[Three-year follow-up study of clinical effectiveness of antiangiogenic therapy for neovascular age-related macular degeneration]. / Klinicheskaya effektivnost' antiangiogennoi terapii neovaskulyarnoi vozrastnoi makulyarnoi degeneratsii po rezul'tatam trekhletnego nablyudeniya.

PURPOSE: The study analyzes long-term (three years) clinical effectiveness of anti-VEGF treatment of neovascular age-related macular degeneration (nAMD) and attempts to identify the most clinically significant associations between the functional and structural parameters. MATERIAL AND METHODS: The study included 122 patients (122 eyes) diagnosed with nAMD, mean age -73.4±6.6 years old. Prospective follow-up lasted 144 weeks. All patients were treated with angiogenesis inhibitor (aflibercept 2 mg), and most of them (72.9%) - according to the Treat-and-Extend protocol. RESULTS: The average number of injections was 7.39±1.28, 4.63±0.97 and 4.06±0.81 during the first, second and third years of the follow-up, respectively. The mean baseline best-corrected visual acuity (BCVA) was 0.24±0.21. After three loading doses, BCVA increased to 0.33±0.26 (+0.09; 37.5%), by the end of follow-up BCVA was 0.35±0.27 (+0.11; 45.8%). Central retinal thickness (CRT) decreased from 314.89±88.07 µm to 234.4±42.8 µm (a 25.5% decrease) by the end of the follow-up. After three loading injections baseline functional and anatomical parameters had the most significant correlations (r≥0.7, p<0.05) with intraretinal fluid, ellipsoid zone integrity and the area of macular atrophy. CONCLUSIONS: Analysis of the morphological and functional outcomes by the end of the first year demonstrates the feasibility of preserving the results while reducing the number of visits and injections according to the Treat-and-Extend protocol. Achieving maximum improvement of functional parameters most significantly correlated with changes in such biomarkers as central retinal thickness, area of macular atrophy and integrity of the ellipsoid zone.

[Diagnosis and clinical features of non-exudative macular neovascularization]. / Diagnostika i klinicheskie osobennosti neekssudativnoi makulyarnoi neovaskulyarizatsii.

Macular neovascularization (MNV) is the process of new abnormal blood vessels formation in the choroid and/or retina. The widespread adoption of optical coherence tomography angiography (OCTA) has significantly expanded the possibilities of not only detecting pathological blood flow before the development of exudation and deterioration of visual acuity, but also determining its characteristics. The purpose of this review is to substantiate the criteria for choosing terminology and diagnostic markers of MNV. The term "non-exudative MNV" refers to type 1 neovascularization without intraretinal or subretinal exudation detected on repeated OCT scans in the course of at least 6 months. This type of MNV may include previously untreated, non-exudative membranes with a low tendency to exudate, as well as previously treated membranes that have become inactive or dormant and no longer require anti-angiogenic therapy. The criterion for dividing the non-exudative form of MNV into inactive (with a low growth rate and vascular density (VD) at baseline) and subclinical (with a high growth rate and VD) is the time of its activation, generally recognized as 6 months. The diagnostic criteria is the visualized "double layer" sign on OCT scans (retinal pigment epithelium and Bruch's membrane), as well as patterns of neovascular membranes of varying sizes, morphology and localization on OCTA scans. The cumulative risk of conversion from subclinical to exudative at two years of follow-up is 13.6 times higher than in eyes without detectable neovascularization, which highlights the importance of frequent monitoring in this healthy eye population for early detection of MNV signs.

[Prognosis criteria of optical coherence tomography angiography for the long-term efficacy of anti-VEGF therapy of neovascular age-related macular degeneration]. / Prognosticheskie kriterii opticheskoi kogerentnoi tomografii-angiografii v otsenke dolgosrochnoi effektivnosti anti-VEGF-terapii neovaskulyarnoi vozrastnoi makulyarnoi degeneratsii setchatki.

