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Pro: Intravitreal Avastin too beneficial not to use
With impressive results after only one injection, the argument for using intravitreal Avastin to treat AMD is solid, says one surgeon.
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A drug that has shown early efficacy against all forms of exudative age-related macular degeneration should be considered for use, even if that use is off-label, according to one retina subspecialist.
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Avastin (bevacizumab, Genentech) is approved for use in the United States as a systemic treatment for colorectal cancer. Paul E. Tornambe, MD, is one of an increasing number of ophthalmologists who are finding the drug to be effective as an intravitreal treatment for AMD.
“The key seems to be preoperative vision, as [Avastin] really stabilizes the eye at the entry level vision,” Dr. Tornambe said in an interview with Ocular Surgery News. “In the case of Avastin, stabilization means ‘stabilization,’ not the definition that has been used in other trials, where stabilization means up to three lines loss of vision.”
According to Dr. Tornambe, virtually every patient he has treated with intravitreal Avastin has shown reduction in retinal thickness on optical coherence tomography between 1 and 4 weeks after an initial injection.
“The visual acuity does not seem parallel with the OCT improvement initially,” he said, “but as the OCT continues to show no edema, vision tends to improve over subsequent months.”
Not just for AMD
“Avastin also works for choroidal neovascularization from other causes such as myopia and histoplasmosis,” Dr. Tornambe said. It has also been effective in treating rubeosis and “may have” an IOP-lowering effect in some cases, he said.
“It is also effective in decreasing neovascularization of the disc and neovascularization elsewhere in proliferative diabetic retinopathy,” he said. “This is an extremely interesting area, for those terrible proliferative diabetic retinopathy cases, to pre-treat with Avastin before panretinal photocoagulation and/or vitrectomy to potentially improve the prognosis.”
Dr. Tornambe said intravitreal Avastin does not seem to be effective in every retinal disease. In central retinal vein occlusion, some patients have shown improvement on OCT after an intravitreal dose, but “few get better vision,” he said. In diabetic macular edema, the drug has been ineffective if there is evidence of posterior hyaloid traction by OCT. The drug has also been “disappointing” in treatment of perifoveal capillary telangiectasis, and it works only for a time in treating branch vein occlusions.
Combination therapy
Dr. Tornambe said he believes intravitreal Avastin may prove beneficial as one part of a combination therapy. For instance, he said, photodynamic therapy has been shown to decrease choroidal neovascularization already present in an eye, while Avastin may “prevent further growth of the CNV present by inhibiting VEGF’s effect on the endothelial cell receptors.”
Investigators are exploring the effectiveness of Avastin in combination with a steroid and PDT, Dr. Tornambe said.
“My only concern with combining a long-acting steroid with Avastin would be the possibility that the steroid will decrease the leakage of the choroidal neovascular membrane but may not prevent its growth,” he said. “So it’s possible the CNV membrane may grow as the Avastin wears off. Unless a fluorescein angiogram is performed, we may not be aware that the membrane is growing even when the OCT shows no leakage.”
He recommended that physicians who are investigating Avastin in a combination therapy use both OCT and fluorescein angiography to monitor patients’ progress.
Safety concerns
Dr. Tornambe acknowledged that physicians must be aware of potential systemic safety concerns with intravitreal Avastin, but he said those concerns may generally be unwarranted.
“Of course we must always temper initial enthusiasm with the test of time,” he said. “We deal with an older population who have strokes and heart attacks, so it is important to monitor the incidence of such problems to be sure our treatment is not having significant negative systemic effects.
“Avastin is a larger molecule than Lucentis (ranibizumab, Genentech/Novartis), and may be detected in the systemic circulation for a month after a single intravenous bolus injection” he continued. “However, we are giving what amounts to just a few drops into the vitreous cavity. It is hard to believe that this amount of drug will enter the systemic circulation and have a catastrophic effect on the patient’s well-being.”
Having said that, he noted that other drugs – such as sarin gas and intravenous potassium – have been found to be deadly in certain combinations at low doses, so he said he does not rule out potential safety issues with intravitreal Avastin.
Informed consent
Obtaining proper informed consent from patients is paramount when physicians are treating with intravitreal Avastin, Dr. Tornambe said.
The bottom line, he said, is that “We are using an off-label drug with little data on long-term effects and safety when injected into the eye.” He recommended that physicians obtain informed consent before beginning any therapy that includes intravitreal Avastin.
The Lucentis factor
As promising a treatment as intravitreal Avastin initially appears, Dr. Tornambe said he will stop using it for AMD if and when Lucentis is approved.
Lucentis, which like Avastin is a pan-VEGF blocker developed by Genentech, has been accepted for fast-track review by the Food and Drug Administration and could be approved before the end of this year.
“Once it’s approved for payment, I will use Lucentis for AMD,” Dr. Tornambe said. “Lucentis has undergone extensive safety testing, it is a much shorter-acting drug than Avastin, which makes systemic side effects even less likely, and it has a much higher affinity for VEGF. Also, we have good clinical trial data for Lucentis”
Presuming Lucentis receives regulatory approval in the United States, Dr. Tornambe said physicians who would then continue using Avastin for AMD in lieu of Lucentis could be exposed to “significant” medicolegal risks.
For Your Information:
- Paul E. Tornambe, MD, can be reached at 12630 Monte Vista Road, Suite # 104, Poway, Calif. 92064; 858-451-1911; e-mail: TornambePE@aol.com.
- Michelle Dalton is Managing Editor of the OSN SuperSite.com. She writes daily updates on all aspects of ophthalmology.