Cover Story

Successful retinal injection practice depends on clinical efficiency, patient satisfaction

Anti-VEGF injections can help maintain and sometimes improve visual acuity in patients with degenerative retinal diseases, but there is an associated high treatment burden that requires patient and caregiver dedication, and well-organized, streamlined delivery from ophthalmologists.

Anti-VEGF injections have revolutionized treatment of neovascular age-related macular degeneration, diabetic eye disease and macular edema secondary to retinal vein occlusions, among other vitreoretinal diseases, OSN Retina/Vitreous Board Member Seenu M. Hariprasad, MD, said.

Patients, who must visit their ophthalmologists at fixed intervals for therapy, risk degrading vision if treatment is ignored, so the experience for both patients and their caregivers must be “pleasant.”

Seenu M. Hariprasad
Injections can be physically demanding, according to Seenu M. Hariprasad, MD, and physicians should take precautions to ensure their self-care when performing such repetitive actions.

Source: Seenu M. Hariprasad, MD

“A pleasant experience means clinical efficiency, which translates to quick and comfortable appointments and as little pain as possible during the injection procedure,” Hariprasad said. “Proper anesthetic techniques are key.”

The key challenge facing both the patient and the clinic is the demanding treatment burden associated with frequent clinic visits, according to Healio/OSN Board Member Arshad M. Khanani, MD, MA.

Patients, who are generally older, need to arrange multiple clinic appointments and often travel arrangements as well, while clinic staff are faced with the challenge of accommodating a constant stream of patients daily.

“We need to take care to not burn out our staff because we’re seeing 80 to 100 patients each day and performing up to 30 to 40 injections daily,” Khanani said. “Accommodating patients and allocating space in the clinic requires a coordinated, concerted effort.”

For neovascular AMD, clinical trials have demonstrated treatment efficacy of Lucentis (ranibizumab, Genentech), Eylea (aflibercept, Regeneron) and Avastin (bevacizumab, Genentech) dosed at fixed intervals between 4 and 8 weeks.

The MARINA and ANCHOR trials showed a ranibizumab 0.5 mg injection once monthly was the most effective regimen for the drug, whereas three monthly injections of ranibizumab 0.5 mg followed by regular assessment but less frequent dosing were less effective. Similarly, the CATT trial deemed once-monthly injections with bevacizumab 1.25 mg to be that drug’s best regimen. The preferred dosing regimen for aflibercept was determined in the VIEW 1 and VIEW 2 clinical trials to be once every 4 weeks for 3 months, followed by injections at 8-week intervals.

Success begins in clinic

Arshad M. Khanani
Arshad M. Khanani

Because age is the greatest risk factor for AMD, the prevalence of AMD in the U.S. has been projected to reach 22 million by 2050 due to an increase in the aging population. This increase in the number of patients who require treatment every 4 to 8 weeks has prompted some clinics to devote entire days to only performing intravitreal injections, Khanani said.

To maximize efficiency, Hariprasad has split injection visit types into two categories. One day is for those who need a full examination, with dilation and imaging along with an injection. The second day is dedicated solely to performing injections and other retinal procedures such as lasers.

At Khanani’s clinic, injections are integrated in every clinic day, and the need for an examination before injections depends on the patient’s pathology and insurance. Having a dedicated employee for prior authorization from the insurance companies as well as copay assistance programs is a necessity, he said.

Most patients have Medicare, which does not require preapproval for most branded anti-VEGFs, but if they have secondary or commercial insurance, preapproval may be needed for certain injections, he said.

“If we know a patient is coming and they need an injection, we’ll look at their insurance prior to their appointment to see what they’re covered for, or our preauthorization specialist will work to get the patient approved for a certain drug we’d like to give them,” Khanani said.

In many cases the designated employee can acquire insurance approval for a drug on the day of the appointment. If insurance approval is not acquired, the employee can assist the patient with signing up for a copay assistance program.

“We have an authorization employee working to get their authorization the day of the appointment, we have a copay and foundation assistance employee to find the cheapest solution, and we have two employees solely dedicated to solving problems with insurance. Between these people, we have full confidence in getting coverage for our patients and being reimbursed for the injections,” Khanani said.

