Impact of retinal fluid in patients with diabetic macular edema treated with anti-VEGF in routine clinical practice

Published:April 05, 2022DOI:



      This study aims to determine the effect of intraretinal (IRF) and subretinal (SRF) fluid on visual outcomes for diabetic macular edema (DME) patients treated with anti–vascular endothelial growth factor (anti-VEGF) in routine clinical practice.


      Optical coherence tomography scans were analyzed with a deep-learning artificial intelligence software to quantify IRF, SRF, and total retinal fluid (TRF) at baseline and at 3, 6, and 12 months. Predictive variables for best-corrected visual acuity (BCVA) were evaluated with linear mixed-effects regression models.


      A total of 220 DME eyes of 220 patients from the Cole Eye Institute at Cleveland Clinic.


      Retrospective, nonrandomized cohort study.


      BCVA improved from baseline to 12 months (63.36 ± 14.72 to 68.49 ± 13.14 Early Treatment Diabetic Retinopathy Study letters, p < 0.001, respectively). Central subfield thickness improved from baseline to 12 months (411.74 ± 129.7 to 335.94 ± 116.91 mm, p < 0.001, respectively). Injection frequency per patient was 8.25 ± 2.5 injections over 12 months. The linear mixed-effects regression model in the foveal region for TRF, IRF, and SRF volume at the fourth quartile showed BCVA losses of –8.29 letters (range, –10.96 to –5.62 letters, p < 0.001), –7.52 letters (range, –10.3 to –4.74 letters, p < .001), and –6.93 letters (range, –10.54 to –3.41 letters, p < .001), respectively.


      The highest quartile of TRF, IRF, and SRF volumes led to worse visual outcomes after 12 months of anti-VEGF treatment in patients with DME. Further studies designed to investigate the effect of anti-VEGF treatment on retinal fluid morphology could provide greater insight into individualized DME treatment.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Canadian Journal of Ophthalmology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Willis JR
        • Doan QV
        • Gleeson M
        • et al.
        Vision-related functional burden of diabetic retinopathy across severity levels in the United States.
        JAMA Ophthalmol. 2017; 135: 926-932
        • Wells JA
        • Glassman AR
        • Ayala AR
        • et al.
        Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial.
        Ophthalmology. 2016; 123: 1351-1359
        • Bressler NM
        • Odia I
        • Maguire M
        • et al.
        Association between change in visual acuity and change in central subfield thickness during treatment of diabetic macular edema in participants randomized to aflibercept, bevacizumab, or ranibizumab: a post hoc analysis of the Protocol T Randomized Clinical Trial.
        JAMA Ophthalmol. 2019; 137: 977-985
        • Keenan TDL
        • Chakravarthy U
        • Loewenstein A
        • Chew EY
        • Schmidt-Erfurth U.
        Automated quantitative assessment of retinal fluid volumes as important biomarkers in neovascular age-related macular degeneration.
        Am J Ophthalmol. 2021; 224: 267-281
        • Korobelnik J-F
        • Lu C
        • Katz TA
        • et al.
        Effect of baseline subretinal fluid on treatment outcomes in VIVID-DME and VISTA-DME studies.
        Ophthalmol Retina. 2019; 3: 663-669
        • Nguyen QD
        • Brown DM
        • Marcus DM
        • et al.
        Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials RISE and RIDE.
        Ophthalmology. 2012; 119: 789-801
        • Gerendas B
        • Simader C
        • Deak GG
        • et al.
        Morphological parameters relevant for visual and anatomic outcomes during anti-VEGF therapy of diabetic macular edema in the RESTORE trial.
        Invest Ophthalmol Vis Sci. 2014; 55: 1791
        • Kaakour A-H
        • et al.
        Association for Research in Vision and Ophthalmology Annual Conference.
        Investigative Ophthalmology and Visual Science. 2021; 2021
        • Otani T
        • Yamaguchi Y
        • Kishi S.
        Correlation between visual acuity and foveal microstructural changes in diabetic macular edema.
        Retina. 2010; 30: 774-780
        • Maheshwary AS
        • Oster SF
        • Yuson RMS
        • et al.
        The association between percent disruption of the photoreceptor inner segment–outer segment junction and visual acuity in diabetic macular edema.
        Am J Ophthalmol. 2010; 150 (e1): 63-67
        • Uji A
        • Murakami T
        • Nishijima K
        • et al.
        Association between hyperreflective foci in the outer retina, status of photoreceptor layer, and visual acuity in diabetic macular edema.
        Am J Ophthalmol. 2012; 153 (e1): 710-717
        • Whitcup S
        • et al.
        Association for Research in Vision and Ophthalmology Annual Meeting.
        Investigative Ophthalmology and Visual Science. 2017; : 58
        • Roberts PK
        • Vogl W-D
        • Gerendas BS
        • et al.
        Quantification of fluid resolution and visual acuity gain in patients with diabetic macular edema using deep learning: a post hoc analysis of a randomized clinical trial.
        JAMA Ophthalmol. 2020; 138: 943-945
        • Ehlers JP
        • Uchida A
        • Sevgi DD
        • et al.
        Retinal fluid volatility associated with interval tolerance and visual outcomes in diabetic macular edema in the VISTA phase III trial.
        Am J Ophthalmol. 2021; 224: 217-227
        • Markan A
        • Agarwal A
        • Arora A
        • et al.
        Novel imaging biomarkers in diabetic retinopathy and diabetic macular edema.
        Ther Adv Ophthalmology. 2020; 122515841420950513
        • Sophie R
        • Lu N
        • Campochiaro PA.
        Predictors of functional and anatomic outcomes in patients with diabetic macular edema treated with ranibizumab.
        Ophthalmology. 2015; 122: 1395-1401
        • Gupta A
        • Raman R
        • Mohana KP
        • et al.
        Communications between intraretinal and subretinal space on optical coherence tomography of neurosensory retinal detachment in diabetic macular edema.
        Oman J Ophthalmol. 2013; 6: 183-188
        • Weinberger D
        • Fink-Cohen S
        • Gaton DD
        • Priel E
        • Yassur Y.
        Non-retinovascular leakage in diabetic maculopathy.
        Br J Ophthalmol. 1995; 79: 728-731
        • Tsai M-J
        • Hsieh Y-T
        • Shen EP
        • Peng Y-J.
        Systemic associations with residual subretinal fluid after ranibizumab in diabetic macular edema.
        J Ophthalmol. 2017; 20174834201
        • Wenick AS
        • Bressler NM.
        Diabetic macular edema: current and emerging therapies.
        Middle East Afr J Ophthalmol. 2012; 19: 4-12