Total macular volume as a potential biomarker in the assessment of anti-VEGF response in patients with diabetic macular edema: real-life data analysis

Year 2023, , 65 - 70, 20.01.2023

Eren Ekici , Ayşegül Koçak Altıntaş

https://doi.org/10.38053/acmj.1205486

Abstract

Aim: To evaluate the functional and anatomic efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with diabetic macular edema (DME) and investigate the association between central macular thickness (CMT) and total macular volume (TMV) in real-life settings.
Material and Method: In this retrospective, observational, longitudinal study 38 eyes of 23 consecutive patients with center-involving DME were included. A loading phase of three monthly intravitreal anti-VEGF injections was initiated, followed by anti-VEGF injections if needed as per clinicians’ discretion.
Results: Mean Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained was 3.2 letters at month 12. The reduction in the mean of CMT and TMV were 60 μm and 1.33 mm3 respectively at the end of 12 months. Best-corrected visual acuity (BCVA) was negatively correlated with CMT (r=-0.573, p < 0.01) and TMV (r=-0.533, p < 0.01) initially. There was a statistically significant positive correlation between the CMT and the TMV initially (r=0.765, p < 0.01) and month 12 (r=0.937, p < 0.01). Baseline TMV was found to be more predictive of treatment response at the 9th month than baseline CMT.
Conclusion: It is demonstrated that TMV may be a suitable biomarker in the assessment of treatment response of the macular region when regarded as a complete three-dimensional macular unit instead of central vertical thickness only. Although the present study contributes to a better understanding of managing DME in real-life settings, further prospective, and controlled investigations are needed.

Keywords

Aflibercept, anti-VEGF, central macular thickness, diabetic macular edema, total macular volume

References

• Lang GE. Diabetic macular edema. Ophthalmologica 2012; 227: 21-9.
• Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol 2009; 54: 1-32.
• Murakami T, Yoshimura N. Structural changes in individual retinal layers in diabetic macular edema. J Diabetes Res 2013; 2013: 920713.
• Nicoară SD. Spectral domain optical coherence tomography in the diagnosis and monitoring of diabetic macular edema. In: OCT-Applications in Ophthalmology: IntechOpen; 2018.
• Wu PC, Chen YJ, Chen CH, et al. Assessment of macular retinal thickness and volume in normal eyes and highly myopic eyes with third-generation optical coherence tomography. Eye 2008; 22: 551-5.
• Yeung L, Sun CC, Ku WC, et al. Associations between chronic glycosylated haemoglobin (HbA1c) level and macular volume in diabetes patients without macular oedema. Acta ophthalmol 2010; 88: 753-8.
• Browning DJ, Glassman AR, Aiello LP, et al. Optical coherence tomography measurements and analysis methods in optical coherence tomography studies of diabetic macular edema. Ophthalmology 2008; 115: 1366-71, 71 e1.
• Dhoot DS. Incidence of new diabetic macular edema in fellow eyes of patients in the VISTA and VIVID studies. Investig Ophthalmol Vis Sci 2020; 61: 278-278.
• Bakri SJ, Malhotra M, Stoilov I. Course of diabetic retinopathy in untreated fellow eyes in RIDE and RISE: a post hoc analysis. Ophthalmic Surg Lasers Imaging Retina 2022; 53: 202-7.
• Group ETDRSR. Fundus photographic risk factors for progression of diabetic retinopathy: ETDRS report number 12. Ophthalmology 1991; 98: 823-33.
• Gregori NZ, Feuer W, Rosenfeld PJ. Novel method for analyzing snellen visual acuity measurements. Retina. 2010; 30: 1046-50.
• Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015; 372: 1193-203.
• Lai TT, Chen TC, Yang CH, Yang CM, Ho TC, Hsieh YT. Treat-and-extend vs. Pro Re nata regimen of ranibizumab for diabetic macular edema-a two-year matched comparative study. Front Med (Lausanne) 2021; 8: 781421.
• Group ETDRSR. Early Treatment Diabetic Retinopathy Study design and baseline patient characteristics: ETDRS report number 7. Ophthalmology 1991; 98: 741-56.
• Itoh Y, Petkovsek D, Kaiser PK, Singh RP, Ehlers JP. Optical coherence tomography features in diabetic macular edema and the impact on anti-VEGF response. Ophthalmic Surg Lasers Imaging Retina 2016; 47: 908-13.
• 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 :1351-9.
• Heier JS, Bressler NM, Avery RL, et al. Comparison of aflibercept, bevacizumab, and ranibizumab for treatment of diabetic macular edema: extrapolation of data to clinical practice. JAMA Ophthalmol 2016; 134: 95-9.
• Csaky KG, Richman EA, Ferris FL, 3rd. Report from the NEI/FDA Ophthalmic Clinical Trial Design and Endpoints Symposium. Invest Ophthalmol Vis Sci 2008; 49: 479-89.
• Panozzo G, Parolini B, Gusson E, et al. Diabetic macular edema: an OCT-based classification. Semin Ophthalmol 2004; 19: 13-20.
• Lukic M, Williams G, Shalchi Z, et al. Intravitreal aflibercept for diabetic macular oedema: Moorfields’ real-world 12-month visual acuity and anatomical outcomes. Eur J Ophthalmol 2020; 30: 557-62.
• Korobelnik JF, Daien V, Faure C, et al. Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: results from the APOLLON study. Graefes Arch Clin Exp Ophthalmol 2020; 258: 521-8.
• Wykoff CC, Hariprasad SM. DRCR Protocol-T: Reconciling 1- and 2-Year Data for Managing Diabetic Macular Edema. Ophthalmic Surg Lasers Imaging Retina 2016; 47: 308-12.
• Nguyen QD, Tatlipinar S, Shah SM, et al. Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol 2006; 142: 961-9.
• Dong N, Xu B, Chu L, Tang X. Study of 27 aqueous humor cytokines in type 2 diabetic patients with or without macular edema. PloS one 2015; 10: e0125329.
• Hillier RJ, Ojaimi E, Wong DT, et al. Aqueous Humor Cytokine Levels and Anatomic Response to Intravitreal Ranibizumab in Diabetic Macular Edema. JAMA Ophthalmol 2018; 136: 382-8.
• Figueras-Roca M, Sala-Puigdollers A, Zarranz-Ventura J, et al. Anatomic response to intravitreal dexamethasone implant and baseline aqueous humor cytokine levels in diabetic macular edema. Invest Ophthalmol Vis Sci 2019; 60: 1336-43.
• Chatziralli I, Kazantzis D, Theodossiadis G, Theodossiadis P, Sergentanis TN. Retinal layers changes in patients with diabetic macular edema treated with intravitreal anti-VEGF agents: long-term outcomes of a spectral-domain OCT study. Ophthalmic Res 2021; 64: 230-6.
• Heier JS, Korobelnik JF, Brown DM, et al. Intravitreal Aflibercept for Diabetic Macular Edema: 148-Week Results from the VISTA and VIVID Studies. Ophthalmology 2016; 123: 2376-85.