The Disorganization of Retinal Inner Layers Is Correlated to Müller Cells Impairment in Diabetic Macular Edema: An Imaging and Omics Study

The disorganization of retinal inner layers (DRIL) is an optical coherence tomography (OCT) biomarker strictly associated with visual outcomes in patients with diabetic macular edema (DME) whose pathophysiology is still unclear. The aim of this study was to characterize in vivo, using retinal imaging and liquid biopsy, DRIL in eyes with DME. This was an observational cross-sectional study. Patients affected by center-involved DME were enrolled. All patients underwent spectral domain optical coherence tomography (SD-OCT) and proteomic analysis of aqueous humor (AH). The presence of DRIL at OCT was analyzed by two masked retinal experts. Fifty-seven biochemical biomarkers were analyzed from AH samples. Nineteen eyes of nineteen DME patients were enrolled. DRIL was present in 10 patients (52.63%). No statistically significant difference was found between DME eyes with and without DRIL, considering the AH concentration of all the analyzed biomarkers except for glial fibrillary acidic protein (GFAP), a biomarker of Müller cells dysfunction (p = 0.02). In conclusion, DRIL, in DME eyes, seems to strictly depend on a major dysfunction of Müller cells, explaining its role not only as imaging biomarker, but also as visual function Müller cells-related parameter.

[1]  Shu-zhi Zhao,et al.  Aqueous Humor Biomarkers of Retinal Glial Cell Activation in Patients With or Without Age-Related Cataracts and With Different Stages of Diabetic Retinopathy , 2022, Investigative ophthalmology & visual science.

[2]  R. Chow,et al.  Prevalence of diabetic macular edema based on optical coherence tomography in people with diabetes: A systematic review and meta-analysis. , 2022, Survey of ophthalmology.

[3]  Suber S. Huang,et al.  Optical Coherence Tomography Classification Systems for Diabetic Macular Edema and Their Associations With Visual Outcome and Treatment Responses – An Updated Review , 2021, Asia-Pacific journal of ophthalmology.

[4]  E. Pilotto,et al.  Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy , 2021, Graefe's Archive for Clinical and Experimental Ophthalmology.

[5]  E. Pilotto,et al.  Subthreshold Micropulse Laser Modulates Retinal Neuroinflammatory Biomarkers in Diabetic Macular Edema , 2021, Journal of clinical medicine.

[6]  E. Pilotto,et al.  Diabetic Macular Edema Treated with 577-nm Subthreshold Micropulse Laser: A Real-Life, Long-Term Study , 2021, Journal of personalized medicine.

[7]  M. Luís,et al.  Dril Influences Short-term Visual Outcome after Intravitreal Corticosteroid Injection for Refractory Diabetic Macular Edema , 2021, Current eye research.

[8]  J. Chhablani,et al.  Disorganization of retinal inner layers as a biomarker in patients with diabetic macular oedema treated with dexamethasone implant , 2020, Acta ophthalmologica.

[9]  M. Mirghorbani,et al.  Multifocal electroretinogram in diabetic macular edema and its correlation with different optical coherence tomography features , 2019, International Ophthalmology.

[10]  A. Fawzi,et al.  Imaging and Biomarkers in Diabetic Macular Edema and Diabetic Retinopathy , 2019, Current Diabetes Reports.

[11]  E. Pilotto,et al.  Sub-threshold micropulse laser treatment reduces inflammatory biomarkers in aqueous humour of diabetic patients with macular edema , 2019, Scientific reports.

[12]  K. Yamashiro,et al.  Correlation between metamorphopsia and disorganization of the retinal inner layers in eyes with diabetic macular edema , 2019, Graefe's Archive for Clinical and Experimental Ophthalmology.

[13]  Chris A. Johnson,et al.  Disorganization of Retinal Inner Layers (DRIL) and Neuroretinal Dysfunction in Early Diabetic Retinopathy , 2018, Investigative ophthalmology & visual science.

[14]  T. Gardner,et al.  Proteomic Analysis of Early Diabetic Retinopathy Reveals Mediators of Neurodegenerative Brain Diseases , 2018, Investigative ophthalmology & visual science.

[15]  Hyewon Chung,et al.  Association Between Soluble CD14 in the Aqueous Humor and Hyperreflective Foci on Optical Coherence Tomography in Patients With Diabetic Macular Edema. , 2018, Investigative ophthalmology & visual science.

[16]  Usha Chakravarthy,et al.  Disorganization of Inner Retina and Outer Retinal Morphology in Diabetic Macular Edema , 2018, JAMA ophthalmology.

[17]  S. Mohr,et al.  Müller cells and diabetic retinopathy , 2017, Vision Research.

[18]  C. Cebulla,et al.  Activation of glucocorticoid receptors in Müller glia is protective to retinal neurons and suppresses microglial reactivity , 2015, Experimental Neurology.

[19]  Arup Das,et al.  Diabetic Macular Edema: Pathophysiology and Novel Therapeutic Targets. , 2015, Ophthalmology.

[20]  F. V. van Kuijk,et al.  Association of Disorganization of Retinal Inner Layers With Vision After Resolution of Center-Involved Diabetic Macular Edema. , 2015, JAMA ophthalmology.

[21]  S. Vujosevic,et al.  Aqueous Humor Biomarkers of Müller Cell Activation in Diabetic Eyes. , 2015, Investigative ophthalmology & visual science.

[22]  Jennifer K. Sun,et al.  Neural Retinal Disorganization as a Robust Marker of Visual Acuity in Current and Resolved Diabetic Macular Edema , 2015, Diabetes.

[23]  Jennifer K. Sun,et al.  Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. , 2014, JAMA ophthalmology.

[24]  A. Reichenbach,et al.  New functions of Müller cells , 2013, Glia.

[25]  Jennifer K. Sun,et al.  Spectral Domain Optical Coherence Tomography Parameters Associated with Visual Acuity in Patients with Resolved Center-Involved Diabetic Macular Edema , 2012 .

[26]  Joshua A. Smith,et al.  Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases , 2012, Brain Research Bulletin.

[27]  T. Mimura,et al.  Vascular Endothelial Growth Factor and Interleukin-6 are Correlated With Serous Retinal Detachment in Central Retinal Vein Occlusion , 2012, Current eye research.

[28]  Dominic McHugh,et al.  Optical coherence tomography may be used to predict visual acuity in patients with macular edema. , 2011, Investigative ophthalmology & visual science.

[29]  P. O S I T I O N S T A T E M E N T,et al.  Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[30]  V. Sarthy Focus on molecules: glial fibrillary acidic protein (GFAP). , 2007, Experimental eye research.

[31]  S. Vujosevic,et al.  CHANGES OF AQUEOUS HUMOR MÜLLER CELLS' BIOMARKERS IN HUMAN PATIENTS AFFECTED BY DIABETIC MACULAR EDEMA AFTER SUBTHRESHOLD MICROPULSE LASER TREATMENT. , 2018, Retina.

[32]  E. Pilotto,et al.  Emerging Insights into Pathogenesis. , 2017, Developments in ophthalmology.