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Current anti-VEGF drugs offer hope for choroidal neovascularization
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Before anti-vascular endothelial growth factor drugs were introduced more than 2 years ago, patients with choroidal neovascularization faced continued deterioration of their vision.
Today, ophthalmologists and patients alike benefit from these medications that improve vision despite chronic diseases such as age-related macular degeneration.
“Prior to 2005, we were largely into transpupillary thermotherapy, and the main aim was to salvage and maintain vision. Today, we are able to restore vision,” Anand Rajendran, MBBS, DO, DNB, FRCS, told Ocular Surgery News in a telephone interview.
“Also reflected is the increase in acceptance rates and the increased follow-up rate. People are happier,” he said.
OSN spoke with Dr. Rajendran and other retina experts about their experience with anti-VEGFs, the evolution of their use and the future of treatment.
Introduction of anti-VEGFs
Each of the experts said they began using anti-VEGFs, specifically Avastin (bevacizumab, Genentech), in late 2005 and early 2006.
“I think the patient already read about it on the Internet, and they knew there were anti-VEGFs available. When we started using them, they were happy to have them,” S. Natarajan, MBBS, DO, FRVS, MABMS, MORCE, FABMS, said.
OSN Editorial Board Member Manish Nagpal, MS, DO, FRCS, said India is facing a greater number of AMD patients, making these successful treatments necessary.
“Before it was only [photodynamic therapy] and TTT,” he said. “At the end of the day, PDT was just about stabilizing things and not really improving the vision.”
“Today, we are able to tell these patients we have some therapy,” R. Kim, MBBS, DO, DNB, said.
Avinash Pathengay, MBBS, DO, FRCS, said, “For the first time, they saw that their vision was improving.”
Evolution of treatment
The benefits of anti-VEGF treatment were quickly evident to patients and ophthalmologists.
“We started injecting, and within a week or 10 days, the patients would come back happy, saying they were seeing better, which was never there before,” Dr. Nagpal said.
Dr. Natarajan said treatment must begin with detailed documentation.
“[Ophthalmologists] should properly document and diagnose the patients and give the full details of the anti-VEGF therapy,” he said. “And then conduct follow-ups.”
Dr. Rajendran said baseline evaluation should consist of biomicroscopy, fluorescein angiography and optical coherence tomography (OCT), as well as visual acuity evaluation. Then, patients should choose their preferred treatment after they have been informed about their therapeutic options, he said.
To prevent complications such as endophthalmitis, Drs. Nagpal and Rajendran said close observation must be maintained for about 1 month after injection. In subsequent visits, OCT should then be used to determine the patient’s progression or regression and the need for re-treatment.
“We usually like to see them within a month. Thereafter, we decide on the treatment and the injection protocol based on how they’re performing,” Dr. Rajendran said. “The treatment regimen is entirely customized to each individual patient. … A customized approach rather than an empirical one is what appears to yield the best results.”
These experts reported good follow-up rates because of educated patients. They said if patients fully understand the chronic nature of the disease when they agree to treatment, they will return to maintain their improved vision.
“They keep coming back because they know that something’s working for them,” Dr. Nagpal said.
Combination vs. monotherapy
Much of the current debate surrounding anti-VEGF therapy centers on whether to use monotherapy or combination therapy of one anti-VEGF medication and a more traditional therapy.
Dr. Kim said his center is concentrating on monotherapy with Lucentis (ranibizumab, Genentech) or bevacizumab, while another center within the Aravind Eye Care System is using mainly combination therapy of bevacizumab or ranibizumab paired with PDT. Although this is not a planned study, the two centers will be comparing their results in the near future.
“Our experience with monotherapy has been good and the cost is less,” Dr. Kim said. “But the other center felt that combination therapy was effective.”
Dr. Nagpal said he is subscribing to monotherapy because, in contrast to studies conducted in the United States and Europe where patients receive eight to 12 injections, he had not injected any one patient more than three or four times.
Although he said he is unsure of the cause of this difference, he is using only monotherapy.
“We are not using PDT because the monotherapy is working well,” Dr. Nagpal said. “There will be a few people who are using combinations of PDT with this, but that is a minority, and in big cities like Bombay[Mumbai] or Delhi where there’s a larger-paying capacity of the patient.”