Insurance companies may also only approve branded drugs if step therapy is initiated. If so, Khanani starts the patient on bevacizumab. If the treatment response is inadequate, then the insurance company typically grants approval for a branded drug.

When no insurance coverage solution is determined on the day of the patient’s appointment, drug samples can be used and drug authorization acquired for the patient’s next appointment, Khanani said.

Balancing drug choices

Michael D. Ober
Michael D. Ober

Drug choice can simply boil down to what is best for the patient and the economy as a whole. Michael D. Ober, MD, FACS, of Retina Consultants of Michigan, said he will typically use bevacizumab as a first injection and monitor its efficiency before moving to a more expensive drug.

“If somebody doesn’t respond as well as I want them to, then I advance them to another anti-VEGF. The majority of people do very well on Avastin, and they would probably have done equally well on a more expensive drug, but by starting with Avastin, it can reduce the overall financial burden on health care,” Ober said.

Bevacizumab usually results in rapid anatomic improvement when used for neovascular AMD. If no effect or worsening is noticed after the first injection, switching to a different drug is appropriate. However, a single injection of bevacizumab often does not induce an anatomic change as rapidly when used for diabetic macular edema, so patients with this disease need to be monitored closely after several injections to see how they respond, Ober said.

If a patient does not respond well to bevacizumab, alternative anti-VEGFs should be considered. Each patient who is switched to a more expensive drug receives a full benefit analysis and is offered enrollment in a copay assistance program if any out-of-pocket expenses are required, he said.

“I look at these drugs, especially the expensive ones, as a potential liability more so than a profit center. I pay for these drugs first, so if I’m going to outlay $2,000, I want to be as assured as humanly possible I’ll be reimbursed for the full amount. If there is any question about an out-of-pocket cost, or if the insurance company won’t pay, I need to know up front so we can enroll the patient in copay assistance or make arrangements for drug prepayment,” Ober said.

The economy must be taken into consideration when choosing a drug, Hariprasad said. Ranibizumab costs close to $2,000 a vial, while brolucizumab and aflibercept are closer to $1,800 a vial. Both brolucizumab and aflibercept require fewer injections than ranibizumab. “Therefore, we rarely use ranibizumab in our practice,” he said.

OSN Retina/Vitreous Section Editor Andrew A. Moshfeghi, MD, MBA, who integrates injection patients into his regular clinic practice, said, “Using Avastin is an easy choice that will rarely result in delays in treatment, except for HMO plans that may still require a preauthorization.”

Bevacizumab procured from a compounding pharmacy is kept on hand in a commercial-grade locked refrigerator with battery back-up and temperature excursion monitoring and alarms.

No matter what drug is used, Moshfeghi said that only he performs injections in his clinics. While ophthalmology residents and fellows are also present, patients are grateful for the consistency of their injection experiences, and it “provides a more personal service.”

Brolucizumab is available

A fourth anti-VEGF, Beovu (brolucizumab-dbll, Novartis), may alter the way clinics treat retinal diseases and could lessen the need for such frequent injections. The therapy was approved by the FDA in October 2019 as the first anti-VEGF approved for 3-month dosing intervals in most patients following a 3-month loading phase, and CMS has issued a permanent J-code for the drug, effective Jan. 1, 2020.

Phase 3 results of the HAWK/HARRIER studies supported the approval by showing brolucizumab to be noninferior to aflibercept with regard to change in best corrected visual acuity at week 48. In both studies, patients were treated with three loading doses and then doses every 12 weeks during the maintenance phase, unless disease activity was noted, at which point patients were dropped to a permanent every 8 week dosing regimen until the end of the trial.

Brolucizumab is being quickly integrated into Ober’s clinic.

“This has just become a part of our armamentarium,” Ober said. “If patients respond to the drug as it was prescribed in the trials and we don’t see different or more numerous side effects, then it will receive even more use. It’s still in the early adoption phase for us right now.”

Monitoring missed appointments

With treatments necessary at such fixed intervals, clinics must have an efficient system to monitor patients who miss injection dates. Moshfeghi said an automated phone call is placed from his clinic to the patient if an appointment is missed, and a letter is mailed as well.

