Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2021; 12(4): 437-452
Published online Apr 15, 2021. doi: 10.4239/wjd.v12.i4.437
Malfunction of outer retinal barrier and choroid in the occurrence and progression of diabetic macular edema
Ştefan Ţălu, Simona Delia Nicoara
Ştefan Ţălu, Directorate of Research, Development and Innovation Management (DMCDI), Technical University of Cluj-Napoca, Cluj-Napoca 400020, Romania
Simona Delia Nicoara, Department of Ophthalmology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania
Author contributions: Ţălu S and Nicoară SD contributed equally to this work; Ţălu S and Nicoară SD designed the research study, performed the research, analyzed the data and wrote the manuscript. The authors have read and approve the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest regarding the publication of this paper.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Simona Delia Nicoara, MD, PhD, Chief Doctor, Full Professor, Department of Ophthalmology, Iuliu Haţieganu University of Medicine and Pharmacy, 8 Victor Babes St, Cluj-Napoca 400012, Romania.
Received: January 13, 2021
Peer-review started: January 13, 2021
First decision: February 12, 2021
Revised: February 23, 2021
Accepted: March 24, 2021
Article in press: March 24, 2021
Published online: April 15, 2021

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy, affecting 1 in 15 patients with diabetes mellitus (DM). The disruption of the inner blood-retina barrier (BRB) has been largely investigated and attributed the primary role in the pathogenesis and progression in DME, but there is increasing evidence regarding the role of outer BRB, separating the RPE from the underlying choriocapillaris, in the occurrence and evolution of DME. The development of novel imaging technologies has led to major improvement in the field of in vivo structural analysis of the macula allowing us to delve deeper into the pathogenesis of DME and expanding our vision regarding this condition. In this review we gathered the results of studies that investigated specific outer BRB optical coherence tomography parameters in patients with DM with the aim to outline the current status of its role in the pathogenesis and progression of DME and identify new research pathways contributing to the advancement of knowledge in the understanding of this condition.

Keywords: Diabetic macular edema, External limiting membrane, Hyperreflective foci, Inner segment/outer segment line, Optical coherence tomography, Outer retinal barrier

Core Tip: Progress in optical coherence tomography technology allowed the identification of new pathogenic pathways in diabetic macular edema (DME) involving the outer retina and underlying choroid. The presence of fluid in the subretinal space is suggestive for the alteration of the outer blood retinal barrier and responds better to intravitreal triamcinolone as compared to anti- vascular endothelial growth factor. The disruption of external limiting membrane (ELM) is associated with visual impairment being a predictor of poor outcomes following the treatment with triamcinolone. The integrity of ELM and of the inner segment/outer segment line was found to correlate positively with best corrected visual acuity in DME.