Is There Tachyphylaxis to Intravitreal Anti-Vascular Endothelial Growth Factor Pharmacotherapy in Age-Related Macular Degeneration?
Presented in part at: the Annual Meeting of the American Academy of Ophthalmology, New Orleans, November 2007 and chosen as the “Best Paper” in the Retina section.
Received 30 October 2007; received in revised form 5 June 2008; accepted 15 July 2008. published online 20 October 2008.
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 μL), preservative-free triamcinolone acetonide (pfTA) (4.0 mg/100 μL), or a combination of bevacizumab (1.25 mg/50 μL) and pfTA (2.0 mg/50 μL). 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% (INJ50).
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 INJ50 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.
Available online: October 18, 2008.
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville School of Medicine, Louisville, Kentucky
Correspondence: Tongalp H. Tezel, MD, Kentucky Lions Eye Center, Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd, Louisville, KY 40202
Manuscript no. 2007-1412.
Financial Disclosure(s): The author(s) have made the following disclosure(s): Tongalp H. Tezel, MD, was supported in part by a Career Development Award from Research to Prevent Blindness, Inc., New York.
Commercial relations: None.
Conflict of Interest statement: The authors declare that no conflicting relationship exists for any author.
ABSTRACT