern, no drusen and RPE detachment, predominantly classic form of CNV (without occult pattern), formation of well-organized newly developed vessels.

[Optic disc drusen. Communication 1. The possibilities of diagnosis].

The study enrolled 63 patients (108 eyes) suspected for optic disc drusen (ODD). ODD were found in 45 patients (83 eyes). Ophthalmoscopic study determined only visible superficial drusen, which accounted for 36.4% of all the found cases. The autofluorescence technique could reveal mainly superficial or shallow drusen in 70.1% of cases and differentiate pseudodrusen. The most reliable and sensitive diagnostic method was B-scanning that determined ODD in 100% of cases. However, B-scanning could not differentiate true drusen from pseudodrusen.

[Central serous chorioretinopathy: etiology and pathogenesis].

The review of the literature is devoted to the topical problem of retinology, namely the etiology and pathogenesis of central serous chorioretinopathy (CSC). It presents historical facts of studying this problem, basic theories of the development of the disease, and principles of its classification. The bulk of the review touches upon the impact of stress on the development of choriocapillary-Bruch's membrane-retinal pigment epithelium system dysfunction. A human stress reaction is accompanied by the poorest hypokinetic type of circulation. This gives rive to a significant hypertensive reaction (the highest systemic pressure), by showing a considerable increase in the total peripheral vascular resistance; there is also a high baseline cortisol level with a tendency towards depleted reserves of the pituitary-adrenal system and imbalance in the pituitary-thyroid system. A chief role has been recently assigned to these changes in the recurrence and development of complications in CSC.

[Multifocal electroretinography in ophtalmological symptoms in patients with antiphospholipid syndrome].

The paper describes the first experience in using multifocal electroretinography (mfERG) in patients with antiphospholipid syndrome (APS). In the latter, thrombogenesis is mosaic in most cases so the techniques providing a spatial imaging of the pathological process is of interest in the examination of patients with this disease. These techniques include mfERG. The quadrant mfERG analysis that reveals pathological changes in relation to the vascular involvement area is of the greatest informative value in patients with APS-associated retinal vascular occlusions.

[Eye fundus autofluorescence technique in the early diagnosis of age-related macular degeneration].

Autofluorescence (AF) of the eye fundus is one of the most promising studies. AF provides specific molecular information on the retinal pigment epithelium and enables one to diagnose early phenotypic changes that are predictors for progression of age-related macular degeneration. Many investigations have demonstrated that AF is a valuable clinical technique that should be improved in order to have information accessible to a patient on the diagnosis and prediction of age-related macular degeneration.

[Feasibilities of photodynamic therapy in the treatment of corneal mycotic lesions: an experimental study].

The paper presents the results of studying the photofungicidal activity of a photosens (octacationic phthalocyanine) in the in vitro and in vivo systems. Cultured Candida guilliermondii were employed in in vitro investigations. The single combined action of octacationic phthalocyanine at a concentration of up to 1 microM and laser irradiation at a wavelength of 675 nm were established to allow the high activation (up to 100%) of yeast fungi to be achieved in the in vitro system. In vivo investigations were performed on 14 rabbits (28 eyes) with induced keratomycosis. In the first series, fluorescent diagnosis of photosens accumulation in the pathological corneal areas was made in 9 (18 eyes). Based on the data obtained in the second series of experiments, the authors examined the feasibilities of photodynamic therapy for corneal mycotic lesions with the above photosensitizer in 5 rabbits (10 eyes).

[Photodynamic therapy in treatment of chorioid neovascularization].

The authors studied the effectiveness of photodynamic therapy (PDT) with Photosence, a Russian photosensitizer, in treatment of chorioid neovascularization (CNV) in cases of age-related macular degeneration (ARMD) and pathological myopia (PM). The subjects were 73 patients with CNV suffering from ARMD and PM. The efficiency of PDT and complex conservative therapy was compared using vision acuity measurement, retinal morphometry, and fluorescent eye ground angiography (FEGA), performed before treatment, immediately after treatment, and 1, 3, 6, and 12 months later. The study showed that PDT in patients with CNV, ARMD and PM was more efficient than pharmacotherapy. Vision acuity improved or stabilized, and the parameters of retinal morphometry and FEGA improved as well. The results of the study evidence high efficiency of PDT with Photosence in treatment of CNV with ARMD and PM.

[Role of pentoxifylline retard dosage forms in the correction of hemodynamic disorders in retinal venous occlusion and diabetic retinopathy].

The investigation was undertaken to study the effect of the pentoxifylline retard dosage form Vasonit on ocular hemodynamics in patients with retinal vein occlusions and non-proliferative diabetic retinopathy (DR). Forty-two patients aged 45 to 75 years, including 20 patients (20 eyes) with retinal vein occlusion in the presence of hypertensive disease and atherosclerosis (Group 1) and 22 patients (44 years) with non-proliferative DR (Group 2), were examined. All the patients received the pentoxifylline retard dosage form Vasonit, 600 mg twice a day, for 2 months. After a course of pentoxifylline therapy, the patients were observed to have improved visual functions, positive clinical changes in the fundus of the eye as a reduction in the frequency and extent of retinal hemorrhages, in the degree of manifestations of macular edema, in the number of retinal microaneurysms and ischemic areas. The results of color Doppler mapping of ocular and orbital vessels are indicative of improved hemodynamics as an increase in the values of blood flow velocity and normalization of blood flow resistance and pulsation indices in the arteries supplying blood to the retina and optic nerve.

[Diagnostic value of lifetime retinal morphometry in patients with subretinal neovascularization].

The paper presents the comparative data of retinal tomography in the presence of choroidal neovascularization. In all patients, life-time morphometry of a 6x6-mm central retinal area (at 20 degrees from the point of fixation) was made on a retinal thickness analyzer (Talia, Israel). During the study, the authors analyzed the most significant indices: mean retinal posterior pole thickness; mean retinal paracentral region thickness; mean retinal central region thickness; mean neuroepithelial thickness above the subretinal neovascular membrane (SNM). Statistical analysis showed that the increase in neuroepithelial thickness was directly related to that in the intensity of SNM fluorescence. The mean neuroepithelial thickness above SNM, intra- and subretinal hemorrhages, intraretinal microcysts in patients with age-related macular degeneration and the presence and extent of thinning and fibrotic area permitted evaluation of the magnitude of activity and presumptively the duration of choroidal neovascularization.