Maintenance, re-treatments for AMD challenge retina practices

In order to create a more streamlined process, doctors have made changes to their dosing regimens, schedules and staffing.

With the introduction of new pharmacotherapeutic options for retinal diseases such as age-related macular degeneration, retina practices are confronted with the challenges of providing regular maintenance for a growing number of patients.

Retina specialists are just beginning to feel the strain of keeping up with frequent repeat injections and combinations of therapies.

Judy E. Kim

“If most of our slots are being filled by these returning patients, then something has to give,” Ocular Surgery News Retina/Vitreous Section Member Judy E. Kim, MD, said.

“Either the doctor has to work longer hours, become more efficient or cut out some of the new patient slots,” she said. “Since new patients generate surgeries, and we generate more revenue doing surgeries than these injections, there are financial implications to the practice as well as office flow and providing best care.”

Several retina experts spoke with OSN about the adaptations they are making to their surgical techniques, office flow, staff involvement and the type of written information they provide to patients.

“Patients always come first, but we’re trying to strike a balance,” Philip J. Rosenfeld, MD, PhD, said. “In the reality of most people’s lives, seeing the physician every month for 2 years or longer just isn’t a practical option. But, patients and doctors will do whatever is necessary to preserve and improve vision.”

These changes, along with current research supporting combination therapy, sustained release drugs and new medications will greatly affect this process in the future (see sidebar).

“I think that the evolution in the modern management of AMD is continuing,” Abdhish R. Bhavsar, MD, said. “However, we are still at the Neanderthal stage of where the evolution will eventually take us. We have really started with pharmacotherapy in its infancy right now.”

Frequent injections

Dr. Bhavsar said the introduction of drugs such as bevacizumab (Avastin, Genentech) and ranibizumab (Lucentis, Genentech/Novartis) has created a need for repeat injections as often as every month.

Carl D. Regillo, MD, FACS, OSN Retina/Vitreous Section Member, pointed out that this began with the launch of pegabtanib (Macugen, Eyetech) in January 2005 and then escalated rapidly with the adoption of bevacizumab and ranibizimab in practice over the past year or so.

“In order to accommodate the increased number of patient visits and procedures, we’ve had to increase our staffing in each of our offices,” Dr. Regillo said.

Dr. Bhavsar said similar problems arise regardless of the dosing regimen employed.

“Even when we attempt to perform an alternate dosing regimen with three injections followed by an as-needed dosing regimen, by and large we are following those patients at nearly similar intervals to the injection intervals,” Dr. Bhavsar said.

With any dosing regimen, he said, there is a need for appointments, even if just for monitoring because there is still an uncertainty about long-term risks and benefits.

“The volume of patients who we need to continue to follow on an ongoing basis, is increasing to a staggering proportion,” Dr. Bhavsar said. “That taxes our clinic staff, our clinic schedule, taxes our use of ancillary testing, mostly with respect to optical coherence tomography (OCT).”

Regardless of how frequently the patient needs to be dosed, Dr. Kim said the new treatments entail spending more time per patient.

“If we [make a decision based on] the OCT, then the patient will come in, have an OCT and an examination. Then the doctor will have to make a decision to treat or not. If the patient needs treatment, there is that extra time factor involved,” she said. “If the patient is deemed not to need treatment, then the doctor will need to counsel the patient, so there is additional time of either talking or treating. There’s that X-factor.”

Rethinking practice management styles

Clinicians are now forced to rethink their practice management style to create a more streamlined process.

“I would rather function at a little bit more reasonable pace where I don’t need to worry as much, if I am able to spend a few extra minutes talking to the patient about how their day was,” Dr. Bhavsar said. “I’m starting to miss that personal interaction, and it’s becoming a little bit more difficult to find time to do that.”

One way for physicians to actively change their practice is to change the dosing regimen to allow for more time between each patient’s injections.

“When I talk to other physicians, I find that each of us has come up with different approaches,” Dr. Kim said. “We are still trying to maximize treatment effect with fewer treatments, if possible, rather than performing automatic monthly treatment without concern for what is going on inside the eye.”

She said if she has a patient who cannot return every month as prescribed with ranibizumab for examination and possible injection, she does as-needed injections of bevacizumab after a thorough informed consent. The patient usually needs to return only every 6 to 8 weeks.

