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40 EW FEATURE February 2011International techniques and technology June 2012 Expanding indications for the use of anti-VEGF drugs by Maxine Lipner Senior EyeWorld Contributing Editor AT A GLANCE • With their ability to shore up blood vessels and stop their proliferation, anti-VEGF agents are being used to treat ocular conditions from RAP lesions to Coat's disease • Building on the fact that these agents can be used by so many different patients can help to circumvent potential infection problems with multi-dose anti-VEGF vials • For all indications, economics still play a pivotal role that will likely in- fluence emerging anti-VEGF agents Looking beyond the obvious Growing 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 neovasculariza- tion of any etiology, pathological myopia, ocular histoplasmosis, idiopathic choroidal rupture, any inflammatory disease, and android streaks," said Susan B. Bressler, M.D., professor of ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Balti- more. "Others may subdivide out neovascular macular degeneration RAP lesions [retinal angiomatous proliferans] or retinal mastomatic lesions." Anti-VEGF (anti-vascular endothelial growth factor) agents are also commonly used in the pediatric realm for retinopathy of prematu- rity. Some less common uses Dr. Bressler pointed out include the Japan's continued from page 39 Similarly, for diabetic cases, pan reti- nal photocoagulation [PRP] can be engaged to the far peripheral por- tion." Modern phacoemulsification and vitrectomy also have minimized inflammation post-op, which can be further managed with topical or sub- conjunctival steroids in challenging cases, Dr. Oshima said. Cons Dr. Oshima said some minor compli- cations do exist with combining the procedure. "The most often seen complica- tion in the combined phaco/ vitrectomy may be the posterior synechiae," Dr. Oshima said. "Ac- cording to previous literature, the rate of posterior synechiae has been estimated to range from 10-30%. This complication will be highly seen in the cases with inflammatory retinal pathologies such as advanced proliferative diabetic retinopathy and in cases with the use of a gas tamponade. When these two risk factors combine, the incidence rate will be much higher, reaching to over 50% reportedly." In eyes in which a gas tampon- ade has been performed, the IOL could also slide out of the capsular bag, he said. "Overall there are no serious drawbacks with the combined procedure," he said. EW Editors' note: Dr. Oshima has financial interests with Alcon. Dr. Kusaka has financial interests with Bausch + Lomb. Contact information Kusaka: skusaka@ophthal.med.osaka-u.ac.jp Oshima: yusukeoshima@gmail.com 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), according to Amar Agarwal, M.D., 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 op- tions. "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 Lucen- tis, 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 compara- tively much cheaper." Dr. Agarwal tries to keep the patient's budget in mind. "It's not necessary that every- one has to drive a Mercedes, but at the same time he has to reach the destination," he said. "So I give him Anti-VEGF agents provide a good option for conditions such as retinal vein occlusion, which were otherwise very limited the advantages, the pros and cons of all the products." He tells patients that the big ad- vantage 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 disad- vantage 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 pa- tients 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 with diabetic retinopathy are among the expanding group that can benefit from anti-VEGF agents Source (all): Amar Agarwal, M.D. 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 unfortu- nately occur in some cases. In Japan, investigators led by Mayumi Inoue, M.D., Yokohama City University Medical Center, Yokohama, Japan, found that Avastin was associated with a higher incidence of endoph- thalmitis infections. In this July 2011 retrospective study e-published in Ophthalmologica, investigators reported on the incidence of infec- tious and non-infectious endoph- thalmitis 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 conclu- sions that investigators reached was that consideration of an appropriate injection protocol should be given.