Intravitreal Steroids, Anti-VEGF Combination May Resolve Resistant Wet AMD

Alexandra Warter, MD

Combination therapy including standard-of-care anti-VEGF and concomitant intravitreal steroids may help improve the overall disease of patients with neovascular age-related macular degeneration (nAMD) who were resistant to monotherapy, according to new research.

In a study presented at the Association for Research in Vision and Ophthalmology (ARVO) 2022 Meeting this week, a team of investigators from the Shiley Eye Institute of the University of California at San Diego (UCSD) found a combination of steroids and anti-VEGF therapy provided improvement to recalcitrant choroidal neovascularization (CNV), indicating likely benefit of care for patients with resistant nAMD.

Led by Alexandra Warter, MD, the research team evaluated anatomic and visual changes to occur following simultaneous intervention of adjuvant steroids with anti-VEGF in patient eyes with resistant, chronic nAMD.

"Controversy exists regarding the therapeutic use of concomitant intravitreal steroids with anti-VEGF in CNV resistant to mainstay treatment,” the team wrote. “We performed a retrospective observational clinical study in a consecutive cohort of patients’ eyes with persistent CNV anatomically unresponsive to aggressive high-dose high-frequency monotherapy (i.e, monthly 4 mg aflibercept).”

Their assessment included 12 patient eyes with unresponsive CNV despite alternating anti-VEGF agent therapy; treatment resistance was defined as persistent retinal fluid following high-dose, high-frequency (HDHF) monotherapy.

Warter and colleagues administered simultaneous anti-VEGF and steroids, followed by Timolol 0.5%/Dorzolamide 2%—a prophylactic topical antiglaucoma therapy—for 2 weeks. They recorded patient scores on slit-lamp, best-corrected visual acuity (BCVA), intraocular pressure (IOP), optical coherence tomography (OCT) and measures on central retina thickness (CRT) every 4 weeks for 4 consecutive months.

Investigators sought outcomes in BCVA and IOP improvement, as well as reductions in CRT. They evaluated predictors relating to treatment efficacy at baseline.

At trial’s end, investigators observed statistically significant anatomic outcomes including reduction in CRT versus baseline (P <.0001). Mean CRT reduction was 50.90 mcm at 1 month (P <.05), 76.5 mcm at 2 months (P = .0336), and 86.33 mcm at 3 months (P = .034). Initial safety assessment showed no complications in patients receiving the combination therapy regimen.

The team concluded that the findings evidenced a “clear anatomic improvement” in recalcitrant CNV, enough so that it may be suggested that combination therapy may be beneficial in treatment resistant nAMD.

“Our results show that the combination of intravitreal long-lasting steroids with anti-VEGF is effective in difficult highly resistant chronic cases that previously lacked an adequate response to HDHF anti-VEGF therapy,” investigators wrote.

The study, “Adjuvant use of long-acting intravitreal steroids and anti-VEGF agents in monotherapy resistant chronic Wet-Age Related Macular Degeneration,” was presented at ARVO 2022.