December 2016




Retina consultation corner
Approaches to intravitreal anti-VEGF injections differ

by Rich Daly EyeWorld Contributing Writer



Dr. Charles performs an intravitreal injection at Charles Retina Institute.

Source: Steve Charles, MD

David Boyer, MD, and Lloyd Clark, MD, have played key roles in many AMD, diabetic macular edema and vein occlusion clinical trials. Not only have they recruited large numbers of patients, they have been involved in clinical trial design, data safety monitoring committees, data analysis, and reporting the results at key society meetings and in the peer-reviewed literature. They have vast clinical experience in treating these disorders and others treated with anti-VEGF therapy outside the clinical trial space; real world experience is crucial. Their comments provide significant insight into the management of patients with wet AMD, DME, and RVO. I strongly agree with their approach to sterile injection technique, OCT monitoring, adjusting treatment intervals based on response, and using the more effective FDA-approved agents when feasible from a patient cost and reimbursement perspective. Close adherence to treatment intervals correlated with pharmacokinetic information and patient response is crucial. Understanding that DME and CRVO produce approximately 5,000 times more VEGF than wet AMD coupled with knowledge that Lucentis and Eylea have much greater affinity for VEGF than Avastin is crucial. Avastin produced somewhat worse outcomes than Lucentis in the Comparison of AMD Treatment Trials (CATT); this does not apply to DME. Protocol T showed that Eylea was more effective than Lucentis and Lucentis was more effective than Avastin when there was significant edema.

Steven Charles, MD, Chair, ASCRS Retina Clinical Committee

Surgeons outline keys to their approach to the treatment, which has a role in a growing number of conditions

Increasing use of anti-VEGF agents in ocular conditions has led to differing roles among retina specialists.

Lloyd Clark, MD, assistant clinical professor of ophthalmology, University of South Carolina School of Medicine, Columbia, South Carolina, uses Eylea (aflibercept, Regeneron Pharmaceuticals, Tarrytown, New York), Lucentis (ranibizumab, Genentech, South San Francisco), and Avastin (bevacizumab, Genentech) for intravitreal injections.

“That being said, I prefer utilizing [Food and Drug Administration]-approved therapies as an initial drug choice,” Dr. Clark said.

Dr. Clark noted that some circumstances—such as payer and reimbursement issues—necessitate the choice of Avastin, “and the good news is that these patients often respond well to treatment.” Dr. Clark prefers Lucentis and Eylea based less on efficacy than “the possible, but infrequent, risks of contamination or reduced activity of Avastin as it is compounded.” “In terms of the choice between Eylea and Lucentis, they are both great options, and by and large I see them as equivalent for primary treatment of age-related macular degeneration,” Dr. Clark said.

David Boyer, MD, clinical professor of ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, starts all patients on Avastin unless the patients do not want to use a non-FDA approved drug after the risks, benefits, and alternatives of the three drugs are explained.

“I change drugs depending on the treatment response,” Dr. Boyer said.

Keys to technique

Dr. Clark’s injection technique typically involves the use of a dedicated injection room and a highly skilled and experienced technician who prepares patients for the injection. Once a patient has been examined and Dr. Clark has decided an injection is warranted, the technician prepares the patient’s eye with a sterile betadine solution. Dr. Clark uses sterile gloves, inserts a sterile lid speculum, and then performs the intravitreal injection.  “We think this technique, although somewhat time-consuming and costlier, is the safest for our patients,” Dr. Clark said.

For Dr. Boyer, the key to endophthalmitis prevention is the use of 5% povidone iodine.

Dr. Clark has discontinued his use of perioperative antibiotics due to research that found no ability to decrease the incidence of infections. “We do perform a complete betadine prep, use sterile gloves and speculum, and proactively manage patients with blepharitis,” Dr. Clark said.

Optical coherence tomography (OCT) is an important diagnostic tool in the initial evaluation of patients receiving intravitreal injections, Dr. Clark said. But OCT is also critical in the ongoing evaluation of treatment response to anti-VEGF agents.  “It is critical to examine more than just topography or the central scan, but also to take the time to look at multiple images, particularly in areas of pathology from fluorescein or indocyanine green angiography,” Dr. Clark said. “For example, subretinal fluid is a worrisome finding and needs to be addressed, even if it is not under the geometric center of the fovea.”

Treatment schedules

The treatment schedules for both Dr. Clark and Dr. Boyer focus on the treat-and-extend schedule for all patients receiving anti-VEGF agents.

For Dr. Clark, patients with age-related macular degeneration (AMD) are treated monthly until the macula is “dry” or the OCT and vision is stable for several visits. Dr. Clark extends AMD patients slowly, every 2 weeks until about 8 weeks, and then extends by 1 week. “By reducing the extension interval to 1 week, my anecdotal experience is that I am able to identify recurrences much easier, perhaps a small increase in retinal thickness without a significant change in vision, rather than the severe recurrences that have been seen with longer extension intervals or as-needed dosing,” Dr. Clark said.

For non-AMD indications, Dr. Clark uses the same approach but typically extends patients with 2-week intervals.  “These patients are not at risk for the devastating complications of wet AMD recurrence, namely submacular hemorrhage and retinal pigment epithelium tear,” Dr. Clark said.

Other conditions

Diabetic macular edema (DME) and central retinal vein occlusion (CRVO) both have far more vascular endothelial growth factor than AMD, but it is important to remember that they are very different diseases.

Dr. Clark noted that patients with DME and CRVO respond better to the FDA-approved anti-VEGF agents Eylea and Lucentis. The superior efficacy of the two FDA-approved medications in DME patients was demonstrated in clinical trials, while CRVO efficacy lacks randomized data but is based on Dr. Clark’s anecdotal observation.

“The difference in response is likely due to molecular affinity to VEGF, which is much higher with the FDA-approved agents,” Dr. Clark said.

Editors’ note: Dr. Clark has financial interests with Bayer (Leverkusen, Germany), Regeneron Pharmaceuticals, Genentech, Ohr Pharmaceutical (New York), and Santen (Osaka, Japan). Dr. Boyer has financial interests with Genentech, Allergan (Dublin, Ireland), Bayer, Regeneron, Novartis (Basel, Switzerland), and Roche (Basel, Switzerland).

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