• Community Eye M.D.s Tackle The Intravitreal Injection

    By Miriam Karmel, Contributing Writer

    This article is from March 2008 and may contain outdated material.

    The intravitreal injection, once considered a subspecialty skill, is becoming more common in the daily work of comprehensive Eye M.D.s.

    James M. Coombs, MD, is a community ophthalmologist in Twin Falls, Idaho, a city that serves the needs of people in the state’s rural southern region. He and his partner at the Fitzhugh Vision Clinic offer everything from cataract and refractive surgery to glaucoma care and even minor oculoplastics.

    They also administer intravitreal bevacizumab (Avastin) injections to patients with neovascular age-related macular degeneration.

    Whether a general ophthalmologist should be injecting drugs into the back of the eye is a matter of opinion—and some controversy. Prior to the availability of bevacizumab and ranibizumab (Lucentis), few people questioned the primacy of retina specialists in administering intravitreal (IVT) injections. The complexity of earlier treatments dictated that they be managed by retina experts, according to Thomas A. Oetting, MD. “But it’s beginning to get into a simpler treatment protocol.” Dr. Oetting is an associate professor of ophthalmology at the University of Iowa in Iowa City.

    In fact, IVT injections are becoming common in some clinics. “Injections of bevacizumab, ranibizumab and triamcinolone are more common than all retina laser treatments combined in our vitreoretinal clinics at the University of Iowa,” said James C. Folk, MD. “That is a huge shift from three years ago.” Dr. Folk is a professor of ophthalmology, also at the University of Iowa.

    A New Scope of Practice Debate

    This mini-revolution in care has fomented a rather prickly debate over scope of practice between specialists and generalists. Some retina specialists adamantly oppose the practice, arguing that IVT injections should be performed only by a fellowship-trained vitreoretinal surgeon. Others more willingly accept the practice, albeit with caveats. All of them raise the specter of endophthalmitis, questioning whether the generalist has the skills to cope with it and other injection-induced complications.

    But many ophthalmologists, like Dr. Coombs—and Dr. Oetting, who was his mentor at the University of Iowa—contend that the general ophthalmologist can readily acquire the requisite skills and training to diagnose, evaluate and follow a patient with wet AMD, and even manage the complications. In areas where subspecialists are scarce, it may even be necessary for the comprehensive ophthalmologist to assume this responsibility. In fact, as the population ages and the AMD incidence increases, some general ophthalmologists are wondering whether the time-consuming evaluation and injection protocol will overwhelm the practices of vitreoretinal surgeons, even in areas where no scarcity of subspecialists exists.

    Great expectations of eye residents. As director of the residency program at the University of Iowa, Dr. Oetting gave a lot of thought to this question: What is the scope of practice that is expected of a general ophthalmologist? “Is managing folks with macular degeneration in today’s world something we should encourage our residents to become proficient in?” He regards the treatment of AMD with IVT injections as “one of those border areas between what is expected of a general ophthalmologist and what is expected of a retina specialist.”

    Dr. Oetting noted that general ophthalmologists perform focal laser treatment and panretinal photocoagulation without any objections. “Nobody argues that our residents shouldn’t do those procedures, even though focal laser, like intravitreal injections, requires facility with OCT and angiography.” He said it is ironic that while most academic centers are filled with subspecialists, resident ophthalmologists are expected to graduate with a broad set of skills. “We’ve been trying to figure out what do our residents need to know to be a good general ophthalmologist? Should IVT be in that bag of tricks?”

    He has decided it should. “IVT injections are something that some general ophthalmologists will need to be doing.”

    Patients Who Don’t Live Near Specialists

    There are no retina specialists in Twin Falls, Idaho, but there are a large number of AMD patients in Dr. Coombs’ practice. Knowing that if he didn’t treat them, they’d have to drive two hours to Boise or three hours to Salt Lake City, he and his partner started to give the injections.

    As a resident, Dr. Coombs did a few IVT injections, but anti-VEGF therapy wasn’t yet mainstream when he graduated in 2006. So he learned the technique by observing his partner and by viewing a video. He estimates that last year he gave about 70 injections, all without adverse outcomes. “The more injections I’ve done, the more comfortable I feel doing them.”

    Technique, yes, but use judgment, too. Administering the injection isn’t the primary objection of retina specialists. “Injection, per se, is not the issue for me,” said Dr. Folk, who has developed a resident training protocol for IVT injections. “The issue for me is deciding when you need to do an injection and when you do not.”

    Peter K. Kaiser, MD, agrees. “The intravitreal injection is absolutely something a general ophthalmologist can do.” Dr. Kaiser is director of the OCT Reading Center at the Cole Eye Institute of the Cleveland Clinic. The question, he said, is “knowing when to do it and when not to do it. That’s where it becomes harder. You really have to know retina pretty well to know when to deliver this or not, especially when talking about off-label drugs, like Avastin or triamcinolone.”

