EyeWorld Asia-Pacific September 2012 Issue

40 EWAP RETINA September 2012 Expanding indications for the use of anti-VEGF drugs by Maxine Lipner Senior EyeWorld Contributing Editor Looking beyond the obvious G rowing applications Practitioners here and abroad have adopted these neovascular wonder drugs for a host of ocular problems well beyond FDA-approved macular degeneration. “Many people use them for choroidal neovascularization of any etiology, pathological myopia, ocular histoplasmosis, idiopathic choroidal rupture, any inflammatory disease, and android streaks,” said Susan B. Bressler, MD, professor of ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore. “Others may subdivide out neovascular macular degeneration RAP lesions [retinal angiomatous proliferans] or retinal mastomatic lesions.” Anti-VEGF (antivascular endothelial growth factor) agents are also commonly used in the pediatric realm for retinopathy of prematurity. Some less common uses Dr. Bressler pointed out include the treatment for things such as the rare congenital condition Coats’ disease, also known as exudative retinitis, or for choroidal neovascularization in the setting of idiopathic perifoveal telangiectasia. “That’s a smattering of entities throughout the world,” Dr. Bressler said. In India, at one of the three Agarwal Eye Hospitals, patients with retinal problems such as age-related macular degeneration, retinal vein occlusion, diabetic retinopathy, or macular edema are routinely offered a choice of Avastin or Lucentis (bevacizumab and ranibizumab, Genentech, South San Francisco, Calif., USA), according to Amar Agarwal, MD , director, Dr. Agarwal’s Group of Eye Hospitals, Chennai, India. Dr. Agarwal counts himself lucky to have these anti-VEGF agents for varying diseases for which there may be few or no other treatment options. “The advantage with these drugs is we have a good option to treat these conditions that was not there before,” Dr. Agarwal said. “In the past, if a retinal vein occlusion came to me I might not have had a good treatment for it—today I do.” Optimizing against infection Choosing between the available anti-VEGF agents, Avastin or Lucentis, often comes down to the reality of economics. “Lucentis is a fantastic drug, but the problem is cost; that is a factor especially in a country like India,” Dr. Agarwal said. “Here is the reality: If a patient can’t afford it, we give him Avastin, which is comparatively much cheaper.” Dr. Agarwal tries to keep the patient’s budget in mind. “It’s not necessary that everyone has to drive a Mercedes, but at the same time he has to reach the destination,” he said. “So I give him the advantages, the pros and cons of all the products.” He tells patients that the big advantage of Lucentis is its single dose usage. “When I give Lucentis it is one dosage—once I inject it I throw it out,” Dr. Agarwal said. Meanwhile with Avastin he finds that the disadvantage is that since this is supplied in multi-dose format and is kept on the shelf once opened, there is a chance of infection. “One vial is used in 30 patients,” Dr. Agarwal said. So a chance of infection exists. To help minimize the risk, Dr. Agarwal has tried a unique strategy at the Agarwal Retinal Center, where he sees patients with a variety of conditions that could benefit from the drug. He schedules all of those who need Avastin for any ocular condition for appointments on the same day. “Let’s say we have 30 patients I block on Friday; we open one vial on Friday and by evening we throw it out,” Dr. Agarwal said. “The advantage of this method is that infection will not happen.” The same cannot be said if he keeps the Avastin vial lingering for a month as patients trickle in. If somewhere along the line a mistake is made and the vial that has been sitting there is contaminated, multiple infections can occur. Serious infections can unfortunately occur in some cases. In Japan, investigators led by Mayumi Inoue, MD, Yokohama City University Medical Center, Yokohama, Japan, found that Avastin was associated with a higher incidence of endophthalmitis infections. In this July 2011 retrospective study e-published in Ophthalmologica , investigators reported on the incidence of infectious and non- infectious endophthalmitis after intravitreal injection of anti-VEGF agents. Included in this study were 1,209 intravitreal bevacizumab injections, 3,827 ranibizumab injections, and 200 injections of pegaptanib sodium. Of these, investigators found five bevacizumab eyes that developed endophthalmitis. One of the conclusions that investigators reached was that consideration of an appropriate injection protocol should be given. Latest anti-VEGF With expanding uses for anti- VEGF also comes the need for innovation. One new anti-VEGF agent available to combat the multitude of retinal conditions that has been found to be successful is Eylea (aflibercept, Regeneron Pharmaceuticals, Tarrytown, NY, USA). “This has been approved in the U.S. for neovascular AMD, but once it is approved and available it can be used in an off-label fashion,” Dr. Bressler said. The less frequent dosing schedule makes the drug desirable, she finds. “Dosed eight times over the course of a year and a dosing regimen of monthly for the first 3 months and Q8 weeks for the following 9 months has been shown to be equivalent to Lucentis given every single month for neovascular AMD,” she said. Once again, however, economics may play a role in in-roads that Eylea ultimately makes globally. On the upside, Dr. Bressler pointed out that from the perspective of price, Eylea has the edge compared with ucentis.”Given that the price of Eylea is [US]$100 per dose and that one could use eight doses over the course of a year compared to 13, you’d be saving money per dose and per ann[um] and allegedly not sacrificing vision or anatomical results,” Dr. Bressler said. Dr. Bressler suspects that many Anti-VEGF agents provide a good option for conditions such as retinal vein occlusion. Patients with diabetic retinopathy are among the expanding group that can benefit from anti-VEGF agents. Source: Amar Agarwal, MD continued on page 42