Quantitative Study Of The Neural Structure And Microcirculation Of The Optic Disc And Macula In Early Diabetic Patients

Part1.Quantification of neural structures and microcirculation in the optic disc and macula of early diabetic patientsPurpose:To quantify the retinal neuronal structure and microcirculation changes of optic disc and macula in the early diabetic mellitus（DM）with no diabetic retinopathy（noDR）by using optical coherence tomography angiography（OCTA）,and to guide the early health management and personalized treatment of diabetic retinopathy（DR）in clinical practice.Method:The study was a cross-sectional study.A total of 52 patients（97 eyes）diagnosed with DM without diabetic retinopathy by senior ophthalmologists and endocrinologist according to the American Diabetes Association’s diagnostic criteria for diabetes mellitus from October 2020 to October 2021 at Subei People’s Hospital affiliated to Yangzhou University were included in this study（noDR group）.A total of 53 eyes of 30 healthy volunteers（control group）and 20 eyes of 30 patients with mild to moderate nonproliferative diabetic retinopathy（NPDR）（mild-moderate NPDR group）were selected as controls.Age,sex,eye category,history of hypertension,history of smoking,systolic pressure,diastolic pressure,body mass index（BMI）,total cholesterol（TC）,serum creatinine（Scr）,glomerular filtration rate（GFR）were collected for each group.The type of DM,duration of DM,and glycaemic haemoglobin A1c（HbA1c）were also collected from DM patients.All subjects underwent routine eye examination,including best-corrected visual acuity（BCVA）,intraocular pressure,fundus examination,fundus photography and OCTA.The Optovue RTVue XR OCTA instrument was used to scan the optic disc area of 4.5mm*4.5mm and the macular area of 3.0mm*3.0mm,and OCTA images were obtained.The data were quantified using the Angio Vue software system.The retinal nerve fiber layer（RNFL）thickness and vessel density（VD）of the optic disc,the neurosensory retina（NR）thickness and VD of macula and foveal avascular zone（FAZ）were analyzed.Results:（1）There were no statistical differences between the control group,noDR group and mild-moderate NPDR group in terms of gender,age,eye type,systemic indexes and BCVA.（2）RNFL thickness in the peripapillary:The peripapillary RNFL thickness in the noDR group was（111.37±10.19）μm,which was significantly thinner than that in the control group（P<0.001）.The peripapillary RNFL thickness in the mild-moderate NPDR group was（116.70 ±10.81）μm,which was significantly thicker than that in the noDR group（P=0.015）.Compared to the control group,the RNFL thickness in the nasal and inferior quadrants of peripapillary in the noDR group was thinner,and the differences were statistically significant（H=2.830,P0.014;H=4.422,P<0.001）.The RNFL thickness was thicker in all four quadrants of peripapillary in the mild-moderate NPDR group than in the corresponding area in the noDR group,with a statistically significant difference only in the inferior quadrant（H=-0.276,P=0.020）.（3）NR thickness in the macula:The NR thickness in the macula,fovea,parafovea in the noDR group was（312.61 ± 12.49）μm,[242（230-253）]μm and（321.31 ± 13.19）μm respectively,although they were all lower than the corresponding areas in the control group,but the differences were not statistically significant（P>0.05）.The macula and parafovea NR thicknesses were thicker in the mild-moderate NPDR group than in the noDR group,and the differences were all statistically significant（P=0.013;P=0.018）.（4）VD in the optic disc:The optic disc VD in the noDR group was[48.6（47.1,50.2）]%,significantly lower than that in the control group[51.0（49.1,52.1）]%（H=5.113,P<0.001）.Inside disc VD in noDR group showed no significant difference with that in the control group（F=0.531,P>0.05）,while peripapallary VD in noDR group was significantly lower than that in the control group（H=3.147,P=0.005）.No significant differences were seen in the optic disc,inside disc and peripapillary VD in the mild-moderate NPDR group compared to the noDR group（P>0.05）.（5）VD in the macula:The superficial capillary plexuses（SCP）VD in the macula,fovea and parafovea in the noDR group were all lower than those in the control group,but the difference was only statistically significant in the macula and parafovea（P<0.001;H=3.656,P=0.001）.The SCP VD in the macula,fovea and parafovea VD in mild-moderate NPDR were all lower than those in the noDR group,but the difference was only statistically significant in the macula and fovea（P=0.031;P=0.001）.The deep capillary plexuses（DCP）VD in the macula,fovea and parafovea in the noDR group were all lower than those in the control group,but the difference were only statistically significant in the parafovea（H=2.607,P=0.027）.The DCP VD in the macula,fovea and parafovea VD in mild-moderate NPDR were all lower than those in the noDR group,but the differences was only statistically significant in the macula and parafovea（H=2.938,P=0.01;H=2.814,P=0.015）.