Philip J. Rosenfeld

“Whether that’s correct or not, nobody knows,” she said. “It’s a number I arrived at, after having treated a number of patients. It is still better for patients to receive some form of treatment than to decide not to have treatment due to difficulties with frequent follow-up.”

Dr. Rosenfeld relies upon his own clinical experience, as well as the results of the PRONTO (Prospective OCT imaging of patients with neovascular AMD treated with intraocular Lucentis) and PIER (Phase 3b, multi-center, randomized, double-masked, sham injection-controlled study of the efficacy and safety of ranibizumab in subjects with subfoveal choroidal neovascularization with or without classic CNV secondary to AMD) studies to derive his own treatment regimen.

Based on the phase 3 MARINA and ANCHOR results, he said injecting ranibizumab every month for 2 years is safe and produces excellent visual acuity outcomes.

However, the PRONTO study suggested an alternative dosing regimen, Dr. Rosenfeld said. “Using the broad re-treatment criteria in the PRONTO study, we showed that once the macula is dry by OCT following Lucentis therapy, additional treatment as needed based on the re-accumulation of fluid in the macula yielded results similar to the monthly phase 3 injection regimen,” he said.

Of course, he added, the ideal regimen would be to re-treat before any fluid re-accumulates in the macula. “PRONTO was an exploratory study designed to show that when the earliest manifestation of recurrent fluid is detected by OCT and no treatment is given, then more fluid will continue to re-accumulate and vision will eventually deteriorate. If we had treated at the earliest sign of fluid, our critics would have argued that it may not have been necessary. Now we know that if we don’t treat, more fluid will accumulate, so we can’t justify waiting until vision is affected.

“PRONTO also showed us that even if the fluid does re-accumulate, it will usually accumulate slowly, and there’s a window of opportunity to reinject that can span weeks. Once the re-treatment interval is established for the individual patient, we have much greater flexibility in scheduling and treatment. We found that some patients can go 9 months or longer without needed additional treatments,” Dr. Rosenfeld said.

He said the PIER study demonstrated that a fixed quarterly regimen does not work for all patients. Currently, Dr. Rosenfeld said he treats every patient monthly until OCT shows no sign of fluid, and then, he either observes monthly until the fluid re-accumulates or he treats even when the macula is dry and extends the next visit for 2 months and continues to treat and extend the visits as long as the macula is dry. That way, he said, he can schedule his patients less frequently and still maintain their dry macula as assessed by OCT. The down side of injecting an eye with a dry macula is that it may not be necessary, but the upside is that the follow-up can be extended.

“For example, if somebody needed a reinjection 8 weeks after a previous injection, I would bring them back thereafter at 7 weeks,” he said. “I would do that for several 7-week intervals, and then I would try to extend the re-treatment interval to see if we could get away with 8 weeks and then 12 weeks. However, if the macula is dry 1 month after an injection, then I would offer them the option of returning every month to see when they might start re-accumulating fluid in the macula or I could inject them at that visit and not see them back for 2 months, and if dry at 2 months, they could receive an injection and not be seen for 3 months,” he said. This regimen allows the patient to come in less frequently.

“All of these treatment decisions are made with the patient, and I give the patient a choice,” he said. “Some patients prefer to avoid an injection and be monitored monthly, while others prefer less frequent visits. I want to emphasize that this is the approach I feel comfortable using,” he said. “It’s not meant as a paradigm for everybody to use. Everybody needs to work in their own comfort zone.”

Office flow and scheduling

In addition to trying different dosing regimens, some clinicians have tried to adapt their scheduling to improve patient flow.

“Some doctors are doing [injections] between their other follow-up patients,” Dr. Kim said. “Others have decided to do an injection clinic where a number of patients during that time frame are just coming back for injections. Then some have decided to carve out that extra time in addition to what they were doing before.”

Dr. Kim schedules most of her injections in one afternoon where she meets with other patients in between the injections.

Carl D. Regillo

Although Drs. Regillo and Rosenfeld said they have not reserved any specific time for injections, they have made changes.

“In order to accommodate the increased number of visits, intraocular injections and OCT tests, we increased our staffing in each of our offices. We’ve even had to create additional space for the procedures,” Dr. Regillo said. “This has helped quite a bit with flow, to have extra personnel and an extra room as a designated injection room or procedure room.”

At each office of his extended practice there is a room dedicated to injections, but he said they have also prepared every exam room with the equipment necessary to perform injections.