Andrew A. Moshfeghi
Andrew A. Moshfeghi

“I also pay attention to the ‘no-shows’ myself and ask the clinic staff to separately go out of their way to contact them to reschedule for an appropriate follow-up,” he said.

It can be a big problem if multiple injections are missed. It is a challenging issue with no readily apparent solution, Hariprasad said.

Manually making notes in a patient’s file if they miss an injection appointment and having an assistant reach out to them at the end of the business day is an effective follow-up method, he said.

“It’s a very archaic, manual, labor-intensive process, but it does work, and it helps us reschedule these patients as quickly as we possibly can,” he said.

These are usually older patients who depend on others to provide transportation. Illnesses are frequent, and months of appointments can be missed, Khanani said.

It is the clinic’s job to follow up and recognize when several appointments in a row are missed. These patients need to be contacted for expedited injections, he said.

“They receive a full examination, including a vision check and an OCT exam, and we give them their injections. My goal is also to dilate a patient once every 3 to 4 months, so we’ll monitor their disease and decide if they need to be dilated as well,” Khanani said.

Pay attention to ergonomics

With a multitude of injections being performed, ergonomics can be a particular challenge for the ophthalmologist. Injections can be physically demanding, Hariprasad said, and physicians should take precautions to ensure their self-care when doing such repetitive actions.

Proper posture, shoes with adequate arch support and stretching exercises can greatly reduce wear and tear on physicians who do many injections each week, he said.

“Self-care is so important. Meditation, stretching exercises and working out several times a week can help a lot. Of course, getting a great night’s sleep can help you be on top of your game. Try to keep your back straight when giving injections and remember not to hunch over. It all adds up and really helps prevent physical and mental burnout,” he said.

The procedure can be strenuous for physicians, and also for patients, both mentally and physically, Ober said.

Proper anesthetic choices can greatly reduce the physical and emotional discomfort an anti-VEGF injection can have on a patient. Most ophthalmologists will only offer a topical anesthesia during the procedure, but Ober strongly urged the use of a subconjunctival anesthesia for all patients, at least for their first injection.

“I tend to use subconjunctival anesthesia for everybody for their first injection, just so they know it can be a painless procedure. Then I will offer them a topical anesthesia for the second injection, and I’d say about half or more choose the topical anesthesia because they get less of a red eye and less irritation,” he said.

Subconjunctival anesthesia allows an ophthalmologist to guarantee no pain during an injection, which can greatly reduce anxiety over the first procedure, he said.

Avoiding injection burnout

The procedures can also take a toll on clinical staff, Khanani said. Several employees are required to take on specific responsibilities during a retina clinic to ensure everything moves smoothly. Employees are needed for drug authorizations, for signing up patients for copay programs, for communication with insurance companies or other agencies to ensure injections are provided, and for all aspects of service during these high-traffic days.

Attention needs to be paid to staff morale as clinic days can be busy and run late due to emergencies and add-ons, he said.

“Everyone working together in a clinic can result in a very productive practice where your patients are treated quickly, injections are provided efficiently, and all efforts are made to provide branded drugs at the lowest out-of-pocket costs for patients,” Khanani said.

With decisions on anti-VEGF drugs, insurance coverage challenges and the monotony of giving retinal injections, ophthalmologists can often forget to make appointments personalized experiences for these often-elderly patients depending on this therapy to maintain their quality of life.

“These patients are oftentimes the most recognized patients in our practice. We see them so frequently, they’ve been part of our practice for years, so it’s nice to know them by name and to know something personal about them to try to make it an individualized experience. These are older patients; many of them enjoy the social interaction of the appointments, and we need to help foster that personalized experience for all of them,” Hariprasad said. – by Robert Linnehan

Disclosures: Hariprasad reports he is a consultant or on the speakers bureau for Graybug, Allergan, Novartis, EyePoint, Alimera Sciences, Spark and Regeneron. Khanani reports he is a consultant for Genentech, is a consultant and speaker for Novartis and Allergan, and receives research funding from Allergan, Genentech and Novartis. Moshfeghi reports he is a consultant to and receives research support from Novartis, Regeneron, Genentech and Allegro, is a consultant to and receives speaking compensation from Allergan and is a consultant to Alimera. Ober reports no relevant financial disclosures.

Click here to read the Point/Counter to this Cover Story.

