Abstract
Purpose
To evaluate Microperimetry (MP) and multifocal electroretinogram (mfERG) as whole-macula functional markers of treatment response in naive diabetic macular oedema (DMO) patients undergoing ranibizumab treatment.
Methods
An exploratory sub-analysis of a prospective study (NCT01947881-CHARTRES). Patients received three monthly ranibizumab injections (loading dose) followed by pro re nata (PRN) regimen during 1 year. At baseline, during and after treatment (Months 0, 3, 6 and 12), subjects were tested using BCVA, OCT, MP and mfERG. MP was performed in the central 12°, and retinal sensitivity was measured overall (mean sensitivity (MS)), and in three concentric rings (R1–R3). mfERG P1 amplitude and implicit time were measured over six concentric rings (R1–R6).
Results
Thirty-two eyes were included. MP mean and rings sensitivity were significantly lower in DMO (p < 0.001). After loading dose, a significant improvement in retina sensitivity was observed, particularly in good BCVA responders (MS = +2.28 dB; R1 = +2.33 dB, R2 = +2.20 dB, R3 = +2.25 dB; p = 0.049). Overall retinal sensitivity was significantly correlated with BCVA improvement (r = 0.54; p = 0.026) and inversely correlated with OCT central subfield thickness improvement (r = −0.39; p = 0.026). mfERG amplitude and implicit time were also lower in DMO (p < 0.011). An improvement of mfERG P1 amplitude and implicit time in R1 was noted in good responders after ranibizumab loading dose (+16.49 nV/deg2; p = 0.013 and −0.005 ms; p = 0.048, respectively). When changing to PRN treatment regimen, BCVA was maintained during the 12 months of follow-up but worsening of the visual function was detected by MP and mfERG.
Conclusions
Microperimetry and mfERG were able to demonstrate DMO functional improvement after treatment loading dose, as well as early visual changes when treatment regimen was switched to PRN.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Bunce C, Wormald R. Leading causes of certification for blindness and partial sight in England & Wales. BMC Public Health. 2006;6:58.
Heier JS, Korobelnik J-F, Brown DM, Schmidt-Erfurth U, Do DV, Midena E, et al. Intravitreal aflibercept for diabetic macular edema: 148-week results from the VISTA and VIVID studies. Ophthalmology. 2016;123:2376–85.
Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, et al. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmol. 2011;118:615–25.
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.
Csaky KG, Richman EA, Ferris FL. Report from the NEI/FDA ophthalmic clinical trial design and endpoints symposium. Investig Ophthalmol Vis Sci. 2008;49:479–89.
Ranibizumab (Lucentis): Visual Impairment due to Choroidal Neovascularization Secondary to Pathologic Myopia. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2015. https://pubmed.ncbi.nlm.nih.gov/26962598/
Beck RW, Maguire MG, Bressler NM, Glassman AR, Lindblad AS, Ferris FL. Visual acuity as an outcome measure in clinical trials of retinal diseases. Ophthalmology. 2007;114:1804–9.
Chakravarthy U, Pearce I, Banerjee S, Burton BJL, Downey L, Gale R, et al. Patient-reported outcomes in the RELIGHT clinical trial of ranibizumab in diabetic macular oedema. BMJ Open Ophthalmol. 2019;4:1–8.
Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Nakamura M. New insights into the pathophysiology of diabetic retinopathy: potential cell-specific therapeutic targets. Diabetes Technol Ther. 2000;2:601–8.
Barber AJ. A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:283–90.
Jackson GR, Barber AJ. Visual dysfunction associated with diabetic retinopathy. Curr Diabetes Rep. 2010;10:380–4.
Santos AR, Ribeiro L, Bandello F, Lattanzio R, Egan C, Frydkjaer-Olsen U, et al. Functional and structural findings of neurodegeneration in early stages of diabetic retinopathy: cross-sectional analyses of baseline data of the EUROCONDOR project. Diabetes. 2017;66:2503–10.
Yohannan J, Bittencourt M, Sepah YJ, Hatef E, Sophie R, Moradi A, et al. Association of retinal sensitivity to integrity of photoreceptor inner/outer segment junction in patients with diabetic macular edema. Ophthalmology. 2013;120:1254–61.
Shen Y, Liu K, Xu X. Correlation between visual function and photoreceptor integrity in diabetic macular edema: spectral-domain optical coherence tomography. Curr Eye Res. 2016;41:391–9.
Wang J, Jie C, Tao Y, Meng N, Hu Y, Wu Z. Macular integrity assessment to determine the association between macular microstructure and functional parameters in diabetic macular edema. Int J Ophthalmol. 2018;11:1185–91.
Sutter EE, Tran D. The field topography of ERG components in man–I. The photopic luminance response. Vis Res. 1992;32:433–46.
Han Y, Adams AJ, Bearse MA, Schneck ME. Multifocal electroretinogram and short-wavelength automated perimetry measures in diabetic eyes with little or no retinopathy. Arch Ophthalmol. 2004;122:1809–15.
