Findings from the PERMEATE study used novel diagnostics to quantify response to intravitreal injections
Intravitreal aflibercept (Eylea, Regeneron) can improve visual and anatomic outcomes in patients with diabetic macular edema (DME) or retinal vein occlusion (RVO), according to findings from the PERMEATE study that used ultra widefield angiography and a novel quantitative angiographic assessment tool developed at the Cleveland Clinic.
Justis P. Ehlers, MD, Cole Eye Institute at the Cleveland Clinic, noted that although “significant success has been demonstrated in multiple clinical trials [with intravitreal pharmacotherapy], there are still eyes that have limited response to various therapeutics.” Newer imaging analysis tools and imaging modalities “are emerging that hold promise for potential new insights into therapeutic response and prognosis.” Dr. Ehlers presented results of the PERMEATE study, designed to characterize imaging features in DME and RVO by using “novel image analysis platforms” in patients undergoing intravitreal aflibercept treatment. These platforms include retinal vascular dynamics with an angiographic quantitative assessment tool, ellipsoid zone integrity and fluid feature extraction; and radiomics/machine learning.
Ultra-widefield fluorescein angiography and OCT angiography were performed at multiple time points to assess the changes in retinal vascular leakage, ischemia, and vascular abnormalities throughout the study duration and compare these alterations to baseline, Dr. Ehlers said.
The key inclusion criteria were foveal-involving retinal edema secondary to DME or RVO and a best-corrected visual acuity (BCVA) of 20/25 or worse in the study eye. Patients were excluded who had been treated previously with intravitreal pharmacotherapy or laser photocoagulation in the study eye.
Dr. Ehlers said PERMEATE identified significant changes in retinal vascular leakage, retinal ischemia, and microaneurysms in 30 patients undergoing treatment with intravitreal aflibercept, which previously had not been quantified. In PERMEATE, ellipsoid zone integrity was assessed with manual verification of 128 B-scans used to reconstruct a macular cube. Quantitative retinal parameters included the ellipsoid zone-retinal pigment epithelium (RPE) central subfield thickness (CST), the ellipsoid zone-RPE volume, and the percentage of ellipsoid-RPE total and partial attenuation. (See Modern Retina’s previous coverage on the 6-month results at http://www.modernretina.com/modern-retina/news/ultra-widefield-angiography-new-window-retinovascular-features?qt-resource_topics_rightrail=1)
The PERMEATE researchers compared baseline ultra widefield features between eyes that developed rebound edema and worsening VA with aflibercept every-8-weeks dosing (on-label) to eyes that had sustained edema improvement following every-8-weeks dosing switch.
Vision and Anatomic Outcomes
At baseline, the mean visual acuity was 20/80, which improved to 20/40 month 12 (p<0.0001). Similarly, the change in CST was a decrease of 259 Î¼m (an improvement of 55%; p<0.0001). Quantitative angiographic outcomes were mixed, with a leakage index improving from 3.4% to 0.5% (p<0.0001), but a change in ischemic index increasing from 5.5% to 8.7% (p=0.2).
However, advanced radiomics analysis with baseline vascular tortuosity assessment was shown to identify eyes that could tolerate longer dosing intervals in macular edema, Dr. Ehlers noted.
When evaluating the ellipsoid zone integrity, all changes were statistically significant, as were all changes in fluid feature analyses (change in intraretinal and subretinal fluid, the latter of which improved from 0.026 mm2 to 0 mm2.
Dr. Ehlers said the vascular tortuosity measures “differed significantly” between those groups who fared well with on-label dosing of every-8-weeks and those that did not. Further, he said there was increased baseline tortuosity in eyes that could not tolerate that dosing.
“This study had its limitations,” Dr. Ehlers said, including a small sample size and a lack of a control or comparative therapy group.
“However, this was an integrative assessment of the interplay between the various quantitative metrics,” Dr. Ehlers said. In the future, he would suggest expanding the radiomics assessment to OCT features, and applying radiomics assessment to a larger independent dataset.
“Additional research is needed to further validate these measures and their potential role as imaging biomarkers for DME and retinal vein occlusion,” Dr. Ehlers said.
Dr. Ehlers presented his results at the American Society of Retinal Surgeons’ meeting in Vancouver.