Abstract

Subthreshold micropulse laser (SMPL) is a tissue-sparing technique whose efficacy is demonstrated for diabetic macular edema (DME) treatment. However, its mechanism of action is poorly known. A prospective observational study was performed on naïve DME patients treated with SMPL, to evaluate the changes of aqueous humor (AH) inflammatory and vaso-active biomarkers after treatments. AH samples of eighteen DME eyes were collected before and after SMPL. Ten non-diabetic AH samples served as controls. Full ophthalmic evaluation, spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography were performed in DME group. Glass chip protein array was used to quantify 58 inflammatory molecules. Central retinal thickness (CRT) and visual acuity were also monitored. Several molecules showed different concentrations in DME eyes versus controls (p value < 0.05). Fas Ligand (FasL), Macrophage Inflammatory Proteins (MIP)-1α, Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) and Vascular Endothelial Growth Factor (VEGF) were increased in DME at baseline versus controls and decreased after SMPL treatments (p < 0.05). CRT reduction and visual acuity improvement were also found. Inflammatory cytokines, mainly produced by the retinal microglia, were significantly reduced after treatments, suggesting that SMPL may act by de-activating microglial cells, and reducing local inflammatory diabetes-related response.

Highlights

  • Diabetic macular edema (DME) is a common complication of diabetic retinopathy (DR), representing the main cause of visual impairment in these patients[1,2,3]

  • It has been hypothesized that Subthreshold Micropulse Laser (SMPL), by inducing a controlled thermal elevation of the retinal tissue, is able to selectively stimulate the retinal pigment epithelium (RPE)[12,18]

  • The feasibility of aqueous humour (AH) sampling is considered appropriate to study the pathophysiology of many retinal disorders, such as DR and diabetic macular edema (DME), and to evaluate any changes induced by treatments[19,20,21,22,23,24,25,26,27,28,29,30]

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Summary

Introduction

Diabetic macular edema (DME) is a common complication of diabetic retinopathy (DR), representing the main cause of visual impairment in these patients[1,2,3]. The main role of Müller cells, biologically connecting retinal neurons and vessels, is to maintain retinal water control. They participate in the inflammatory response, especially when activated by diabetes[8]. Microglial cells (MGC) are considered the local immune cells of the retina[8], to the central nervous system (CNS) microglial cells They are activated by stress conditions, such as DM, and are able to change their morphology and function. Visual acuity and retinal thickness changes of DME patients, measured by spectral domain optical coherence tomography (SD-OCT), were evaluated

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