Schneck ME, Bearse MA, Han Y, Barez S, Jacobsen C, Adams AJ. Comparison of mfERG waveform components and implicit time measurement techniques for detecting functional change in early diabetic eye disease. Doc Ophthalmol. 2004;108:223–30.
Tehrani NM, Riazi-Esfahani H, Jafarzadehpur E, Mirzajani A, Talebi H, Amini A, et al. Multifocal electroretinogram in diabetic macular edema; correlation with visual acuity and optical coherence tomography. J Ophthalmic Vis Res. 2015;10:165–71.
Greenstein VC, Chen H, Hood DC, Holopigian K, Seiple W, Carr RE. Retinal function in diabetic macular edema after focal laser photocoagulation. Investig Ophthalmol Vis Sci. 2000;41:3655–64.
Bearse MA, Ozawa GY. Multifocal electroretinography in diabetic retinopathy and diabetic macular edema. Curr Diabetes Rep. 2014;14:526.
Santos AR, Costa MÂ, Schwartz C, Alves D, Figueira J, Silva R, et al. Optical coherence tomography baseline predictors for initial best-corrected visual acuity response to intravitreal anti-vascular endothelial growth factor treatment in eyes with diabetic macular edema: the CHARTRES Study. Retina. 2018;38:1110–9.
Hood DC, Bach M, Brigell M, Keating D, Kondo M, Lyons JS, et al. ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol. 2012;124:1–13.
Elman MJ, Ayala A, Bressler NM, Browning D, Flaxel CJ, Glassman AR, et al. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology. 2015;122:375–81.
Massin P, Bandello F, Garweg J, Hansen L, Harding S. Efficacy of ranibizumab in diabetic macular edema (RESOLVE Study*). Diabetes Care. 2010;33:2399–405.
Vujosevic S, Midena E, Pilotto E, Radin PP, Chiesa L, Cavarzeran F. Diabetic macular edema: correlation between microperimetry and optical coherence tomography findings. Investig Ophthalmol Vis Sci. 2006;47:3044–51.
Bonnin S, Tadayoni R, Erginay A, Massin P, Dupas B. Correlation between ganglion cell layer thinning and poor visual function after resolution of diabetic macular edema. Investig Ophthalmol Vis Sci. 2015;56:978–82.
Mendoza-Santiesteban CE, Fernández-Cherkasova L, Echavarria OH, Rodríguez RC, Columbié-Garbey Y, Riesgo TJ. Multifocal electroretinography. Semin Ophthalmol. 2010;25:155–64.
Weiner A, Christopoulos VA, Gussler CH, Adams DH, Kaufman SR, Kohn HD, et al. Foveal cone function in nonproliferative diabetic retinopathy and macular edema. Investig Ophthalmol Vis Sci. 1997;38:1443–9.
Drum B, Calogero D, Rorer E. Assessment of visual performance in the evaluation of new medical products. Drug Discov Today Technol. 2007;4:55–61.
Hafner J, Karst S, Schmidt-Erfurth U. Potential imaging biomarkers in the development and progression of diabetic retinopathy. In book: Early events in diabetic retinopathy and intervention strategies. IntechOpen; 2018. p. 9–36.
Diabetic Retinopathy Clinical Research Network, Browning DJ, Glassman AR, Aiello LP, Beck RW, Brown DM, et al. Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. Ophthalmology. 2007;114:525–36.
Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmol. 2010;117:1064–77.e35.
Prünte C, Fajnkuchen F, Mahmood S, Ricci F, Hatz K, Studnička J, et al. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J Ophthalmol. 2016;100:787–95.
Baker CW, Glassman AR, Beaulieu WT, Antoszyk AN, Browning DJ, Chalam KV, et al. Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical trial. JAMA. 2019;321:1880–94.
Baget-Bernaldiz M, Romero-Aroca P, Bautista-Perez A, Mercado J. Multifocal electroretinography changes at the 1-year follow-up in a cohort of diabetic macular edema patients treated with ranibizumab. Doc Ophthalmol. 2017;135:85–96.
Comyn O, Sivaprasad S, Peto T, Neveu MM, Holder GE, Xing W, et al. A randomized trial to assess functional and structural effects of ranibizumab versus laser in diabetic macular edema (the LUCIDATE study). Am J Ophthalmol. 2014;157:960–70.
Malagola R, Spinucci G, Cofone C, Pattavina L. Prospective microperimetry and OCT evaluation of efficacy of repeated intravitreal bevacizumab injections for persistent clinically significant diabetic macular edema. Int Ophthalmol. 2013;33:261–7.
Wu Z, Ayton LN, Guymer RH, Luu CD. Comparison between multifocal electroretinography and microperimetry in age-related macular degeneration. Investig Ophthalmol Vis Sci. 2014;55:6431–9.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Santos, A.R., Raimundo, M., Alves, D. et al. Microperimetry and mfERG as functional measurements in diabetic macular oedema undergoing intravitreal ranibizumab treatment. Eye 35, 1384–1392 (2021). https://doi.org/10.1038/s41433-020-1054-2
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41433-020-1054-2