（6）FAZ:No significant differences were found in the area and circumference of the FAZ in the control,noDR and mild-moderate NPDR groups.FD-300 in the noDR group was（46.79±3.84）%,which was significantly lower than that in the control group（48.92 ±4.42）%（P=0.003）.The FD-300 in the mild-moderate NPDR group was（44.46±4.23）%,which was significantly lower than that in the noDR group（P=0.007）.Conclusion:Neurostructural and micro vascular damage to the retina in the optic disc and macula had already occurred as early as the preclinical DR,and the neurostructural change occurred first in the optic disc.Both neurostructural and microvascular changes may be important in the development of DR.Part2.Correlation between neurostructural and microvascular indicators of the optic disc and macula and systemic factors in early diabetic patientsPurpose:To analyze the correlation between the retinal neuronal structure,vessel density（VD）in the optic disc and macula region and systemic factors of diabetic mellitus（DM）patients,in order to investigate the relevant factors affecting the retinal neurovascular structure in DM patients and provide theoretical support for the study of the mechanism of diabetic neurovascular damage.Methods:This study included 72 patients（127 eyes）with DM diagnosed by ophthalmologists and endocrinologists at Subei People’s Hospital affiliated to Yangzhou University from October 2020 to October 2021,including 52 patients（97 eyes）without diabetic retinopathy（DR）and twenty patients（30 eyes）with mild or moderate non-proliferative diabetic retinopathy（NPDR）.Age,gender,eye category,history of hypertension,history of smoking,systolic pressure,diastolic pressure,body mass index（BMI）,total cholesterol（TC）,serum creatinine（Scr）,glomerular filtration rate（GFR）were collected from all participants.Type of DM,duration of DM and glycated haemoglobin A1c（HbA1c）were collected from DM.All subjects underwent routine eye examination and OCTA,including best corrected visual acuity（BCVA）,intraocular pressure,fundus examination,fundus photography and OCTA.The Optovue RTVue XR OCTA instrument was used to scan the subject’s optic disc region with 4.5mm*4.5mm and macula region with 3.0mm*3.0mm,and to obtain OCTA-related parameters,including RNFL thickness and VD in the optic disc region,NR thickness and VD in macula region.The correlation between retinal nerve fiber layer（RNFL）thickness,neurosensory retina（NR）thickness,vessel density（VD）in the optic disc and macula region and systemic factors in DM was analysed.Results:（1）Correlation analysis between systemic factors and OCTA indicators:The peripapillary RNFL thickness was mildly positively correlated with HbA1c in DM（r=0.203,P=0.022）,and peripapillary VD was mildly positively correlated with systolic pressure（r=0.23 8,P=0.007）.The macula NR thickness in DM had correlation with gender,duration of DM,smoking history,and HbA1c（r=0.332,P<0.001;r=0.239,P=0.007;r=0.185,P=0.037;r=-0.274,P=0.002）.The SCP VD in the macula had a low negative correlation with age and DM duration in DM patients（r=-0.250,P=0.005;r=-0.200,P=0.024）and the DCP VD in the macula had a low negative correlation with age and HbA1c（r=-0.175,P=0.049;r=-0.182,P=0.041）.（2）Correlation analysis of retinal neuronal structure and microcirculation:The peripapillary RNFL thickness in DM patients had a moderate positive correlation with VD in peripapillary（r=0.436,P<0.001）.The macula NR thickness was positively correlated with SCP VD in the macula（r=0.176,P=0.048）,while it was negatively correlated with DCP VD in the macula（r=-0.259,P=0.003）.（3）Correlation analysis between optic disc area indicators and macular area indicators:The peripapillary RNFL thickness was negatively correlated with DCP VD in the macula（r=-0.218,P=0.014）.The peripapillary VD was moderately positively correlated with SCP VD in the macula（r=0.354,P<0.001）and lowly correlated with NR thickness in the macula（r=0.256,P=0.004）.（4）Systemic risk factors for the occurreance of DR:The occurrence of DR in DM patients was associated with the type of DM（OR=0.049,95%CI 0.004-0.579,P=0.017）,the duration of DM（OR=1.195,95%CI 1.054-1.354,P=0.005）,history of hypertension（OR=4.782,95%CI 1.247-18.338,P=0.023）and BMI（OR=1.236,95%CI 1.017-1.501,P=0.033）.Conclusion:Age,duration of DM,HbA1c,systolic pressure,gender and history of smoking are factors influencing the neurovascular structure of the retina in patients with DM.Changes in the neurovascular structure and microvascular of the retina in DM patients may interact with each other.