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Sustained IOP increase after anti-VEGF injection reported
 Malik Y. Kahook |
Specialists have been using anti-VEGFs with considerable success, according to one speaker at Hawaiian Eye 2011, but there have been some reports of increased IOP after injection.
Malik Y. Kahook, MD, discussed increased IOP related to the injection of two popular anti-VEGF compounds, Avastin (bevacizumab, Genentech) and Lucentis (ranibizumab, Genentech).
Bevacizumab has not gone through the U.S. Food and Drug Administration approval process for ocular injection, but it has been proven to be very safe, according to Dr. Kahook. Nevertheless, an important complication that has been reported is an increase in IOP.
“I’m not talking about a brief increase in intraocular pressure that happens from a volume effect. This was a sustained increase in IOP, which in many cases is resistant to medical therapy,” he said.
The most prominent example is a single practice in Utah that reported more than 60 cases of sustained increased IOP after injection of bevacizumab, representing 12% of patients injected.
“These patients required therapy with either medication or laser and in some cases required trabeculectomy,” he said.
One potential explanation for the phenomenon is inflammation. In 2006, Genentech issued a notification concerning reports of 32 patients who had experienced uveitis or sterile endophthalmitis related to the same batch of intravitreal bevacizumab. “But most cases report open-angle glaucoma with normal anatomy,” Dr. Kahook said.
Another culprit could be toxicity, which Dr. Kahook and colleagues investigated by studying in vitro the trabecular meshwork cells of both bevacizumab and ranibizumab.
“What we found is that you have to increase the dose fourfold with bevacizumab to see any toxic response,” he said. The study found no toxic response with ranibizumab.
Dr. Kahook also considered that IOP spikes might be related to concentration levels. “Maybe certain pharmacies just don’t compound their bevacizumab the same as others,” he said. However, in vial samples from two compounding pharmacies studied by Dr. Kahook and colleagues, immunoglobulin (IgG) concentrations were actually lower than expected.
Dr. Kahook eventually honed in on silicone deposits in repackaged anti-VEGFs, resulting in a 2010 study published in Investigative Ophthalmology and Visual Science. The study concluded that refreezing anti-VEGFs, storing them longer than 2 weeks or exposing them to sunlight may cause silicone to leach from the syringe and into the vial. This is just one potential cause, Dr. Kahook noted, and there may be other causes that are yet unknown.
“Basically what you are doing in some cases is giving an injection of silicone into the vitreous cavity,” Dr. Kahook said. “The silicone deposits are subvisible. You won’t see these with the naked eye. These are about 1 µm to 5 µm in diameter,” he said.
Orientation of syringes in relation to ice packs in shipment (eg, vertical, horizontal, side by side with the ice pack or sandwiched between ice packs) may also play a role. Dr. Kahook has even received samples in his clinic that arrived frozen on top of the ice. “This is something you want to pay attention to,” he said. – by Bob Kronemyer
- Malik Y. Kahook, MD, can be reached at 1675 Aurora Court, P.O. Box 6510, Aurora, CO 80045; 720-848-2020; email: malik.kahook@ucdenver.edu.
- Disclosure: Dr. Kahook disclosed financial interests in Alcon, Allergan, Actelion, Genentech, Heidelberg Engineering, Merck and Shape Ophthalmics.