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Purpose: This article aims to review the impact of detecting and quantifying intraocular biomarkers (liquid biopsy) in both aqueous and vitreous humor in eyes of people affected by diabetes mellitus. Methods: This is a detailed review about aqueous and/or vitreous humor sampling in human diabetic eyes for proteomic and/or metabolomic analysis contributing to the understanding of the pathophysiology and treatment effects of diabetic retinopathy. Results: Aqueous and vitreous humor molecular biomarkers proved to be directly correlated to each other and valuable to study retinal conditions. Moreover, proteomic and metabolomic analysis showed that the biomarkers of neuroinflammation, neurodegeneration, and vasculopathy are detectable in intraocular fluids and that their concentration changes in different stages of disease, and in response to treatment of all diabetic retinopathy aspects, mainly diabetic macular edema and proliferative retinopathy. Conclusions: Liquid biopsy offers the possibility to improve our knowledge of intraocular eye disease induced by diabetes mellitus. The exact quantification of intraocular biomarkers contributes to the precision medicine approach even in the diabetic retinopathy scenario. The diffusion of this approach should be encouraged to have quantifiable information directly from the human model, which may be coupled with imaging data. [ABSTRACT FROM AUTHOR]

Purpose: To better understand the pathophysiology of geographic atrophy (GA), secondary to age-related macular degeneration, eyes affected by unilateral GA (and CNV in the fellow eye; U-GA group) or by bilateral GA (B-GA group) were evaluated using an integrated morpho-functional approach and quantifying biomarker of retinal macroglial activity. Methods: Patients with U-GA and B-GA and foveal-sparing were consecutively enrolled in a prospective study. All included eyes underwent fundus photography, fundus autofluorescence (FAF), foveal retinal and choroidal thicknesses (RT, CT), contrast sensitivity, best-corrected visual acuity (BCVA), low-luminance VA (LLVA) and low-luminance deficit (LLD), and mesopic and scotopic microperimetry and multifocal electroretinography (mfERG). Glial fibrillary acidic protein (GFAP), biomarker of Müller cell activation, was quantified in the aqueous humor (AH). Results: Forty eyes of 40 patients (18 in the U-GA group and 22 in the B-GA group) were studied. RT, GA area, BCVA, contrast sensitivity, mfERG, and microperimetry (at both background luminances) were not different between groups. CT was significantly thinner in U-GA compared to B-GA group (p = 0.020). Both LLVA and LLD were significantly worse in the B-GA vs U-GA group (p = 0.033 and p = 0.048, respectively). GFAP intraocular concentration was significantly higher in the B-GA group (p = 0.01). Conclusions: Different pathophysiologic mechanisms may be responsible for GA in unilateral (with CNV in the fellow eye) compared to bilateral GA cases. In unilateral cases, a thinner choroid seems to play a key role. Whereas, in bilateral cases, Müller cells and their supported photoreceptors may be primarily involved. [ABSTRACT FROM AUTHOR]

We agree that also the analysis of the proteomic and metabolomic profiles of aqueous (AH) and vitreous humor (VH) in different stages and types of diabetes and their changes in response to different levels of metabolic control and treatments may be of great interest in the pathophysiology of diabetic eye damage, both from an ophthalmologic and systemic points of view. Dear Editor, We are grateful for the possibility to reply to the comment about our paper "Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy" proposed by Dmuchowska DA et al,. and we thank these authors for their interest in our work (1). Response to comment on "Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy.". [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]