Baseline characteristics help predict visual acuity outcomes after anti-VEGF treatment for wet AMD

Issue: January 10, 2016

Lower best corrected visual acuity, younger age and smaller total area of choroidal neovascularization at baseline may be significant predictors for visual acuity outcomes when treating wet age-related macular degeneration patients with ranibizumab, according to an analysis.

The retrospective analysis of the phase 3 HARBOR study evaluated demographic and baseline characteristics that may predict visual acuity outcomes in patients with subfoveal wet AMD.

“Understanding which biomarkers are predictive of visual and treatment frequency response to anti-VEGF treatment may help retina specialists manage patient expectations and guide treatment decisions from the start of therapy,” OSN Retina/Vitreous Board Member Carl D. Regillo, MD, told Ocular Surgery News.

Predictive factors

Over 12 months, 249 patients were treated with 0.5 mg of Lucentis (ranibizumab, Genentech) monthly, and 251 patients were treated with the same dose on an as-needed basis after three monthly loading doses.

First, the predictive factors of greatest mean BCVA improvement and of three-line gain, or 15 letters or more, on the ETDRS chart were evaluated. Baseline predictors for BCVA change from baseline to month 12 were lower BCVA at presentation, younger age, and smaller total CNV leakage area and area of occult CNV. Baseline predictors for BCVA gain of 15 letters or more from baseline to month 12 were lower BCVA at presentation, smaller total CNV leakage area and presence of subretinal fluid.

Next, predictive factors of achieving 20/40 vision or better were assessed because that is the threshold required to obtain a valid U.S. driver’s license, Regillo said. Baseline predictors for 20/40 visual acuity or better at month 12 were higher BCVA at presentation, smaller total CNV leakage area and presence of subretinal fluid.

“The apparent discrepancy between the predictive value of baseline vision for the three-line gainers (worse BCVA) and 20/40 achievers (better BCVA) is due to a ceiling effect; patients who gained 15 or more letters had baseline visual acuity of at least three lines poorer than normal, giving them more room for improvement,” Regillo said. “Patients were more likely to achieve 20/40 vision if they had a better starting vision at baseline.”

The only baseline predictor for total number of injections over the 12-month period was greater subretinal fluid thickness at presentation.

“Repeated intravitreal injections can be burdensome for patients, their caregivers and physicians, and we consider the predictive value of factors associated with injection frequency the most impactful finding,” Regillo said.

New data

The study was able to offer new predictive data that were generated as a result of post hoc analyses from a large clinical trial supported by another retrospective post hoc analysis of pooled data from patients treated with 0.5 mg ranibizumab in four wet AMD trials: ANCHOR, MARINA, PIER and HARBOR, Regillo said.

“Based on these new analyses, we provide new, confirmatory information that may be used to better guide future treatment decisions, especially in the PRN setting,” he said.

In the future, Regillo would like to see if other baseline characteristics, such as intraocular VEGF levels and other cytokines involved in retinal pathology, might predict treatment response to ranibizumab in patients with wet AMD.

“Well-validated objective biomarkers predictive of injection frequency with anti-VEGF molecules may enable retina specialists to individualize dosing regimens at the time of a patient’s first treatment,” he said. – by Kristie L. Kahl

Reference:
Regillo CD, et al. Am J Ophthalmol. 2015;doi:10.1016/j.ajo.2015.07.034.

For more information:
Carl D. Regillo, MD, can be reached at Wills Eye Institute, 840 Walnut St., Suite 1020, Philadelphia, PA 19107; email: cregillo@aol.com.

Disclosure: Regillo reports he receives research grant support from and does consulting for Genentech.