[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.

[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.

[New findings on pathogenetic mechanisms in the development of age-related macular degeneration]. / Novye dannye o patogeneticheskikh mekhanizmakh razvitiya vozrastnoi makulyarnoi degeneratsii.

Age-related macular degeneration (AMD) is a complex multifactorial disease that occurs due to disfunction and degeneration of retinal pigment epithelium (RPE) and choriocapillaris, as well as death of photoreceptors. The exact pathogenetic mechanism remains uncertain. The aging process is the main and the clearest risk factor of AMD. In the development of this condition, a special role belongs to the secretory phenotype of aging spreading from one cell to another and mediated by the secretion and release of growth factors, cytokines, chemokines, proteases, and other molecules. Another major contributor is oxidative stress caused by violations in the recirculation of vitamin A in the vision cycle and accompanied by accumulation of lipofuscin, which mediates the formation of iron-based oxidants that are toxic for mitochondria. Furthermore, prolonged oxidative stress and constant light exposure induce the development of inflammation in the retina. Accumulation of metabolic products and cellular defects with age can induce an inflammatory reaction that amplifies the damage. The inflammatory processes including innate immune response, activation of microglia and parainflammation that occur locally in the vascular membrane, pigment epithelium and neuroretina are very significant contributors to the age-related changes, their progression, and the development of advanced stages of AMD. Various growth factors play a special role in the development of choroidal neovascularization (CNV). Vascular endothelial growth factor A (VEGF-A) has traditionally been considered the main factor of neoangiogenesis and, consequently, the main therapeutic target, but in recent years various studies have determined the role of other factors - VEGF-B, C, D, PGF, Gal-1, angiopoietins. This article describes the main underlying mechanisms in the development of choroidal neovascularization including retinal aging, impaired metabolic activity, mitochondrial dysfunction, inflammatory reactions and genetic variations, as well as the role of various growth factors.

[Anti-VEGF therapy for diabetic macular edema. From theory to clinical practice]. / Antiangiogennaia terapiia diabeticheskogo makuliarnogo oteka. Ot teorii k klinicheskoi praktike.

PURPOSE: To evaluate clinical effectiveness of aflibercept therapy for patients with diabetic macular edema (DME) - both naïve to the drug and unresponsive to previous anti-VEGF treatment. MATERIAL AND METHODS: The study included 127 patients (127 eyes) divided into two groups. The first group consisted of 100 primary DME patients (100 eyes) with mean age of 68.48±2.56 years and average disease duration of 12.50±7.85 years. The second group comprised 27 patients (27 eyes) with resistant macular edema who had received three or more 0.5 mg ranibizumab loading injections. Their average age was 66±4.12 and the mean number of previous anti-VEGF injections before changing therapy was 4.56±1.21. The evaluation parameters included Best Corrected Visual Acuity (BCVA) and Central Retinal Thickness (CRT) that were assessed initially and after each 2 mg aflibercept injection (at 1-month intervals during the 6 months of DME therapy). RESULTS: The average number of aflibercept injections in the first group was 4.34±1.22. BCVA improved in 100% of patients of that group after the 3rd injection with resulting mean value of 0.32±0.15. Maximum BCVA improvement was seen after the 6th injection amounting to 0.46±0.2. CRT decreased in 100% of patients of that group after the 1st injection. One month after the therapy start, CRT decreased in average by 17.96% - to 370.89±50.55 µm; at 3 months, CRT was 344.65±48.56 µm; after 6 month - 283.40±49.76 µm. All patients of the second group had retinal morphology restored, visual function improved in 55% of patients. Mean CRT decrease was 180±44 µm, BCVA improvement - 0.13±0.08, mean number of aflibercept injections - 4.86±0.9. CONCLUSION: Aflibercept can be used as first-choice drug for treatment of DME patients (both therapy-naïve and unresponsive to previous ranibizumab therapy) to improve anatomical parameters and visual function.

[Anti-VEGF therapy for age-related macular degeneration]. / Antiangiogennaia terapiia vozrastnoi makuliarnoi degeneratsii.

PURPOSE: To evaluate the clinical effectiveness of aflibercept in treatment of patients with neovascular age-related macular degeneration (nAMD). MATERIAL AND METHODS: The first group included 156 treatment-naive nAMD patients (156 eyes). The second group consisted of 29 patients (38 eyes) with nAMD who had previously received at least 3 loading injections of 0.5 mg ranibizumab but exhibited no morphological effect from the therapy. All patients included in the study were treated with 2.0 mg aflibercept. The follow-up period was 13 months. RESULTS: In the first group, the average number of injections was 5.1±0.39. A change in best corrected visual acuity (BCVA) after three loading injections was observed in all eyes of the group and amounted to 0.43±0.2. The final visual acuity was 0.47±0.22. After the first injection, central retinal thickness (CRT) in all patients of the group decreased to 346.14±54.53 µm; by the end of treatment it was 281.64±34 µm. Dry macula was achieved in 109 patients (69.9%), which corresponded to the highest BCVA of 0.84±0.14. In 26 patients (16.7%), subretinal fluid (SRF) remained and visual acuity was 0.57±0.22; 14 patients (9%) had pigment epithelium detachment (PED) and visual acuity of 0.63±0.08. Presence of residual intraretinal fluid (IRF) in 7 patients (4.5%) reliably defined the lowest functional result of 0.1±0.22. In the second group, 100% of patients after the first injection of aflibercept had decreased retinal thickness (by an average of 36.99 µm), while the increase in visual acuity was noted only after 3 injections in 67.5% of the eyes. By the end of the follow-up, CRT was 231.44±18.4 µm, decreased on average by 83.65 µm, and the final BCVA was 0.31±0.19. The number of injections was 5.7±1.7. CONCLUSION: Aflibercept can be used as the first choice drug in the treatment of nAMD for it improves the anatomical parameters of the retina and the visual functions.

