Hussain Ahmad Khaqan, et al
occlusion which results in severe irreversible vision
loss.
Bevacizumab for the treatment of edema caused by
diabetes mellitus, RVO and wet AMD.
The WESDR (Wisconsin Epidemiologic Study of
Diabetic Retinopathy) found that there are 26%
chances of developing DME after 14 years in type I
diabetes, whereas Diabetes Control and Complication
Trial (DCCT) reported that 27% of type I diabetics
develop DME after 9 years4. Type II diabetes in older
patients is associated with higher incidence of macular
edema5. Retinal Ischemia promotes VEGF production,
which in turns mediates the development of
neovascularization in diabetic retinopathy and may
lead to severe irreversible vision loss.
MATERIAL AND METHODS
A prospective, comparative interventional study was
conducted in the Ophthalmology department, Unit II
of Lahore General Hospital, Lahore from July 2018 to
June 2019. Institutional Review Board approval was
obtained and study followed tennets of declaration of
Helsinki. Informed consent was obtained from the
patients. All patients with resistant, center involving
macular edema due to diabetes; retinal vein occlusion
and wet age related macular degeneration were
recruited in this study. Patients with only eye,
uncontrolled diabetes, uncontrolled hypertension,
advanced cataract, uncontrolled glaucoma, epiretinal
membrane (ERM) or vitreo macular traction and prior
intervention with laser and intravitreal injection were
excluded from the study.
The basic problem in wet age related macular
degeneration (AMD) leading to 1.6% of blindness of
American population is abnormal neovascularization
and vascular permeability. Positive regulators like
vascular endothelial growth factor A (VEGF-A),
transforming growth factor α and β (TGF α and β),
fibroblast growth factor, hepatocyte growth factor,
connective tissue growth factor and interleukins; and
negative regulators: pigment epithelium-derived factor
(PEDF), thrombostatin, angiostatin and endostatins
play an important role in angiogenesis6. Intraocular
VEGF is reduced by the anti-VEGF agents
administered in the eyes of patients, which reduces the
vascular permeability and stops vascular leakage7.
Complete baseline ocular examination was
performed at presentation including best corrected
visual acuity (BCVA), anterior segment examination,
posterior segment examination and indirect
ophthalmoscopy, intra-ocular pressure assessment,
OCT and FFA (optical coherence tomogram and
fundus fluorescein angiography respectively). BCVA
was performed using Snellen’s visual acuity chart and
also using Log MAR scale. The OCT was performed
using Cirrus 5000 (Zeiss, Dublin, CA). Thickness of
central retina was measured in a 3 mm circle centered
on point of fixation. Central 1 mm zone was taken as
central macular thickness (CMT).
Ranibizumab was the first approved anti-VEGF
agent that revolutionized DME treatment8. Recently,
newer anti-VEGF (vascular endothelial growth factor)
drug, aflibercept (Eyelea®, Bayer Healthcare,
Germany), approved by Food and
Drug
Administration (FDA), has shown good treatment
outcomes in patients with macular edema secondary
to CRVO7. Eylea (Aflibercept) is approved therapy for
macular edema caused by Age related macular
degeneration, diabetes and retinal vein occlusion8.
All the patients that fulfilled the inclusion and
exclusion criteria were assigned to one of the two
different treatment groups randomly: 1.25 mg
(0.05 ml) of Ziv-aflibercept (ZALTRAP; Regeneron
Pharmaceuticals Inc) (IVZ group) and 1.25 mg
(0.05 ml) of Bevacizumab (Avastin; Genentech Inc,
South San Francisco, CA) (IVB group).
Randomization was performed using random number
table. Participants and the investigators were masked
of the study groups. Surgeons other than the study
investigators performed all the interventions.
Ziv-aflibercept (Zaltrap; Regeneron, New York,
USA) is pharmacologically similar to aflibercept, and
the mechanism of action is also similar to Aflibercept
i.e. it acts on all VEGF subtypes as well as placental
growth factor. It is approved by FDA for the treatment
of colon cancer, and is available at pharmacies much
cheaper than aflibercept particularly for ocular use9.
Toxicity to RPE (retinal pigment epithelial cells) has
never been studied in previous studies by using
approved cancer protein, ziv-aflibercept10.
After taking aseptic measures, each eye received
intravitreal injection of 0.05 ml of filtered ziv-
aflibercept (1.25 mg) or 0.05 ml of fresh filtered
Bevacizumab in the operation theater. 30-guage
tuberculin syringes were used to deliver the injection
under topical anesthesia. All eyes underwent slit-lamp
The aim of our study was to compare the efficacy
and safety of intravitreal ziv-aflibercept with that of
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Pakistan Journal of Ophthalmology, 2020, Vol. 36 (3): 205-210