PURPOSE: The study aimed to determine the most significant optical coherence tomography angiography (OCTA) parameters in terms of predicting anti-VEGF therapy effectiveness during long-term (3-year) follow-up of patients with neovascular age-related macular degeneration (nAMD). MATERIAL AND METHODS: The study included 122 patients (122 eyes) with mean age of 73.4±6.6 years who were diagnosed with nAMD. Subgroup analysis included 50 patients (50 eyes) with detailed OCT angiography examination of macular neovascularization (MNV) characteristics and their changes in the course of the follow-up, which lasted 144 weeks. All patients were treated by angiogenesis inhibitor (aflibercept 2 mg), most of them - according to Treat-and-Extend protocol. RESULTS: Treatment response (either 'good' or 'partial') was achieved in all patients, and the proportion of the response types was similar in both types 1 and 2 MNV. Key OCTA parameters associated with the number of injections, as well as morphological and functional response (best-corrected visual acuity, retinal neuroepithelium and pigment epithelium detachment), were vascular network area and MNV area assessed at baseline and three months after treatment initiation. Both of these parameters were closely related in both MNV types during the follow-up. Key parameter with maximum number of clinically significant correlations ('very high' strength, p<0.05) in eyes with 'good' response was MNV area, in eyes with 'partial' response - vascular density and greatest vascular caliber. CONCLUSIONS: Vascular network area and MNV area assessed at baseline and after three loading doses were determined as the most significant OCTA characteristics for predicting the number of injections and treatment response based on functional and morphological parameters. MNV area was found to be the most clinically significant marker in 'good' response, vascular density and greatest vascular caliber - in 'partial' response.

[Features of structural and microvascular changes of the choroid in angioretinopathy of various etiologies]. / Osobennosti strukturnykh i mikrovaskulyarnykh izmenenii khorioidei pri angioretinopatii razlichnoi etiologii.

PURPOSE: To study structural and microvascular changes in the choroid in patients with chronic kidney disease (CKD), diabetic retinopathy (DR) and arterial hypertension (AH), and their relationship with the level of renal function, carbohydrate metabolism and blood pressure. MATERIAL AND METHODS: The study involved 172 patients (325 eyes): 56 patients with CKD (109 eyes); 66 patients with DR (121 eyes); 50 patients with AH (95 eyes). All patients underwent comprehensive ophthalmological examination including visometry, biomicroscopy, ophthalmoscopy, optical coherence tomography (OCT) and OCT angiography. RESULTS: In patients with DR and CKD, a decrease in the thickness of the ganglion cell complex and the inner plexiform layer (GCL+IPL) was noted: in proliferative DR (PDR) - 62.45±4.25 µm, in stage 4-5 CKD - 75.23±6.43 µm; a decrease in choroidal thickness (CT) of minimal values in stage 4-5 CKD (179.9±37.72 µm) and PDR (211.0±40.7 µm). The decrease in choroidal vascularity index (CVI) depended on the stage of CKD and PDR (in PDR - 63.47±1.37, in stage 4-5 CKD - 65.93±2.01). Maximum decrease in perfusion density and vascular density was found in patients with DR (37.22±9.00% and 15.11±3.39 mm, respectively). An increase in the area, perimeter of the foveolar avascular zone (FAZ), and a decrease in the circularity index were noted in all groups, with most pronounced changes in PDR and stage 4-5 CKD. Patients with CKD were found to have strong correlations of CT and CVI with creatinine, urea, proteinuria and glomerular filtration rate (GFR). Patients with diabetes mellitus and PDR were revealed to have strong relations of CT, CVI, GCL+IPL, the area and perimeter of FAZ with creatinine levels and the duration of diabetes mellitus. CONCLUSION: Choroidal thickness and choroidal vascularity index are important diagnostic markers of disorders of chorioretinal microcirculation that allow stratifying individual assessment of risk factors for progression of both chronic kidney disease and diabetic retinopathy.

[Structural and microvascular changes in the retina and choroid in patients with chronic kidney disease]. / Osobennosti strukturnykh i mikrovaskulyarnykh izmenenii setchatki i khorioidei pri khronicheskoi bolezni pochek.

PURPOSE: To study the main structural and microvascular changes in the retina and choroid in patients with diabetic retinopathy (DR) and chronic kidney disease (CKD), and their relationship with impaired renal function. MATERIAL AND METHODS: The study included 158 patients (304 eyes). The 1st group consisted of 50 patients with CKD (97 eyes); group 2 - 65 patients with DR (119 eyes), group 3 - 43 patients with CKD and DR (86 eyes). All study patients underwent complete ophthalmological examination, including optical coherence tomography (OCT) and OCT angiography (OCTA) of the macular region. RESULTS: The analysis of structural parameters in groups of patients showed a decrease in the thickness of the ganglion cell layer and the inner plexiform layer of the retina in patients with DR (70.85±14.49 µm), with the lowest value in the CKD+DR group (65.84±15.34 µm) in comparison with the CKD group (75.64±10.32 µm). In the groups of patients with CKD, the thickness of the choroid (207.3±40.36 µm) was significantly reduced in comparison with the group of patients with DR (258.8±26.63 µm) and correlated with the stage of the disease. Patients in the CKD+DR group had the lowest perfusion and vascular density in the macular region (31.23±10.91% and 13.15±2.73 mm), an increase in the area and perimeter of the foveal avascular zone (0.55±0.26 mm2, 3.30±0.84 mm). Pronounced correlations of decrease in choroidal thickness, vascular density, and perfusion volume with low glomerular filtration rate and CKD stage, as well as urea and creatinine levels were determined. An increase in the area of the foveal avascular zone correlated with lower retinal capillary density, decreased perfusion volume, and the stage of both DR and CKD. CONCLUSION: Structural and hemodynamic disorders of the retina and choroid can be recognized as significant biomarkers for non-invasive diagnosis of microvascular complications of diabetes mellitus and impaired renal function.

