Optical Coherence Tomography Monitoring Strategies for A-VEGF-Treated Age-Related Macular Degeneration: An Evidence-Based Analysis

Abstract

Background: New anti-angiogenesis pharmacotherapies have dramatically altered treatment of age-related macular degeneration (AMD), the leading cause of blindness in older adults. Monthly intraocular injections however, are extremely burdensome to ophthalmologists, patients, and their families. Repeated injections also increase risks of complications or adverse events. Although the pharmacokinetics of anti-vascular endothelial growth factor (A-VEGF) drugs are fairly well known, an individuals' AMD presentation and their pharmacodynamics or response to the drug has been shown to be extremely variable. Therefore treating everyone on the same fixed or standard regimen has potential for undertreating or overtreating patients, and drug costs are not trivial.

Objectives: To review monitoring strategies and to evaluate the role of optical coherence tomography (OCT) in guiding management of A-VEGF-treated neovascular AMD (n-AMD) patients.

Data sources: Systematic reviews of biographic databases for studies published between 2008 and February 2013 involving A-VEGF-treated n-AMD patients monitored in longitudinal follow-up.

Review methods: Studies were grouped according to varying treatments, monitoring schedules, and re-treatment protocols reported for n-AMD patients treated with A-VEGF. Several outcomes were evaluated across strategies including visual acuity (VA), retinal anatomy, re-treatment criteria and frequencies of clinical follow-up, OCT imaging investigations, and intravitreal injections. Results were summarized qualitatively, as heterogeneity in study objectives and methods precluded formal meta-analysis.

Results: A systematic review identified 18 randomized controlled trials (RCTs) and 20 observational studies involving A-VEGF treatment employing various monitoring and as-needed (PRN) re-treatment protocols. Several maintenance strategies were unsuccessful, resulting in lower VA gains and stabilization than monthly injections in A-VEGF-treated n-AMD. These included fixed quarterly treatment; fixed quarterly monitoring and PRN re-treatment; and monthly monitoring with either VA-guided re-treatment or quantitative-only VA/OCT- (central retinal thickness [CRT] > 100 μm) guided re-treatment. PRN re-treatment strategies with A-VEGF on the basis of monthly follow-up and rigorous reviews of OCT qualitative and quantitative measures of disease activity did decrease injection burden while maintaining visual gains. Gains in VA obtained with PRN re-treatment in usual clinical practice, however, were not as high as gains in clinical trials.

Conclusions: To reduce treatment burden and provide a more individualized treatment strategy for n-AMD patients, OCT/VA-guided PRN treatment strategies have become the preferred and the dominant maintenance strategy. Success of these strategies, however, is dependent on close monitoring and adherence to tightly defined re-treatment criteria.