Lessons Learned From Avastin and OCT-The Great, the Good, the Bad, and the Ugly: The LXXV Edward Jackson Memorial Lecture

Abstract

Purpose: To describe the synergistic benefits and cost savings from the use of optical coherence tomography (OCT) and vascular endothelial growth factor (VEGF) inhibitors, particularly intravitreal bevacizumab, in the treatment of exudative age-related macular degeneration (AMD).

Design: Retrospective literature review and personal perspective.

Methods: Retrospective literature review and personal perspective.

Results: The introduction of the first clinically useful OCT instrument coincided with early-phase clinical trials of a drug that would become known as ranibizumab. OCT provided a noninvasive imaging strategy that unambiguously showed the macular fluid associated with exudative AMD and the ability of anti-VEGF therapy to resolve this fluid with concomitant visual acuity improvement. Clinicians came to embrace the use of OCT imaging as the basis for dosing with anti-VEGF drugs, rather than the fixed-interval dosing that was the standard in clinical trials and recommended by industry after approval. But, before ranibizumab was approved for the treatment of exudative AMD, intravenous bevacizumab was approved to treat cancer. Both drugs shared a common molecular lineage, and this led to a clinical trial using intravenous bevacizumab for the treatment of exudative AMD. Intravenous bevacizumab resulted in visual acuity and OCT improvements similar to ranibizumab, and this observation soon led to the intravitreal use of bevacizumab in 2005. Fortuitously, both ranibizumab and bevacizumab were packaged at similar molar concentrations, so similar volumes of both drugs when injected into an eye would result in similar anti-VEGF activity. With ranibizumab not yet commercially available, intravitreal bevacizumab rapidly became adopted worldwide for the treatment of VEGF-driven ocular diseases. Despite numerous attempts by industry and anonymous sources to discredit and prevent its use, bevacizumab spread globally owing to its availability; its low treatment cost, which was $5.50 per 1 mg in the United States; the evidence of efficacy based on OCT imaging and vision improvement; and its perceived safety. In the United States alone, the use of OCT-guided therapy and the use of bevacizumab for the treatment of exudative AMD has saved Medicare over $40 billion since 2008.

Conclusions: The rapid adoption of OCT-guided therapy and the use of intravitreal bevacizumab by the global retinal community has prevented blindness from exudative and neovascular ocular diseases worldwide while saving healthcare providers and patients billions of dollars.