[Optical coherence tomography angiography in the diagnosis of retinal microvascular changes in chronic kidney disease (clinical observations)]. / Opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike mikrovaskulyarnykh izmenenii setchatki pri khronicheskoi bolezni pochek (klinicheskie nablyudeniya).

One distinctive pathological sign of chronic kidney disease (CKD) is microcirculatory disorders, which mark it as a microvascular disease. Similarity in the blood supply of the retina and kidneys, in the anatomy of their vascularization lead to identical complications in these organs. The retinal-choroidal microvascular system is easily accessible for clinical and morphological assessment and can be examined by the reproducible and non-invasive method - optical coherence tomography (OCT) and OCT angiography (OCTA). The study of significant diagnostic tomographic retinal biomarkers in CKD and monitoring of their changes are of great clinical importance. The article presents clinical cases of changes in the retina and choroid depending of the stage of CKD. Retinal microvascular changes precede functional impairment. A significant decrease in retinal and choroidal thickness correlates with a decrease in the glomerular filtration rate (GFR) and the degree of albumin excretion in the urine. All clinical cases were observed to exhibit retinal microcirculation disorders, capillary rarefaction in both capillary plexuses accompanied by a decrease in vessel density and a decrease in the circularity index of the foveal avascular zone as a result of regression of the parafoveal capillary networks. OCTA allowed visualization of morphological changes at the microcirculatory level in the form of blunt ends of capillaries, their increased tortuosity and the presence of local areas of decreased perfusion. The severity of retinal microvascular changes varied depending on the stage of CKD and was not associated with either age or the presence of diabetes mellitus. Assessment of the retinal microvasculature can help with monitoring of microvascular lesions, early prediction of the risk of development and progression of decreased renal function, as well as allow avoiding aggressive diagnostic biopsy.

[Ophthalmic safety profile of antiangiogenic therapy]. / Profil' oftal'mologicheskoi bezopasnosti antiangiogennoi terapii.

Antiangiogenic therapy with inhibitors of vascular endothelial growth factor (anti-VEGF) has not only fundamentally changed the treatment outcomes of vasoproliferative eye diseases, but also became the most common ophthalmic surgical manipulation. At the same time, in 36-48% of bilateral lesions there is a need to perform injections in both eyes, making relevant the issues of safety and prevention of severe complications that threaten irreversible loss of visual function. The article reviews the results of randomized clinical trials and real clinical practice, analyzes the incidence and causes of its most dangerous complication - endophthalmitis, characterizes the clinical course depending on the type of drug used, and considers the possibility of reducing the risk of this complication occurring. Special attention is paid to the safety profile of a new VEGF inhibitor - brolucizumab - which has received registration for the treatment of neovascular age-related macular degeneration (nAMD). Specialists dealing with retinal pathologies acknowledge the need to monitor the state of the anterior and posterior parts of the eye in order to detect the signs of intraocular inflammation as quickly and early as possible. Drug efficacy, treatment regimen, duration of action and safety are the main characteristics that should determine the personalized approach in each clinical case.

[Development, clinical manifestations and diagnosis of retinal changes in chronic kidney disease]. / Osobennosti razvitiya, klinicheskie proyavleniya i diagnostika izmenenii setchatki pri khronicheskoi bolezni pochek.