“We have built-in flexibility, so a patient can get injections in an exam room in addition to the procedure room,” Dr. Regillo said.

Dr. Rosenfeld said his practice now has individuals in full-time positions dedicated to the injection procedure, and Dr. Regillo said his practice is considering hiring another physician to further accommodate patients.

Dr. Kim said her practice is considering hiring a medical retina associate to handle AMD cases.

Small modifications can increase efficiency

Without making drastic changes such as setting aside injection-only time or hiring new retina specialists, the experts who spoke to OSN discussed how they streamlined their existing processes.

“I think the main ways that we have tried to be efficient are with our method of preparation of the injection materials,” Dr. Bhavsar said.

His process begins at the beginning of the clinic day with five or six prepared injection trays that are missing only the patient’s drug of choice.

“After I have examined the patient, discussed the treatment options, the patient has made his/her decision and I have marked the treatment eye with a piece of tape with the drug and OD or OS written on it, those trays are just brought into the examining room prior to the injection, and then I simply present to the room to do topical anesthesia along with antisepsis with Betadine (povidone-iodine 5%, Purdue Frederick), followed by the injection itself,” Dr. Bhavsar said.

Afterward, he said he relies on his staff to monitor and counsel the patient and to prepare the tray for the next injection.

“I can perform 20 injections in a half-day clinic and not run out of a sterile instrument,” he said “We avoid needing to sterilize these instruments in the middle of a clinic, which can take staff time and take away attention from the direct care of the patients.”

Dr. Kim said her method of grouping her injections into one afternoon helped her technicians better prepare and be more efficient.

In Dr. Regillo’s office, he said they have formalized the policies and procedures to devise a standardized preparation.

“We’re pretty much doing the same thing we’ve always done, but it’s definitely much more efficient after we’ve standardized things and created more space for the procedures,” he said.

He also said they began marking the eye that should be injected, just as they do for surgery, to prevent errors.

Advancing technologies could reduce AMD treatment burden by Katrina Altersitz As retina physicians attempt to adapt to the demands of maintenance therapy, research is under way to further decrease the treatment burden through advanced technology. “We are early in our evolution. I believe that in the mid-term we will be evolving further, so that we will not need to see patients as often,” Abdhish R. Bhavsar, MD, said. “There is also a possibility that, with other exploration of adjunct or combination treatment, we may be able to improve treatment with respect to frequency of administration.” Currently, the ongoing SAILOR (Safety assessment of intravitreal Lucentis for age-related macular degeneration) and CATT (Complications of AMD Treatments Trial) trials seek to delineate the difference in efficacy and dosing for Lucentis (ranibizumab, Genentech/Novartis) and Avastin (bevacizumab, Genentech). “To know for sure whether this as-needed regimen is as good as monthly dosing or maybe even better than monthly dosing, we need to do a head-to-head trial,” Philip J. Rosenfeld, MD, PhD, said. “Hopefully, we should get some information from the CATT, the [National Institutes of Health] trial, and hopefully Genentech will run an as-needed trial as well, as part of its post-marketing obligation.” Some physicians, however, feel that funding could be better spent researching new treatments rather than those already proved to be effective. “We should focus our efforts on developing the next generation of pharmacotherapies that will be superior to both Lucentis and/or Avastin,” Dr. Bhavsar said. “I would be hopeful that in 4 years we are treating with a regimen of either a combination of existing drugs or newer drugs that will allow us to treat the disease in a more effective manner that requires less frequent treatments.” He added that, despite what is already known about Lucentis and what is still unknown about Avastin, physicians are using both agents; therefore, he said he doubts the study would change the regimens of many retina specialists. “We should be in a better place half a decade from now, if we use our resources not to just figure out differences about what we’re doing today but figure out what the next level should be,” Dr. Bhavsar said. Perhaps a combination approach with photodynamic therapy would work, he suggested, but Dr. Rosenfeld said he was not yet convinced of that method. “I’ve yet to see a study with photodynamic therapy in which the visual acuity outcome is as good as with Lucentis,” Dr. Rosenfeld said. “As long as doctors and patients know they may be sacrificing acuity for convenience, I think it’s a perfectly reasonable option, but it, too, needs to be studied, and it is being studied.” He added, “Hopefully there will be several studies over the next year that will show that various combination therapies prolong the fluid-free interval, thus decreasing the treatment burden, but these combination therapies need to preserve or hopefully improve upon the visual acuity outcome seen with Lucentis alone.” Katrina Altersitz is the Managing Editor of OSN Latin America and India Editions.

