Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Functional outcomes of sustained improvement on Diabetic Retinopathy Severity Scale with intravitreal aflibercept in the VISTA and VIVID trials

Eye volume 37, pages 2020–2025 (2023)Cite this article

Subjects

Abstract

Aims

To assess time to, cumulative incidence of, and functional benefit of achieving sustained ≥2-step Diabetic Retinopathy Severity Scale (DRSS) improvement in diabetic macular oedema (DMO).

Methods

Post hoc analysis of VISTA/VIVID including eyes with DMO treated with intravitreal aflibercept injections (IAI), 2 mg q4 weeks (2q4, n = 250) or q8 weeks after 5 monthly doses (2q8, n = 249), or laser control (n = 249). Changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were evaluated in sustained (≥2 consecutive visits) DRSS subgroups (≥1-step worsening, no change, ≥2-step improvement).

Results

Time to sustained ≥2-step DRSS improvement was shorter for both the IAI 2q4 and IAI 2q8 groups versus laser (both log-rank p < 0.001). Cumulative incidences of sustained ≥2-step DRSS improvement with IAI 2q4 and IAI 2q8 versus laser were 40.0% and 42.8% versus 15.5% (both p < 0.001) through week 100. Mean differences (95% CI) in BCVA gains from baseline at weeks 52 and 100 between eyes with sustained ≥2-step DRSS improvement versus sustained ≥1-step DRSS worsening were –3.0 (–8.9, 2.9) and 6.2 (0.2, 12.2) letters with laser, and 4.2 (0.8, 7.6) and 4.9 (1.3, 8.4) letters with IAI combined, respectively. Difference (95% CI) in CST reduction was significantly greater only with IAI combined at week 100 (–83.0 [–140.8, –25.3]). Correlations between BCVA and CST changes were weak.

Conclusions

DMO eyes treated with IAI achieved sustained ≥2-step DRSS improvement significantly earlier and more frequently versus laser. This improvement was associated with greater BCVA gains, independent of CST reductions.

Trial registration

ClinicalTrials.gov (https://clinicaltrials.gov/) identifiers: NCT01363440 and NCT01331681.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Flow diagram.
Fig. 2: Cumulative incidence of sustained ≥2-step DRSS improvement from baseline through week 100.
Fig. 3: Change from baseline in BCVA and CST by treatment and sustained DRSS subgroups at week 52.
Fig. 4: Change from baseline in BCVA and CST by treatment and sustained DRSS subgroups at week 100.

Similar content being viewed by others

Data availability

Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in this manuscript. Individual anonymised participant data will be considered for sharing once the indication has been approved by major health authorities, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification. Submit requests to https://vivli.org/.

References

  1. Early Treatment Diabetic Retinopathy Study Research Group. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Ophthalmology. 1991;98:823–33.

    Article  Google Scholar 

  2. Coyne KS, Margolis MK, Kennedy-Martin T, Baker TM, Klein R, Paul MD, et al. The impact of diabetic retinopathy: perspectives from patient focus groups. Fam Pract. 2004;21:447–53.

    Article  PubMed  Google Scholar 

  3. Mazhar K, Varma R, Choudhury F, McKean-Cowdin R, Shtir CJ, Azen SP, et al. Severity of diabetic retinopathy and health-related quality of life: the Los Angeles Latino Eye Study. Ophthalmology. 2011;118:649–55.

    Article  PubMed  Google Scholar 

  4. Willis JR, Doan QV, Gleeson M, Haskova Z, Ramulu P, Morse L, et al. Vision-related functional burden of diabetic retinopathy across severity levels in the United States. JAMA Ophthalmol. 2017;135:926–32.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology. 1995;102:7–16.

    Article  CAS  PubMed  Google Scholar 

  6. Mitchell P, McAllister I, Larsen M, Staurenghi G, Korobelnik JF, Boyer DS, et al. Evaluating the impact of intravitreal aflibercept on diabetic retinopathy progression in the VIVID-DME and VISTA-DME studies. Ophthalmol Retin. 2018;2:988–96.

    Article  Google Scholar 

  7. Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121:2247–54.

    Article  PubMed  Google Scholar 

  8. Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology. 2015;122:2044–52.

    Article  PubMed  Google Scholar 

  9. Ip MS, Zhang J, Ehrlich JS. The clinical importance of changes in diabetic retinopathy severity score. Ophthalmology. 2017;124:596–603.

    Article  PubMed  Google Scholar 

  10. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985;103:1796–806.

    Article  Google Scholar 

  11. Browning DJ, Glassman AR, Aiello LP, Beck RW, Brown DM, Fong DS, et al. Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. Ophthalmology. 2007;114:525–36.

    Article  PubMed  Google Scholar 

  12. Bressler SB, Odia I, Maguire MG, Dhoot DS, Glassman AR, Jampol LM, et al. Factors associated with visual acuity and central subfield thickness changes when treating diabetic macular edema with anti-vascular endothelial growth factor therapy: an exploratory analysis of the Protocol T randomized clinical trial. JAMA Ophthalmol. 2019;137:382–9.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Brown DM, Wykoff CC, Boyer D, Heier JS, Clark WL, Emanuelli A, et al. Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy: results from the PANORAMA randomized clinical trial. JAMA Ophthalmol. 2021;139:946–55.

    Article  PubMed  Google Scholar 

  14. Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789–801.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Medical writing support was provided by Melissa Purves, PhD, and Rob Campbell, PhD, of Core (London, UK) according to Good Publication Practice guidelines (link) and was funded by Regeneron Pharmaceuticals, Inc.

Funding

This study was funded by Regeneron Pharmaceuticals, Inc.

Author information

Authors and Affiliations

  1. California Retina Consultants/Retina Consultants of America, Santa Barbara, CA, USA

    Dilsher S. Dhoot

  2. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA

    Hadi Moini, Kimberly Reed, Weiming Du, Robert Vitti & Alyson J. Berliner

  3. Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA

    Rishi P. Singh

Authors
  1. Dilsher S. Dhoot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hadi Moini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kimberly Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Weiming Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Vitti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alyson J. Berliner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rishi P. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the concept and design of the study; acquisition, analysis, and interpretation of the data; drafting of the manuscript; and critical revision of the manuscript for important intellectual content. WD provided the statistical analysis.

Corresponding author

Correspondence to Rishi P. Singh.

Ethics declarations

Competing interests

DSD is a consultant for Bayer, Novartis, Regeneron Pharmaceuticals, Inc., Genentech, Allergan, Alimera, Santen, Allegro, Notal Vision, and Eyepoint Pharmaceuticals. HM, KR, WD, RV and AJB are employees of and hold equity in Regeneron Pharmaceuticals, Inc. RPS is a consultant for Genentech/Roche, Regeneron Pharmaceuticals, Inc., Novartis, Zeiss, Bausch and Lomb, Asclepix, Alcon, and Gyroscope and has received research funding from Apellis and NGM Biopharma.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dhoot, D.S., Moini, H., Reed, K. et al. Functional outcomes of sustained improvement on Diabetic Retinopathy Severity Scale with intravitreal aflibercept in the VISTA and VIVID trials. Eye 37, 2020–2025 (2023). https://doi.org/10.1038/s41433-022-02058-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41433-022-02058-7

Search

Advanced search

Quick links