Article

Retina Therapy in an International Context

Does location affect how patients receive care?

An elderly patient with a condition like diabetic retinopathy or diabetic macular edema will have somewhat different experiences as he or she navigates through the health care system of various countries. Retinal Physician spoke with clinicians within and outside the United States to explore where there is common ground and where there are dissimilar approaches.

SCREENING FOR DIABETIC RETINOPATHY

Across the pond in the United Kingdom, the existence of a national screening program, where patients with diabetes are screened annually for diabetic retinopathy, facilitates early detection of diabetic retinopathy before it progresses to more severe disease, according to Clare Bailey, MD, FRCP, FRCOphth, a consultant ophthalmologist at Bristol Eye Hospital and a principal/chief investigator for many clinical trials in diabetic retinopathy.

“There is a database of all patients with diabetes and a whole network of systematic screening for diabetic retinopathy,” said Dr. Bailey. “The program defines what level of retinopathy needs referral into the hospital for a closer look. The aim is to pick it up at a much earlier stage before any symptoms develop.”

The American Academy of Ophthalmology guidelines call for yearly screening of patients with diabetes, but whether patients are screened yearly in the United States is a result of an individual’s health-seeking behavior rather than a collective effort like a national retinal screening program in the United Kingdom.

Michael Trese, MD, chief of adult and pediatric vitreoretinal surgery at Oakland University William Beaumont University School of Medicine, Rochester, Michigan, added that advances like telemedicine and apps will potentially increase annual screenings of patients with diabetes for ophthalmological complications related to their chronic condition.

“I think there is a real opportunity for telemedicine,” said Dr. Trese. “In the not-so-distant future, there will be home monitoring to test visual acuity, and innovations like those will improve screening of patients with diabetes. This type of screening is going to replace what we think of as conventional screening.”

Current limitations around telemedicine include the existence of just two ophthalmologic codes as well as issues of licensing and liability, noted Dr. Trese.

Anjali Shah, MD, Clinical Instructor, Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Health System, Ann Arbor, echoed that, in the absence of a country-wide screening program in the US, telemedicine is a strategy to expand the numbers of US patients who are screened for conditions like diabetic retinopathy and diabetic macular edema.

“There is no systematic pressure to screen all patients with diabetes annually, but there is an effort to improve the number of patients being screened using telemedicine,” explained Dr. Shah, pointing to the new telemedicine program at the Kellogg Eye Center, and her local Veterans Affairs hospital as an avid user of telemedicine as a tool to screen patients with diabetes for potential complications like diabetic retinopathy.

DIAGNOSTIC TOOLS FOR SCREENING

Common tools used for diagnosing diabetic retinopathy include optical coherence tomography (OCT). That would be a global standard, but in the United States, and to some extent Canada and the United Kingdom, special investigations would likely be conducted by subspecialists, depending on the patient case.

“The comprehensive ophthalmologist will not order as much testing,” said Dr. Shah. “They would refer to a retinal specialist who will have [wide-field] fluorescein angiography and spectral-domain OCT.”

In continental Europe, comprehensive ophthalmologists are the clinicians who make the diagnosis, largely with OCT and perhaps fluorescein angiography, of diabetic retinopathy and who manage the patients.

“In the United States, it would more often be the retina specialists who would be involved in the care of these patients and it would be more general ophthalmologists who would be involved in the care of these patients in Germany. But in Germany, the ophthalmologist would refer a patient who would require treatment to a specialized center,” explained Frank G. Holz, FEBO, Director and Chairman, Department of Ophthalmology, University of Bonn, Germany.

Formal subspecialty fellowships in Germany are uncommon, said Professor Holz. “Ophthalmologists [in Germany] would cover a broader range of eye diseases,” he told Retinal Physician in an interview. “There is more subspecialization in the United States.”

USE OF MEDICAL THERAPIES

In countries that have socialized medicine, such as Germany, Switzerland, France, and the United Kingdom, the high price tag of vascular endothelial growth factor (VEGF) inhibitors such as ranibizumab (Lucentis; Genentech) and aflibercept (Eylea; Regeneron Pharmaceuticals) does, for the most part, not represent a barrier to prescription of these medical therapies to treat diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR).