Staff involvement

With the changes needed to make a retina practice run efficiently with this influx of patients, a lot of responsibility is put upon the staff of technicians, requiring more training and instruction.

“My staff is much more involved with the entire preparation of the injection, counseling pre- and post-injection,” Dr. Bhavsar said. “That places a much heavier burden on the staff, of course, because they’re spending much more time with every patient prior and after each injection.”

He said his staff is trained to counsel the patient in regards to the medications, the injection, the alternatives, the risks and the efficacy, so that they are able to repeat everything that he has discussed with the patient and family members.

Dr. Regillo said his staff was also educated on injection set-up, patient counseling and OCT.

“We had to expand personnel and do additional training for our staff to be able to do OCTs because our OCT volume has correspondingly gone up quite a bit,” he said. “We have more people who have been trained to do OCT, and that part of the process has been streamlined and made more efficient.”

In her practice, Dr. Kim uses technicians to prepare the patient’s eye for injection, assist during injection and counsel each person post-injection.

“Some doctors are uncomfortable having technicians prepare the eye, but I have two technicians I work with very closely,” she said. “I spent a lot of time in the beginning teaching them exactly how I want the lid specula put in, betadine flush to be done, and to apply topical anesthetic with a pledget of cotton tip. During this time, I am in the same room doing the necessary paper work, observing the tech and preparing the drug to be injected. I apply betadine to the area to be injected, mark the distance, inject and inspect. During injection, the tech holds out a hand for the patient to fixate on, which makes the injection safer.

“I give post-injection instructions to the patients, but then all the paperwork and additional questions are handled by the technician, so I can go to the next patient with another tech during that time,” she said. “With proper training, our technicians are valuable assistants.”

More written information

With less time to spend with each patient who is receiving an injection, physicians often now send the patient home with additional written instructions.

“We rely much more heavily on printed information now, which helps with efficiency as well, because in the down time when my staff is not dealing with patient or when I’m not dealing with the patient, the patient and/or their family can review the information and then be well versed in it prior to and after the injection is performed,” Dr. Bhavsar said.

The materials include pre-injection material, education materials for the patient and family and a patient responsibility form, he said.

The patient responsibility form outlines the symptoms they are supposed to watch out for and the need to call the physician if they have any problems or concerns.

“Our patients end up accumulating a lot of these papers over time with their monthly injections, Dr. Kim. “We still give them, because we want to make sure that they know what symptoms to look for and how to contact us.”

For more information:

• Judy E. Kim, MD, can be reached at the Medical College of Wisconsin, 925 N. 87th St., Milwaukee, WI 53226; 414-456-7875; fax: 414-456-6300; e-mail: judykim@mcw.edu. Dr. Kim does not have any financial interest in any of the products mentioned, nor is she a paid consultant.
• Abdhish R. Bhavsar, MD, can be reached at 710 E. 24th St., Suite 304, Minneapolis, MN 55404; 612-871-2292; fax: 612-871-0195; e-mail: bhavs001@umn.edu. Dr. Bhavsar has received research funds from Genentech, Novartis, ISTA and Allergan. He has also served as a consultant to Genentech, Eyetech, Novartis and ISTA.
• Philip J. Rosenfeld, MD, PhD, can be reached at Bascom Palmer Institute, University of Miami School of Medicine, 900 NW 17th St., Miami, FL 33163; 305-326-6148; fax: 305-326-6417; e-mail: prosenfeld@med.miami.edu. Dr. Rosenfeld receives grant support from Genentech, Eyetech, Alcon and Quark and is on the speakers’ bureau for Genentech. He is also an advisory board honorarium for Genentechm, Allergan, Tanox, Genaera, Jerini AG, Quark Inc., Athenagen (Comentis), Othera and TargeGen.
• Carl D. Regillo, MD, FACS, can be reached at Retina Service, Wills Eye Institute, 840 Walnut St., Suite 1020, Philadelphia, PA 19107; 856-755-1278; fax: 856-667-9082; e-mail: cregillo@aol.com. Dr. Regillo has received research funds and has consulted for Genentech, Novartis, QLT, and OSI/Eyetech.

• Katrina Altersitz is Managing Editor of OSN Latin America and India Editions.