Reduced minimum rim width of optic nerve head: a potential early marker of retinal neurodegeneration in children and adolescents with type 1 diabetes

Piona, Claudia; Cozzini, Tiziano; Marchini, Giorgio; Merz, Tommaso; Brighenti, Tommaso; Mazzo, Umberto; Marigliano, Marco; Olivieri, Francesca; Pedrotti, Emilio; Maffeis, Claudio

doi:10.1016/j.diabres.2020.108420

Cited by 4 publications

(7 citation statements)

References 31 publications

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“…Diabetes induces neural apoptosis of ganglion, amacrine, and Muller cells, activation of microglia caused by chronic glutamate toxicity, inflammatory glial activation, ganglion cell layer/inner plexiform (GCL) thickness, retinal thickness, and retinal nerve fiber layer thickness [97][98][99][100][101][102][103]. Piona et al [104] reported that the reduction of the neuroretinal rim in minimum rim width (MRW) which is the shortest distance between Bruch's membrane opening (BMO) and internal limiting membrane (ILM), may be a potential early marker of retinal degeneration detectable in T1DM-children. A relationship between MRW and mean HbA1c suggests that the control of glucose metabolism may affect an early neurodegeneration of the retina, starting from childhood.…”

Section: A Potential Link Between Retinal Neurodegeneration and Micromentioning

confidence: 99%

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Mrugacz

Bryl

Zorena

2021

JCM

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Diabetes mellitus (DM) has become a vital societal problem as epidemiological studies demonstrate the increasing incidence of type 1 and type 2 diabetes. Lesions observed in the retina in the course of diabetes, referred to as diabetic retinopathy (DR), are caused by vascular abnormalities and are ischemic in nature. Vascular lesions in diabetes pertain to small vessels (microangiopathy) and involve precapillary arterioles, capillaries and small veins. Pericyte loss, thickening of the basement membrane, and damage and proliferation of endothelial cells are observed. Endothelial cells (monolayer squamous epithelium) form the smooth internal vascular lining indispensable for normal blood flow. Breaking its continuity initiates blood coagulation at that site. The endothelium controls the process of exchange of chemical substances (nutritional, regulatory, waste products) between blood and the retina, and blood cell passing through the vascular wall. Endothelial cells produce biologically active substances involved in blood coagulation, regulating vascular wall tension and stimulating neoangiogenesis. On the other hand, recent studies have demonstrated that diabetic retinopathy may be not only a microvascular disease, but is a result of neuroretinal degeneration. Neuroretinal degeneration appears structurally, as neural apoptosis of amacrine and Muller cells, reactive gliosis, ganglion cell layer/inner plexiform (GCL) thickness, retinal thickness, and retinal nerve fiber layer thickness, and a reduction of the neuroretinal rim in minimum rim width (MRW) and functionally as an abnormal electroretinogram (ERG), dark adaptation, contrast sensitivity, color vision, and microperimetric test. The findings in early stages of diabetic retinopathy may precede microvascular changes of this disease. Furthermore, the article’s objective is to characterize the factors and mechanisms conducive to microvascular changes and neuroretinal apoptosis in diabetic retinopathy. Only when all the measures preventing vascular dysfunction are determined will the risk of complications in the course of diabetes be minimized.

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Section: A Potential Link Between Retinal Neurodegeneration and Micromentioning

confidence: 99%

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Mrugacz

Bryl

Zorena

2021

JCM

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“…In two previous studies, we applied these techniques showing that corneal and retinal alterations are present in children and adolescents with T1D compared to healthy peers [ 5 , 6 ]. Moreover, we also evaluated the role of classical risk factors for diabetes complications demonstrating that the presence of early ocular neurodegenerative signs in our cohort was partially predicted by worse long-term glycometabolic control and high blood pressure.…”

Section: Discussionmentioning

confidence: 99%

“…Inc.) were performed in both eyes and for each parameter the mean of right and left eyes measurements was calculated. All the examinations were performed by the same expert operator (TC) as previously described [ 5 , 6 ].…”

Section: Methodsmentioning

confidence: 99%

“…In recent years, two new ophthalmologic imaging techniques, Spectral domain-optical coherence tomography (SD-OCT) and In vivo confocal microscopy (IVCM), emerged for their ability to identify early neurodegenerative changes in retina and cornea of subjects with diabetes [ 4 ]. Concerning the evaluation of these early ocular changes during the pediatric age, we demonstrated that a significant impairment of the minimum neuroretinal rim width (MRW) of the optic nerve head (ONH) measured with SD-OCT and of the corneal subbasal nerve plexus (SBP) measured with IVCM is present in T1D children and adolescents compared with age and gender-matched controls [ 5 , 6 ]. Our results also showed that long-term glycometabolic control and blood pressure partially predicted the presence of early damage signs, in agreement with recent findings that recognized glycemic control and hypertension as major risk factors for DN development and progression [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

