Neurodegeneration in Type 2 Diabetes: Evidence From Spectral-Domain Optical Coherence Tomography

Chhablani, Jay; Sharma, Anita; Goud, Abhilash; Peguda, Hari Kumar; Rao, Harsha L.; Begum, Viquar U.; Barteselli, Giulio

doi:10.1167/iovs.15-17334

Cited by 148 publications

(129 citation statements)

References 36 publications

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“…Similarly, some studies have shown diabetes to have an early neurodegenerative effect on the retina, causing neuronal dysfunction, leading to thinning of both the RNFL and GCC, with associated functional visual deficits. Chhablani et al 79 showed that inner retinal thinning was present in patients with type 2 diabetes, even before signs of retinopathy were visible, while Salvi et al 80 showed a significant association of GCC thinning in patients with diabetic polyneuropathy but not in those with retinopathy. We did not find an association between a diagnosis of diabetes and GCC thickness, nor with fasting serum glucose and insulin levels.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a Healthy Aging British Cohort

et al. 2017

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IMPORTANCE Measurement of ganglion cell complex (GCC) thickness may be more sensitive than current methods for glaucoma diagnosis and research. However, little is known about the factors influencing GCC thickness in the general population.OBJECTIVES To investigate the heritability of and factors associated with GCC thickness in a healthy aging population. DESIGN, SETTING, AND PARTICIPANTSA cross-sectional twin study was conducted from August 27, 2014, to March 31, 2016, among 1657 participants of white British ancestry from the TwinsUK study cohort without ocular pathologic conditions. Heritability analyses were conducted in 1432 twins (426 monozygous and 290 dizygous pairs). Association analyses were performed using univariable and multivariable stepwise linear regression models, taking family structure into account. Heritability analyses were conducted using maximum likelihood structural equation twin modeling. MAIN OUTCOMES AND MEASURESParameters measured included GCC thickness, autorefraction, intraocular pressure, blood pressure, body mass index, and cholesterol, creatinine, glucose, insulin, triglycerides, and urea levels. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. RESULTS Among the 1657 participants (mean [SD] age, 56.0 [15.3] years; 89.5% women and 10.5% men), the mean [SD] inner GCC thickness was 96.0 [7.6] μm (95% CI, 95.1-96.2). In multivariable modeling, the mean inner GCC thickness was associated with advancing age (β, -0.14; P < .001), increased body mass index (β, -0.15; P = .001), spherical equivalent (β, 0.70; P < .001), and higher estimated glomerular filtration rate (β, 0.03; P = .02). A 1-U increase in age or body mass index was associated with a 0.14-μm and 0.15-μm decrease in GCC thickness, respectively (P < .001), while a 1-U increase in spherical equivalent or estimated glomerular filtration rate was associated with a 0.70-μm (P < .001) and 0.03-μm (P = .02) increase in GCC thickness, respectively. Ganglion cell complex thickness was not associated with sex, intraocular pressure, or diabetes. Age-adjusted GCC thickness was highly heritable, with additive genetic effects explaining 81% (95% CI, 78%-84%) of phenotypic variance and individual environmental factors explaining the remaining 19% (95% CI, 16%-22%).CONCLUSIONS AND RELEVANCE Ganglion cell complex thickness appears to be highly heritable and further genetic analysis may help identify new biological pathways for glaucoma. The results suggest it may be important to account for age, body mass index, refractive error, and sex when using GCC thickness as a diagnostic tool. Replication of their results is required, as is further research to explain the association between renal function and GCC thickness.

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Section: Discussionmentioning

confidence: 99%

Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a Healthy Aging British Cohort

et al. 2017

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“…In diabetes, early thinning of the macular GCIPL thickness has been reported even before visible vascular signs of diabetic retinopathy (DR). [10] Neurodegeneration in the early stages of diabetes compromises the functions of neurons, resulting in subtle but significant impairment of vision. [11] Despite its clinical importance, little is known about the systemic risk factors associated with inner retina thinning in diabetes.…”