In Switzerland, for example, prescriptions of ranizumab and aflibercept make up 98% of anti-VEGF treatments for ophthalmological conditions like DME or PDR, according to Sebastian Wolf, MD, PhD, FEBO, FARVO, Professor of Ophthalmology, Director and Chairman, University Eye Hospital Bern, Switzerland.

“Treatment [with VEGF inhibitors] is fully reimbursed in Switzerland,” explained Professor Wolf. “Our [health care] system allows for monthly treatments of both drugs.”

In time, there may be greater intervals between treatments, resulting in less frequency of injections, but patients and clinicians accept that injections will be lifelong coupled with ensuring patients make efforts to sustain proper glycemic control, said Professor Wolf.

It is a similar situation in Germany, where the cost of the anti-VEGF agents does not represent a barrier to their prescription. “The reimbursement scheme ensures each person has access (to anti-VEGF agents),” said Professor Holz.

Although America’s neighbor to the north has a socialized health care system, individual provinces in Canada control the strings of the public purse when it comes to medication access. There can be variations across provinces, where some provinces cover the cost of a given medication and others do not.

Most provinces in Canada cover the cost of the VEGF inhibitor aflibercept, but the province of Alberta does not, meaning patients, private insurance, or compassionate industry-funded programs would have to absorb the cost of the newest VEGF inhibitor, pointed out Amin Kherani MD, FRCPC, a vitreoretinal surgeon, associate clinical professor at the University of Calgary, Alberta, and president of the Canadian Retina Society. Because of this, Dr. Kherani and his colleagues in that province would prescribe bevacizumab (Avastin; Genentech) or ranibizumab to their patients.

“Retina specialists in Alberta would use Avastin as a first-line treatment,” said Dr. Kherani. “We are trying to be socially responsible for the public purse. If Avastin failed, we would move to another VEGF inhibitor (Lucentis or Eylea).”

In the United Kingdom, the National Institute of Health and Care Excellence has recommended that 400 microns of retinal thickness develops before anti-VEGF treatment is funded, noted Dr. Bailey.

Concerns about the safety of bevacizumab remain, owing to complications like endophthalmitis, but many contend the incidents were a result of poor procedures in compounding the therapy. Complications like infections can occur with exposure to any VEGF inhibitor.

For Americans without health insurance or who are unable to afford their copayments, bevacizumab may be the only viable choice as a VEGF inhibitor.

“There is usually a discussion with the patient,” said Dr. Trese. “What you select and choose takes into account factors like insurance and reimbursement. There is usually a discussion with the patient explaining the pros and cons of the drugs including the expense and frequency of injections. Some patients may not be able to afford newer (anti-VEGF) treatments, and they have to use Avastin.”

THE ROLE OF LASER TREATMENT

Anti-VEGF therapies are now considered the gold standard in the treatment of DME, and they are utilized in combination with laser treatment for PDR in numerous countries, including the US, Canada, the UK, Switzerland, Germany, and France.

With superior diagnostic technology, such as wide-field fluorescein angiography, Dr. Trese argued he can strategically offer laser therapy to diminish an ongoing need for anti-VEGF treatments.

“Wide-field (fluorescein) angiography gives me a good idea of the whole circulation and would tell me if there is peripheral ischemia that I want to treat with laser,” he explained. “That would then require much less in the way of injections.”

Indeed, panretinal laser photocoagulation is very effective and does not require a commitment of lifelong injections and patient visits with anti-VEGF therapies.

“Panretinal laser only requires 1 or 2 visits while (VEGF inhibitor) injections will need ongoing care for life,” said Dr. Shah, adding the clinical advantage that VEGF inhibitors offer with respect to improved vision does not always justify the total costs of chronic treatment.

In both Germany and Switzerland, laser photocoagulation is a first-line therapy for PDR. Concern about side effects drives the decision to avoid using energy-based modalities like laser for treating DME in Switzerland, added Professor Wolf. “We are more in fear of late complications with the laser for macular edema, so we try to avoid using laser treatment for that condition,” said Professor Wolf, citing possible complications like vision loss after laser scar expansion.

Didier Ducournau, MD, a founder and past-president of the European VitreoRetinal Society and vitreoretinal surgeon based in Nantes, France, underlined that there is a role for surgery in managing DME, particularly when DME is associated with retinal vein occlusion.

“We found superior results with surgery (vitrectomy with internal limiting membrane) when compared to the use of (anti-VEGF) injections,” noted Dr. Ducournau.

