First Author: N.Wadhwa INDIA
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Anti-VEGF agents are mainstay of treatment in patients with DME, aflibercept being the most recent addition which has been extensively studied and proven superior to other anti-VEGF agents. In this study, we evaluated the long-term efficacy and safety of off-label use of intravitreal Ziv-aflibercept (IVZ), a similar molecule as aflibercept in patients suffering from DME and compared the results with off-label use of intravitreal bevacizumab (IVB).
Randomised controlled prospective single centre trial
After assigning eyes randomly to one of the groups, all the patients were given initial loading dose of three monthly injections (1.25 mgm /0.05 ml) followed by pro re nata treatment. Patients with any history of laser photocoagulation or intraocular anti-VEGF/steroid injection, proven vitreo-macular traction (VMT)/ERM on the macula, evidence of macular ischaemia (FAZ > 1000 micrometers), proven glaucoma, tractional retinal detachment, visually significant cataract were excluded from the study. Treatment response was monitored with best corrected visual acuity (BCVA) and central macular thickness (CMT) measurements and patients monitored for any adverse events. Treatment was continued till CMT reduced to below 250 um and there was resolution of subretinal fluid and intraretinal cystic changes. Any change of central macular thickness of +10% was considered significant and treatment reinitiated. Laser photocoagulation treatment was offered to the patient if there was no improvement with anti-VEGF treatment (no or insignificant change with two continuous injections). The primary objective was to access the efficacy and safety of ziv-aflibercept and compare the changes in BCVA and CMT from baseline, secondary objective being number of rescue laser / intravitreal treatments required as compared to patients who received IVB.
Out of 140 eyes enrolled, 135 (n= 68 IVZ, n=67 IVB) could complete the minimum follow-up period of three months. The average follow-up period was 7.7 ± 2.15 and 7.58 ± 2.24 months respectively (p=0.715). While CMT improved by 260.44±133.11 μm in the IVZ group (p<0.001 ), the figures in the IVB group were 340.37±191.9 micrometers (p<0.001) (paired sample t-test). The mean BCVA increased by 13.2±4.6 ETDRS letters in the IVZ group and 14.08±3.8 letters in the IVB group (p=0.7). The mean number of intravitreal injections required to achieve the goal of treatment was 3.92±1.38 in the IVZ group as compared to 5.68±2.26 in the IAI group (p<0.001). Rescue laser/repeat injections were needed more frequently in the IVB group (n=13) as compared to IVZ group (n=5)(p<0.001). Most common serious adverse effects noted was cataract in both the groups (n= 10 eyes, 4 in IVZ group, 6 in IVB group). Other adverse effects noted were raised IOP in five eyes of five patients in IZI group and six eyes of five patients in IAI group which was controlled by medical treatment. One eye in each group had a single episode of mild iritis after the injection which resolved with topical treatment.
The strength of our study is the uniformity of included eyes with absence of confounding factors leading to strict inclusion/exclusion criteria, upto one year of follow up and sample size. The limitations of the study include single centre non-blind trial and usage of non standard treatment protocols. However, the study results clearly point to a role of ziv-aflibercept in the treatment of patients with diabetic macular edema as a safe and effective drug with distinct advantage of fewer treatments as compared to bevacizumab and significantly cheaper alternative to aflibercept. Future prospective studies can evaluate various protocols in treatment of DME utilising ziv-aflibercept, and establish the efficacy vis a vis other established anti-VEGF treatments.