Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance?

The effect of the drug can be improved if the dosage is increased or given over shorter time intervals, but efficacy is not restored if the treatment is halted temporarily. 1 In the literature both words are used synonymously, for example in relation to anti-TNF-α biopharmaceuticals (infliximab) in chronic inflammatory diseases (including rheumatoid arthritis) where immunogenicity is suspected. 2 In diabetes research where rapid tachyphylaxis at the level of gastric nervous activation was described 3 and during treatment with salmeterol (a bronchodilator for chronic obstructive pulmonary disease), β2-receptor down-regulation was assumed to be a causative factor. 4 Furthermore, tachyphylaxis is known to occur with chronic aerosol use in patients with asthma, 5 and with drugs used for analgesia and anaesthesia. 6 In the ophthalmic literature, tachyphylaxis/tolerance is reported with the use of selective α-2 receptor agonists (brimonidine) due to up-regulation of α-2 receptors because the basal norepinephrine level in the synaptic junctions is chronically depressed. 7 The worldwide use of intravitreal application of anti-vascular growth factor (a-VEGF) in patients with neovascular age-related macular degeneration (AMD) and the realisation that regular applications over long periods of time are necessary to maintain vision in these eyes, has revealed the problem of tolerance/tachyphylaxy.