scholarly journals Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus

2016 ◽  
Vol 113 (19) ◽  
pp. E2655-E2664 ◽  
Author(s):  
Elliott H. Sohn ◽  
Hille W. van Dijk ◽  
Chunhua Jiao ◽  
Pauline H. B. Kok ◽  
Woojin Jeong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Plexiform Layer ◽  
Capillary Density ◽  
Diabetic Mouse ◽  
Inner Plexiform Layer ◽  
Fiber Layer ◽  
Microvascular Changes ◽  
Retinal Neurodegeneration

Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced “type 1” and B6.BKS(D)-Leprdb/J “type 2” diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

scholarly journals Detecting retinal neurodegeneration in people with diabetes: Findings from the UK Biobank

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257836
Author(s):  
Roomasa Channa ◽  
Kyungmoo Lee ◽  
Kristen A. Staggers ◽  
Nitish Mehta ◽  
Sidra Zafar ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Glycated Hemoglobin ◽  
Retinal Thickness ◽  
Self Report ◽  
Inner Plexiform Layer ◽  
Uk Biobank ◽  
Fiber Layer ◽  
Cross Sectional ◽  
Retinal Neurodegeneration ◽  
The Uk

Importance Efforts are underway to incorporate retinal neurodegeneration in the diabetic retinopathy severity scale. However, there is no established measure to quantify diabetic retinal neurodegeneration (DRN). Objective We compared total retinal, macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness among participants with and without diabetes (DM) in a population-based cohort. Design/setting/participants Cross-sectional analysis, using the UK Biobank data resource. Separate general linear mixed models (GLMM) were created using DM and glycated hemoglobin as predictor variables for retinal thickness. Sub-analyses included comparing thickness measurements for patients with no/mild diabetic retinopathy (DR) and evaluating factors associated with retinal thickness in participants with and without diabetes. Factors found to be significantly associated with DM or thickness were included in a multiple GLMM. Exposure Diagnosis of DM was determined via self-report of diagnosis, medication use, DM-related complications or glycated hemoglobin level of ≥ 6.5%. Main outcomes and measures Total retinal, mRNFL and GC-IPL thickness. Results 74,422 participants (69,985 with no DM; 4,437 with DM) were included. Median age was 59 years, 46% were men and 92% were white. Participants with DM had lower total retinal thickness (-4.57 μm, 95% CI: -5.00, -4.14; p<0.001), GC-IPL thickness (-1.73 μm, 95% CI: -1.86, -1.59; p<0.001) and mRNFL thickness (-0.68 μm, 95% CI: -0.81, -0.54; p<0.001) compared to those without DM. After adjusting for co-variates, in the GLMM, total retinal thickness was 1.99 um lower (95% CI: -2.47, -1.50; p<0.001) and GC-IPL was 1.02 μm lower (95% CI: -1.18, -0.87; p<0.001) among those with DM compared to without. mRNFL was no longer significantly different (p = 0.369). GC-IPL remained significantly lower, after adjusting for co-variates, among those with DM compared to those without DM when including only participants with no/mild DR (-0.80 μm, 95% CI: -0.98, -0.62; p<0.001). Total retinal thickness decreased 0.40 μm (95% CI: -0.61, -0.20; p<0.001), mRNFL thickness increased 0.20 μm (95% CI: 0.14, 0.27; p<0.001) and GC-IPL decreased 0.26 μm (95% CI: -0.33, -0.20; p<0.001) per unit increase in A1c after adjusting for co-variates. Among participants with diabetes, age, DR grade, ethnicity, body mass index, glaucoma, spherical equivalent, and visual acuity were significantly associated with GC-IPL thickness. Conclusion GC-IPL was thinner among participants with DM, compared to without DM. This difference persisted after adjusting for confounding variables and when considering only those with no/mild DR. This confirms that GC-IPL thinning occurs early in DM and can serve as a useful marker of DRN.

scholarly journals Peripapillary microvasculature in patients with diabetes mellitus: An optical coherence tomography angiography study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yong-Il Shin ◽  
Ki Yup Nam ◽  
Seong Eun Lee ◽  
Min-Woo Lee ◽  
Hyung-Bin Lim ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Optical Coherence Tomography ◽  
Optical Coherence Tomography Angiography ◽  
Plexiform Layer ◽  
Control Group ◽  
Diabetic Patients ◽  
Inner Plexiform Layer ◽  
Optical Coherence ◽  
Regression Analyses ◽  
Fiber Layer