Anti-VEGF injections can help maintain and sometimes improve visual acuity in patients with degenerative retinal diseases, but there is an associated high treatment burden that requires patient and caregiver dedication, and well-organized, streamlined delivery from ophthalmologists.

Anti-VEGF injections have revolutionized treatment of neovascular age-related macular degeneration, diabetic eye disease and macular edema secondary to retinal vein occlusions, among other vitreoretinal diseases, OSN Retina/Vitreous Board Member Seenu M. Hariprasad, MD, said.

Patients, who must visit their ophthalmologists at fixed intervals for therapy, risk degrading vision if treatment is ignored, so the experience for both patients and their caregivers must be “pleasant.”

Seenu M. Hariprasad
Injections can be physically demanding, according to Seenu M. Hariprasad, MD, and physicians should take precautions to ensure their self-care when performing such repetitive actions.

Source: Seenu M. Hariprasad, MD

“A pleasant experience means clinical efficiency, which translates to quick and comfortable appointments and as little pain as possible during the injection procedure,” Hariprasad said. “Proper anesthetic techniques are key.”

The key challenge facing both the patient and the clinic is the demanding treatment burden associated with frequent clinic visits, according to Healio/OSN Board Member Arshad M. Khanani, MD, MA.

Patients, who are generally older, need to arrange multiple clinic appointments and often travel arrangements as well, while clinic staff are faced with the challenge of accommodating a constant stream of patients daily.

“We need to take care to not burn out our staff because we’re seeing 80 to 100 patients each day and performing up to 30 to 40 injections daily,” Khanani said. “Accommodating patients and allocating space in the clinic requires a coordinated, concerted effort.”

For neovascular AMD, clinical trials have demonstrated treatment efficacy of Lucentis (ranibizumab, Genentech), Eylea (aflibercept, Regeneron) and Avastin (bevacizumab, Genentech) dosed at fixed intervals between 4 and 8 weeks.

The MARINA and ANCHOR trials showed a ranibizumab 0.5 mg injection once monthly was the most effective regimen for the drug, whereas three monthly injections of ranibizumab 0.5 mg followed by regular assessment but less frequent dosing were less effective. Similarly, the CATT trial deemed once-monthly injections with bevacizumab 1.25 mg to be that drug’s best regimen. The preferred dosing regimen for aflibercept was determined in the VIEW 1 and VIEW 2 clinical trials to be once every 4 weeks for 3 months, followed by injections at 8-week intervals.

Success begins in clinic

Arshad M. Khanani
Arshad M. Khanani

Because age is the greatest risk factor for AMD, the prevalence of AMD in the U.S. has been projected to reach 22 million by 2050 due to an increase in the aging population. This increase in the number of patients who require treatment every 4 to 8 weeks has prompted some clinics to devote entire days to only performing intravitreal injections, Khanani said.

PAGE BREAK

To maximize efficiency, Hariprasad has split injection visit types into two categories. One day is for those who need a full examination, with dilation and imaging along with an injection. The second day is dedicated solely to performing injections and other retinal procedures such as lasers.

At Khanani’s clinic, injections are integrated in every clinic day, and the need for an examination before injections depends on the patient’s pathology and insurance. Having a dedicated employee for prior authorization from the insurance companies as well as copay assistance programs is a necessity, he said.

Most patients have Medicare, which does not require preapproval for most branded anti-VEGFs, but if they have secondary or commercial insurance, preapproval may be needed for certain injections, he said.

“If we know a patient is coming and they need an injection, we’ll look at their insurance prior to their appointment to see what they’re covered for, or our preauthorization specialist will work to get the patient approved for a certain drug we’d like to give them,” Khanani said.

In many cases the designated employee can acquire insurance approval for a drug on the day of the appointment. If insurance approval is not acquired, the employee can assist the patient with signing up for a copay assistance program.

“We have an authorization employee working to get their authorization the day of the appointment, we have a copay and foundation assistance employee to find the cheapest solution, and we have two employees solely dedicated to solving problems with insurance. Between these people, we have full confidence in getting coverage for our patients and being reimbursed for the injections,” Khanani said.

Insurance companies may also only approve branded drugs if step therapy is initiated. If so, Khanani starts the patient on bevacizumab. If the treatment response is inadequate, then the insurance company typically grants approval for a branded drug.

