Effects Of Ocular Surface Caused By Intravitreal Injection Of Ranibizumab In Patients With Diabetes

Objective 1 To clinically observe the effect of repeated intravitreal ranibizumab injection on ocular surface and conjunctival sac flora in patients with diabetic retinopathy(DR).2 Animal experiments were conducted to explore the effect of ranibizumab in different modes on corneal neovascularization(CNV)in diabetic rats.Methods 1 55 patients(55 eyes)diagnosed with retinal macular edema were enrolled from the Affiliated Hospital of North China University of Technology between September 2020 to September 2021.they received more than 3 intravitreal injections of ranibizumab,including DR group and non-DR group.Some ophthalmological examination,including best corrected visual acuity(BCVA),tear break-up(TBUT),Ocular Surface Disease Index(OSDI)questionnaire,fluorescein staining(FL),intraocular pressure(IOP)and Schirmer I test(SIt)were detected 1 day before the first injection,1 day after the first injection and 7 days after the third injections.Besides,the bacterial culture and drug sensitivity of the conjunctival sac were performed 3 days before the first and 3 injections.2 58 healthy male SD rats,including 48 rats intraperitoneal injected with one-time Streptozotocin(STZ)to induce diabetes,were fed for 1 month.All rats were sutured to establish CNV.Excluding rats with complications,40 rats were randomly divided into 5groups,8 in each group,Group A: non-diabetic rats received saline 4 times a day,Group B: diabetic rats received saline 4 times a day,Group C: diabetic rats received subconjunctivally injection 0.05 m L(0.5mg)of ranibizumab,group D: diabetic rats received instillation of 1.0% ranibizumab 4 times a day,group E : diabetic rats received intravitreal injection 0.02 m L(0.2mg)of ranibizumab.The corneal and the area of??CNV were observed on the 4th,7th and 14 th days after the model was established.The rats were sacrificed in order to get the specimen 14 days later.All rats need to be observed the morphology of cornea by HE staining,and measured VEGF-A and TNF-a expression by immunohistochemistry.Results 1 There was no significant difference in gender and age between the two groups(P>0.05).Before injection,DR group have shorter TBUT and higher BCVA than those in the non-DR group(P<0.05).The first day after 1injection: the BCVA,IOP,OSDI and FL scores of the two groups were significantly higher than those before the injection,the TBUT became shorter(P<0.05).The OSDI score and TBUT were lower than those in the control group(P<0.05).7 days after 3 injections,Compared with those before the injection,the batter BCVA and shorter TBUT was significant in 2 groups(P<0.05).the DR group had less improvement in BCVA and shorter TBUT(P<0.05).Moreover,the result showed that the positive rate of bacterial culture in the conjunctival sac in the DR group was higher than that in non-DR group after repeated intravitreal injection(P<0.05).2 There was a statistically significant difference in the CNV area of ??each group(P<0.05).the use of ranibizumab by conjunctival injection and local instillation could reduce the area of ??CNV compared to the other 3 groups during the observation period(P<0.05).the modes of conjunctival injection was more effective in controlling CNV than local instillation early(P<0.05).After 14 days,the diabetes rats had less CNV area than the normal group(P<0.05).rats received intravitreal ranibizumab injection could not reduce its area of ??CNV(P>0.05).the CNV in each group was mainly concentrated in the superficial stromal layer of the cornea,and the CNV in groups C and D was less than that in groups A,B,and E.VEGF-A and TNF-a were expressed in all layers of the cornea in each group,and the expression levels of VEGF-A and TNF-a in groups C and D were lower than those in groups A,B,and E(P<0.05).Conclusion 1 Intravitreal ranibizumab injection can aggravate the symptoms and signs of dry eye in diabetic patients 1day after the first of injection,and the symptoms are relieved after 7 days,but the tear film was still unstable,and there is separation of symptoms and signs.Repeated intravitreal injection of ranibizumab can change the conjunctival sac flora in diabetic patients.2 instillation and subconjunctival injection of ranibizumab can effectively control CNV.Besides,It canont control CNV in diabetic rats by intravitreal ranibizumab injection.Figure 8;Table 17;Reference 155...