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A Biomarker of Visual Acuity Response to Treatment

Santos, Ana Rita, MSc*,†; Alves, Dalila, MSc*; Santos, Torcato, BSc*; Figueira, João, MD, PhD*,‡,§; Silva, Rufino, MD, PhD*,‡,§; Cunha-Vaz, José G., MD, PhD*,‡

doi: 10.1097/IAE.0000000000001905
Original Study

Purpose: To evaluate the effects of anti–vascular endothelial growth factor treatment on retinal fluid in patients with diabetic macular edema by using optical coherence tomography leakage (OCT-L), a new method of quantifying sites of lower than normal optical reflectivity (LOR) in OCT, and to correlate these findings with best-corrected visual acuity (BCVA) response.

Methods: Prospective analysis of 21 eyes with diabetic macular edema, naive to anti–vascular endothelial growth factor treatment. Macular cube 512 × 128 and OCT angiography 6 × 6-mm scans (CIRRUS AngioPlex; ZEISS, Dublin, CA) were acquired in all eyes before the first ranibizumab injection (V1) and 1 week after treatment (V2). Optical coherence tomography leakage analysis was performed with Angioplex raw scan data used to calculate LOR map ratios. Lower optical reflectivity ratios at baseline and differences from V1 to V2 and other OCT morphological features such as central retinal thickness measurements, disorganization of the inner retinal layers, and disruption of ellipsoid zone were compared with BCVA response 1 month after the first intravitreal injection.

Results: After the first intravitreal injection of ranibizumab, eight patients (38%) were identified as good responders, 5 (24%) as moderate, and 8 (38%) as poor. There were no significant BCVA differences at baseline. Significant differences were found in LOR ratio changes between the different treatment response groups after 1 week of treatment, especially in outer segment and outer plexiform layer (outer segment—good responders: −53%, responders: −12%, and poor responders: 7% [P = 0.026]; outer plexiform layer—good responders: −49%, responders: 18%, and poor responders: 5% [P = 0.010]). Lower optical reflectivity ratios differences after 1 week of treatment predict better the BCVA treatment response at 1 month than changes of central retinal thickness, disorganization of the inner retinal layer, and ellipsoid zone disruption, especially in the outer segment and outer plexiform layer (area under the curve = 0.82 and 0.73, respectively).

Conclusion: Optical coherence tomography leakage changes after anti–vascular endothelial growth factor treatment of diabetic macular edema, identifying the degree of decrease in retinal fluid in the outer layers of the retina is a more robust biomarker of BCVA recovery than central retinal thickness, disorganization of the inner retinal layer, or ellipsoid zone disruption changes.

Treatment of diabetic macular edema is not always followed by visual function recovery. Identification of visual outcome predictors of anti–vascular endothelial growth factor therapy is needed for better diabetic macular edema treatment management. Optical coherence tomography leakage, which maps sites of lower reflectivity within the retina, appears to be a robust biomarker of diabetic macular edema treatment response.

*Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal;

Superior School of Health, Polytechnic Institute of Porto, Porto, Portugal;

Faculty of Medicine, University of Coimbra, Coimbra, Portugal; and

§Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal.

Reprint requests: Ana Rita Santos, MSc, AIBILI, Azinhaga de Santa Comba, Celas 3000-548, Coimbra, Portugal; e-mail:

R. Silva and J. Figueira are consultants of Bayer, Novartis, Alimera Sciences, Alcon, and Allergan. R. Silva is also consultant of Thea. J. G. Cunha-Vaz reports grants from Carl Zeiss Meditec, outside the submitted work and is consultant for Alimera Sciences, Allergan, Bayer, Gene Signal, Novartis, Pfizer, Precision Ocular Ltd, Roche, Sanofi-Aventis, Vifor Pharma, and Carl Zeiss Meditec. The remaining authors have no financial/conflicting interests to disclose.

© 2019 by Ophthalmic Communications Society, Inc.