When no insurance coverage solution is determined on the day of the patient’s appointment, drug samples can be used and drug authorization acquired for the patient’s next appointment, Khanani said.

Balancing drug choices

Michael D. Ober
Michael D. Ober

Drug choice can simply boil down to what is best for the patient and the economy as a whole. Michael D. Ober, MD, FACS, of Retina Consultants of Michigan, said he will typically use bevacizumab as a first injection and monitor its efficiency before moving to a more expensive drug.

“If somebody doesn’t respond as well as I want them to, then I advance them to another anti-VEGF. The majority of people do very well on Avastin, and they would probably have done equally well on a more expensive drug, but by starting with Avastin, it can reduce the overall financial burden on health care,” Ober said.

PAGE BREAK

Bevacizumab usually results in rapid anatomic improvement when used for neovascular AMD. If no effect or worsening is noticed after the first injection, switching to a different drug is appropriate. However, a single injection of bevacizumab often does not induce an anatomic change as rapidly when used for diabetic macular edema, so patients with this disease need to be monitored closely after several injections to see how they respond, Ober said.

If a patient does not respond well to bevacizumab, alternative anti-VEGFs should be considered. Each patient who is switched to a more expensive drug receives a full benefit analysis and is offered enrollment in a copay assistance program if any out-of-pocket expenses are required, he said.

“I look at these drugs, especially the expensive ones, as a potential liability more so than a profit center. I pay for these drugs first, so if I’m going to outlay $2,000, I want to be as assured as humanly possible I’ll be reimbursed for the full amount. If there is any question about an out-of-pocket cost, or if the insurance company won’t pay, I need to know up front so we can enroll the patient in copay assistance or make arrangements for drug prepayment,” Ober said.

The economy must be taken into consideration when choosing a drug, Hariprasad said. Ranibizumab costs close to $2,000 a vial, while brolucizumab and aflibercept are closer to $1,800 a vial. Both brolucizumab and aflibercept require fewer injections than ranibizumab. “Therefore, we rarely use ranibizumab in our practice,” he said.

OSN Retina/Vitreous Section Editor Andrew A. Moshfeghi, MD, MBA, who integrates injection patients into his regular clinic practice, said, “Using Avastin is an easy choice that will rarely result in delays in treatment, except for HMO plans that may still require a preauthorization.”

Bevacizumab procured from a compounding pharmacy is kept on hand in a commercial-grade locked refrigerator with battery back-up and temperature excursion monitoring and alarms.

No matter what drug is used, Moshfeghi said that only he performs injections in his clinics. While ophthalmology residents and fellows are also present, patients are grateful for the consistency of their injection experiences, and it “provides a more personal service.”

Brolucizumab is available

A fourth anti-VEGF, Beovu (brolucizumab-dbll, Novartis), may alter the way clinics treat retinal diseases and could lessen the need for such frequent injections. The therapy was approved by the FDA in October 2019 as the first anti-VEGF approved for 3-month dosing intervals in most patients following a 3-month loading phase, and CMS has issued a permanent J-code for the drug, effective Jan. 1, 2020.

PAGE BREAK

Phase 3 results of the HAWK/HARRIER studies supported the approval by showing brolucizumab to be noninferior to aflibercept with regard to change in best corrected visual acuity at week 48. In both studies, patients were treated with three loading doses and then doses every 12 weeks during the maintenance phase, unless disease activity was noted, at which point patients were dropped to a permanent every 8 week dosing regimen until the end of the trial.

Brolucizumab is being quickly integrated into Ober’s clinic.

“This has just become a part of our armamentarium,” Ober said. “If patients respond to the drug as it was prescribed in the trials and we don’t see different or more numerous side effects, then it will receive even more use. It’s still in the early adoption phase for us right now.”

Monitoring missed appointments

With treatments necessary at such fixed intervals, clinics must have an efficient system to monitor patients who miss injection dates. Moshfeghi said an automated phone call is placed from his clinic to the patient if an appointment is missed, and a letter is mailed as well.

Andrew A. Moshfeghi
Andrew A. Moshfeghi

“I also pay attention to the ‘no-shows’ myself and ask the clinic staff to separately go out of their way to contact them to reschedule for an appropriate follow-up,” he said.

