Physician discusses clinical presentations, treatment options for 2 cases.
Reviewed by Daniel Kiernan, MD, FACS
Wet age-related macular degeneration (AMD) can be a persistent problem for many patients. Daniel Kiernan, MD, FACS, a retina specialist with The Eye Associates in Sarasota, Venice and West Bradenton, Florida, discusses the clinical presentations, treatment strategies, and patient outcomes of 2 cases of wet AMD that did not react to treatment as expected.
A 79-year-old woman was referred for a retinal examination with more blurred vision in the left eye than the right eye for several months. Her medical history included controlled hypertension, heart disease, cholesterol, and chemotherapy for lung and breast cancer. The patient was pseudophakic bilaterally, with a previous history of bilateral dry AMD. In May 2021, the right and left visual acuities (VAs) were 20/30 and 20/50, respectively, with normal intraocular pressures. The patient has Medicare with a secondary plan.
Fundus photographs showed drusen bilaterally and some macular edema (ME) in the left eye. Optical coherence tomography of the left eye showed subretinal/intraretinal fluid in the central macula and some exudation consistent with wet AMD. Angiography shows classic late leaking choroidal neovascularization in the left eye, with scattered drusen staining also consistent with neovascular AMD. The left eye was treated with aflibercept (Eylea; Regeneron Pharmaceuticals, Inc) in May 2021.
This began a series of 7 aflibercept injections over the course of approximately 1.25 years, during which time the patient’s VA mostly continued to improve and the macula in the left eye was essentially dry despite postponements of injections because of chemotherapy-related health issues, Kiernan demonstrated. In this case, the insurance allowed the patient to be treated with aflibercept without the need for step therapy, he explained.
Kiernan said his general practice is to follow patients after 3 loading doses, then treat every other month and personalize the treatment schedules as needed. This patient was remarkable in that she had a response that was better than average, and he could schedule her ocular treatments out to 12 weeks during the first year, longer than he would generally, to accommodate her comorbilities, then to 6 months after that, he explained. Quarterly dosing was effective for this patient. Kiernan advised not to extend patients out too far in the event of an untoward event (eg, permanent VA loss happens because of a subretinal hemorrhage).
The takeaways are that these injections work, some patients respond better, and some responses last longer than others. However, extending treatments past 2 or 3 months may increase the risk margin too much. He advised to exercise caution about treatment durations despite clinical trial results. “More treatments may preserve VA longer,” he said.
An 83-year-old man with neovascular AMD presented with worsening vision in the left eye and retinal edema for 1 month, hypertension and reflux disease controlled medically, and bilateral dry AMD. The patient has Medicare and a secondary insurance.
In February 2020, the right and left eye VAs were 20/50 and 20/150, respectively, with normal pressures, drusen and retinal pigment epithelial changes bilaterally, and ME in the left eye. Angiography of the left eye showed early hyperfluorescence with drusen staining, perimacular leakage, and disc leakage, perhaps from cystoid ME or postoperative inflammation due to a lens exchange 6 months previously. Kiernan restarted cataract surgery drops in the left eye to dry the ME.
A re-examination 3 weeks later showed fluid and increased central subfield thickening, with a VA of 20/250 in the left eye, which seemed more consistent with wet AMD and not postoperative cystoid ME. Aflibercept was injected into the left eye.
In April, the VA was 20/150 with reduced retinal thickening and a second aflibercept injection was given. A month later, the VA increased to 20/50 but the fluid increased and a third injection was administered.
One month later, the VA decreased to 20/60 with persistent edema and a fourth injection was then administered, with another VA decrease 5 weeks later to 20/70 with more ME. When the patient was seen in 1 week after a fifth injection to identify a tachyphylactic response to aflibercept, it was determined that he had limited response to the drug.
Kiernan noted that after 3 weeks, the patient was switched to faricimab (Vabysmo; Genentech). In 1 month, the VA decreased to 20/200 in the left eye with a dramatic fluid increase without iritis or vitritis. Aflibercept was restarted, the VA improved to 20/60 with some fluid present and another aflibercept injection was administered.
“This was a curious case. I had never seen an idiosyncratic reaction to faricimab, which tends to dry persistent fluid a bit better than aflibercept,” Kiernan said. He added that he had concerns about postoperative inflammation and resultant ME, but the clinical picture worsened.
“This convinced me of the presence of a choroidal neovascular component,” he said.
Kiernan said he believed the patient still had an inflammatory component, and the reaction to faricimab might have been a fluke because of the inflammation. “Persistent administration of aflibercept may have helped fluid resolution,” he said. “More likely, adding a steroidal anti-inflammatory might have been reasonable, such as subtenon Kenalog, intravitreal dexamethasone implant, or intravitreal fluocinolone acetonide 0.18-mg implant for posterior uveitis, along with the (anti-VEGF) therapy for wet AMD.
“Sometimes there are overlapping components not necessarily in response to wet AMD because of a previous ocular surgery,” Kiernan said.