Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration?

Ophthalmology. 2008 Dec;115(12):2199-205. doi: 10.1016/j.ophtha.2008.07.007. Epub 2008 Oct 18.


Purpose: To determine whether repetitive injections of intravitreal bevacizumab and/or triamcinolone acetate in patients with exudative age-related macular degeneration (AMD) results in a decrease in biological response.

Design: Retrospective comparative case series.

Participants: Forty-three eyes of 43 patients with exudative AMD.

Methods: Pre- and postinjection optical coherence tomography (OCT) sections of 43 patients with AMD were analyzed to determine the change in the biologic response after each subsequent injection of intravitreal bevacizumab (2.5 mg/100 microL), preservative-free triamcinolone acetonide (pfTA) (4.0 mg/100 microL), or a combination of bevacizumab (1.25 mg/50 microL) and pfTA (2.0 mg/50 microL). The retinal thickness of each OCT sector was determined and expressed as volume. Standardized volumetric change index (SVCI) was determined to identify a statistically significant change. Pre- and postinjection (6 weeks) SVCI differences were plotted as a function of time to determine the biological response after each intravitreal treatment.

Main outcome measures: Change in SVCI after intravitreal injections and the number of injections required to decrease the biological response by 50% (INJ(50)).

Results: There was no difference in the age, gender, and preinjection thickness of the retina in each of the 3 groups. The SVCI after intravitreal bevacizumab injections decreased, indicating a possible tachyphylactic response to bevacizumab. This decrease in biological response was partially alleviated with the addition of pfTA. Combination of pfTA and bevacizumab increased the INJ(50) from 2.9 with bevacizumab alone to 5.1 injections. A biphasic biologic response was observed with pfTA characterized by a rapid increase in efficacy with the second injection, peaking at the third injection and gradually decreasing afterward.

Conclusions: Repeated intravitreal injections of bevacizumab in exudative AMD seemed to be associated with decreased bioefficacy. However, combined pharmacotherapy with triamcinolone acetate lessened this effect. Thus, multitargeted pharmacotherapy in exudative AMD may have a therapeutic benefit.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Drug Therapy, Combination
  • Exudates and Transudates
  • Female
  • Humans
  • Injections
  • Macular Degeneration / diagnosis
  • Macular Degeneration / drug therapy*
  • Male
  • Retina / pathology
  • Retreatment
  • Retrospective Studies
  • Tachyphylaxis*
  • Tomography, Optical Coherence
  • Triamcinolone Acetonide / therapeutic use*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vitreous Body


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Triamcinolone Acetonide