Pharmacological Analysis of Resistance to Anti-VEGF Therapy

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.