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). 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. In our work, we strongly underlined the clinical perspectives of liquid biopsy in ophthalmology. The possibility to correlate (clinical) morphological (and possibly functional) phenotypes to precise biochemical profiles may allow a personalized and targeted treatment, which is of primary interest in the current era of precision medicine, at least from an ophthalmologic point of view [1]. We also agree about the relevance of the choroid involvement in the pathogenesis of ocular diabetic damage, and on the importance to be able to differentiate choroidal and retinal contributions to the pathophysiology of chorio-retinal diabetic damage [2]. However, attention should be paid when correlating AH analysis and choroid. It is true that AH is produced by the ciliary body; however, one of the main player in this process is the non-pigmented ciliary epithelium which represents the continuation of the retina [3]. Moreover, as previously shown by other studies and reported in our review, there is a passage of molecules from the VH to the AH, and retinal molecules—such as glial fibrillary acidic protein (GFAP)—have been detected in the VH, and consequently in AH, secondary to retinal involvement by several mechanisms of stress, damage, and degeneration [1, 4]. Therefore, the current evidences confirm the main influence of the retinal processes on the AH composition. Notwithstanding, it may be relevant taking into account the contribution of the choroid in the complex pathological mechanisms induced by diabetes to the posterior segment of the eye. The study of proteomics and particularly metabolomics is, at present, not well known by the majority of clinicians, and their methodology may be not so familiar. The authors’ effort to explain the different modalities and results of previous studies and the possibility of a multiplatform approach for an integrated and more comprehensive analysis may help to plan more numerous and well-planned proteomic and metabolomic studies [5].