Clinical Observation Of Anti-VEGF Drugs Treatment For Moderate And Severe Non-Proliferative Diabetic Retinopathy

Objectives:To observe the safety and efficacy of anti-VEGF(Vascular ascular Growth Factor)drugs treatment for moderate and severe non-pro liferative diabetic retinopathy(NPDR)with or without diabetic macular edema(DME).Methods:Longitudinal retrospective study.A total of 19 moderate and severe non-proliferative diabetic retinopathy patients(30 eyes)with a DRSS score(Diabetic Retinopathy Severity Scale scores)of 43 to 53 from October 2018 to February 2021 in the Department of ophthalmology,First Affiliated Hospital of Kunming Medical University were enrolled in this study.The NPDR eyes underwent three initial monthly intravitreal anti-VEGF drugs injections followed by pro re nata(3+PRN)dosing.If there were subfoveal neuro-retinal detachment(SND)or poor response to anti-VEGF drugs,we added intravitreal dexamethasone implants(Ozurdex)injection for the treatment of DME.The Best Corrected Visual Acuity(BCVA)and intraocular pressure(IOP)were collected at monthly follow-up before and 6 months after treatment.Optical Coherence Tomography(OCTA)was used to measure Central Macular Thickness(CMT),and DRSS score was performed based on fundus color photography.Image J software was used to semi-automatically measure the area of Hard Exudate(HE),and the changes of the above data before and after treatment were compared.Statistical analyses were performed by SPSS 23.0 using the repeated measurement analysis of variance for comparison the data before and after treatment,and paired t test was used for pair comparison when the difference was significant.The grade data were compared by Wilcoxon rank sum test,and P<0.05 was considered statistically significant.Results:1.To compares the changes of NPDR eyes without DME before and after treatment After anti-VEGF drugs treatment,there was no statistical difference in BCVA at monthly follow-up for 6 months after treatment compared to preoperative results(P1=0.570,P2=0.703,P3=0.489,P4=0.564,P5=0.637,P6=0.156).NPDR eyes with average CMT value of(268.60±40.50)μm before treatment,the mean CMT were(256.20±29.30)μm、(252.00±24.24)μm、(250.20±20.03)μm、(248.20±17.01)μm、(265.800±50.23)μm、(248.40±21.55)μm respectively after treatment for 6 months follow-up.While there was no statistical difference with the CMT values between the 1st to 6th month follow-up and the preoperative comparison(Pi=0.098,P2=0.114,P3=0.176,P4=0.153,Ps=0.735,P6=0.150).In terms of DRSS scores,there was no significant difference between preoperative and follow-up visits from 1 to 3 months(P1=0.180,P2=0.414,P3=0.288).On the contrary,there was a statistical difference between the preoperative and the follow-up period from 4 to 6 months(P4=0.026,P5=0.027,P6=0.048),and the proportion of the regression of the DRSS score>2 reached 54.56%.2.To compares the changes of NPDR eyes with DME before and after treatment.After 6 months of treatment,there was statistical significant difference in BCVA at monthly follow-up for 6 months compared to preoperative results(Pi=0.001,P2=0.034,P3=0.001,P4=0.024,Ps=0.001 P6=0.047).NPDR eyes with average CMT value of(354.78±78.72)μm before treatment,the mean CMT were(282.33±52.95)μm、(268.53±48.32)μm,(269.84±58.31)μm,(323.84±135.05)μm、(300.84±88.72)μm、(307.68±105.60)μm respectively after treatment for 6 months follow-up.The change of CMT value during the follow-up from the first month to the third month was statistically significant(P1<0.001,P2<0.001,P3<0.001).While there was no statistical difference with the CMT values between the 4th to 6th month follow-up and the preoperative comparison(P4=0.451,P5=0.012,P6=0.178).In terms of DRSS scores,there was statistically significant difference between preoperative and follow-up visits from 1 to 6 months(P1=0.018,P2=0.004,P3=0.001,P4<0.001,P5<0.001,P6<0.001),and the proportion of the regression of the DRSS score>2 reached 68.42%.3.To compares the changes of refractory DME eyes before and after treatment.All the 16 eyes received at least six anti-VEGF injections,and 8 eyes received anti-VEGF in combination with Ozurdex during treatment.The comparison of BCVA in monthly follow-up within 6 months after treatment with that in preoperative BCVA indicated that there were statistical differences in BCVA changes during the first,third,fourth and fifth month follow-up(Pi=0.043,P3=0.005,P4=0.024,P5=0.004).However,there was no significant difference in BCVA at the second and sixth month follow-up(P2=0.055,P6=0.055).Repeated measure analysis of variance was used to compare the changes in BCVA during the 1st to 6th month follow-up,F=0.318,P=0.900,suggesting that there was no statistically significant difference in BCVA changes during the 1st to 6th month follow-up after treatment.The mean CMT before treatment was(367.79±84.36)μm,and the mean CMT of 6 months follow-up were(292.73±49.38)pm,(273.75±46.53)pm,(274.94±58.98)μm,(338.00±141.82)μm,(311.69±93.94)μm,(319.44±110.37)μm respectively.During the first 3 months of follow-up,there was a statistically significant difference of CMT compared with preoperative CMT((P1<0.001,P2=0.001,P3=0.003).However there was no statistically significant difference of CMT from the fourth to sixth months of follow-up than that before treatment(P4=0.762,P5=0.231,P6=0.413).In terms of DRSS score,there was no statistically significant difference between preoperative and the first month follow-up(Pi=0.18),but there was statistically significant difference between preoperative and the second to sixth month follow-up(P2=0.031,P3=0.004,P4=0.001,P5=0.001,P6=0.001),and the proportion of regression of DRSS score>2 reached 62.5%.In the measurement of HE area,there were different degrees of HE in the surrounding area of the macular in 13 eyes,accounting for as high as 81.25%.Comparing the HE area in the follow-up from the second month to the sixth month with that in the first month,the differences were statistically significant(P2=0.016,P3=0.006,P4=0.002,P5=0.002,P6=0.002),and the HE area decreased distinctly after treatment.Conclusions:Patients with moderate or severe NPDR who receive early intensive anti-VEGF therapy,good baseline visual acuity was maintained in the eyes without DME.Patients with poor baseline visual acuity with DME can obtain significant visual acuity improvement,reduction of macular fovea thickness.Whatever there is DME,it was obeservated significant improvement of DRSS score,slow down the progression of DR,and even reverse the severity of DR after therapy.NPDR patients with HE in the area of the macular vascular arch tend to develop refractory DME.For refractory DME with SND or showed poor response to anti-VEGF drug,the combination of anti-VEGF drugs with Ozurdex in the treatment of DME is safe and effective,and the HE area is significantly reduced after treatment.