Real-world approaches to managing DME: Improving durability, drying, and patient burden

María Berrocal, MD, related the highlights of an Ophthalmology Times Case-Based Roundtable® that convened at the recent EnVision Summit in Río Grande, Puerto Rico. She is an associate professor at the University of Puerto Rico and CEO of Drs Berrocal and Associates, San Juan, Puerto Rico.

The participants discussed topics relevant to clinical practice, including the roles of VEGF, angiopoietin-2 (ANG2), and inflammatory cytokines in treating diabetic macular edema (DME); the most challenging patient profiles; and the impact of dual inhibition of ANG2 and VEGF-A.

“These patients have long-standing edema, cystoid macular edema, subretinal detachment, localized detachments, and an abundance of inflammatory cytokines. There is a great deal of inflammation that responds better to dual inhibition with VEGF and ANG2,” she said.

Previous studies have shown that because of the poor response to anti-VEGF therapy, patients also received steroids, a treatment that she has moved away from. “Now with the dual inhibition provided by faricimab (Vabysmo, Genentech), the vessel walls are stabilized, and there is less serum leakage into the retina caused by inflammatory cytokines,” she explained.

Case discussions

Case 1: Bilateral macular edema with diabetic retinopathy

A 58-year-old man with a background of diabetic retinopathy and clinically significant bilateral macular edema had been on oral medications and was treatment-naive. The left eye has significant cystoid macular edema and a small, localized foveal detachment.

The visual acuities (VAs) were 20/60 and 20/100 in the right and left eyes, respectively. The patient received 1 injection of faricimab; optical coherence tomography (OCT) showed a significantly reduced central foveal thickness and improved VA. The cystoid spaces mostly resolved in the left eye, and the VA improved to 20/50 and 20/70, respectively.

Two months later, insurance issues resulted in the patient receiving fewer injections. His eyes improved after the first 6 weeks; however, 2 months later, new fluid started to accumulate. The patient received another injection, and 1 month later, OCT showed a VA improvement to 20/50 in the right eye and 20/60 in the left eye, with markedly less edema.

Six weeks after the third injection, the VA was 20/40 bilaterally with a few unresolved cystic spaces. Six weeks after the fourth injection, the VA remained at 20/40 with much less edema and a much more normal retina contour in the foveal area.

The treatment was extended to 8 weeks. After the fifth injection, the VA improved to 20/30 bilaterally, and 8 weeks after the sixth injection, it remained 20/30. The patient’s treatment was ultimately extended to 12 weeks, and the VA remained stable at 20/30 bilaterally.

The roundtable participants discussed the impressive effectiveness of faricimab in these patients with poorly controlled, significant edema and substantial inflammation on OCT.

“This is a big benefit [for] these patients. Regarding durability, despite significant edema, we can quickly extend them, and often, patients may be completely dry after 1 or 2 injections. I then start injecting them, usually at 2-week intervals,” Berrocal commented.

Case 2: Severe refractive disease

A man with very severe disease had been treated with 13 previous anti-VEGF injections of bevacizumab (Avastin, Genentech) and aflibercept (Eylea, Regeneron) over 18 months. The VA was 20/200. The left eye had numerous retinal cysts, a large subretinal foveal detachment, and numerous hard retinal exudates.

The patient received 3 faricimab injections that resulted in substantially less edema in the left eye with some cysts remaining, central foveal improvement, and much less fluid; the subfoveal detachment remained.

After 5 faricimab injections, both eyes continued to improve, and the subfoveal detachment resolved with some cystic spaces remaining. Fewer hard exudates were seen bilaterally. After 7 injections, the VA improved to 20/80 in the right eye and 20/100 in the left eye.

Despite this, he did not improve as much as had been hoped, which underscores the importance of starting an effective treatment as early as possible. “The longer the retinal fluid is present, with subretinal fluid, cysts, and hard exudates, the more damage the retina sustains, and the less improvement is seen in the long term,” Berrocal emphasized.

The roundtable participants agreed that faricimab is their go-to drug when switching patients with diabetes and very severe disease. In patients with insurance issues, the idea is to switch them to faricimab as quickly as possible to achieve the fastest retinal drying.

Another discussion point was the formation of epiretinal membranes. While VEGF agents increase the risk of epiretinal membrane formation by 3 times, that risk is significantly less with faricimab.

Case 3: Left-eye cystic macular edema

A 57-year-old man with cystic macular edema in the left eye had a VA of 20/70. The patient received 2 steroid injections with no significant edema resolution. After 1 faricimab injection, the edema essentially resolved, and the VA improved to 20/50.

With later injections at 8 weeks and 12 weeks, the VA remained at 20/50, with no significant edema. “The eye had a great response, and we were able to extend him very quickly to a very short interval,” Berrocal commented.

When patients question how long their treatment will continue, she explains that while they will need to be treated over their lifetime, physicians now have access to a medication that provides rapid responses, and only 3 to 4 injections may be required annually. The treatments are individualized to obtain the best response with the fewest injections to minimize the treatment burden.

Case takeaways

Berrocal explained that case 1 demonstrated the importance of starting treatment early with the best medication to achieve rapid drying and extension.

Case 2 showed the benefit of reducing the long-term edema as quickly as possible. The presence of substantial edema for 1 or 2 years results in less improvement in the VA gains. Case 3 demonstrated that patients who did not have a good response to steroids can have a great response to faricimab.

“The most important consideration when treating DME is using the most effective agent with the lowest treatment burden that allows us to extend these patients so that they require only 3 or 4 injections annually. This will also reduce complications such as fibrosis,” she concluded.