Atrophy of the optic chiasm is associated with microvascular diabetic complications in type 1 diabetes

IntroductionDiabetic neuropathy and diabetic eye disease are well known complications of type 1 diabetes. We hypothesized that chronic hyperglycemia also damages the optic tract, which can be measured using routine magnetic resonance imaging. Our aim was to compare morphological differences in the optic tract between individuals with type 1 diabetes and healthy control subjects. Associations between optic tract atrophy and metabolic measures, cerebrovascular and microvascular diabetic complications were further studied among individuals with type 1 diabetes.MethodsWe included 188 subjects with type 1 diabetes and 30 healthy controls, all recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent a clinical examination, biochemical work-up, and brain magnetic resonance imaging (MRI). Two different raters manually measured the optic tract.ResultsThe coronal area of the optic chiasm was smaller among those with type 1 diabetes compared to non-diabetic controls (median area 24.7 [21.0-28.5] vs 30.0 [26.7-33.3] mm2, p<0.001). In participants with type 1 diabetes, a smaller chiasmatic area was associated with duration of diabetes, glycated hemoglobin, and body mass index. Diabetic eye disease, kidney disease, neuropathy and the presence of cerebral microbleeds (CMBs) in brain MRI were associated with smaller chiasmatic size (p<0.05 for all).ConclusionIndividuals with type 1 diabetes had smaller optic chiasms than healthy controls, suggesting that diabetic neurodegenerative changes extend to the optic nerve tract. This hypothesis was further supported by the association of smaller chiasm with chronic hyperglycemia, duration of diabetes, diabetic microvascular complications, as well as and CMBs in individuals with type 1 diabetes

Subfoveal choroidal thickness in ipsi- and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy : a prospective study

Purpose To compare subfoveal choroidal thickness (SFCT) and associated clinical variables in patients with carotid stenosis (CS) before and 6 months after carotid endarterectomy (CEA). Methods The prospective non-randomized Helsinki Carotid Endarterectomy Study - Brain and Eye Sub-sTudy included seventy patients (81% male, mean age 69 years) and 40 control subjects (77% male, 68 years), from March 2015 to December 2018. Ophthalmological examination included SFCT measured with enhanced-depth imaging-optical coherence tomography. Carotid stenosis (CS) was more severe (>= 70% stenosis in 92%) ipsilateral to the CEA than contralaterally ( Results At baseline, patients had thinner mean SFCT than control subjects in both eyes (ipsilateral, 222 versus 257 mu m and contralateral, 217 versus 258 mu m, p Conclusions Subfoveal choroidal thickness (SFCT) is thinner in patients with CS without association between SFCT and the grade of CS. Unchanged SFCT after CEA suggests, that choroidal vessels in severe CS are unable to react to increased blood flow. Bilaterally thin SFCT could be considered as yet another sign of CS.Peer reviewe

Ocular signs of carotid stenosis in ipsi- and contralateral eyes before and after carotid endarterectomy : a prospective study

Purpose We describe hypoperfusion-related and embolic ocular signs of carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) in a CS population. Methods We enrolled prospectively 70 CEA patients (81% male, mean age 69) and 41 non-medicated control subjects (76%, 68), from March 2015 to December 2018, assessing intraocular pressure (IOP), best-corrected visual acuity (BCVA) in logMAR units and performing a bio-microscopy examination. Results Main index symptoms included amaurosis fugax (Afx) (29, 41%) and hemispheric TIA (17, 24%), and 17 (24%) were asymptomatic. Of the 70, 17 patients (24%, 95% CI 16-36) showed ocular signs of CS. Of four embolic (Hollenhorst plaques) findings, one small macular plaque disappeared postoperatively. Four had hypoperfusion, that is ocular ischaemic syndrome (OIS), requiring panretinal photocoagulation: one for multiple mid-peripheral haemorrhages, two for iris neovascularization and one for neovascular glaucoma (NVG); only the NVG proved irreversible. Nine (de novo in three) showed mild OIS, that is only few mid-peripheral haemorrhages, ranging pre- /postoperatively in ipsilateral eyes from one to eleven (median two)/ one to two (median one), and in contralateral eyes from three to nine (median five)/ one to six (median three). Pre- and postoperative median BCVA was 0 or better, and mean IOP was normal, except in the NVG patient. Temporary visual impairment from 0 to 0.3 occurred in one eye soon after CEA due to ocular hyperperfusion causing macular oedema. Conclusions Ocular signs of CS are common in CEA patients, ranging from few mid-peripheral haemorrhages to irreversible NVG. Clinicians should be aware of these signs in detecting CS.Peer reviewe

