Abstract
Purpose
To evaluate retinal thickness fluctuations in patients with diabetic macular oedema (DMO) treated with anti-vascular endothelial growth factor (anti-VEGF) injections.
Methods
Visual acuity (VA) and central subfield thickness (CST) were collected at baseline, 3, 6, 9 and 12 months. Retinal thickness fluctuation was quantified by standard deviation (SD) of CST across 12 months. A mixed effects regression model evaluated the relationship between CST SD and VA at 12 months. Multiple linear regression analysis was performed to investigate predictors of CST SD.
Results
Mean baseline and 12-month VAs were 63.5 ± 15.7 and 69.0 ± 13.8 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (change = +5.1 ± 16.1 letters, p < 0.001). Mean baseline and 12-month CSTs were 396.9 ± 109.7 and 337.7 ± 100.7 μm (change = −59.2 ± 114.8 μm, p < 0.001). Retinal thickness variability across the first 12 months was 59.4 ± 43.6 μm. Stratification of patient eyes by CST SD demonstrated 9.7 letters difference in 12-month VA between first and fourth quartiles. Significant predictors of CST SD include baseline CST, injection type, laser treatment, and DR stage.
Conclusions
Larger retinal thickness fluctuations are associated with poorer visual outcomes in eyes with DMO treated with anti-VEGF injections. Retinal thickness variability may be an important prognostic biomarker for DMO patients.
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References
Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis. 2015;2:17.
Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376:124–36.
Varma R, Bressler NM, Doan QV, Gleeson M, Danese M, Bower JK, et al. Prevalence of and risk factors for diabetic macular edema in the United States. JAMA Ophthalmol. 2014;132:1334–40.
Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–64.
Flaxel CJ, Adelman RA, Bailey ST, Fawzi A, Lim JI, Vemulakonda GA, et al. Diabetic retinopathy preferred practice pattern(R). Ophthalmology. 2020;127:P66–145.
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.
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.
Sheu SJ, Lee YY, Horng YH, Lin HS, Lai WY, Tsen CL. Characteristics of diabetic macular edema on optical coherence tomography may change over time or after treatment. Clin Ophthalmol. 2018;12:1887–93.
Ou WC, Brown DM, Payne JF, Wykoff CC. Relationship between visual acuity and retinal thickness during anti-vascular endothelial growth factor therapy for retinal diseases. Am J Ophthalmol. 2017;180:8–17.
Bressler SB, Qin H, Beck RW, Chalam KV, Kim JE, Melia M, et al. Factors associated with changes in visual acuity and central subfield thickness at 1 year after treatment for diabetic macular edema with ranibizumab. Arch Ophthalmol. 2012;130:1153–61.
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.
Islam F. Retinal thickness and visual acuity in diabetic macular edema: an optical coherence tomography-based study. J Coll Physicians Surg Pak. 2016;26:598–601.
Bressler NM, Odia I, Maguire M, Glassman AR, Jampol LM, MacCumber MW, 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.
Farjood F, Vargis E. Novel devices for studying acute and chronic mechanical stress in retinal pigment epithelial cells. Lab Chip. 2018;18:3413–24.
Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron. 2012;75:26–39. https://doi.org/10.1016/j.neuron.2012.06.018.
Evans RN, Chakravarthy U, Reeves B. Associations between variation in retinal thickness and visual function. Investig Ophthalmol Vis Sci. 2019;60:3456.
Chen AX, Greenlee TE, Conti TF, Briskin IN, Singh RP. Fluctuations in macular thickness in patients with retinal vein occlusion treated with anti-vascular endothelial growth factor agents. Ophthalmol Retin. 2020;4:1158–1169.
Gupta P, Sidhartha E, Tham YC, Chua DK, Liao J, Cheng CY, et al. Determinants of macular thickness using spectral domain optical coherence tomography in healthy eyes: the Singapore Chinese Eye study. Invest Ophthalmol Vis Sci. 2013;54:7968–76.
