Real-world evidence on latest retinal disease therapies

(Image Credit: AdobeStock/Sanchai)

Reviewed by Nikolas J. S. London, MD, FACS

Nikolas J. S. London, MD, FACS, shared highlights from a recent Ophthalmology Times Case-Based Roundtable that explored 2 of the latest therapies—aflibercept 8 mg (Eylea HD; Regeneron Pharmaceuticals, Inc) and faricimab (Vabysmo; Genentech)—for treating diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). London is president and CEO of Retina Consultants San Diego in California.

Personal experience

London reported having extensive experience with the drugs, which both work well for recalcitrant cases of DME and nAMD. However, his go-to drug is faricimab, which has facilitated extended treatment durations ranging from 2 to 4 months in patients who previously were able to achieve only short treatment intervals.

A drawback to aflibercept 8 mg is the dosing requirements, which require using 8 mg of the drug every 4 months times 3 for the loading phase, followed by a mandated extension to every 8 weeks, according to London. In his experience, these dosing requirements are challenging for some patients, in that they could not be extended out to every 8 weeks after the loading doses.

Case 1

A 92-year-old woman had a lengthy history of bilateral nAMD and multiple serious comorbidities such as colon cancer, myocardial infarction, and pericarditis; she was also wheelchair bound because of lower leg amputation. Her ocular history included bilateral treatment with anti-VEGF therapy with aflibercept 2 mg, but she prefers not to be treated in both eyes on the same day.

Before London switched the patient to faricimab, she had short treatment intervals of approximately 4 weeks, during which subretinal and intraretinal fluid persisted and increased toward the end of the treatment interval. The patient's right eye was more severely affected with subretinal and intraretinal fluid over a pigment epithelial detachment (PED).

After switching to faricimab, both fluid compartments decreased markedly and the treatments extended out to 6 weeks, after which she remained stable. The patient had no serious ocular adverse effects.

“The results indicate the increased potency of the drug’s effect that translated into increased durability for this patient. She went from always having disease activity for many years to having no disease activity in both eyes on faricimab,” London said.

Case 2

A 70-year-old man had insulin-dependent diabetes mellitus with persistent DME that was treated with multiple injections of aflibercept 2 mg and a dexamethasone intravitreal implant (Ozurdex; Allergan plc) every 4 to 6 weeks. The DME showed very little response to treatment and some response to dexamethasone, but the fluid persisted.

Moreover, after switching to faricimab12 weeks after a steroid injection, the intraretinal fluid began to respond. By the ninth faricimab injection, the fluid had resolved. The patient is currently receiving injections every 8 to 10 weeks and has had no adverse ocular reactions to the treatment.

Case 3

A 73-year-old treatment-naive man had new-onset nAMD with a large PED and overlying mild subretinal fluid. The first-line treatment was faricimab. His vision was 20/50 with some metamorphopsia. One faricimab injection resulted in a slight reduction in fluid with 20/40 vision. He then received a ranibizumab injection (Lucentis; Genentech) when his vision was 20/80 and 4 weeks later with aflibercept 2 mg, after which the subretinal fluid increased slightly.

Two additional aflibercept 2-mg injections resulted in increased subretinal fluid and an enlarged PED; another aflibercept injection resulted in a slight fluid reduction and the persistently large PED. Generally, the treatment interval was every 4 to 5 weeks with very little progress, but the patient insisted on continuing treatment.

A switch to aflibercept 8 mg achieved a marked reduction in the PED and no discernible fluid. Five weeks later, the scans showed a slight increase in the PED size and no fluid. Four weeks later, no injection was done, per the dosing instructions.

At the 8-week time point, increased fluid was observed. After another 4 weeks, the patient had a good response, with a decrease in the PED and no fluid. The patient was observed at this point and then treated 4 weeks later.

This treatment course proved to be challenging because of the dosing requirements, and the patient remained stable at 8 weeks, London explained.

"This case highlights the questions around the course of action in patients who seem to do well with aflibercept 8 mg but cannot tolerate the every-8-week treatment interval following the first 3 loading doses,” London pointed out.

Nikolas J. S. London, MD, FACS

E: nik.london@gmail.com

London is president and CEO of Retina Consultants San Diego in San Diego, California.