In 2015, Dr. Ducournau and international colleagues published findings in BioMed Research International demonstrating the efficacy of vitrectomy with internal limiting membrane in producing vision gains.

GUIDELINES THAT INFORM TREATMENT CHOICES

Clinicians around the world do share a common long-term approach to employing anti-VEGF treatments. Clinicians in Switzerland, Germany, the United Kingdom, Canada, France, the United States, and Brazil indicated that a dosing strategy of “treat and extend” that supports longer intervals between injections of anti-VEGF agents as long as 12 weeks between office visits and injections is followed in their respective countries.

“Most people try to treat with ‘treat and extend,’” said Michel Eid Farah, MD, professor of ophthalmology specializing in retina vitreous at the Federal University in Sao Paulo, Brazil, who has done a research fellowship at Bascom Palmer Eye Institute at the University of Miami, Florida.

The reality for many of these patients is they will need treatment for years. Despite some differences in practice patterns, retina specialists across the globe recognize the need to implement a sustainable management strategy like treat and extend for patients with chronic retina conditions. RP

One Patient, 5 Countries

Retinal Physician asked clinicians in various parts of the globe about their management approach to the same patient. The patient is 50-something with diabetes and diabetic retinopathy, is poorly controlled, poorly compliant, presents with active proliferating events, and has moderate macular edema with associated epimacular membrane in one eye. The patient’s fellow eye has preproliferate retinopathy with mild non-fovea-involving edema. The patient’s visual acuity is 20/25 OD and OS, the intraocular pressure is 15 mmHg in both eyes, and there is no neovascularization of the anterior segment.

The options provided include vitrectomy with PRP and membrane peeling; laser and anti-VEGF injections; and treating the fellow eye with PRP as well in an effort to prevent likely proliferative changes in the near future.

“I would favor laser and anti-VEGF injections after having a frank and detailed communication about the importance of compliance and control,” said Canadian clinician Dr. Kherani. “If the active proliferative disease was largely hemorrhagic, tractional surgery would be an important consideration. Early PRP laser in the fellow eye would be considered depending on the result of communication with the patient.”

Professor Holz of Bonn, Germany, said he would choose anti-VEGF treatments for the eye with proliferative diseases and diabetic macular edema, followed by vitrectomy and membrane peeling and intraoperative pan-retinal endolaser photocoagulation. “For the fellow eye, it would depend on the extent of nonfoveal edema: either focal laser photocoagulation or anti-VEGF therapies,” he said.

Anti-VEGF therapy combined with panretinal laser coagulation within 1 session for the eye with proliferative diabetic retinopathy is the treatment of choice for Professor Wolf of Bern, Switzerland. “I would prefer to avoid vitrectomy. Anti-VEGF therapy combined with panretinal laser coagulation may be sufficient. Given poor patient compliance, PRP is a good option for the fellow eye.”

Dr. Shah, of the Kellogg Eye Center in Michigan, said she would choose to inject anti-VEGF medication to reduce macular edema in the eye with proliferative changes and macular edema. Panretinal photocoagulation laser within a month would follow and another anti-VEGF injection would likely be in order.

“For the eye with no proliferative changes, I would have a discussion with the patient with regards to treatment vs observation,” she said. “Given the patient’s good vision, non-center-involving edema, and no proliferative changes, in addition to the fact that there will be close follow-up due to ongoing treatment in the other eye, I would lean toward close observation.”

Dr. Shah’s colleague in the United States, Dr. Michael Trese, would choose a similar management approach, opting for PRP and anti-VEGF injections, but would look to vitrectomy with PRP and membrane peeling if the patient failed to get better and instead got worse.

Dr. Bailey of the United Kingdom supports performing PRP for active proliferative retinopathy and vitrectomy if there is vitreous hemorrhage that does not resolve or tractional changes threatening the fovea. “In the UK, we would not be funded to give ongoing anti-VEGF injections for proliferative retinopathy, so laser remains the mainstay here,” she said.

Regarding the fellow eye, Dr. Bailey said PRP is not generally performed in the UK for nonproliferative retinopathy, but she noted that there are caveats.

“If there is very severe nonproliferative diabetic retinopathy, and the patient might be unreliable about reattending, or if the other eye progressed very rapidly, then PRP) might be considered,” she said.