Abstract To evaluate changes in peripapillary microvascular parameters in diabetes mellitus (DM) patients using optical coherence tomography angiography (OCTA). Seventy-one diabetic patients (40 in the no diabetic retinopathy [DR] group and 31 in the non-proliferative DR [NPDR] group) and 50 control subjects. OCTA (Zeiss HD-OCT 5000 with AngioPlex) 6 × 6 mm scans centered on the optic disc were analyzed. Peripapillary vessel density (VD), perfusion density (PD) in superficial capillary plexus (SCP) were automatically calculated. The average macular ganglion cell-inner plexiform layer (mGC-IPL) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses of the no DR and NPDR groups were significantly thinner than those of the control group. The no DR and NPDR groups showed lower peripapillary VD and PD in SCP compared with the control group. Using univariate regression analyses, the average mGC-IPL thickness, the pRNFL thickness, the no DR group and NPDR group were significant factors that affected the peripapillary VD and PD in SCP. Multivariate regression analyses showed that the grade of DR was a significant factor affecting the peripapillary VD and PD in SCP. OCTA revealed that peripapillary microvascular parameters in the no DR and NPDR groups were lower than those of normal controls. The peripapillary VD and PD in SCP were correlated with the mGC-IPL thickness, the pRNFL thickness, and the no DR and NPDR groups. Changes in peripapillary OCTA parameters may help with understanding the pathophysiology of DM and evaluating a potentially valuable biomarker for patients with subclinical DR.

Ophthalmic, systemic, and genetic characteristics of patients with Wolfram syndrome

2019 ◽  
Vol 30 (5) ◽  
pp. 1099-1105
Author(s):  
Melih Ustaoglu ◽  
Feyza Onder ◽  
Murat Karapapak ◽  
Hasan Taslidere ◽  
Dilek Guven
Keyword(s):  
Diabetes Mellitus ◽  
Optic Atrophy ◽  
Genetic Disorder ◽  
Plexiform Layer ◽  
Wolfram Syndrome ◽  
Inner Plexiform Layer ◽  
Fiber Layer ◽  
Genetic Analyses ◽  
Genetic Characteristics ◽  
The Mean

Purpose: To evaluate the ophthalmic, systemic, and genetic characteristics of patients with Wolfram syndrome. Methods: In total, 13 patients with suspected or clinically diagnosed Wolfram syndrome underwent ophthalmic and systemic examinations and genetic analyses for Wolfram syndrome between August and October 2018. Results: The mean age of the subjects was 24.2 ± 7.1 years, of which 5 (38.5%) subjects were male and 8 (61.5%) were female. The mean best-corrected visual acuity ranged from counting fingers to 20/40, with a mean of 20/250 (1.10 ± 0.69 logarithm of the minimum angle of resolution). Dyschromatopsia was present in all patients (100%). There was a severe decrease in the average peripapillary retinal nerve fiber layer and macular ganglion cell–inner plexiform layer thicknesses (54.7 ± 6.5 and 51.9 ± 4.8 µm, respectively). Optical coherence tomography angiography showed significantly lower whole-image, inside disk, and peripapillary vessel densities in the patients with Wolfram syndrome than in the healthy controls (p < 0.001 for all). All patients who underwent genetic analyses had mutations in the WFS1 gene. Moreover, two novel mutations, p.Met623Trpfs*2 (c.1867delA) and p.Arg611Profs*9 (c.1832_11847del16) at exon 8, were detected. The frequency of systemic findings was as follows: optic atrophy (100%), diabetes mellitus (92.3%), central diabetes insipidus (38.5%), sensorineural hearing loss (38.5%), and presence of urological (30.8%), psychiatric (30.8%), and neurological (23.1%) diseases. Conclusion: Wolfram syndrome is a rare genetic disorder that can be associated with severe ophthalmic and systemic abnormalities. All patients who present with unexplained optic atrophy should be evaluated for Wolfram syndrome, even if they do not have diabetes mellitus because optic atrophy can sometimes manifest before diabetes mellitus.

scholarly journals Evaluation of microvascular changes in the perifoveal vascular network using optical coherence tomography angiography (OCTA) in type I diabetes mellitus: a large scale prospective trial

