Next-generation retinal disease treatments: Advancing care in nAMD and DME
Modern Retina’s recent Case-Based Roundtable focused on next-generation treatments for retinal disease that provide advanced care for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).
(Image credit: ©THANANIT/AdobeStock)
Michael A. Klufas, MD, of the retina service at Wills Eye Hospital in Philadelphia, Pennsylvania, presented 3 cases and discussed how second-generation retinal vascular agents, such as high-dose aflibercept 8 mg (Eylea HD; Regeneron Pharmaceuticals, Inc) and faricimab (Vabysmo; Genentech), show promising results for treating these 2 common disorders. The presentation placed particular emphasis on extended treatment intervals out to 20 to 24 weeks and strategies for managing persistent exudation while maintaining vision.
Case 1: Suboptimal response in bilateral nAMD
The patient was a 74-year-old woman with neovascular age-related macular edema (nAMD) who achieved improved disease control and vision in her right eye after switching from ranibizumab (Lucentis; Genentech) to aflibercept 8 mg treatment, successfully extending her treatment intervals to 10 weeks. The patient had undergone a cataract surgery in the right eye and had nuclear sclerosis in the left eye. Her ocular history included a 3-year history of bilateral wet AMD, for which she was treated with ranibizumab and biosimilar ranibizumab-eqrn (Cimerli; Coherus BioSciences, Inc) in both eyes every
4 to 6 weeks.
Treatment provided suboptimal control of the nAMD in the right eye, with a visual acuity (VA) of 20/40 and central subfield thickness (CST) of 397 µm; the left eye VA was 20/30, and the CST was 297 µm. Treatment with aflibercept 8 mg was started in the right eye, and ranibizumab was continued in the left eye. She was subsequently switched to aflibercept in both eyes for better disease control and extended treatment intervals. VA Improvement in the right eye to 20/30 was seen 6 weeks following the treatment switch; the left eye remained stable. The treatment intervals were able to be extended over time, and the VAs in the right and left eyes improved to 20/20 and 20/25, respectively.
Klufas explained that the lesson in this case was the ability to have 8-week treatment intervals with no other adverse effects. He said that having several treatments for retinal vascular disease is an advantage and facilitates switching treatments when patients have less-than-optimal responses, noting the importance of continuing with a particular treatment for 3 injections to get a clear picture of either disease progression or a suboptimal response.
Case 2: DME with aflibercept 8 mg
The patient was a 79-year-old man with a 20-year history of diabetes and treatment-naive diabetic macular edema (DME). The patient had undergone cataract extractions. The right eye had a partial posterior vitreous detachment, with a VA of 20/60 and a CST of 344 µm; an epiretinal membrane, central cyst, and a microaneurysm were seen on imaging. The left eye was asymptomatic. Treatment with aflibercept 8 mg was started on every-4-week loading doses with slight VA improvement but thickening of the central retina. The CST decreased slightly to 310 µm, but the patient complained of VA loss (VA, 20/40).
At one point, the treatment interval was extended to 11 weeks because the patient missed a visit; however, continued improvement was seen. Treatment was adjusted back to 8-week intervals to regain control, which resulted in continued resolution of the DME, with the VA at 20/25. Klufas tried a 10-week treatment interval, during which anatomic improvements were seen, and the VA was 20/30.
He and his colleagues like to consider objective and subjective improvement measures in these patients with retinal vascular disease treated with anti-VEGF drugs. “Aflibercept has been an amazing compound for treating DME and diabetic retinopathy, making it the first choice for my physicians. However, other patients respond to faricimab,” Klufas said.
Case 3: Rapid fluid resolution in nAMD with faricimab
This 77-year-old woman, who had undergone cataract surgery, presented with decreased VA in the right eye. A pigment epithelial detachment occurred, but no apparent subretinal fluid was present. Fluorescein angiography showed leakage in the right eye. She ultimately was diagnosed with nAMD in the right eye and drusen in the left eye; the right and left VAs were 20/100 and 20/25, respectively.
The patient received 13 injections of aflibercept 2 mg in the right eye every 4 to 5 weeks. The vision became distorted in the left eye, and conversion to wet AMD was seen, which was also treated with aflibercept 2 mg. Better disease control was then achieved in the left eye. The right eye vision remained 20/100, and the left eye vision was 20/30.
With persistent exudation in the right eye, the treatment was switched to ranibizumab. Aflibercept was not an option because of previous inflammation with that drug. A switch to faricimab resulted in a dramatic reduction of the subretinal fluid in that eye. Insurance issues resulted in the waxing and waning fluid levels when treatment went between ranibizumab and faricimab.
“This case showed that some patients may respond better in one eye than the other to certain treatment agents. In the patient under discussion, treatment continues with faricimab in the right eye and ranibizumab in the left eye,” Klufas said.
Related viewing: Case 3: Achieving Rapid Fluid Resolution in nAMD With Faricimab
A discussion of the persistence of fluid indicated that observing a dry or wet retina with any treatment after 2 weeks may indicate a durability issue or tachyphylaxis.
In the current case, the patient was not treatment naive. Although on-label dosing initially requires monthly treatments, Klufas noted, many clinicians prescribe different treatment approaches in patients who had been treated previously. “It is the doctor’s choice whether they follow the on-label recommendations or follow a modified treat-and-extend regimen when switching patients, depending on the previous treatment intervals,” he said.
An important point is that second-generation treatments are well tolerated and safe, and clinicians are fortunate to have a variety of available options. Presently, there is no consensus regarding the choice of a first-line therapy. If a patient does not do well on a particular choice, physicians commit to a series of 3 injections before switching to another drug.
For some clinicians, a factor in choosing treatments is the ability to extend patients beyond 16 weeks. The major faricimab trials do not have data for extensions beyond 16 weeks, but with aflibercept, some patients are able to extend to 20 to 24 weeks. The effective monitoring of those patients for exudation remains to be determined.
Takeaways
If there is persistent exudation but no VA decrease, a recommendation may be to stick with the treatment before immediately switching to another drug. The 3-year data from the aflibercept 8 mg trials in patients with nAMD and DME indicate that almost 50% of patients are achieving 20-week treatment intervals, and approximately 25% can achieve 24-week intervals in patients with nAMD and DME.
Newsletter
Keep your retina practice on the forefront—subscribe for expert analysis and emerging trends in retinal disease management.