Dissemination of use
As the topic of anti-VEGF medications becomes more widespread, so will its use, these experts said.
“In India, especially, the scope for the general ophthalmologist to expand their practice to retina can increase,” Dr. Kim said.
He said general ophthalmologists can seek the education needed to perform these intravitreal injections.
“They should basically orient themselves to medical retina first. Today, a lot of facilities are available, especially in India, for this kind of training, and once they go through that, I think it would definitely help in their practice to start treating these kinds of patients,” he said.
Dr. Pathengay said a small number of general ophthalmologists are likely beginning to perform these injections, but he warned against possible abuse.
“It is not a cure for each and every disease. It should be in the right hands,” he said.
Dr. Rajendran said some would be surprised at the number of general ophthalmologists who are already administering anti-VEGF drugs because of the procedure’s relative simplicity as compared with PDT or TTT.
“The procedures are straightforward and simple, so it has already disseminated in the last couple of years and become the current rage at our conferences, not just retina society conferences,” he said.
He urged physicians to consider the negative as well as the positive effects of this treatment.
“I think we have to underscore to the ophthalmic community that it is an invasive procedure, and we need to carefully monitor these patients and follow them closely,” Dr Rajendran said.
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Looking ahead
Looking to the future, these experts said they are intently watching studies on monotherapy vs. combination therapy, as well as the new developments, such as long-term drug delivery systems.
“Anti-VEGF is there to stay. The only thing that will have to be done and what is happening is that the negative of repeated injections has to be addressed,” Dr. Rajendran said.
“If you ask me from the future, I think we would all be waiting for some of these long-acting ones like the [small interfering] RNA and the VEGF trap,” Dr. Nagpal said.
Additionally, he and others are looking at expanded uses for anti-VEGF drugs. In Dr. Nagpal’s practice, he is involved in the phase 3 study looking at Macugen (pegaptanib sodium, (OSI) Eyetech/Pfizer) to treat diabetic edema.
“I think we have a lot of choices, not only in the age-related macular degeneration,” Dr. Kim said. “We will have a lot of variety of drugs, more choices for us to treat these patients.”
Today, standards have been set by bevacizumab, ranibizumab and pegaptanib, Dr. Pathengay said.
“Ten years before, we were not even thinking about treating these diseases,” he said. “Now, we are talking about visual improvement. I think standards are set high now.”
For more information:
- R. Kim, MBBS, DO, DNB, can be reached at Aravind Eye Hospital, 1, Anna Nagar, Madurai, 625020, India; +91-452-4356100; fax: +91-452-2530984; e-mail: kim@aravind.org. Dr. Kim has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.
- Manish Nagpal, MS, DO, FRCS, can be reached at the Retina Foundation, Near Shahibag, Underbridge, Rajbravan Road, Gujarat, Ahmedabad, 380004, India; +91-79-2286-5537; fax: +91-79-2286-6381; e-mail: drmanishnagpal@yahoo.com. Dr. Nagpal has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.
- Avinash Pathengay, MBBS, DO, FRCS, can be reached at Vitreo-Retina Service, LV Prasad Eye Institute, GMR Varalakshmi Campus, Hanumanthuwaka Junction, Visakhapatnam, Andhra Pradesh 530040, India; +91-891-3206161; e-mail: avinash@vizag-lvpei.org. Dr. Pathengay has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.
- Anand Rajendran, MBBS, DO, DNB, FRCS, can be reached at Aravind Eye Hospital, 1, Anna Nagar, Madurai, 625020, India; +91-452-4356100; fax: +91-452-2530984; e-mail: anandr@aravind.org. Dr. Rajendran has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.
- S. Natarajan, MBBS, DO, FRVS, MABMS, MORCE, FABMS, can be reached at Aditya Jyot Eye Hospital, Plot No. 153, Road No. 9, Major Parmeshwaran Road, Opp. SIWS College Gate 3, Wadala, Mumbai 40003, India; +91-22-2418-1001; fax: +91-22-2417-7630; e-mail: drsnatarajan@vsnl.net.