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Javier Zarranz-Ventura ◽  
Marina Barraso ◽  
Anibal Alé-Chilet ◽  
Teresa Hernandez ◽  
Cristian Oliva ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Optical Coherence Tomography ◽  
Diabetic Retinopathy ◽  
Large Scale ◽  
Optical Coherence Tomography Angiography ◽  
Vascular Network ◽  
Microvascular Changes ◽  
Systemic Factors ◽  
The Relationship

Abstract Background Diabetic retinopathy (DR) is the leading cause of blindness in type 1 Diabetes Mellitus (DM) patients, as a consequence of impaired blood flow in the retina. Optical coherence tomography angiography (OCTA) is a newly developed, non-invasive, retinal imaging technique that permits adequate delineation of the perifoveal vascular network. It allows the detection of paramacular areas of capillary non perfusion and/or enlargement of the foveal avascular zone (FAZ), representing an excellent tool for assessment of DR. The relationship of these microvascular changes with systemic factors such as metabolic control or duration of the disease still needs to be elucidated. Methods Prospective, consecutive, large-scale OCTA study. A complete ocular examination including a comprehensive series of OCTA images of different scan sizes captured with 2 OCT devices (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA, USA, and Triton Deep Range Imaging OCT, Topcon Corp, Topcon, Japan) will be obtained as part of the yearly routine follow up visits in type 1 DM patients seen in the Diabetes Unit of the Endocrinology department which give written informed consent to participate in the project. The aim of this study is to investigate the relationship between OCTA-derived parameters and systemic factors, as metabolic control (Hb1Ac, lipid profile, cholesterol, etc), and other relevant clinical factors as demographics or duration of the disease. Discussion This study is directed to investigate the relationship between the status of the perifoveal vascular network and systemic markers of the disease, and in particular to study whether these changes reflect those occurring elsewhere in the body affected by diabetic microvascular disease, as the kidneys or the brain. If these relationships were demonstrated, early detection of these microvascular changes by OCTA could lead to modifications in the pharmacological management of type 1 diabetic patients, as a way to reduce the risk of future complications in both the eye and other organs. Trial registration ClinicalTrials.gov, trial number NCT03422965.

Study of inner retinal neurodegeneration in Diabetes Mellitus using spectral domain optical coherence tomography

2021 ◽  
pp. 112067212110487
Author(s):  
Vikas Ambiya ◽  
Ashok Kumar ◽  
Veerabhadra Rao Bhavaraj ◽  
Vijay Sharma ◽  
Neeraj Sharma
Keyword(s):  
Diabetes Mellitus ◽  
Optical Coherence Tomography ◽  
Diabetic Retinopathy ◽  
Negative Correlation ◽  
Spectral Domain ◽  
Inner Plexiform Layer ◽  
Optical Coherence ◽  
Rnfl Thickness ◽  
Retinal Neurodegeneration ◽  
Group D

Purpose: To study inner retinal neurodegeneration in Diabetes Mellitus using spectral domain optical coherence tomography (OCT). Methods: This cross-sectional study included 40 eyes of age matched healthy subjects (group N), 40 eyes of diabetic patients without diabetic retinopathy (group D) and 160 eyes with diabetic retinopathy (group R) having 40 each in subgroups R1 (mild), R2 (moderate), R3 (severe/very severe) non-proliferative stages and R4 (proliferative stage). Spectral domain OCT was used to measure the ganglion cell-inner plexiform layer (GC-IPL) thickness and retinal nerve fibre layer (RNFL) thickness. Results: The average GC-IPL thickness was significantly lower, both in groups D ( p = 0.005) and R ( p = 0.009), when compared with group N. The minimum GC-IPL thickness was also significantly lower in groups D ( p < 0.001) and R ( p < 0.001). There was no statistically significant difference in the average RNFL thickness among the groups. The minimum RNFL thickness was significantly lesser in group D ( p = 0.027). The minimum RNFL thickness had a strongly negative correlation with the severity of DR ( R = −0.828; p = 0.042). The thinning of both GC-IPL and RNFL was most pronounced in subgroup R4. Conclusion: There is a significant reduction in the GC-IPL thickness and the RNFL thickness in diabetes even before the onset of DR. The changes in both GC-IPL thickness and RNFL thickness are most pronounced after the onset of PDR. There is a strongly negative correlation between the minimum RNFL thickness with the severity of DR.

