Evaluation of Retinal Function and Flicker Light-Induced Retinal Vascular Response in Normotensive Patients with Diabetes without Retinopathy

Lecleire–Collet, A.; Audo, Isabelle; Aout, Mounir; Girmens, Jean-François; Sofroni, R.; Erginay, Ali; Gargasson, Jean-François Le; Mohand‐Saïd, Saddek; Méas, T.; Guillausseau, Pierre-Jean; Vicaut, Éric; Pâques, M.; Massin, Pascale

doi:10.1167/iovs.10-5960

Cited by 122 publications

(107 citation statements)

References 33 publications

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“…31 Because retinal blood flow is coupled with neuronal activity, reduced flicker light induced vasodilatation might also reflect neurodegeneration. In a recent investigation by Lecleire-Collet et al, a linear association was found between flicker light induced retinal arterial vasodilatation and electroretinographic abnormalities, 16 indicating that a reduced neural activity in the retina might cause a decreased flicker response in DM. We did not find a significant difference in the vascular response to flicker light between the patients with or without neuropathy.…”

Section: Discussionmentioning

confidence: 91%

“…[13][14][15] In addition, the microvascular response to flicker light requires retinal neural integrity, and electroretinographic investigations confirmed an impaired flicker response caused by disturbed neurovascular coupling. 16 Beside these functional disturbances in retinal microvascular blood flow, morphological alterations in retinal angioarchitecture are a common feature in developing diabetic retinopathy. 17,18 In a recent study, an increase in retinal vascular caliber could be observed in association with peripheral diabetic neuropathy.…”

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confidence: 99%

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Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy

Forst

Weber

Mitry

et al. 2014

J Diabetes Sci Technol

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In patients with diabetes mellitus (DM), early retinal microvascular alterations can be observed even before the clinical diagnosis of diabetic retinopathy. This study aimed to investigate morphological and functional changes in retinal microvascular blood flow in type 1 diabetic patients with and without peripheral neuropathy (PNP) as compared to nondiabetic controls. Retinal microvascular blood flow (RBF) was assessed using scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter, Heidelberg Engineering, Germany) before and after stimulation with flicker light. PNP was assessed using the neuropathy disability score (NDS) and by the evaluation of the vibration perception threshold (VPT). A total of 41 subjects were recruited for study participation and were stratified to 3 different groups according to their metabolic and neurological status: 14 nondiabetic subjects without PNP, 14 diabetic patients without PNP, and 13 diabetic patients with PNP. All subjects were free from diabetic retinopathy as assessed by fundoscopy. In diabetic patients with PNP, baseline and stimulated RBF was higher compared with diabetic patients without PNP and the nondiabetic control group. No difference with regard to RBF could be observed between the nondiabetic control subjects and patients with type 1 DM without PNP. No difference in the arterial WLR could be observed between the 3 groups. A linear correlation was found for VPT and RBF (r = .38, P < .001) and for NDS and RBF (r = .44, P < .0001). In our study population of patients with type 1 diabetes, PNP was associated with functional but not morphological changes in RBF. Keywords diabetic polyneuropathy, retinal blood flow, wall to lumen ratio, type 1 diabetes mellitus

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy

Forst

Weber

Mitry

et al. 2014

J Diabetes Sci Technol

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“…This is possible in the pre-DR stage (14)(15)(16)(17). Some functional studies have suggested visual impairment in diabetic patients without apparent DR, but these studies did not exclude changes in integrity of the barrier function using a quantitative method (2,(18)(19)(20)(21)(22)(23)(24)(25). The occurrence of structural changes indicating vascular damage is also quite disputed in type 1 diabetic patients at a preclinical stage (23,26), possibly because the way patients are phenotyped may vary across studies.…”

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confidence: 99%

“…A link of such deficits with parvo-and magnocellular impairment is, however, missing. Besides the changes in achromatic contrast sensitivity (20,22), there are also studies showing changed psychophysical and physiologic changes in these patients without DR, related to color contrast sensitivity (24,25) and multifocal electroretinogram (mfERG) responses (21). It remains unclear whether these changes can be present independently of vascular damage (e.g., if they could reflect direct neural damage).…”

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confidence: 99%

Neuroretinal Dysfunction With Intact Blood-Retinal Barrier and Absent Vasculopathy in Type 1 Diabetes

et al. 2014

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It is unknown whether independent neural damage may occur in the pre-/absent vascular diabetic retinopathy (DR). To exclude vasculopathy, it is important to measure the integrity of the blood-retinal barrier (BRB). This cross-sectional study addressed this problem in type 1 diabetic patients with normal ocular fundus and absent breakdown of the BRB (confirmed with vitreous fluorometry). These were compared with a group with disrupted BRB (with normal fundus or initial DR) and normal controls. Multifocal electroretinography and chromatic/achromatic contrast sensitivity were measured in these 42 patients with preserved visual acuity. Amplitudes of neurophysiological responses (multifocal electroretinogram) were decreased in all eccentricity rings in both clinical groups, when compared with controls, with sensitivity >78% for a specificity level of 90%. Implicit time changes were also found in the absence of initial DR. Impaired contrast sensitivity along chromatic axes was also observed, and achromatic thresholds were also different between controls and both clinical groups. The pattern of changes in the group without baseline BRB permeability alterations, as probed by psychophysical and electrophysiological measurements, does thereby confirm independent damage mechanisms. We conclude that retinal neuronal changes can be diagnosed in type 1 diabetes, independently of the breakdown of the BRB and onset of vasculopathy.

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“…The flicker response has also been demonstrated to correlate with altered retinal neural function detected by electroretinogram [111], and with changes in retinal vessel caliber [112].…”

Section: Ocular-based Biomarkersmentioning

confidence: 97%

Biomarkers in Diabetic Retinopathy

et al. 2015

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■ AbstractThere is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat diabetic retinopathy, there is need to reliably identify and triage people with diabetes. Biomarkers may facilitate a better understanding of diabetic retinopathy, and contribute to the development of novel treatments and new clinical strategies to prevent vision loss in people with diabetes. This article reviews key aspects related to biomarker research, and focuses on some specific biomarkers relevant to diabetic retinopathy.

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Evaluation of Retinal Function and Flicker Light-Induced Retinal Vascular Response in Normotensive Patients with Diabetes without Retinopathy

Abstract: In patients with diabetes, neural and neurovascular dysfunctions both precede the onset of clinically detectable DR. To which extent these abnormalities are related to each other remains to be determined. (ClinicalTrials.gov number, NCT00839150.)

Cited by 122 publications

References 33 publications

Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy

Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy

Neuroretinal Dysfunction With Intact Blood-Retinal Barrier and Absent Vasculopathy in Type 1 Diabetes

Biomarkers in Diabetic Retinopathy

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