It can be a big problem if multiple injections are missed. It is a challenging issue with no readily apparent solution, Hariprasad said.

Manually making notes in a patient’s file if they miss an injection appointment and having an assistant reach out to them at the end of the business day is an effective follow-up method, he said.

“It’s a very archaic, manual, labor-intensive process, but it does work, and it helps us reschedule these patients as quickly as we possibly can,” he said.

These are usually older patients who depend on others to provide transportation. Illnesses are frequent, and months of appointments can be missed, Khanani said.

It is the clinic’s job to follow up and recognize when several appointments in a row are missed. These patients need to be contacted for expedited injections, he said.

“They receive a full examination, including a vision check and an OCT exam, and we give them their injections. My goal is also to dilate a patient once every 3 to 4 months, so we’ll monitor their disease and decide if they need to be dilated as well,” Khanani said.

PAGE BREAK

Pay attention to ergonomics

With a multitude of injections being performed, ergonomics can be a particular challenge for the ophthalmologist. Injections can be physically demanding, Hariprasad said, and physicians should take precautions to ensure their self-care when doing such repetitive actions.

Proper posture, shoes with adequate arch support and stretching exercises can greatly reduce wear and tear on physicians who do many injections each week, he said.

“Self-care is so important. Meditation, stretching exercises and working out several times a week can help a lot. Of course, getting a great night’s sleep can help you be on top of your game. Try to keep your back straight when giving injections and remember not to hunch over. It all adds up and really helps prevent physical and mental burnout,” he said.

The procedure can be strenuous for physicians, and also for patients, both mentally and physically, Ober said.

Proper anesthetic choices can greatly reduce the physical and emotional discomfort an anti-VEGF injection can have on a patient. Most ophthalmologists will only offer a topical anesthesia during the procedure, but Ober strongly urged the use of a subconjunctival anesthesia for all patients, at least for their first injection.

“I tend to use subconjunctival anesthesia for everybody for their first injection, just so they know it can be a painless procedure. Then I will offer them a topical anesthesia for the second injection, and I’d say about half or more choose the topical anesthesia because they get less of a red eye and less irritation,” he said.

Subconjunctival anesthesia allows an ophthalmologist to guarantee no pain during an injection, which can greatly reduce anxiety over the first procedure, he said.

Avoiding injection burnout

The procedures can also take a toll on clinical staff, Khanani said. Several employees are required to take on specific responsibilities during a retina clinic to ensure everything moves smoothly. Employees are needed for drug authorizations, for signing up patients for copay programs, for communication with insurance companies or other agencies to ensure injections are provided, and for all aspects of service during these high-traffic days.

Attention needs to be paid to staff morale as clinic days can be busy and run late due to emergencies and add-ons, he said.

“Everyone working together in a clinic can result in a very productive practice where your patients are treated quickly, injections are provided efficiently, and all efforts are made to provide branded drugs at the lowest out-of-pocket costs for patients,” Khanani said.

With decisions on anti-VEGF drugs, insurance coverage challenges and the monotony of giving retinal injections, ophthalmologists can often forget to make appointments personalized experiences for these often-elderly patients depending on this therapy to maintain their quality of life.

PAGE BREAK

“These patients are oftentimes the most recognized patients in our practice. We see them so frequently, they’ve been part of our practice for years, so it’s nice to know them by name and to know something personal about them to try to make it an individualized experience. These are older patients; many of them enjoy the social interaction of the appointments, and we need to help foster that personalized experience for all of them,” Hariprasad said. – by Robert Linnehan

Disclosures: Hariprasad reports he is a consultant or on the speakers bureau for Graybug, Allergan, Novartis, EyePoint, Alimera Sciences, Spark and Regeneron. Khanani reports he is a consultant for Genentech, is a consultant and speaker for Novartis and Allergan, and receives research funding from Allergan, Genentech and Novartis. Moshfeghi reports he is a consultant to and receives research support from Novartis, Regeneron, Genentech and Allegro, is a consultant to and receives speaking compensation from Allergan and is a consultant to Alimera. Ober reports no relevant financial disclosures.

Click here to read the Point/Counter to this Cover Story.