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Early marker of ocular neurodegeneration in children and adolescents with type 1 diabetes: the contributing role of polymorphisms in mir146a and mir128a genes

et al. 2022

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Background Early ocular neurodegenerative signs of diabetic neuropathy (DN) can be found in children and adolescents with type 1 diabetes (T1D). No data are available on the potential role of polymorphisms in miRNAs genes in predisposing T1D subjects to these signs. Aims To determine whether MIR146A rs2910164 and MIR128A rs11888095 polymorphisms are associated with early retinal and corneal neurodegenerative changes in pediatric patients with T1D. Methods A total of 140 T1D children/adolescents underwent spectral domain-optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) with measurement of retinal and corneal nerve fiber parameters. Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were recorded. Genotyping of rs2910164 and rs1188095 SNPs and genotype–phenotype association analysis were performed. Results The C allele of rs2910164 in MIR146A was associated with higher values of IVCM parameters and minimum rim width (MRW) of the peripapillary region of optic nerve head measured in the retina, whereas the T allele of rs1188095 in MIR128A was associated with a significant impairment of them. Multiple regression analysis showed that MIR146A and MIR128A polymorphisms were significantly associated with corneal nerve fiber length (beta = 0.225 and − 0.204, respectively) and other IVCM parameters, independently from age, diabetes duration, HbA1c and systolic blood pressure percentile. Similar results were found for MRW (beta = 0.213 and − 0.286, respectively). Conclusions These results provide new insight into the genetic predisposition to DN showing that two polymorphisms in MIR146A and MIR128A genes could significantly contribute to the development of early ocular preclinical signs of DN.

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“…The potential publication bias for the variables was evaluated using Egger's test. Except for the measurements [19] 290 430 China Type 2 Unclear Foveal, parafoveal, perifoveal thickness Arias (2021) [92] 24 26 Colombia Prediabetes -FAZ area, AI Ulutas et al (2021) [74] Temel and Batioglu (2021) [86] 51 59 Turkey Li et al (2021) [6] Lee et al (2021) [3] Kocer and Sekeroglu (2021) [4] 25 29 Turkey Type 2 7.5 Retinal, foveal, parafoveal, perifoveal VD Kara and Can (2021) [37] 118 120 Turkey Type 1 4.9 Retinal, foveal, parafoveal, perifoveal VD Huru et al (2021) [9] 1638 310/57 * Finland Prediabetes/type 2 † -/unclear ‡ Foveal, parafoveal, perifoveal thickness/GCL thickness Hepokur et al (2021) [46] Endo et al (2021) [2] 62 92 Japan Type 2 10.9 Foveal VD (SCP), foveal thickness Damian et al (2021) [87] 36 38 Romania Type 1/2 mixed 10.31 SFCT Damian and Nicoara (2021) [48] 32 32 Romania Type 2 9.24 Foveal, parafoveal, perifoveal thickness/pRNFL, mRNFL, GCL thickness Chen et al (2021) [36] [5] 50 99 Turkey Type 2 9.62 Retinal, foveal, parafoveal, perifoveal VD/foveal thickness Bontzos et al (2021) [94] 54 54 Greece Unclear 4.62 Retinal VD/GCC thickness Aksoy et al (2021) [75] Unclear Foveal, parafoveal thickness/retinal, foveal, parafoveal VD Lim et al (2020) [16] 63 49 Korea Unclear 7.1 pRNFL thickness Sousa et al (2020) [1] 12.62 Foveal, parafoveal, perifoveal thickness/pRNFL thickness, SFCT Sacconi et al (2020) [18] 12 12 Italy Type 1 35 Foveal, parafoveal thickness/SFCT Pinilla et al (2020) [76] [21] Piona et al (2020) [17] 51 147 Italy Type 1 8.9 pRNFL, GCL thickness Ozturk et al (2020) [77]…”

Section: Quality and Publication Bias Assessmentmentioning

confidence: 99%

Reduced macular thickness and vascular density in abnormal glucose metabolism patients: A meta-analysis of optical coherence tomography (OCT) and OCT angiography studies

Fu,

Ren,

Chen

et al. 2024

Chinese Medical Journal

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Background: Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 Statement was followed as our guideline for this meta-analysis. PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The meta-analysis was conducted using Stata (version 13.1). Results: A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (–0.24, 95% CI [–0.39, –0.08]; P = 0.002, I 2 = 87.7%), all regions of parafovea (–0.32, 95% CI [–0.54, –0.11]; P = 0.003; I 2 = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals. Conclusions: Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes. Registration: PROSPERO; http://www.crd.york.ac.uk/prospero/; No. CRD42021269885.

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Reduced minimum rim width of optic nerve head: a potential early marker of retinal neurodegeneration in children and adolescents with type 1 diabetes

Cited by 4 publications

References 31 publications

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Early marker of ocular neurodegeneration in children and adolescents with type 1 diabetes: the contributing role of polymorphisms in mir146a and mir128a genes

Reduced macular thickness and vascular density in abnormal glucose metabolism patients: A meta-analysis of optical coherence tomography (OCT) and OCT angiography studies

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