DME is mainly caused by increased retinal vascular permeability leading to the accumulation of fluid in the retina with subsequent increase in its thickness. These events are associated with disruption of the blood retinal barrier and increased production of VEGF [13,14]. Several randomized clinical trials have demonstrated the efficacy of VEGF inhibitors (anti-VEGF) in the treatment of DME with improvement in visual acuity and a reduction in central macular thickness (CMT) [4, 5, 15, 16].
Intravitreal injection of ziv-aflibercept has been used in multiple chorioretinal conditions with great success especially in the developing countries [17-20]. In the present study, we investigated the safety and the efficacy of intravitreal injection of 1.25 mg of ziv- aflibercept in 59 eyes with diabetic macular edema resistant to previous ranibizumab injection.
No cases of uveitis or endophthalmitis were found in our study indicating high safety profile of the new drug. However, a previous study reported 0.03–0.05% incidence of endophthalmitis after injection of bevacizumab, ranibizumab and aflibercept .
Among the 59 eyes that received intravitreal injection of ziv-aflibercept in the present study, no cases of glaucoma or ocular hypertension were reported. In contrast, previous studies have reported increased IOP in 6.25–33% of eyes with glaucoma or ocular hypertension and in 1.6–7.1% of non-glaucomatous eyes following anti-
The present study found marked functional and anatomical improvements after six months of follow up, with significant improvement in BCVA and marked reduction in CMT.
In agreement with our study, two randomized
, controlled trials have found the new drug to be effective. Intravitreal ziv-aflibercept (IVZ) and intravitreal bevacizumab (IVB) treatments were compared in 123 eyes with DME. Patients were randomized to one of three loading doses of 1.25 mg IVZ, 2.5 mg IVZ or 1.25 mg IVB administered by injection. At 12 weeks both doses of ziv-aflibercept achieved similar results with greater visual improvement than IVB . After 12 weeks, IVB was injected every 4 weeks, whereas both IVZ groups were injected every 8 weeks through 1 year, after which BCVA outcomes were better in patients with IVZ than in those with IVB treatment .
Other studies have confirmed the efficacy of ziv-aflibercept, in support of our study. The earliest of these was performed on 50 eyes, with ziv-aflibercept injections in 27 eyes and bevacizumab was injected in 23 eyes in a pro renata regimen (PRN). Both groups achieved similar improvements in mean visual acuity at three months but patients receiving ziv-aflibercept required fewer injections (2.4 vs. 3.6) [25-26].
Another 30-month prospective study assessed the efficacy of ziv-aflibercept in18 eyes with DME in a treat and extend regimen. At the 30-month examination, improvements in both mean CMT (p = 0.027) and mean visual acuity (p = 0.042) were reported .
In this study, we aimed to investigate the role of metabolic control of DM and its duration on the anatomical and functional response after a switch to ziv-aflibercept treatment. Our correlation analysis findings indicate poorer response to ziv-aflibercept in patients with poorer metabolic control, higher HbA1C or longer duration of DM. This is not in agreement with a previous study on treatment switching from bevacizumab to aflibercept, which found no association between metabolic control or duration of DM and response to aflibercept .
Our investigation of the possible predictors for better anatomical response to ziv-aflibercept found that the only significant predictor for this outcome was the central macular thickness three months after treatment onset. Thus, cases with lower CMT after three months showed better anatomical response after six months of ziv-aflibercept injection. In contrast, one other study reported that the baseline CMT before the treatment switch is the only significant predictor for a better anatomical response after switching to aflibercept .
The cost of the treatment procedure in the present study included the hospital costs, hospital user fees, cost of investigations such as OCT, fluorescein angiography, and cost of the anti-VEGF drug. The mean number of injections was 3.75 ± 1.68. The costs of one dose of IVB and IVZ are similar ($50 and $30 per dose, respectively) [11, 29]. However, the cost of IVA or IVR is 20-30 times this amount . The relative affordability of IVB or IVZ may be of great benefit to the patients in the developing and low-middle-income countries where there is limited insurance coverage. In addition, a reduction in the number of hospital visits required for patients who receive IVZ may reduce further costs.
A limitation of this study is the small sample with short duration of follow up. In further research, a larger number of patients needs to be evaluated with a longer follow up period to assess the efficacy of this new drug.