| China is a country with a large population of diabetes.According to the data released by the International Diabetes Federation in 2021,the number of diabetes patients in China ranks first in the world(about 140 million).Diabetic retinopathy(DR)is a disorder of the neurovascular unit caused by chronic hyperglycemia and is one of the major microvascular complications of diabetes.Low vision and blindness caused by DR pose a great challenge to the prevention and control of diabetes and DR in China.According to statistics,diabetic retinopathy is present in an average of 1 in 3 diabetic patients.It is well known that long-term chronic hyperglycemia leads to visible retinal vascular disease,but more importantly,it has led to invisible retinal neuronal damage and changes in microvascular structures before the onset of clinically visible retinopathy,both of which together lead to vision loss and visual impairment in diabetic patients.Recognizing the changes in neurological and vascular structures in early DR and identifying clinically meaningful biomarkers can help us gain a better understanding of the pathogenesis of DR and improve the ability to screen for DR.Neurodegenerative changes in DR are an important component of DR,including increased apoptosis,progressive neuronal loss,altered expression of glial fibrillary acidic protein(GFAP)in astrocytes and müller cells,and activation of microglia.When these occur simultaneously,it represents the onset of visual impairment.Clinical observations and studies have found that abnormalities in the electroretinogram(ERG)are detected long before the appearance of retinal vasculopathy,including prolonged implicit time,decreased amplitude,and decreased oscillatory potential.A similar alteration was seen in the multifocal electroretinogram(mf ERG),which is a simpler procedure than the ERG.Along with the ERG abnormalities,there is also a decrease in perception,as evidenced by decreased color vision,decreased contrast sensitivity,and decreased retinal sensitivity during microperimetry examinations.Microperimetry is a testing technique to detect retinal function in the macula,which can objectively observe the changes in the stability of fixation in diabetic patients.In addition,microperimetry can detect and pinpoint abnormalities in focal retinal sensitivity in the posterior pole and quantify them.Functional changes in the retina eventually lead to structural abnormalities in the retina.The retinal nerve fiber layer is the location of ganglion cell axons,and hyperglycemia causes apoptosis and a decrease in the number of neurons,resulting in a decrease in the total number of ganglion cells in the inner retina and a decrease in the number of axons.By using optical coherence tomography(OCT),we can observe that the above abnormalities in the posterior pole of the retina as a decrease in the thickness of the ganglion cell layer(GCL)and in the optic nerve as a decrease in the peripapillary retinal nerve fiber layer(p-RNFL).At the same time,changes in retinal microcirculation may also occur.Fundus fluorescein angiograph(FFA)can observe retinal vascular abnormalities,including microaneurysms,hemorrhages,exudates,intraretinal microvascular abnormality(IRMA)and retinal neovascularization.The discomfort and risk of severe allergic reactions associated with the invasive operation of FFA limit its use in clinical practice.Optical coherence tomography angiography(OCTA)is a blood flow detection technique based on OCT developed in the era of rapid development of fundus imaging technology in recent years.OCTA can non-invasively detect the movement of erythrocytes in the retinal vasculature and obtain two-dimensional and three-dimensional images of the retinal and choroid in the fundus through a special computer algorithm that calculates the difference between the anterior and posterior movements of the erythrocytes.This study will explore the pathogenesis of early DR by observing the structural and functional changes and their relationship in type 2 diabetic patients.The content of the first part is to observe the changes and relationship between microperimetry and OCT,OCTA in patients without significant diabetes retinopathy(no DR,NDR).The second part is to observe the changes and relationships between parameters of mf ERG and OCTA in patients with early DR.Part One Changes and correlation between optical coherence tomography angiography and microperimetry in diabetes without diabetic retinopathyObjectives:In this study,we aimed to analyze the changes in optical coherence tomography(OCT),optical coherence tomographic angiography(OCTA)and microperimetry in diabetic patients without diabetic retinopathy(NDR)and to explore the correlation between structural and functional indicators.Methods:A total of 71 cases(100 eyes)were enrolled in this cross-sectional observational study,with 34 cases(51 eyes)in the NDR group and 37 cases(49 eyes)in the control group.All patients underwent a comprehensive ophthalmic examination.Retinal sensitivity in posterior pole was measured by microperimetry.The peripapillary retinal nerve fibre layer(p-RNFL)thickness,macular retinal thickness,and retinal volume were measured by OCT.The vascular density(VD)and perfusion density(PD)of the radial peripapillary capillary plexus(RPCP),the superficial capillary plexus(SCP)and the deep capillary plexus(DCP)in the macular(6 mm×6mm),and foveal avascular zone(FAZ)area,the FAZ perimeter,and FAZ circularity in the macular of the SCP(3 mm×3 mm)were measured by OCTA.The RPCP was divided into four regions:superior(S),temporal(T),nasal(N)and inferior(I).The macular area was divided into nine sectors based on the early treatment diabetic retinopathy study(ETDRS)chart.The above-mentioned regional parameters were quantified and the correlation between retinal sensitivity and the parameters of OCT and OCTA was analyzed.Results:1.The mean retinal sensitivity was lower in the NDR group than in the control group for all sectors(all P<0.001).2.Compared with controls,the NDR group showed thinner p-RNFL in the T