Keane PA, Mand PS, Liakopoulos S, Walsh AC, Sadda SR. Accuracy of retinal thickness measurements obtained with Cirrus optical coherence tomography. Br J Ophthalmol. 2009;93:1461–7.
Early Treatment Diabetic Retinopathy Study Research G. Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie house classification: ETDRS report number 10. Ophthalmology. 2020;127:S99–119.
Gregori NZ, Feuer W, Rosenfeld PJ. Novel method for analyzing snellen visual acuity measurements. Retina. 2010;30:1046–50.
Arthur E, Young SB, Elsner AE, Baskaran K, Papay JA, Muller MS, et al. Central macular thickness in diabetic patients: a sex-based analysis. Optom Vis Sci. 2019;96:266–75.
Hannouche RZ, Avila MP, Isaac DL, Silva RS, Rassi AR. Correlation between central subfield thickness, visual acuity and structural changes in diabetic macular edema. Arq Bras Oftalmol. 2012;75:183–7.
Kim BY, Smith SD, Kaiser PK. Optical coherence tomographic patterns of diabetic macular edema. Am J Ophthalmol. 2006;142:405–12.
Deak GG, Schmidt-Erfurth UM, Jampol LM. Correlation of central retinal thickness and visual acuity in diabetic macular edema. JAMA Ophthalmol. 2018;136:1215–6.
Singh RP, Wykoff CC, Brown DM, Larsen M, Terasaki H, Silva FQ, et al. Outcomes of diabetic macular edema patients by baseline hemoglobin A1c: analyses from VISTA and VIVID. Opthalmol Retin. 2017;1:382–8.
Campos A, Campos EJ, do Carmo A, Caramelo F, Martins J, Sousa JP, et al. Evaluation of markers of outcome in real-world treatment of diabetic macular edema. Eye Vis. 2018;5:27.
Sun JK, Lin MM, Lammer J, Prager S, Sarangi R, Silva PS, et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014;132:1309–16.
Gerendas BS, Bogunovic H, Sadeghipour A, Schlegl T, Langs G, Waldstein SM, et al. Computational image analysis for prognosis determination in DME. Vis Res. 2017;139:204–10.
Larsen M, Wang M, Sander B. Overnight thickness variation in diabetic macular edema. Invest Ophthalmol Vis Sci. 2005;46:2313–6.
Frank RN, Schulz L, Abe K, Iezzi R. Temporal variation in diabetic macular edema measured by optical coherence tomography. Ophthalmology. 2004;111:211–7.
Chew EY, Davis MD, Danis RP, Lovato JF, Perdue LH, Greven C, et al. The effects of medical management on the progression of diabetic retinopathy in persons with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. Ophthalmology. 2014;121:2443–51.
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group, Lachin JM, Genuth S, Cleary P, Davis MD, Nathan DM. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med. 2000;342:381–9.
Sim DA, Keane PA, Zarranz-Ventura J, Fung S, Powner MB, Platteau E, et al. The effects of macular ischemia on visual acuity in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2013;54:2353–60.
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VYW: research design, data acquisition/research execution, data analysis/interpretation, manuscript preparation. BLK: data acquisition/research execution, manuscript preparation. AXC: research design, data analysis/interpretation. KW: data acquisition/research execution. TEG: research design, data analysis/interpretation, manuscript preparation. TFC: research design, data analysis/interpretation, manuscript preparation. RPS: research design, data analysis/interpretation, manuscript preparation.
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RPS: Genentech/Roche (personal fees), Alcon/Novartis (personal fees), Apellis (grant), Graybug (grant), Zeiss (personal fees), Bausch + Lomb (personal fees), Regeneron Pharmaceuticals, Inc. (personal fees). The other authors declare no competing interests.
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Wang, V.Y., Kuo, B.L., Chen, A.X. et al. Fluctuations in macular thickness in patients with diabetic macular oedema treated with anti-vascular endothelial growth factor agents. Eye 36, 1461–1467 (2022). https://doi.org/10.1038/s41433-021-01672-1
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DOI: https://doi.org/10.1038/s41433-021-01672-1
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