Section: Introductionmentioning

confidence: 99%

Early inner retinal thinning and cardiovascular autonomic dysfunction in type 2 diabetes

et al. 2017

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BackgroundTo investigate changes in the neural retina according to the presence of retinal nerve fiber layer (RNFL) defects in type 2 diabetes, and to determine the association between inner retina thickness and the severity of diabetic complications.MethodsWe studied non-glaucomatous patients with type 2 diabetes and control subjects Circumpapillary RNFL and macula ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured by spectral-domain optical coherence tomography. In patients with type 2 diabetes, a cardiovascular autonomic function test (AFT) was performed, which included the heart rate parameter of beat-beat variation—with deep breathing, in response to the Valsalva maneuver, and on postural change from lying to standing. The results of each test were scored as 0 for normal and 1 for abnormal. A total AFT score of 1 was defined as early cardiovascular autonomic neuropathy (CAN), and an AFT score≥ 2 as definite CAN.ResultsWe compared control eyes (n = 70), diabetic eyes with RNFL defects (n = 47), and eyes without RNFL defects (n = 30). The average RNFL and GCIPL thicknesses were significantly different among groups (all, P<0.05). On post-hoc testing, diabetic eyes with RNFL defects had a significantly thinner average GCIPL thickness than those without RNFL defects. On multivariate analyses, significantly thinner average GCIPL was seen in early CAN staging (B = -4.32, P = 0.016) and in definite CAN staging (B = -10.33, P<0.001), compared with no CAN involvement, after adjusting for confounding parameters.ConclusionsCardiovascular autonomic dysfunction was associated with early neurodegenerative changes in type 2 diabetes.

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“…In type 2 diabetes mellitus (T2DM) patients, however, data from several OCT studies have been conflicting. Jay Chhablani et al [24] suggested that early thinning of the intra-retinal layer occurs in T2DM even before visible vascular signs of DR, whereas van Dijk et al [25,26] reported that GCL thickness was significantly thinner only in patients with apparent microvascular DR lesions. Furthermore, Chen Y et al [27] found that the ganglion cell inner plexiform layer (GCIPL) complex thickness in T2DM patients was not significantly different from that of controls.…”

Section: Introductionmentioning

confidence: 99%

Comparison of spectral-domain optical coherence tomography for intra-retinal layers thickness measurements between healthy and diabetic eyes among Chinese adults

Li¹,

Wang²,

Du³

et al. 2017

PLoS ONE

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PurposeTo compare intra-retinal layer thickness measurements between eyes with no or mild diabetic retinopathy (DR) and age-matched controls using Spectralis spectral-domain optical coherence tomography (SD-OCT).MethodsCross-sectional observational analysis study. High-resolution macular volume scans (30° * 25°) were obtained for 133 type 2 diabetes mellitus (T2DM) patients with no DR, 42 T2DM patients with mild DR and 115 healthy controls. The mean thickness was measured in all 9 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors for 8 separate layers, inner retinal layer (IRL), outer retinal layer (ORL) and total retina (TR), after automated segmentation. The ETDRS grid consisted of three concentric circles of 1-, 3-, and 6-mm diameter. The superior, inferior, temporal, and nasal sectors of the 3- and 6-mm circles were respectively designated as S3, I3, T3, and N3 and S6, I6, T6, and N6. Linear regression analyses were conducted to evaluate the associations between the intra-retinal layer thicknesses, age, diabetes duration, fasting blood glucose and HbA1c.ResultsThe mean age and duration of T2DM were 61.1 and 13.7 years, respectively. Although no significant differences in the average TR and ORL volumes were observed among the groups, significant differences were found in the volume and sectorial thicknesses of the inner plexiform layer (IPL), outer plexiform layer (OPL) and IRL among the groups. In particular, the thicknesses of the IPL (S3, T3, S6, I6 and T6 sectors) and the IRL (S6 sector) were decreased in the no-DR group compared with the controls (P < 0.05). The thickness of the OPL (S3, N3, S6 and N6 sectors) was thinner in the no-DR group than in mild DR (P < 0.05). The average IPL thickness was significantly negatively correlated with age and the duration of diabetes.ConclusionThe assessment of the intra-retinal layer thickness showed a significant decrease in the IPL and IRL thicknesses in Chinese adults with T2DM, even in the absence of visible microvascular signs of DR.

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Neurodegeneration in Type 2 Diabetes: Evidence From Spectral-Domain Optical Coherence Tomography

Cited by 148 publications

References 36 publications

Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a Healthy Aging British Cohort

Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a Healthy Aging British Cohort

Early inner retinal thinning and cardiovascular autonomic dysfunction in type 2 diabetes

Comparison of spectral-domain optical coherence tomography for intra-retinal layers thickness measurements between healthy and diabetic eyes among Chinese adults

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