Flicker-induced retinal vascular dilation in ipsi- and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy : a prospective study

Purpose Retinal vascular function was assessed in patients with carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) and in controls at a six-month interval. Methods We studied 68 patients (81% male, mean age 69) and 41 healthy non-medicated controls (77%, 68) from March 2015 to December 2018. Our ophthalmological examination included flicker-induced arteriolar and venular measurements with a Dynamic Vessel Analyser in both eyes. Results At baseline, flicker-induced arteriolar and venular dilation was reduced in the ipsilateral eyes of the patients compared with dilation in the controls (arteriolar 1.0% versus 2.6%, p = 0.001 and venular 2.2% versus 2.8%, p = 0.049). These differences subsided after CEA. In patients' ipsilateral eyes, flicker-induced arteriolar dilation was borderline postoperatively (preoperative 1.0% versus postoperative 1.6%, p = 0.06), whereas venular dilation increased (2.2% versus 2.8%, p = 0.025). We found various tentative associations with the change in flicker-induced dilations after CEA, but not with the preoperative dilations. Conclusions Postoperative recovery of the reduced flicker-induced arteriolar and venular dilatation in the ipsilateral eye shows that, after CEA, the activity-dependent vascular reactivity of haemodynamically compromised retinal tissue can improve.Peer reviewe

Cerebral small-vessel disease is associated with the severity of diabetic retinopathy in type 1 diabetes

Introduction Cerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain's vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes. Research design and methods For this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33-45) years; 53% female; diabetes duration 21.6 (18.2-30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score). Results In type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20-61) vs 20 (20-35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20-65) vs 20 (20-35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts. Conclusions Presence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.Peer reviewe

Clinical and MRI Features of Cerebral Small-Vessel Disease in Type 1 Diabetes

OBJECTIVETo assess the prevalence of cerebral small-vessel disease (SVD) in subjects with type 1 diabetes compared with healthy control subjects and to characterize the diabetes-related factors associated with SVD.RESEARCH DESIGN AND METHODSThis substudy was cross-sectional in design and included 191 participants with type 1 diabetes and median age 40.0 years (interquartile range 33.0-45.1) and 30 healthy age- and sex-matched control subjects. All participants underwent clinical investigation and brain MRIs, assessed for cerebral SVD.RESULTSCerebral SVD was more common in participants with type 1 diabetes than in healthy control subjects: any marker 35% vs. 10% (P = 0.005), cerebral microbleeds (CMBs) 24% vs. 3.3% (P = 0.008), white matter hyperintensities 17% vs. 6.7% (P = 0.182), and lacunes 2.1% vs. 0% (P = 1.000). Presence of CMBs was independently associated with systolic blood pressure (odds ratio 1.03 [95% CI 1.00-1.05], P = 0.035).CONCLUSIONSCerebral SVD, CMBs in particular, is more common in young people with type 1 diabetes compared with healthy control subjects.Peer reviewe

Comparison of Manual Cross-Sectional Measurements and Automatic Volumetry of the Corpus Callosum, and Their Clinical Impact: A Study on Type 1 Diabetes and Healthy Controls