    Julia A. Haller, MD, ophthalmologist-in-chief at the Wills Eye Hospital in Philadelphia and president of the American Society of Retina Specialists, also agrees that comprehensive ophthalmologists are qualified to do IVT injections. “The issue is: Do they want to manage the kind of complicated vitreoretinal pathology that these injections are designed to treat?”

    While Dr. Coombs and his partner refer out retina surgical cases, he is comfortable treating the majority of his AMD patients without referral. “Most of the AMD cases I see are fairly straightforward,” he said. He stays current with the literature, consults with friends in the retina community and colleagues in Salt Lake City. He plans to buy an OCT for the office, but in the meantime follows patients with repeat fluorescein angiograms. He said he’s comfortable with fluorescein interpretation, which was drilled into him during his residency.

    Finally, Dr. Coombs refers difficult AMD cases, such as the monocular patient with an unusual presentation. “I felt I wanted a retina opinion before commencing,” he said, adding that the specialist gave the injection in that case.

    The Case for Specialists

    Dr. Haller is sympathetic to the needs of rural communities. “I can see how in an underserved area, comprehensive ophthalmologists might want to deal with it. And they should.” But, she added, the comprehensive ophthalmologist should consider referral in areas well-served by retina specialists. “People up on the latest approaches are the specialists because that’s all they do. We’re completely focused on the latest word on treating retinal diseases. Particularly in a time like the pres-ent, when there is a lot of fluidity concerning optimal management strategies, most people would be best served by those who have thought the most about it.”

    Dr. Kaiser agrees that general ophthalmologists can provide an invaluable service in rural areas. His concern is with the generalist who minimizes the complexity of these cases. Specifically, he said, there is an attitude among some general ophthalmologists that they can give patients the injection, and if it doesn’t work out, they can send the patient to a retina specialist. Some community eye care providers are even treating patients with bevacizumab or ranibizumab without a fluorescein angiogram, Dr. Kaiser said. “It’s happening.” He knows because he’s received some of those patients, including one who had been misdiagnosed with AMD and injected unnecessarily.

    First chance is best chance. Dr. Kaiser also had a patient who’d been treated with bevacizumab at two-month intervals (contrary to the four-to-six week intervals many doctors are following). The referring ophthalmologist in that case didn’t have any imaging devices and was treating on the basis of a clinical and vision exam. The delay in getting proper treatment could have cost the patient some vision, Dr. Kaiser said. “We only have so much time with these patients to do well.”

    Because CNV, for example, can be misdiagnosed, “the decision making to begin treatment to go down this anti-VEGF road needs to be done by a retina specialist,” said Sharon Fekrat, MD, associate professor of ophthalmology at Duke University in Durham, N.C. The specialist also needs to decide at what intervals to continue treatment, and when to stop it, she added. However, Dr. Fekrat can appreciate the value of collaboration between the specialist and general ophthalmologists “in select situations,” specifically where travel for care may be a hardship on the patient.

    IVT Injection Pearls

    While the debate continues as to whether intravitreal injections should be performed only by vitreoretinal surgeons, Dr. Folk predicts that comprehensive ophthalmologists will almost certainly see patients who will need an IVT injection, or who already have had one or more injections. “It’s a very common procedure,” he said. What follows is advice from Drs. Folk, Kaiser and Haller on how to give IVT injections, beginning with the cardinal rules for sterile technique:

    Dr. Folk’s advice:

    • Use a lid speculum and anesthetize the eye with subconjunctival lidocaine.
    • Use povidone iodine on the conjunctiva at the injection site.
    • Don’t let the needle (30-gauge) come into contact with anything—including the eyelashes—prior to injection.
    • Inject 3 mm posterior to the limbus in pseudophakic eyes, and 3.5 mm from the limbus in phakic eyes.
    • Direct the needle toward the optic nerve.
    • Insert the needle halfway and then inject.
    • Place a sterile Q-tip over the injection site before withdrawing the needle to prevent backflow of the drug or the vitreous.

    Dr. Kaiser’s advice:

    • Set realistic expectations. Be sure the patient understands that the regimen involves multiple treatments. Explain that a repeat injection does not mean the treatment is failing.
    • Be sure of the diagnosis before injecting.
    • Refer any patient who isn’t doing as well as you’d like.

    Dr. Haller’s advice:

    • Be sure you are comfortable identifying, managing and/or referring the potential complications of the injection, including retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage.
    • At the very least have somebody readily available for referral.


    Dr. Folk, who has developed a resident training protocol for intravitreal injections, demonstrates important aspects of the procedure, from the administration of lidocaine, upper right, to the treatment injection, lower right.

    The Case for Comanagement

    Dr. Folk offered a comanagement scenario, especially for patients who live a distance from the nearest specialist. The retina expert could see the patient initially, make the diagnosis and give the first injection. Then the comprehensive ophthalmologist can give the next two injections. After the third injection, the patient would return to the specialist for evaluation, Dr. Folk said. Returning to the specialist after the third injection is important because that’s the “next real decision point”—the time when treatment intervals may be adjusted according to need, he explained.

