The importance of a sensitive and specific screening method is prompting several groups to identify biomarkers of diabetic retinopathy.
The most common ocular complication in individuals with diabetes and the leading cause of blindness in economically developed countries is diabetic retinopathy (DR). A early diagnosis and one timely therapy are necessary elements to counteract the development and/or progression of DR and thus prevent irreversible eye damage and improving the patient's quality of life.
Traditional diagnosis of DR
The diagnosis of DR, depending on the clinical stage of the diabetic patient, may include theocular fundus examination or a comprehensive eye examinationwhich, as recommended by the 2015 Guidelines, drafted by the Diabetes Eye Complications Study Group of the Italian Society of DiabetologyIt is necessary to assess eye pressure, visual acuity, pupillary reflexes and the anterior and posterior segment of the eye. The diagnosis of DR, in most cases, is conducted using theophthalmoscopewhich allows an adequate assessment of the signs of diabetic retinopathy through an ocular fundus examination. In some cases this examination is accompanied by a biomicroscopy capable of displaying the bulb and ocular adnexa. For a correct assessment of injuries caused by DR, on the other hand, a retinography.
To obtain further information are also recommended:
- l'ocular ultrasoundin cases where the assessment of the ocular fundus is obscured by the opacity of the dioptric media;
- the ocular light tomography consistent (OCT) and thecomputerised retinal thickness analysis (RTA)to obtain clear retinal scans of the macular region and evaluate possible vitreo-retinal tractions;
- the microperimetry (SLO) and theelectroretinography, to assess proper retinal function in the presence of lesions;
- l'iridographyto have an early diagnosis of neo-vascularisation processes in the iris.
The retinal fluoroangiographyinvasive examination, on the other hand, as stated in the 2015 Guidelines, should be performed neither for diagnosis nor for screening of DRbut only in certain clinical conditions in which it is necessary to identify areas of neo-vascularisation and ischaemic retinal zones, assess the pathogenesis of macular oedema and perform a thorough examination of the macula.
New approaches to diagnosing DR
In recent decades, the ocular proteome study of the subject suffering from RDor rather of all the proteins expressed in the different cells of the eye, has led to the identification of biomarkers a diagnostic purpose taken from retina, vitreous humour and aqueous humour samples. However, although these biomarkers provide valuable information on the aetiology-pathogenesis of DR, which is useful for a more complete understanding of the disease, these molecular targets cannot be used for purely diagnostic-preventive purposes, as the samples from which they are analysed can only be collected when the patient undergoes surgery, and is therefore at a stage of the disease that has already been confirmed.
In this context, the need arises for a diagnosis with non-invasive methods through the collection of readily available eye samples, such as those from the tear fluidwhich represents a significant sample in the subject suffering from diabetic pathology, and in particular RD, since the vascularisation problems typical of this pathology induce changes in retinal blood flow which, in turn, modulate the protein composition of the tear.
With this in mind, the authors of the research published in January 2017 in Journal of Proteomics, have tested an identification system for micro-organisationscombined with the proteomic study of tear fluidwhich proved to have interesting sensitivity and specificity values of 0.93 and 0.78 respectively.
In fact, the protein content of tear fluidled to the identification of over 1550 proteins, some of which have expression profiles different among those suffering from Non-proliferating RD (RDNP) and those affected by Proliferating DR (PDR)thus allowing a differential diagnosis of the pathology.
Several studies, moreover, have shown that concomitant with DR there is an alteration in the protein composition of the 'chemical barrier' of tear fluid, i.e. of all those molecules that act as a chemical barrier against external agents. These changes could lead both to a lower defence against bacterial infections and to a significantly slower ocular healing process. Indeed, functional analysis of the tear proteome has confirmed that the most proteins present in the tear are involved in the immune response and inflammatory processes that may occur as a result of, for example, infection by a pathogenic bacterium. In addition, there are numerous peptides and/or proteins present in the tear that belong to the antimicrobial and immunomodulatory peptides (AMP).
Therefore, the tear fluid, could be a excellent candidate for research of specific biomarkers of DRbecause of the ease with which it can be sampled, but mainly because alterations in its protein composition are directly related to the concomitant presence of eye diseases.
Bibliography
- Csòsz E et al. Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms. J Proteomics.2017;150:351-358.
- Study Group on the Ocular Complications of Diabetes of the Italian Society of Diabetology. Guidelines for the screening, diagnosis and treatment of diabetic retinopathy in Italy. 2015
Dr. Carmelo Chines
Direttore responsabile
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Italian