Systematic Assessment of Clinical Methods to Diagnose and Monitor Diabetic Retinal Neuropathy

Abstract

Purpose Diabetic retinal neuropathy refers to retinal neural tissue damage occurring before the structural retinal changes of diabetic retinopathy and fulfils many of the criteria for causality for the subsequent vasculopathy. Developing reliable means of measuring neuronal damage in diabetes may be important in efforts to prevent retinopathy of a clinically significant and irreversible stage. This study aimed at systematically assessing current clinical measurements of diabetic retinal neuropathy so that future studies may utilise a consensual battery of tests in studying this poorly understood disease state between a healthy retina and one that is retinopathic. Methods A systematic search of the medical literature since 1984 was performed on PUBMED and EMBASE, and the evidence supporting each identified method as an indicator for clinically important diabetic retinal neuropathy was graded relatively as compelling, medium, or weak according to criteria assessing its relationship to subsequent diabetic retinopathy, quality of supporting studies, and published reproducibility. Results The systematic search yielded 6432 results. Subsequent assessment by two independent investigators identified 601 multiple subject studies in humans assessing clinical aspects of the retinal structure, function, or psychophysics in the prediabetic retina. The 933 separate instances of clinical methods assessed as being supported by relatively “compelling” evidence included colour vision changes, flash ERG b-wave latency, flash multifocal b-wave latency, scotopic b-wave and oscillatory potentials in ERG, and contrast sensitivity. Conclusion The results showed moderately poor quality of extant evidence and indicate the best clinical methods for assessing diabetic retinal neuropathy that remain to be confirmed. This is the first systematic assessment of the medical literature aiming at assessing the breadth and validity of these methods and represents an early step in identifying and developing clinical endpoints for use in trials designed to identify at-risk patients or prevent diabetic retinopathy.

Flicker electroretinogram in newborn infants

“…Recording only flicker ERGs could potentially shorten the test to the extent that it would gain feasibility as a functional screening test, as only a brief burst of stimuli without previous dark adaptation is required. ERG, including flicker ERG, has previously been suggested to be of value in the assessment of retinal vascular disorders such as diabetic retinopathy, as reviewed elsewhere [ 22 , 23 ].…”

Visual Function Measurements in Eyes With Diabetic Retinopathy: An Expert Opinion on Available Measures

“… 45 The peak of the CSF— which represents an observer’s highest sensitivity and lowest threshold—is typically observed at intermediate spatial frequencies of 1.5 to 6 cycles per degree (cpd), with more contrast needed to perceive larger or smaller visual details. 46 , 47 , 48 Despite compelling evidence for CSF testing revealing vision loss in early DRD stages, 22 , 49 , 50 , 51 , 52 and providing better correlations to real-world functional vision than BCVA, 53 , 54 , 55 it remains a clinical research tool without established standards or analytic validation. 22 , 52 , 56 …”

“…Cross-sectional studies have demonstrated CSF loss in diabetes before clinical signs of retinopathy, and better relation to disease severity in DRD and DME than VA. 49 , 50 , 51 , 52 However, there are limited studies that have explored the association of CSF with DR with most studies exploring different questions. Furthermore, it is unclear if these results will be reproducible across different populations and larger cohorts.…”

Full‐field and multifocal electroretinogram in non‐diabetic controls and diabetics with and without retinopathy

“…Currently, plenty of researches are being conducted on developing novel therapies to treat DR and diabetic macular oedema (DMO) (Mansour et al 2020). As such, full-field (ffERG) and multifocal electroretinography (mfERG) are non-invasive, objective and sensitive methods to detect subtle retinal changes in clinical trials (Hood et al 2012;McCulloch et al 2014;Jenkins et al 2018). Whereas ffERG records summed electrical response from the entire retina, mfERG can detect localized abnormalities from different regions of the retina (Hood et al 2012;McCulloch et al 2014).…”

“… 2014 ; Jenkins et al. 2018 ). Whereas ffERG records summed electrical response from the entire retina, mfERG can detect localized abnormalities from different regions of the retina (Hood et al.…”