scholarly journals Evaluation of thickness of retinal nerve fiber layer and ganglion cell layer with inner plexiform layer in patients without diabetic retinopathy and mild diabetic retinopathy in type 2 diabetes mellitus patients using spectral-domain optical coherence tomography

2018 ◽  
Vol 6 (7) ◽  
pp. 2434
Author(s):  
Mitali Borooah ◽  
Y. Jennifer Nane ◽  
Jayant Ekka
Keyword(s):  
Diabetic Retinopathy ◽  
Ganglion Cell Layer ◽  
Plexiform Layer ◽  
Diabetic Patients ◽  
Inner Plexiform Layer ◽  
Fiber Layer ◽  
Type 2 Diabetic Patients ◽  
Rnfl Thickness ◽  
Type 2 Diabetic

Background: A widely accepted pathogenesis of DR consists of microvascular abnormalities. However recent investigations have demonstrated neurodegenerative alterations before the appearance of microvascular changes in patients with DM. Aim of the study was to evaluate thickness of retinal nerve fiber layer and ganglion cell layer with inner plexiform layer in patent without diabetic retinopathy and mild diabetic retinopathy in type 2 diabetic patients using spectral domain optical coherence tomography.Methods: Thirty patients with type 2 diabetes mellitus without diabetic retinopathy, 30 with mild diabetic retinopathy and 30 healthy controls are taken considering inclusion and exclusion criteria. GCL-ILM and RNFL thickness was measured in each individual and measurements were compared using one way ANOVA test and Pearson’s correlation was performed to evaluate the linear correlation between variables and calculated p value <0.05 was regarded as significant.Results: The average RNFL thickness was 86.18±8.44μm and 91.79±4.77μm in diabetic patients and controls respectively (p=0.002). Furthermore, for two different groups of diabetic patients, the average RNFL thickness was 86.74±11.18μm in the no DR group and 85.62±11.10μm in the mild DR group (p=0.697). The average GCL-IPL thickness was 79.95±4.32μm and 84.66±3.26μm in diabetic patients and controls, respectively (p=<0.001). Furthermore, for two different groups of diabetic patients, the average GCL-IPL thickness was 80.15±5.78μm in the no DR group and 79.75±5.70μm in the mild DR group (p=0.788).Conclusions: There was a statistically significant reduction of the mean GCL-IPL and RNFL thickness in type 2 diabetic patients with no or mild DR compared with a homogenous control group indicating neuroretinal changes occur before vascular changes of diabetic retinopathy. But the correlation of average RNFL thickness and GCL-IPL thickness was not statistically significant with the duration of diabetes and HbA1c value.

scholarly journals The Effect of HbA1c Variability as a Risk Measure for Microangiopathy in Type 1 Diabetes Mellitus

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1151
Author(s):  
Pedro Romero-Aroca ◽  
Raul Navarro-Gil ◽  
Albert Feliu ◽  
Aida Valls ◽  
Antonio Moreno ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Type 1 Diabetes Mellitus ◽  
Risk Measure ◽  
Case Series ◽  
Multivariate Statistical ◽  
Case Series Study ◽  
Prospective Case Series

Background: To measure the relationship between variability in HbA1c and microalbuminuria (MA) and diabetic retinopathy (DR) in the long term. Methods: A prospective case-series study, was conducted on 366 Type 1 Diabetes Mellitus patients with normoalbuminuria and without diabetic retinopathy at inclusion. The cohort was followed for a period of 12 years. The Cox survival analysis was used for the multivariate statistical study. The effect of variability in microangiopathy (retinopathy and nephropathy) was evaluated by calculating the standard deviation of HbA1c (SD-HbA1c), the coefficient of variation of HbA1c (CV-HbA1c), average real variability (ARV-HbA1c) and variability irrespective of the mean (VIM-HbA1c) adjusted for the other known variables. Results: A total of 106 patients developed diabetic retinopathy (29%) and 73 microalbuminuria (19.9%). Overt diabetic nephropathy, by our definition, affected only five patients (1.36%). Statistical results show that the current age, mean HbA1c, SD-HbA1c and ARV-HbA1c are significant in the development of diabetic retinopathy. Microalbuminuria was significant for current age, mean HbA1c, CV-HbA1c and ARV-HbA1c. Conclusions: By measuring the variability in HbA1c, we can use SD-HbA1c and ARV-HbA1c as possible targets for judging which patients are at risk of developing DR and MA, and CV-HbA1c as the target for severe DR.

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