Preliminary Study On The Safety Of Anti-VEGF Treatment For Diabetic Macular Edema

Purpose To observe the effects on retinal ischemia and neural retina in diabetic macular edema(DME)via the optical coherence tomography angiography(OCTA)and spectral domain optical coherence tomography(SD-OCT)before and after the treatment with anti-vascular endothelial growth factor(VEGF).Methods(1)Patients tested by OCTA and fundus fluorescein angiography(FFA)were collected in the same day.To compare whether the FAZ had difference between the two methods in the normal group(49 eyes)and DME group(n = 36).Two ophthalmologists measured the FAZ in FFA and OCTA.The superficial layer and deep layer in OCTA included 3mm × 3mm and 6mm × 6mm range.Use one-way ANOVA to compare differences between two ophthalmologists,and differences between normal group and DME group.Within-group correlation coefficient ICC and Blant-Altman image were used to compare the differences between and within the two ophthalmologists and two methods.(2)9 patients with DME were collected and compared with OCTA before and after anti-VEGF treatment,and the changes of the area and density of FAZ in superficial and deep layers were observed before and after treatment for one hour,one week and one month.Paired t-test was used to compare the changes before and after treatment.(3)To observe the thickness of retinal nerve fiber layer(RNFL),ganglion cell layer(GCL),inner plexiform layer(IPL)and inner nuclear layer(INL)before and after treatment of anti-VEGF for 3 months,6 months,12 months via SD-OCT.The macular was divided into 9 regions according to ETDRS.To compared the changes of retina thickness before and after the treatment on each region of each layer.Use paired t-test to compare the difference before and after the treatment.The variance analysis of repeated measurement data compared the control group and the treatment group before and after treatment.Pearson correlation was analyzed the correlation between the changes of retinal thickness and visual acuity.P<0.05 indicated that the difference was statistically significant.ICC>0.75 showed the reliability was good.0.4≤ICC≤0.75 showed the reliability was general.ICC < 0.4 showed the reliability was low.Results(1)There was no significant difference in the FAZ area measured by the same method in different ophthalmologists(P>0.05),and the FAZ area in FFA and OCTA in the area of 3mm×3mm had good consistency between different ophthalmologists(ICC>0.9).The consistency of the FAZ area between the OCTA 3mm×3mm in superficial layer and FFA was better by the same ophthalmologist(ICC>0.9).The FAZ had general consistency between OCTA and FFA(ICC = 0.4).The consistency of the FAZ area between the OCTA 3mm×3mm in superficial layer and FFA was the best(ICC>0.9).The FAZ in the deep layer in the DME group was significantly larger than that in the normal group(P<0.05).(2)The area and blood flow density of the FAZ had no significant change before and after anti-VEGF therapy in DME wherever in the superficial and deep layers of the retina on OCTA 3mm×3mm and 6mm × 6mm(P>0.05).(3)After anti-VEGF treatment,the visual acuity in DME increased significantly after one year,with an average of 9 letters(ETDRs)(P<0.05).In analysis within the groups,the center macular INL retinal thickness decreased by 21.55±32.10 μm in DME treated group after one year within anti-VEGF(P<0.05).In the control group,the retinal volume and the thickness in the superior and temporal of perifovea GCL became thinner(P<0.05).The analysis between the groups showed that the center macular GCL was thicker than the control group after one-year anti-VEGF therapy(P=0.020).The GCL thickness in the center macular was thinner than that of the control group after treatment(P=0.006).The global analysis results further confirmed that,because of the difference of the groups,the thickness of GCL in the center macular and inferior parafovea were significantly different from that in the control group(P<0.05).In the treatment group,the thickness of GCL in the center macular was always thicker than that in the control group(P=0.017),and the thickness of the GCL in the inferior parafovea decreased faster than that of the control group(P=0.009).Correlation analysis showed that there was no significant correlation between the changes of GCL in the inferior parafovea and that of visual acuity before and after anti-VEGF treatment(P>0.05).Conclusions The consistency of the FAZ area between the OCTA 3mm×3mm in superficial layer and FFA was the best and the FAZ in the deep layer in the DME group was significantly larger than that in the normal group.There was significant change of macular ischemia in DME.FAZ had no obvious ischemic change in DME after anti-VEGF treatment.There was no significant correlation between the changes of GCL in the inferior parafovea and the improvement of visual acuity before and after one-year anti-VEGF treatment.The decline in the thickness of retinal tissue may be edema.Although long-term Anti-VEGF treatment decreased the thickness of neural retina,it had no adverse effects on the function of the retina.