Author: Justis Ehlers (United States)
Co-authors: Kubra Sarici, Thuy Le, Leina Lunasco, Sari Yordi, Hasan Cetin, Duriye Damla Sevgi
Intraocular inflammation (IOI), retinal vasculitis, or vascular occlusion have been reported in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor therapy. This current analysis is a preliminary comparative discovery assessment of eyes with IOI from the HAWK study to evaluate the presence of optical coherence tomography (OCT) features that may precede or develop in association with IOI, and which might serve as OCT biomarkers for IOI.
HAWK (NCT02307682) was a multicenter study conducted in North, Central, and South America; Europe; Asia; Australia; and Japan. The imaging analysis was completed at Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.
HAWK was a randomized, double-masked, 96-week phase 3 study comparing brolucizumab to aflibercept in nAMD. A comparative higher-order discovery analysis was initiated evaluating 34 eyes with IOI and 34 propensity-matched controls from the HAWK study. This analysis includes comparative higher-order OCT, radiomics assessment, and machine learning feature assessment. This report provides an initial assessment of the comparative discovery assessment of the Safety-Specific Next-Generation imaging analysis (SaGe) from HAWK. Images were reviewed frame by frame for specific features prior to or during the IOI event.
Initial comparative assessment of the 34 IOI eyes and the 34 propensity-matched control eyes demonstrated differential findings between the two groups. Qualitative assessment identified characteristic preretinal hyperreflective foci, “stalagmites,” in 20 of 34 eyes (59%) with IOI compared to 1 of 34 eyes (3%) in the control group. The one control subject was noted to have an adverse event secondary to floaters at the time the “stalagmites” were noted on OCT. The presence of the “stalagmites” was first identified at the time IOI was initially noted in 11 subjects. Of these 11 subjects, 8 eyes (72%) were defined as IOI + retinal vasculitis and/or vascular occlusive (IOI+RV/RO). In 9 subjects, the “stalagmites” were visualized at visits prior to the reported IOI event in all 9 eyes, and 7 of these 9 eyes (77%) were identified as having IOI+RV/RO. There were 14 out of 34 eyes (41%) with IOI that did not have the presence of “stalagmites”, of which 8 eyes (57%) were defined as IOI+RV/RO.
In this preliminary discovery evaluation for OCT biomarkers for IOI-related events in the HAWK data set, the presence of hyperreflective preretinal foci (i.e., preretinal “stalagmites”) appears to be a potentially important objective IOI-related OCT finding, and its utility as a signal for clinicians assessing for underlying posterior inflammation requires further investigation. This specific signal also appears to be a potential important biomarker for underlying IOI associated vasculitis/vascular occlusive events. Important limitations of this initial analysis include that the IOI assessment only included eyes treated with brolucizumab and not the aflibercept treatment arm and the analysis did not evaluate eyes from the HARRIER clinical trial. An expanded assessment to include additional eyes with IOI from both phase 3 trials is currently underway.
This study was supported by Novartis Pharmaceuticals, Inc. Justis P. Ehlers, MD: Research grant as a principal or co-principal investigator from Novartis (current research presented here); NIH/NEI K23-EY022947-01A1; NIH/NEI R34-EY029308; Ohio Department of Development TECH-13-059; The Tom and Maryanne Wagner Advanced Imaging Research Fund; The Betty Powers Optical Coherence Tomography Research Fund; The Norman C. and Donna L. Harbert Endowed Chair Fund; and The Tony and Leona Campane Image-Guided Surgery and Advanced Image Analysis Research Fund. Consultant for Novartis, Zeiss, Leica/Bioptigen, Alcon, Allergan, Alimera, Thrombogenics, Santen, and Aerpio; Novartis, Regeneron, Genentech, Thrombogenics, Alcon, and Aerpio for research grants; Bioptigen/Leica for Patents/Intellectual Property/Licensing; and Zeiss for equipment. Thuy K. Le, BA: No financial disclosures. Leina Lunasco, BA: No financial disclosures. Kubra Sarici, MD: No financial disclosures. Sari Yordi, MD: No financial disclosures. Hasan Cetin, MD: No financial disclosures. Duriye Damla Sevgi, MD: No financial disclosures. Jamie Reese, BSN: No financial disclosures. Sunil K. Srivastava, MD: Consultant Novartis and Regeneron.
Additional Co-authors: 7. Katherine Talcott - The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA 8. Jamie Reese - The Tony and Leona Campane Center for Excellence in Image Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA 9. Sunil - Srivastava - The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, US