Aim: To analyze the effectiveness of intravitreal injection of an anti-VEGF agent (ranibizumab) and an dexametazon implant for the intravitreal injection, in real clinical life.Patients and Methods. 137 patients with MO due to retinal venous occlusion were included in the study. Patients were retrospectively divided into groups: patients who received monotherapy with ranibizumab 94 people; and monotherapy with dexamethasone implant — 15 patients; patients who initially were injected with a dexamethasone implant, but due the study transferred to ranibizumab 15 patients; patients who initially received ranibizumab, but then transferred to the dexamethasone implant -13. For the treatment of macular edema were used an anti-VEGF agent — ranibizumab (Lucentis) 0.05 ml (0.5 mg) manufactured by Novartis (Switzerland) or glucocorticosteroid — dexamethasone implant for intravitreal injection of 0.7 mg (Ozurdex) manufactured by Allergan Pharmaceutical Ireland (Ireland). The injections were administered on a pro re nata basis (the presence of macular edema). Standard ophthalmological examination and fluorescent angiography (PAG), optical coherent tomography (OCT), optical coherence tomography angiography (OCT-A) were used. Visual acuity changes (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP) were analyzed depending on the study group (group 1–4), the duration of treatment and the number of injections. Results: In group 1, from 1 to 8 IVVs were performed in 24 months, an average of 3.77. In group 2, from 1 to 4 intravitreal injections were performed in 24 months, an average of 1.37. In group 3, from 1 to 2 of intravitreal injections Ozurdex and from 1 to 4 intravitreal injections of ranibizumab for 24 months. In group 4, from 1 to 4 intravitreal injections of anti-VEGF drug and from 1 to 4 intravitreal dexamethasone implant were performed in 24 months of follow-up. Monotherapy with the Ozurdex drug (12 months) had the most stable effect, with a relapse of the process, repeated injections were required, conducted only in 3 out of 15 patients. Conclusion: In real clinical practice, the dexamethasone implant showed a good safety profile and high efficacy in the resorption of macular edema in patients with retinal vein occlusion, which corresponds to the clinical trials that was made earlier.
Age-related macular degeneration (AMD) is a disease that occurs in adults over 50 years old and the leading cause of irreversible blindness in developed countries. AMD is characterized with a lesion of retina macular area and leads to a deterioration in central vision. Therapy aimed at combating the vascular endothelial growth factor (VEGF) resulted in an increase of corrected visual acuity in patients with neovascular age-related macular degeneration. Possible significant differences in the response to anti-VEGF therapy are due to the existence of several anti-VEGF agents with different molecular configurations. Currently, there is no consensus on classification of the optimal response or its absence with this method of treatment. In particular, there is confusion about such terms as “defendant status” after treatment with n-AMD, “tachyphylaxis” and “resistant” n-AMD. Drug tolerance is a pharmacological concept applicable to a patient’s response to a particular drug, with the physiological drug concentration is reducing in case of re-introduced. It requires the increasement the dose or frequency of drug administration to achieve the desired therapeutic effect. Tachyphylaxis is a term indicating a sudden decrease in response to a drug after its administration. This process can develop both after the initial or several administration in small doses. Tachyphylaxis develops in the background or after treatment with ranibizumab with at least two injections of the drug.Switching the treatment regimen to aflibercept or conbercept can be effective in patients resistant to bevascizumab or ranibizumab.The involvement of other pathological processes in the development mechanism of the neovascular form of AMD in addition to increased expression of VEGF dictates the need for combined therapy for this group of patients.
The World Health Organization considers eye disorders as the serious problem of our time [1]. According to world statistics, the number of people with visual impairment is 1.3 billion, most of this number are people over 50 years old [2]. Over the past 20 years, developments in the treatment of AMD and fundus diseases have advanced and include drugs such as vascular endothelial growth factor inhibitors. The molecular structures of drugs intended for intravitreal use range from RNA aptamers (pegaptanib) to full-length monoclonal antibodies (mAb: bevacizumab) to Fab fragments (ranibizumab) and an antibody conjugate (aflibercept). In addition, single-chain variable fragment (scFv: brolucizumab), bispecific monoclonal antibody (faricimab) and DARPin (abigar pegol) show promising results in clinical trials.[6],[7] Brolucizumab (RTH258) was developed by ESBATech (ES-BATech AG — Schlieren ZH, Switzerland) originally under the name ESBA1008, an inhibitor of the humanized single chain antibody fragment (scFv) of all isoforms of vascular endothelial growth factor-A (VEGF-A). [6],[7],[11]. The Faricimab (ROCHE, Switzerland) molecule is characterized by the presence of a bispecific antibody that simultaneously binds to both VEGF-A and Ang-2; the drug consists of an anti-Ang-2 antigen-binding fragment (Fab), an anti-VEGF-A Fab and a crystallizing modified fragment (Fc region) with a total size of 150 kDa. This “crossover” effect provided high affinity for both targets while also maintaining a good stability profile compared to natural antibodies [8]. Abicipar Pegol (Abicipar, Allergan. Dublin, Ireland) is a DARPin aimed at binding all VEGF-A isoforms, like ranibizumab. It has a higher affinity and a longer half-life from the eye than ranibizumab (>13 days versus 7.2 days), making it a potential drug with a longer duration of action and the need for less frequent injections [15]. In this article, we tried to summarize the literature data on new anti-VEGF drugs being developed and ready for release. We hope that the appearance of these drugs on the market will make it possible to reduce the injection load on the patient and optimize their material costs.
Age-related macular degeneration (AMD) is a chronic disease of the central retina and one of the main causes of blindness in patients over 60 years of age in industrialized countries. Currently, anti-vascular endothelial growth factor therapy (anti-VEGF therapy) has become the standard of neovascular AMD treatment, leading to the prevention of progressive vision loss in more than 90 % of treated patients during a two-year follow-up period. In the modern world there are transition from quantitative assessment of “fluid” according to optical coherence tomography (OCT) — the thickness of the central retinal zone, to qualitative — the presence of IRF, SRF, fluid under RPE. The data obtained by Zinkernagel have shown that, despite good functional results (an increase in visual acuity), the administration of the drug once every 2 months leads not only to fluctuations in IRF and SRF, but also to serous PED [4]. The existing qualitative and quantitative analysis is not perfect. Fluctuation is a new qualitative marker of the study of disease activity, it is defined as the sum of all types of fluid (IRF + SRF + fluid under RPE) in a certain time interval (with monthly measurement of the indicator). The fluctuation index was determined from the cumulative change in the thickness of the retina in the fovea over time [6]. Thus, the fluid is considered as a key morphological criterion for the activity of nVMD and an indication for (initiation or continuation) of antiangiogenic therapy. At the same time, there is evidence that a lower level of each type of fluid (IRF, SRF, fluid under RPE) is associated with better BCVA results against the background of anti-VEGF therapy [17]. The stability of retinal thickness during anti-VEGF therapy is no less important parameter than the statement of fluid resolution at a certain time, and it appears that better control of the central retinal thickness was associated with higher overall NEI VFQ-25 scores and individual scales reflecting important daily activities of the patient [16].
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