Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation

Abstract

Proliferative diabetic retinopathy (PDR) the sequel of diabetic retinopathy (DR), a frequent complication of diabetes mellitus (DM), is the leading cause of blindness in the working-age population. The current screening process for the DR risk is not sufficiently effective such that often the disease is undetected until irreversible damage occurs. Diabetes-associated small vessel disease and neuroretinal changes create a vicious cycle resulting in the conversion of DR into PDR with characteristic ocular attributes including excessive mitochondrial and retinal cell damage, chronic inflammation, neovascularisation, and reduced visual field. PDR is considered an independent predictor of other severe diabetic complications such as ischemic stroke. A “domino effect” is highly characteristic for the cascading DM complications in which DR is an early indicator of impaired molecular and visual signaling. Mitochondrial health control is clinically relevant in DR management, and multi-omic tear fluid analysis can be instrumental for DR prognosis and PDR prediction. Altered metabolic pathways and bioenergetics, microvascular deficits and small vessel disease, chronic inflammation, and excessive tissue remodelling are in focus of this article as evidence-based targets for a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary DR care management.

Short communication: Unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities – Preliminary data for PPPM validation

“…Further, PDR, demonstrates characteristic systemic attributes including mitochondrial impairment, increased cell death and chronic in ammation. This is an independent predictor for the cascade of subsequent DMcomplications such as ischemic stroke [17]. Unfortunately, early DR as the reliable predictor appearing upstream of the "domino effect" is neglected by the current practice of reactive medicine.…”

“…However, the role and impact of individual lipid classes remain underexplored [30]. To this end, association between the hypertriglyceridemia in blood of DM patients and the lower-extremity amputation risk have been demonstrated [31], which is a complication down-stream towards the DR in the overall cascade of DM-complications [17]. Further, blood triglycerides have been demonstrated as a more reliable pre/diabetes biomarker and predictor compared to the total cholesterol, LDL, HDL, LDL/HDL ratio, cholesterol/HDL ratio, and LDL/HDL ratio [32].…”

“…For this reason, tear uid is highly relevant for predicting long-term effects such as a health-to-disease transition and disease progression in DM-associated complications [19]. Further, shifted metabolic pathways and bioenergetics, compromised mitochondrial health, microvascular de cits and small vessel disease, chronic in ammation and excessive tissue remodelling, all relevant for PDR pathogenesis and DM-related complications, are per-evidence re ected in human tear uid metabolite patters [17,18].…”

“…As a diagnostic tool, the tear uid advantages over other bodily uids due to non-invasive approach, re ection of systemic affects as well as stability and speci city of biomarker panels [18]. Tear uid is rich in metabolites associated with signalling pathways, abnormal stress reactions, metabolic and bioenergetic shifts, compromised mitochondrial health, microvascular de cits, systemic in ammation and apoptosis, amongst others -all involved in pre-diabetes and cascading diabetes-related complications [17,18]. Contextually, tear uid metabolomics is of great clinical utility for stratifying patients, predicting the health-to-disease transition and targeting cost-effective prevention and individualised treatments in advanced primary and secondary pre/diabetes care.…”

“…Cost-effective primary and secondary prevention is envisaged based on the validated diagnostic targets for both DR and PDR with co-morbidities. Depending on the individually affected metabolic pathways and sub-cellular structures, corresponding mitigation and preventive measures will be focused on microvascular de cits and small vessels disease [17,46,47] adequate stress reactions [12,45,48,49] systemic in ammation and impaired wound healing [50,51] mitochondrial health sustainability and bioenergetics [45,49,[52][53][54],…”