Chronic kidney disease (CKD) is a significant public health problem with a high risk of developing age-dependent eye diseases. Renal glomeruli and the choroid have similar structures and vascular networks; the internal hematoretinal barrier and the glomerular filtration barrier have similar developmental path; the renin-angiotensin-aldosterone hormonal system is found in both the eye and the kidneys. All this determines the similarity of physiological and pathogenetic features of the development of diseases associated with these organs. The article discusses general risk factors and pathophysiological mechanisms of development of retinal and renal lesions in CKD, the influence of various factors of pathogenesis on their development and progression. The anatomical similarity of vascularization, accompanied by microvascular changes in the retina and kidneys, leads to similar complications in both organs. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) are accurate, well reproducible and non-invasive methods for diagnosing and assessing changes in the retinal microvascular bed, which make it possible to assess microvasculature changes in the kidneys. In CKD, the retina shows signs of impaired capillary perfusion, a decrease in their density, expansion of intercapillary spaces, a rarefaction of the density of the parafoveolar capillary network, which may indicate a decrease in peritubular capillary blood flow, blood circulation of the kidneys in general and their ischemia. Significant thinning of the retina and choroid, along with a decrease in macular volume, even in the initial stages of CKD, is accompanied by impaired renal function (changes in the estimated glomerular filtration rate and urinary albumin excretion), which is a sign of systemic microvascular lesion and pathological process in the kidneys. Therefore, monitoring of retinal vessels using OCT and OCT-A can become a reliable indicator of the progression of renal microvascular changes at any stage of the disease.

[Leukocyte telomere length and response to antiangiogenic therapy in patients with neovascular age-related macular degeneration.]

Age-related macular degeneration (AMD) is becoming the leading cause of vision loss in people over 60 years of age. The neovascular form of AMD (nVMD) is characterized by choroidal neovascularization (CNV), the main trigger of which is vascular endothelial growth factor (VEGF), the inhibition of which is the current standard of treatment. Significant variability of response to anti-VEGF therapy determines the relevance of the search for biological markers - prognostic criteria of treatment response. We analyzed the response of 110 nVMD patients to anti-VEGF therapy depending on the functional and anatomical parameters of the retina (according to optical coherence tomography, OCT) and leukocyte telomere length (LTL, was assessed by quantitative PCR). Positive dynamics of best corrected visual acuity (BCVA) was observed in 100% of eyes. The central retinal thickness (CRT) decreased after the 3rd injection to 265 [234-306] µm, by the end of the observation period - to 211 [190-262] µm. The retention of activity of the subretinal neovascular membrane (SNM) at the end of the observation period correlated with lower values of the initial BCVA and high values of the initial CRT. An association of LTL with response to treatment was revealed: in patients with higher LTL the active form of SNM was more often switched to inactive after three injections, while with lower LTL, the activity of SNM was more often preserved, which determined the need for more intravitreal injections.

[Different types localisation of retinal fluid as prognostic biomarkers in the choice of anti-VEGF therapy for age-related macular degeneration]. / Rol' razlichnykh tipov lokalizatsii retinal'noi «zhidkosti¼ kak prognosticheskikh biomarkerov v vybore rezhima antiangiogennoi terapii pri vozrastnoi makulyarnoi degeneratsii.

Age-related macular degeneration is an advanced chronic disease and the main cause of vision loss in geriatric patients. Optical coherence tomography (OCT) is a modern method of retinal imaging allowing to detect different types of fluid: intraretinal fluid (IRF), subretinal fluid (SRF) and fluid under pigment epithelial detachment (PED). Finding relevant imaging biomarkers is necessary for identification of basic activity criteria of the disease, choosing treatment algorithms, determining treatment duration and termination criteria, and predicting the outcomes. Presence of IRF is associated with poor functional outcomes. Its presence is an indication for early beginning of treatment aimed at full resorption of the fluid with further possible careful extension of anti-VEGF therapy intervals with a regular follow-up. Degenerative intraretinal cysts developing in the background of subretinal fibrosis in absence of choroidal neovascularization (CNV) should be a sign for discontinuation of anti-VEGF therapy due to the lack of targets. Presence of SRF is associated with favorable outcomes and good treatment prognosis and is not a barrier to the extension of treatment intervals even up to the maximum of 16 weeks as described in existing randomized controlled trials, on the condition of no other CNV activity. PED with active CNV is one of the biomarkers that reveal the need for long-term aggressive therapy. In case of its size gain, it is necessary to restart the anti-VEGF treatment to prevent visual loss in the long-term. Combination of different fluid types is a sign of lasting disease history with a poor outcome prognosis. In this case, anti-VEGF treatment should be started as soon as possible with long-term fixed regimen or Treat-and-extend (T&E) with minimal suitable interval for the patient and precise monitoring of the condition of retina until complete suppression of activity. Developing a personalized approach in each case plays an important role in preserving visual functions.