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Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study
  1. Amy Babiuch1,
  2. Charles Clifton Wykoff2,
  3. Jenna Hach1,
  4. Sunil Srivastava1,
  5. Katherine E Talcott1,
  6. Hannah J Yu2,
  7. Muneeswar Nittala3,4,
  8. SriniVas Sadda3,4,
  9. Michael S Ip3,4,
  10. Thuy Le1,
  11. Ming Hu1,5,
  12. Jamie Reese1,
  13. Justis P Ehlers1
  1. 1 The Tony and Leona Campane Center for Excellence in Image-guided Surgery and Advanced Imaging Research, Cleveland Clinic, Cleveland, Ohio, USA
  2. 2 Blanton Eye Institute, Houston Methodist Hospital & Weill Cornell Medical College, Retina Consultants of Houston, Houston, Texas, USA
  3. 3 Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California, USA
  4. 4 Ophthalmology, University of California Los Angeles David Geffen School of Medicine, Pasadena, California, USA
  5. 5 Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
  1. Correspondence to Justis P Ehlers, Cleveland Clinic Cole Eye Institute, Cleveland, OH 44195, USA; ehlersj1{at}


Background/Aims Quantifying microaneurysms (MAs) turnover may be an objective measure for therapeutic response in diabetic retinopathy. This study assesses changes in MA counts on ultra-widefield fluorescein angiography (UWFA) in subjects undergoing treatment with intravitreal aflibercept injection (IAI) for proliferative diabetic retinopathy (PDR) in the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy(RECOVERY) study using an automated MA detection platform.

Methods RECOVERY is a prospective study that enrolled 40 subjects with PDR randomised 1:1 to receive 2 mg IAI every 4 weeks(q4wk) or every 12 weeks (q12wk). UWFA images were obtained at baseline, 6 months and 1 year. Images were analysed using an automated segmentation platform to detect and quantify MAs. Zones 1, 2 and 3 correspond to the macula, mid-periphery and far-periphery, respectively.

Results The q4wk cohort demonstrated a significant decline in MAs in all zones and panretinally at baseline versus month 6, baseline versus year 1, and month 6 versus year 1 (−20.0% to −61.8%; all p<0.001). In the q12wk cohort, baseline versus month 6 showed a significant decline panretinally (mean: −34.2%; p<0.001) and in zone 3 (mean −44.18%; p<0.001). Addiitonally, baseline to year 1 in the q12wk group demonstrated significant decline panretinally (mean: −47.7%; p<0.001) and in zone 3 (mean: −59.8%; p<0.001). All zones demonstrated significantly decline from month 6 to year 1 in the q12wk group.

Conclusion Therapy with IAI demonstrates significantly reduced panretinal MA counts in PDR at 1 year in both treatment groups. The use of automated platforms to detect and quantify MAs may provide a novel imaging marker for evaluating disease activity and therapeutic impact.

Trial registration number NCT02863354.

  • Imaging
  • Macula
  • Retina
  • Treatment Medical

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  • Ethics approval The RECOVERY study was an IRB-approved study. Written informed consent was obtained from all participants.

  • Contributors All authors provide input on data analysis, manuscript revision and data interpretation. CCW and JPE provided supervisory support and funding support. MH provided statistical analysis support.

  • Funding This work was supported by NIH/NEI K23-EY022947-01A1 (JPE) and Regeneron RCH1804JE (CCW, JPE and RECOVERY Study Group).

  • Competing interests AB, research support—Genentech, Allergan; consulting—Genentech; CCW, research support—Adverum, Allergan, Apellis, Clearside, EyePoint, Genentech/Roch, Neurotech, Novartis, Opthea, Regeneron, Regenxbio, Samsung, Santen; consulting—Adverum, Alimera Sciences, Allegro, Allergan, Apellis, Bayer, Clearside, DORC, EyePoint, Genentech/Roche, Kodiak, Notal Vision, Novartis, ONL Therapeutics, PolyPhotonix, RecensMedical, Regeneron, Regenxbio, Santen, Takeda; SS, research support—Regeneron, Allergan, Gilead; consulting: Bausch and Lomb, Santen; patent—Leica; SVRS, research support—Carl Zeiss Meditec, consulting—Optos, CenterVue, Heidelberg Engineering, Roche/Genentech, Novartis, Allergan, Amgen, Bayer; research instruments—Carl Zeiss Meditec, Nidek, Topcon; JPE, research support—Aerpio, Alcon, Thrombogenics, Regeneron, Genentech, Novartis; consulting—Aerpio, Alcon, Allegro, Allergan, Genentech/Roche, Novartis, Thrombogenics, Leica, Zeiss, Regeneron, Santen; patent—Leica; MI, consultant: Boehringer Ingelheim, Thrombogenics, Quark, Omeros, Allergan, Amgen, Astellas, Alimera; research support—Novartis, Genentech, Clearside, Biogen. KET, HJY, MN MH, JR, no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article. If additional data may be available by request if for some reason that is required.

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