[Ultrasound biomicroscopy findings in the area of previous surgical intervention in refractory glaucoma patients under topical ocular hypotensive therapy].

AIM: to evaluate the effectiveness of different classes of topical hypotensive medications in refractory primary open-angle glaucoma (POAG), judging from structural changes in artificial pathways for intraocular fluid (IOF) visualized with ultrasound biomicroscopy (UBM). MATERIAL AND METHODS: UBM analysis was performed in 104 eyes of 102 patients, mean age 68.4 ± 0.8 years, including 41 POAG patients with well controlled intraocular pressure (IOP) (group 1) and 41 refractory POAG patients with poorly controlled IOP (group 2), all under topical hypotensive therapy (prostaglandin analogues, beta blockers, carbonic anhydrase inhibitors, or combination drugs). The control group consisted of 20 patients, who maintained normal IOP after a single glaucoma surgery and did not require medical management. RESULTS: The following UBM parameters were evaluated: intrascleral cavity and filtering bleb heights and conjunctival and scleral flap thicknesses. Findings differed depending on the condition of IOF outflow pathways. Unlike the poorly controlled patients, UBM parameters in group 1 were comparable to those in the controls. The optimal control of postoperative IOP was achieved on combination therapy (a beta blocker plus a carbonic anhydrase inhibitor). CONCLUSION: In contrast to well controlled POAG patients, target values of IOP were not achieved in refractory POAG patients with either of the topical therapeutic measures. Moreover, intrascleral cavity and filtering bleb heights in these patients were reliably low (p ≤ 0.01), as confirmed by UBM analysis of the area of surgical intervention.

[Clinical efficacy of dexamethasone intravitreal implant (Ozurdex) in patients with retinal vein occlusions].

Two cases of dexamethasone intravitreal implant (Ozurdex) use are reported. The drug promotes resolution of macular edema and ensures a long-term improvement of visual acuity. The latter may depend on such factors as the duration of the disease and localization of the occlusion. Application of Dexamethasone Intravitreal Implant provides new opportunities for the treatment of retinal vein occlusions.

[Perinatal risk factors of congenital glaucoma].

The aim is to estimate extragenital diseases, course of pregnancy and delivery in mothers of children with congenital glaucoma and to study somatic and neurological status of these children. Extragenital comorbidity was found in 76.3% of studied women. 47.6% of women had burdened obstetric history. In the majority of cases there were complications of the present pregnancy. 30.9% of pregnancies resulted in premature birth. In 69.14% of children comorbidity was revealed. Thus the early diagnosis and treatment of comorbidity are essential in women. Treatment and rehabilitation of children with glaucoma requires multidisciplinary approach including ophthalmologist, neurologist and pediatricians.

[Computer visual syndrome and occupational ophthalmopathy in PC operators].

Information technologies development resulted in occupational ophthalmopathy in PC users. The article covers criteria to define the risk group for prevention and rehabilitation measures.

[Prematurely aging OXYS rats as an animal model of senile cataract in human]. / Prezhdevremenno stareiushchie krysy OXYS kak model' senil'noi katarakty cheloveka.

Cataracts remain the major cause of blindness and acuity of vision deterioration in the elderly. To date there are no effective methods of preventive measures of this disease and surgical removal of cataract-damaged lenses remains the only way to restore vision. To explore cataract pathogenesis and development methods of its prophylaxis are necessary fundamental investigation, which is impossible without biological models. As the first Russian her senile cataract model it is suggested to use the senescence-accelerated OXYS rat strain which was developed 30 years ago by selection and inbreeding of rats Wistar susceptible to cataractogenic effect of galactose (Institute of Cytology and Genetics, Novosibirsk). We conducted strong selection by the early cataract during 13 generations of OXYS rats. As the result at present time changes of OXYS rat lens appear by the 2 month, at 6 months these changes appear in 100% of animals (in rats Wistar--5%), at 12 month cataract affects both eyes. The data suggest that the cataract in rats OXYS develops simultaneously with progressive macular degeneration while changes of the eye lenses morphologically correspond to senile cataract in man.