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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 3, May/June 2020
AFRICA
123
Cardiovascular assessment after treatment for
retinopathy of prematurity: a comparative study between
anti-VEGF agent (aflibercept) and laser
Erman Cilsal, Emine Alyamac Sukgen
Abstract
Objective:
The aim of this study was to compare the cardiac
effects and aortic arterial indices following intravitreal afliber-
cept treatment or diode laser photocoagulation for the treat-
ment of retinopathy of prematurity (ROP) in infants.
Methods:
This single-centre, retrospective study was conduct-
ed in infants who were administered laser photocoagulation
(LPC) or intravitreal aflibercept (IVA) treatment as initial
treatment and had completed at least one year of corrected
age. The patients were evaluated in terms of aortic elastic
parameters, right and left ventricular systolic and dias-
tolic function using conventional, pulsed Doppler and tissue
Doppler imaging (TDI) echocardiographic parameters.
Results:
Fifteen infants were in the LPC group, 16 in the IVA
group, and 20 in the control group. Although there were some
statistically significant differences in terms of pulsed and
TDI echocardiographic parameters between the treatment
and control groups, these values could not clearly be adopted
as a diastolic dysfunction and myocardial performance indi-
ces were not influenced. The aortic elastic parameters were
impaired in both LPC and IVA groups compared to the
control group. Consequently, we observed only minor differ-
ences between the treatment groups, which may suggest subtle
changes due to the anti-angiogenic treatment.
Conclusion:
Although favourable and promising outcomes
were obtained with intravitreal injection of anti-vascular
endothelial growth factor agents for the treatment of ROP,
concerns have been raised about potential systemic side
effects, including potential cardiovascular side effects caused
by these agents. The small reduction in right ventricular
Doppler velocities could probably be explained by the use of
anti-angiogenic or laser treatment in infants.
Keywords:
Doppler, echocardiography, retinopathy of prematu-
rity, vascular stiffness, ultrasonography
Submitted 20/7/19, accepted 2/10/19
Published online 13/1/20
Cardiovasc J Afr
2020;
31
: 123–129
www.cvja.co.zaDOI: 10.5830/CVJA-2019-058
With the increasing number of premature births in the world,
over 15 million preterm neonates (before 37 completed weeks
of gestation) are born annually.
1
With improving survival rates
of premature babies, more than 50 000 children are blind from
retinopathy of prematurity (ROP) in many middle-income
countries.
2
The first option of treatment for ROP has switched from
cryotherapy to diode laser photocoagulation (LPC) after
randomised clinical studies showed the higher efficacy of
LPC therapy.
3
More recent development of novel therapeutic
approaches, including the use of anti-vascular endothelial
growth factor (VEGF) agents to treat ROP, has been possible
with the identification of angiogenesis regulators.
4
Anti-VEGF therapy may allow posterior retinal and foveal
avascular zones to develop better and induce vascular regression
promptly in comparison to laser treatment. It has been shown
that laser treatment requires general anaesthesia and causes
more ocular morbidity (visual field loss, myopia, astigmatism)
due to peripheral ablation. Despite the fact that it was iniated in
2007, bevacizumab (Avastin; Genentech, South San Francisco,
CA) has not been approved by the US Food and Drug
Administration (FDA) for intra-ocular use in the treatment of
ocular neovascular diseases in adults. However, the FDA did
approve it for only intravenous administration in the treatment
of colorectal, breast, lung and renal cell cancer. By contrast,
ranibizumab (Lucentis; Genentech) and aflibercept (Eylea;
Regeneron) have been approved by the FDA for intra-ocular use
in adults.
Despite the lack of studies on the safety of off-label use of
intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR)
usage for ROP treatment has increased in the past decade.
Although bevacizumab and ranibizumab have been in use for
a while in the treatment of ROP and their efficacy has been
accurately demonstrated, experience is limited for intravitreal
aflibercept (IVA) in neonates, with only a few case series reported
in the literature.
5-7
There is great debate about the use of these anti-VEGF
molecules due to their potential systemic complications. After
injection of these agents into the eye, they leak into the systemic
circulation. As a consequence, a decline in plasma VEGF
levels has been demonstrated.
8,9
Because the role of VEGF
has been proven in the normal developmental stages of the
human brain, lung, heart and kidney, possible adverse effects
of VEGF-dependent development should be closely monitored.
Previous studies attributed the mechanisms of anti-VEGF-
induced hypertension to such action as stimulating arterial
vascular remodelling.
10,11
Abnormal aortic elastic indices affect the relationship
between the pulsatile changes in arterial diameter and pressure
and play a central role as a strong predictor of cardiovascular
Mehmet Akif Ersoy, Gogus Kalp Damar Cerrahisi, Egitim
Arastirma Hastanesi, Istanbul, Turkey
Erman Cilsal, MD,
ermancilsal@gmail.comDepartment of Ophthalmology, Adana City Education and
Research Hospital, Adana, Turkey
Emine Alyamac Sukgen, MD