By Fred Gebhart
SAN FRANCISCO -- October 28, 2009 -- Surgeons who wondered when to give intravitreal bevacizumab before surgery for diabetic vitrectomy now have an initial answer: 10 days beforehand, according to findings released at the 2009 Joint Meeting of the American Association of Ophthalmology and Pan-American Association of Ophthalmology (AAO-PAAO).
"The problem I faced in using intravitreal bevacizumab was the lack of agreement as to the ideal time to administer the drug before surgery for proliferative diabetic retinopathy," explained Hazem El-Sabagh, MD, PhD, Magrabi Eye & Ear Center, Dammam, Saudi Arabia. "Some surgeons inject bevacizumab in the morning and do surgery that same afternoon, and some wait 2 or 3 weeks. We found that 10 days gives the maximum anti-VEGF [vascular endothelial growth factor] effect that we all want from bevacizumab."
Multiple growth factors have been found to be involved with angiogenesis, neovascularisation, and the associated fibrous proliferation in diabetic retinopathy, Dr. El-Sabagh noted in a presentation on October 25. VEGF is largely responsible for angiogenesis and neovascularisation.
Researchers performed histological examinations on epiretinal membranes taken during vitrectomy on 52 eyes in 49 patients at 3 centres in Saudi Arabia, Yemen, and Egypt. All of the patients had active diabetic fibrovascular proliferation. Once scheduled for surgery, the eyes were randomised into 10 groups based on the length of time between intravitreal bevacizumab injection and surgery: no bevacizumab (control) or injection on day 1, 3, 4, 7, 10, 15, 20, 30, or 30+.
Surgery was a standard 3-port pars plana vitrectomy with an en bloc dissection of the epiretinal membrane. The dissected membranes were graded for angiogenesis, smooth-muscle-cell proliferation, and fibrous-tissue proliferation by blinded examiners.
Analysis found a significant reduction in endothelial marker CD34 expression at day 5, and consistently low levels from day 10 onward. Smooth-muscle actin expression rose from day 3, and began to rise significantly at day 15. All membranes were positive for collagen expression, but significant levels did not appear until day 10, and began to peak at day 15.
Histopathology indicated that day 10 is the optimal time for surgery, with neovascularisation significantly reduced and contractile elements still at low levels.
"I don't want surgeons to inject [bevacizumab] and then ignore patients for 2 weeks," said Dr. El-Sabagh. "If you are not going to operate at the optimal time, you should not be using this drug at all."
[Presentation title: Optimal Time Interval for Preoperative Intravitreal Bevacizumab Use as an Adjuvant to Diabetic Vitrectomy: Histopathologic Findings. Abstract PO264]
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