Study On Associations Between Retinopathy And Brain Structure And Function Alterations In Patients With Type 2 Diabetes Mellitus

Background:As a component of the nervous system,there is a close relationship between the retina and brain tissue,and both retina and brain are important target tissues of diabetes damage.However,the relationship between diabetic retinopathy and structural and functional changes of brain tissue remains unclear.Purpose:To explore the relationship between morphological changes of retina and structural and functional changes of brain in type 2 diabetes mellitus（T2DM）patients.Methods and contents:According to the preferred practice pattern（PPP）for diabetic retinopathy,subjects were divided into diabetic retinopathy group（DR group,36 cases）,diabetic retinopathy-free group（DM group,40 cases）,and a non-diabetic control group（n-DM group,48）.For all three groups of subjects,the thickness and volume information of the retinal macula and the surrounding nine sub-regions was collected as well as the thickness information of the retinal nerve fiber layer（RNFL）in each of the six quadrants around the macula and optic papilla.These information was compared among groups and the correlation analysis with the classification of retinopathy was performed.Then,using a general linear model,the retinal morphological indexes with inter-group differences or associated with DR grading were regressively analyzed as well as the gray matter volume（GMV）of the cerebral cortex,the cerebral blood flow（CBF）,and the fractional anisotropy（FA）,the axial diffusivity（AD）,radial diffusivity（RD）and mean diffusivity（MD）of the cerebral white matter skeleton respectively based on voxel level,meanwhile gender and age were used as covariabls.Gaussian Random field（GRF）were used to correct the analysis of GMV and CBF,and the diffusion tensor index analysis were processed by Threshold-free cluster enhancement（TFCE）and were corrected by FWE（family-wise Error）.The correlation brain regions were compared among groups based on ROI（region of interest）,and the functional connections based on seed points and clinical correlation analysis were further carried out.Results:（1）There was statistically significant difference in RNFL thickness in the four regions around the optic papilla（p<0.05）,including the right superior temporal region（ROTs）and inferior nasal region（RONi）,the left superior temporal region（LOTs）and the superior nasal region（LONs）.Compared with n-DM group,the RNFL was significantly thinner in the DR group.（2）DR grading was implemented in 76 patients with diabetes according to color photographs of fundus.The results were as follows:40 cases were Grade I,19 cases were Grade II,nine cases were Grade III,and eight cases were Grade IV.There is a positive correlation between the thickness of retinal RNFL in four areas around the macula and DR grading（p<0.05）,including the right superior temporal region（RMTs）,right subtemporal region（RMTi）,left temporal region（LMT）,and left superior temporal region（LMTs）.（3）Among RNFL regions:LONs was positively correlated with GMV of the right superior temporal gyrus and left lingual gyrus.RONi was positively correlated with GMV of the bilateral parahippocampal gyrus/fusiform gyrus,negatively correlated with CBF of the right middle/superior occipital gyrus,and positively correlated with AD of the right sagittal layer and right thalamic posterior radiation white matter.LOTs was positively correlated with the AD value of left fasciculus arcuatus.RMTi was negatively correlated with GMV of the right middle temporal gyrus.LMT was positively correlated with GMV of the right superior temporal gyrus,and negatively correlated with CBF of the right middle/superior frontal gyrus,and positively correlated with AD,RD and MD value of the left thalamic white matter,respectively.LMTs was negatively correlated with FA of the corpus callosum,right internal capsule,bilateral radioactive coronal,right thalamic radiation,right external capsule,bilateral superior longitudinal tract and right internal sagittal layer,and positively correlated with RD values of corpus callosum,left internal capsule,bilateral radiative coronal,bilateral external capsule,left cingulate gyrus and bilateral superior longitudinal tract.LMTs was positively correlated with MD in corpus callosum,left internal capsule,left coronal radiology,left external capsule and left superior longitudinal tract.MD was positively correlated with the corpus callosum,left internal capsule,left coronal radiology,left external capsule and left superior longitudinal tract.（4）Compared with n-DM group,GMV in bilateral parahippocampal gyrus/fusiform gyrus and right middle temporal gyrus in DR group decreased（p<0.05）,and CBF in right superior middle occipital gyrus increased（p<0.05）.AD values of local white matter in the right sagittal layer in the DM and DR groups were lower than those in the n-DM group（p=0.004 and 0.006）.（5）With RNFL thickness-related gray matter regions as seeds,the functional connectivity areas of the whole brain include primary visual information pathways,ventral visual pathways,dorsal visual pathways,and advanced visual information processing areas in the frontal,temporal,and parietal lobes.（6）Among the brain regions associated with RNFL thickness:GMV of the left lingual gyrus was positively correlated with the course of diabetes.CBF of the right middle/superior occipital gyrus was positively correlated with HBA1c.GMV of bilateral parahippocampal gyrus/fusiform gyrus was negatively correlated with the course of diabetes,fasting blood glucose and HOMA＿IR,respectively.GMV of left lingual gyrus was negatively correlated with right intraocular pressure and smoking.The AD of white matter in the right sagittal layer was negatively correlated with fasting blood glucose and instant blood glucose.GMV of the right middle temporal gyrus was negatively correlated withβ₂microglobulin.Conclusion:（1）The characteristic of retinal changes in T2DM patients was that the RNFL around the optic papilla became thinner,and the RNFL in the local area around the macular gradually became thicker as the DR grading progressd.（2）The structure and function of multiple brain regions were correlated with retinal parameters and clinical indicators,suggesting that when diabetic led to retinal neurodegeneration,the structure and function of many brain regions such as the occipital lobe also changed,and were affected by the course of diabetes,blood sugar,smoking history,intraocular pressure,etc.Retinal changes in T2DM patients can reflect the changes in brain structure and function.