Background and purpose: Degenerative change of the corpus callosum might serve as a clinically useful surrogate marker for net pathological cerebral impact of diabetes type 1. We compared manual and automatic measurements of the corpus callosum, as well as differences in callosal cross-sectional area between subjects with type 1 diabetes and healthy controls. Materials and methods: This is a cross-sectional study on 188 neurologically asymptomatic participants with type 1 diabetes and 30 healthy age- and sex-matched control subjects, recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent clinical work-up and brain MRI. Callosal area was manually measured and callosal volume quantified with FreeSurfer. The measures were normalized using manually measured mid-sagittal intracranial area and volumetric intracranial volume, respectively. Results: Manual and automatic measurements correlated well (callosal area vs. volume: rho = 0.83, p <0.001 and mid-sagittal area vs. intracranial volume: rho = 0.82, p <0.001). We found no significant differences in the callosal measures between cases and controls. In type 1 diabetes, the lowest quartile of normalized callosal area was associated with higher insulin doses (p = 0.029) and reduced insulin sensitivity (p = 0.033). In addition, participants with more than two cerebral microbleeds had smaller callosal area (p = 0.002). Conclusion: Manually measured callosal area and automatically segmented are interchangeable. The association seen between callosal size with cerebral microbleeds and insulin resistance is indicative of small vessel disease pathology in diabetes type 1.Peer reviewe

Frequent physical activity is associated with reduced risk of severe diabetic retinopathy in type 1 diabetes

The aim of this study was to investigate whether leisure-time physical activity (LTPA) is associated with the development of severe diabetic retinopathy in individuals with type 1 diabetes.Peer reviewe

Frequent physical activity is associated with reduced risk of severe diabetic retinopathy in type 1 diabetes

AimsThe aim of this study was to investigate whether leisure-time physical activity (LTPA) is associated with the development of severe diabetic retinopathy in individuals with type 1 diabetes.MethodsProspective observational analysis as part of the Finnish diabetic nephropathy (FinnDiane) Study with a mean follow-up time of 10.7 years was performed. A total of 1612 individuals with type 1 diabetes were recruited, and LTPA was assessed at baseline using a validated self-report questionnaire. Severe diabetic retinopathy was defined as the initiation of laser treatment due to severe nonproliferative, proliferative retinopathy or diabetic maculopathy (identified from the Care Register for Health Care).ResultsA total of 261 patients received laser treatment during the follow-up. Higher frequency of LTPA was associated with a lower incidence of severe diabetic retinopathy (p = 0.024), a finding that remained significant after adjustment for gender, duration, age at onset of diabetes, kidney function, BMI, triglycerides and systolic blood pressure. However, when HbA1c and smoking were added to the Cox regression model the association was no more significant.ConclusionsFrequent LTPA is associated with a lower incidence of severe diabetic retinopathy during the follow-up. The total amount or the other components of LTPA (intensity or duration of a single session) were not associated with severe diabetic retinopathy.</p

CACNB2 Is a Novel Susceptibility Gene for Diabetic Retinopathy in Type 1 Diabetes

Diabetic retinopathy is a common diabetes complication that threatens the eyesight and may eventually lead to acquired visual impairment or blindness. While a substantial heritability has been reported for proliferative diabetic retinopathy (PDR), only a few genetic risk factors have been identified. Using genome-wide sib pair linkage analysis including 361 individuals with type 1 diabetes, we found suggestive evidence of linkage with PDR at chromosome 10p12 overlapping the CACNB2 gene (logarithm of odds = 2.73). Evidence of association between variants in CACNB2 and PDR was also found in association analysis of 4,005 individuals with type 1 diabetes with an odds ratio of 0.83 and P value of 8.6 x 10(-4) for rs11014284. Sequencing of CACNB2 revealed two coding variants, R476C/rs202152674 and S502L/rs137886839. CACNB2 is abundantly expressed in retinal cells and encodes the beta 2 subunit of the L-type calcium channel. Blocking vascular endothelial growth factor (VEGF) by intravitreous anti-VEGF injections is a promising clinical therapy to treat PDR. Our data show that L-type calcium channels regulate VEGF expression and secretion from retinal pigment epithelial cells (ARPE19) and support the role of CACNB2 via regulation of VEGF in the pathogenesis of PDR. However, further genetic and functional studies are necessary to consolidate the findings.Peer reviewe