Managing a challenging case of AMD and DME

David Eichenbaum, MD, FASRS, shared difficult cases of diabetic macular edema (DME) and age-related macular degeneration (AMD) and insights into patient care.

Case 1: Controlling DME

This 74-year-old man has a decade-long history of bilateral DME; his diabetes initially was poorly controlled with vasculopathic complications. His DME, cholesterol ,and hyperthyroidism are now well-managed. The right eye was especially challenging; intraocular steroids resulted in a significant corticosteroid response. He underwent laser therapy and intravitreal injections of ranibizumab (Lucentis, Genentech) and then aflibercept (Eylea, Regeneron), every 4 to 5 weeks in the right eye for years. The right eye remained problematic, with a visual acuity of 20/40. Typically, he has some central cystic changes and intraretinal fluid consistent with DME.

In February 2022, faricimab (Vabysmo, Roche) was offered, with its dual activity of angiopoietin-2 inhibition and vascular endothelial growth factor (VEGF) suppression. He continues on aflibercept treatment to improve his anatomy and potentially lessen the burdensome treatment interval if he achieves better visual and anatomic outcomes. Faricimab resulted in a subjective and objective improvement in vision 5 weeks after injection and a visual increase of 1.5 lines. Imaging showed improved cystic spaces and partial reconstitution of a foveal contour. After the second faricimab injection, the cystic spaces became smaller, the acuity was stable, and the patient was happy. Eichenbaum believes the angiopoietin suppression improved the anatomy. Eichenbaum attempted to extend the treatment slightly, based on the results after the first faricimab injection.

Insights into treatment

He pointed out that this patient is like many others with chronic DME who achieve partial control, and before the introduction of faricimab, that was the acceptable status.

The challenge is that with these patients the response to faricimab is unknown because they would not have been candidates for the study. Those patients were either treatment-naive or well washed out from diabetic treatment, he explained, and said that these patients who are difficult treat with frequent antiangiogenic injections will have some success

His goal is to improve patient anatomy in these patients, and with that, improvement in the subjective and objective acuities.

Importantly, Dr. Eichenbaum explained, faricimab’s bispecific inhibition is moving past antigen monotherapy in durability and efficacy and providing patients similar visual acuity outcomes and fewer intravitreal injections.

Faricimab the first bispecific inhibitor for intraocular use, is remarkable because it inhibits a second cytokine, angiopoietin-2, which mediates vascular destabilization and leakage through damaged vessels.

The YOSEMITE and RHINE trials showed that treatment could be extended out to every 12 or 16 weeks during the first and second treatment years, which may help diabetics adhere to treatment.“I’m hopeful that the addition of this new molecule with its extended durability will allow our patients in the real world to do as well or close to as well as patients in our clinical trials,” he commented.

Case 2: Neovascular AMD

This 81-year-old man had very aggressive neovascular macular degeneration. The visual acuity was 20/200 bilaterally. The left eye is better subjectively; the right eye has outer retinal atrophy and pigment atrophy. Because of excessive leaking and exudation despite alternating aflibercept every 4 weeks with brolucizumab (Beovu, Novartis), significant exudative activity continues. He has controlled hypertension and hypercholesterolemia, and he is anticoagulated from having had a cerebrovascular accident in 2015. A hemorrhagic event in his better eye is worrisome because of the anticoagulation therapy.

The patient received his first faricimab injection in March 2022, and after 4 weeks, the macular anatomy improved dramatically. Eichenbaum reported that in the real-world treatment with faricimab, macular degeneration with exudation is sensitive to angiopoietin-2 inhibition with bispecific faricimab and has a rapid and dramatic response.

The patient had resolution of subretinal and intraretinal fluid here as well. “This case was probably my most striking faricimab switchover response for a patient who has ongoing uncontrolled exudative disease, even with high-affinity antiangiogenic agents,” he commented.

The patient also had significantly reduced central subfield thickness. After his second faricimab injection, he continues to have improved subretinal and intraretinal anatomic presentation on follow-up from the faricimab injection compared with follow-up on a high-potency antiangiogenic monotherapy.

Eichenbaum commented, “It’s very important that this essentially monocular patient enjoy the flexibility of the faricimab label. That gives me confidence that I can continue to treat him at every-4-week intervals and I can think about whether or not I want to extend them. I would be leery to extend aggressively in this patient who’s done poorly with our most potent antiangiogenic monotherapy agents. With faricimab, we have the flexibility to continue more frequent treatment in the real-world setting because of the labeling. This patient is very happy. This is the best the better-seeing eye has been in 2 years. I’m hopeful that we can duplicate this success and move beyond the antiangiogenic monotherapy era and stabilize the outer retina and the current neovascular lesions in ways that we could not do with VEGF-A suppression alone.”