    Dr. Folk suspects the number of comprehensive ophthalmologists giving IVT injections will vary by region. In Iowa, where distances to a retina surgeon can be great, about 10 percent of general ophthalmologists are giving IVT injections, though that number is likely to increase. “AMD is so common and retina doctors are becoming almost overwhelmed with the number of patients who need this,” he said. At the same time, he knows there will be ophthalmologists who choose not to give injections.

    AMD numbers on the rise. Steve L. Gerber, MD, however, wants to treat AMD patients. “I’d like to learn because the number of patients needing injections and the number of injections needed are increasing along with the longevity of our patient populations,” said Dr. Gerber, who is a comprehensive ophthalmologist in private practice in South Bend, Ind. About 15 percent of his patients have AMD, and 10 percent of those have the neovascular form.

    Dr. Gerber said that treating those patients is more feasible because of OCT, which his office has. “OCT has allowed for a much less invasive method of following these eyes over time.” And since he already gives anterior chamber injections and has a glaucoma fellowship, he said, “It’s not much of a leap to treat these patients.”

    In the meantime, Dr. Gerber refers all of his patients to the two “very excellent retina specialists,” in town. So far, his patients are able to get appointments. But since the specialists cover a wide territory in northern Indiana and southern Michigan, he fears they could get overwhelmed, as the indications for these injections grow. Dr. Gerber also wants simply to better serve his patients. “From a patient service standpoint, it would be good not to have to send them elsewhere,” he said.

    So Far: Low Incidence of Adverse Medical or Legal Events

    A number of retina experts interviewed for this article mentioned the risk of serious adverse events from IVT injection and even the potential for lawsuits.

    Few medical complications. The potential hazards of IVT injections generally, including endophthalmitis, retinal detachment and intraocular hemorrhage, can be vision-threatening, but at least one study found that the risk of serious adverse events is low.1 That study, by Rama D. Jager, MD, and colleagues, searched the literature via PubMed from 1996 to 2004 to identify studies evaluating the safety of IVT injection. Data from 14,866 IVT injections in 4,382 eyes turned up 38 cases of endophthalmitis, including pseudo-endophthalmitis (0.3 percent prevalence per injection). The search found that retinal detachment was uncommon after IVT injection, with an overall prevalence of 0.9 percent per injection.

    And few legal worries, as well. The risk of a lawsuit also appears to be low. At least for now, there is little evidence that IVT injections have resulted in legal disputes. A search of the Ophthalmic Mutual Insurance Company’s (OMIC) active files revealed three “incident reports” related to bevacizumab injections out of a total of more than 800 active claims, lawsuits and incident reports for all categories of adverse events. One of the three reports was due to endophthalmitis, one was from a patient unhappy with results and a third was for an injection into the wrong eye.

    “Incidents,” said Paul Weber, JD, vice president of OMIC’s risk management legal department, “are reported on a precautionary basis by insureds. They don’t rise to the level of claims.” Mr. Weber found almost no active reports for other injectable retinal drugs. There was one active case report related to triamcinolone and none for ranibizumab.

    In fact, there have been so few reports involving IVT injections that OMIC hasn’t considered which specialty had the incident. So for now, at least, OMIC doesn’t restrict coverage of its insured comprehensive ophthalmologists who give IVT injections, Mr. Weber said. “Although we have had general discussions at OMIC about the issue, there is no reason to be concerned about general ophthalmologists doing it, unless and until it’s brought to our attention by a number of claims. At this point, it hasn’t come up as an item to take action upon, in either the claims or underwriting departments.”

    1 Retina 2004;24(5):676–698.

    A “Loved One” Rule of Thumb

    So who should be treating AMD with IVT injections? For Dr. Folk, the answer comes down to the “loved one” rule. “If one of my siblings needed an injection, I’d probably want a retina doctor to do it,” he said. “But if she had to drive 50 miles every time, and had a good comprehensive ophthalmologist to do it, I’d be okay with that, too.”

    Dr. Coombs, whose patients have to drive much farther than 50 miles to see a retina specialist, said, “This is something that can be treated safely and effectively by comprehensive ophthalmologists.” But, he added, “One needs to make a commitment to stay current on the evolving data emerging from these treatments, as retina specialists do.”

    Special thanks to Dr. Folk and ophthalmic photographer Brice Critser for images they shared for this story.

    Meet the Experts

    Private practitioner, Twin Falls, Idaho.

    Associate professor of ophthalmology, Duke University, Durham, N.C.

    Professor of ophthalmology, University of Iowa, Iowa City.

    Private practitioner, South Bend, Ind.

    Ophthalmologist-in-chief, Wills Eye Hospital, Philadelphia.

    Director, OCT Reading Center, Cole Eye Institute, Cleveland Clinic.

    Associate professor of ophthalmology, University of Iowa, Iowa City.

    Vice president, risk management legal department, Ophthalmic Mutual Insurance Company, San Francisco.

    None of the interviewees report related financial interests.