sector(76.24±14.29 mm vs.85.47±19.66 mm,P=0.035).The NDR group had a thinner retina in the N2 sector(304.55±16.07 mm vs.312.02±12.30 mm,P=0.010).The PD of DCP was lower in the N2、N1 sector in the NDR group(44.92±11.77%vs.50.27±6.37%,P=0.044;47.55±12.51%vs.50.59±9.81%,P=0.039).The frequencies of perifoveal capillary dropout,notched or punched out borders of the superficial FAZ,and loss of smooth contour were all higher in the NDR group(all P<0.05).The VD of the NDR group in each RPCP sector showed no significant statistical difference compared to the control group(P>0.05),and the PD of the RPCP-T sector decreased,and the difference was statistically significant compared to the control group(96.78±10.82%vs.101.71±15.40%,P=0.030).3.In the T2 sector,PD of SCP was positively correlated with retinal sensitivity(rho=0.262,P=0.008).In the T1 sector,VD of SCP was positively correlated with retinal sensitivity(rho=0.224,P=0.032).No correlation was found with retinal sensitivity in the remaining subdivisions(P>0.05).Conclusion:1.Decreased retinal sensitivity was observed in diabetic patients before the onset of diabetic retinopathy.2.Compared with the control group,we found the changes in vessel density or perfusion density in a certain area,whether in SCP,DCP,or RPCP in the NDR group.The degree of alteration of retinal structure and microvasculature was heterogeneous,and the reduction of retinal thickness and blood flow density in the papillomacular bundle was more pronounced.3.The average retinal sensitivity had a weak correlation with retinal vascular density in the temporal part of the macula.Part Two Alterations and correlation between optical coherence tomography angiography and multifocal electroretinogram in patients with non-proliferative diabetic retinopathyObjectives:The aim of this study was to analyze the changes in various parameters of OCTA and multifocal electroretinogram(mf ERG)in diabetic patients without diabetic retinopathy(NDR),NPDR(mainly mild to moderate NPDR)and normal controls,and to explore the correlation between function and structure.Methods:A total of 90 cases(90 eyes)were enrolled in this cross-sectional observational study,30 cases(30 eyes)in the NDR group,30cases(30 eyes)in the NPDR group and 30 cases(30 eyes)in the control group.All patients underwent a full ophthalmic examination.The foveal avascular zone(FAZ)area,the FAZ perimeter and the FAZ circularity in the macula(3mm×3 mm)of the SCP,as well as the vascular density(VD)and perfusion density(PD)of the superficial capillary plexus(SCP)and the deep capillary plexus(DCP)in the macula(6 mm×6 mm)were measured by OCTA.Based on ETDRS chart it was divided into three concentric regions,M region(corresponding to 1 mm inner circular region),inner ring(corresponding to1-3 mm annular region),and outer ring(corresponding to 3-6 mm annular region).The P1 and N1 implicit time and the average amplitude of P1 and N1were recorded by mf ERG and divided into three concentric annular regions:R1,R 2～3,and R 4～5.The above parameters were quantitatively analyzed to observe the changes of retinal microvascular structure and function,and the effect of Hb A1c level on mf ERG parameters was analyzed,and the indexes of OCTA and mf ERG were correlated.Results:1.The FAZ area,perimeter and circularity increased with increasing degree of DR.Among them,FAZ perimeter and circularity increased in the NPDR group compared with the NDR group,and the difference was statistically significant(2.72±0.54 mm vs.2.67±0.54 mm,P=0.049;0.58±0.96mm vs.0.62±0.97 mm,P=0.032).The inner ring of VD in the SCP decreased in the NPDR group compared with the control group,and the difference was statistically significant(9.10±1.77%vs.11.33±3.31%,P=0.024).The inner and outer rings of VD in the DCP in the NPDR group had lower values compared to the control group,respectively,and the differences were statistically significant(9.92±1.77%vs.11.53±1.67%,P=0.001;8.38±1.64%vs.9.74±1.89%,P=0.030).In terms of the inner ring of PD in the DCP,the NPDR group showed reduced values compared to the NDR and control groups,respectively,and the differences were statistically significant(43.07±10.26%vs.47.94±9.13%,P=0.000;43.07±10.26%vs.57.19±11.12%,P=0.027).2.In the R 4-5,P1 and N1 implicit time delayed in the NPDR group compared to the control group(44.74±1.57 ms vs.41.94±3.47 ms,P=0.001;26.20±1.51 ms vs.24.00±3.58 ms,P=0.027).The P1 amplitude density reduced in the NPDR and NDR groups compared to the control group,respectively,with statistically significant differences(14.08±3.99 n V/deg~2 vs.19.83±5.81 n V/deg~2,P=0.002;16.28±4.78 n V/deg~2 vs.19.83±5.81 n V/deg~2,P=0.034).3.The decrease of VD in the SCP of the NDR group was correlated with the prolongation of P1 implicit time,but not with the amplitude of P1 wave.Among them,the inner ring of VD showed a weak negative correlation with the P1 implicit time of R 2-3(rho=-0.214,P=0.035).The outer ring of VD showed a moderate negative correlation with the P1 implicit time of R 4-5(rho=-0.681,P=0.020).The decrease of VD and PD in the DCP of NDR group was correlated with the prolongation of P1 implicit time and the decrease of P1 amplitude.In the NDR group,the VD and PD of the inner ring of the DCP were negatively correlated with the P1 implicit time of the R 2-3(rho=-0.237,P=0.021;rho=-0.184,P=0.012),and positively correlated with the P1amplitude(rho=0.245,P=0.019;rho=0.223,P=0.023).The outer ring of VD in the DCP showed a weak negative correlation with the P1 implicit time in the R 4-5(rho=-0.219,P=0.021).4.There was no significant correlation between Hb A1c levels and implicit time or amplitudes density of P1 wave.Conclusions:1.As the severity of DR worsens,VD and PD in the macular area gradually decrease.The FAZ perimeter and circularity may be predictors of the severity of DR disease.2.P1、N1 implicit time and P1 amplitude density are more sensitive to reflect retinal functional changes than N1 amplitude density.3.Hyperglycemia-induced decrease in vascular density is morphologically associated with retinal dysfunction and neurodegeneration. |
