Diabetic and “omics” level changes in such pathosis. Due

Diabetic Retinopathy (DR), a primary cause of blindness, a sequela of diabetes mellitus (DM). It is currently one of the most prevalent diseases worldwide with an incidence of 6.9% (1, 2). In the context of early stage diagnosis and effective management of DR, precise systemic markers are to be identified (3). The DR is generally recognized as micro-vasculopathy but recent reports indicated retinal neurodegeneration occurs in this pathosis earlier to any detectable microcirculatory abnormalities (4). Therefore, development of an integrated systemic assessment method may be endeavored in addressing the limitation of conventional diagnostic approaches for DR in unveiling neuro-retinal degeneration in early stage (i.e. non-proliferative diabetic retinopathy). Recent advances in the field of molecular diagnostics have led to an increasing demand for real-time and minimally invasive techniques including high resolution imaging and varied spectroscopy to correlate structural and “omics” level changes in such pathosis. Due to unique fingerprinting ability, vibrational spectroscopy plays a important role in documenting spectropathological information for body fluids, histopathology, cytology, surgical targets, treatment-monitoring and drug studies. So, in this study spectropathological evaluation of omics dimensions in the relevant body fluids (5) was coupled with Quantitative Imaging Biomarkers (QIBs) from conventional imaging attributes in ophthalmology viz. color fundoscopy, Fluorescein Angiography (FA) and optical coherence tomography (OCT) has been attempted for integrated diagnosis of early stage DR that may have neuroretinal degeneration. The color fundoscopy and FA provide retinal surface vascularity pattern and retinal blood circulation status respectively. Aberrations in these dimensions needs to be recognized precisely in such retinal pathologies (6). Whereas, the OCT with newer development is capable to provide retinal tomograms in real-time, at few micron level resolution up to 2 mm depth of layered tissue structure (7) and hence may be effectively employed in unveiling structural aberration or degeneration in retina with appropriate analytics. ‘Lucidity’ is one of the optical intensity descriptors used for OCT images which tends to vary with different regions of layered body structures like skin, mucosa and retinal layers. The OCT based imaging markers were found to be useful for predicting retinal neurodegeneration in early diagnosis of glaucoma (8), age related macular degeneration (9) and Alzheimer’s disease (10). Various neurodegenerative disorders also involve variations in venous branching pattern asymmetry, increased arteriolar length to diameter ratios (11). Researchers evaluated other geometrical attributes like vascular attenuation, complexity of branching pattern, vessel tortuosity and hypothesized that retinal vascular morphological alterations could be correlated with ?-amyloid deposition extending from the CNS to the retina, resulting in vessel wall destruction (12). Recently, QIBs have become widely accepted as well-defined “image characteristics” to objectively measure and assess the indicators for normal physiological conditions, pathogenic progressions or responses to therapeutic interferences (13). In the context of classifying disease conditions using such features the Support Vector Machine (SVM) are used, since it can classify the diseases with high prognostic accuracy and speed (14, 15). The changes in vascular blood circulation and composition in the serum have crucial impacts on retinal structural integrity and aberrations specially in metabolic disorder like DM and related ocular complications (16). The nourishment of the intraocular tissues is accomplished by the retinal vessels, uveal vessels, and by the aqueous humor (17). The retinal vessels are both morphologically and physiologically like those in the brain and transport nutrients through blood for the nourishment of each of the retinal layers. Hence, impairment of this nutrient supply due to aberrant vasculature and altered blood metabolomic status may cause damaging effects on the structure and geometry of the retinal layers (18). Metabolomics is the study of the set of metabolites, i.e. all small endogenous molecules from cells, tissue or bio-fluids (19) and the metabolome is downstream from the proteome and transcriptome (20). A strong advantage of metabolomics is the ability to uncover novel and potentially relevant metabolites which can be the basis of therapeutic approaches or prognostic indicators (21). In respect to documenting omics-dimensions of different body fluids (viz. serum, tear) in DR the spectropathological techniques involving FTIR (Fourier Transform Infrared Spectroscopy), Raman spectroscopy, NMR spectroscopy (Nuclear Magnetic Resonance), GC-HRMS (Gas Chromatography- High Resolution Mass Spectroscopy) and MALDI-TOF-MS (Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometry) (22) become reasonably contributory. Again, exploration of unique biophysical properties of such body fluids may add remarkable value towards precision diagnostics. These spectroscopic approaches if coupled with imaging structural attributes for this pathosis, it becomes really valuable for elucidating precise early diagnostic feature as performed in this study.

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