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Safety of Indocyanine Green Angiography During Pregnancy
A Survey of the Retina, Macula, and Vitreous Societies
Mitchell S. Fineman, MD;
Joseph I. Maguire, MD;
Steven W. Fineman, MD;
William E. Benson, MD
Arch Ophthalmol. 2001;119:353-355.
ABSTRACT
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Objectives To establish current practice patterns and assess the general knowledge
among vitreoretinal-trained physicians regarding the use of indocyanine green
(ICG) angiography during pregnancy, and to review the literature regarding
the established safety of ICG angiography in pregnant women.
Methods A survey was mailed to 1101 members of the Retina, Macula, and Vitreous
Societies.
Results Of the 520 respondents, 434 (83%) had seen at least 1 pregnant woman
who required ICG angiography or fluorescein angiography. Of these, 385 (89%)
withheld fluorescein angiography and 105 (24%) withheld ICG angiography, largely
because of fear of teratogenicity or lawsuit. Diabetic retinopathy and choroidal
neovascular membrane were the most common indications for fluorescein angiography,
and choroidal neovascular membrane and choroidal tumor were the most common
indications for ICG angiography. Only 24% thought that it was safe to use
ICG angiography in a pregnant patient, and only 5% thought it was safer than
fluorescein angiography.
Conclusions Despite the documented safety of ICG when used for retinal angiography
and the extensive experience with the use of intravenous ICG to measure hepatic
blood flow in pregnant women, the results of this survey suggest widespread
hesitation to use ICG for retinal angiography in pregnant women. Current practice
patterns regarding the use of ICG angiography in pregnant patients may be
unnecessarily restrictive.
INTRODUCTION
INDOCYANINE GREEN (ICG) is a water-soluble tricarbocyanine dye introduced
in 1957 by Fox et al1 to measure systemic blood
flow. In 1961, Caesar et al2 first reported
the use of ICG in the measurement of hepatic blood flow and hepatic function.
Since that time, it has been used intravenously for the evaluation of hepatic
function and cardiac output and, more recently, for ophthalmic angiography
and in the calculation of venous contrast transit time during cardiac ultrafast
computed tomography.3 The properties that make
indocyanine green favorable for these uses are its very high degree of hepatic
clearance, predictable volume of distribution, absence of extrahepatic uptake,
lack of enterohepatic circulation, unchanged excretion into the bile, and
high binding affinity for serum lipoproteins.
Although ICG has been used to evaluate and further the understanding
of retinal diseases that are associated with pregnancy4-5
or that occurred in pregnant patients,6 there
is little information in the ophthalmic literature regarding the safety of
its use during pregnancy. We surveyed vitreoretinal-trained physicians to
identify the current practice patterns and general knowledge regarding the
use and safety of ICG angiography in pregnant patients.
MATERIALS AND METHODS
We surveyed 1101 members of the Retina, Macula, and Vitreous Societies
to assess their experience with ICG angiography in pregnant patients. The
questionnaires requested information on the following: general use of ICG
angiography and intravenous fluorescein angiography (IVFA); experience with
pregnant patients requiring angiography; indications for ICG angiography and
IVFA; the number of studies performed; whether ICG angiography or IVFA was
withheld from a pregnant woman and, if so, the reason for this; opinions as
to which trimester was safest to perform an ICG angiogram; whether ICG was
a safe procedure to perform in a pregnant woman; and whether ICG was safer
than IVFA in pregnancy.
RESULTS
Of the 1101 physicians surveyed, 520 responded. Of these, 434 had examined
at least 1 pregnant patient who had an ocular condition necessitating either
IVFA or ICG angiography, and 270 had performed at least 1 IVFA or ICG angiography.
Three hundred eighty-five respondents had withheld IVFA from at least
1 pregnant patient. The reasons were as follows: fear of teratogenicity in
137, ability to treat without test in 96, fear of lawsuit in 118, patient
request in 30, and no reason was given in 4. One hundred five respondents
had withheld ICG angiography from at least 1 pregnant patient. The reasons
were as follows (multiple responses were possible): fear of teratogenicity
in 48, ability to treat without test in 11, fear of lawsuit in 45, and patient
request in 5.
The indications to perform IVFA in pregnancy were as follows: diabetic
retinopathy in 128, choroidal neovascular membrane in 122, uveitis in 7, preeclampsia
in 6, central serous choroidopathy in 37, tumor in 9, and vascular obstruction
in 6. The indications to perform ICG angiography in pregnancy were choroidal
neovascular membrane in 14, preeclampsia in 1, and tumor in 5.
Of the 520 respondents, 388 preferred the third trimester to perform
ICG, 12 preferred the second trimester, 2 preferred the first trimester, and
118 did not answer this question. When respondents were asked whether ICG
angiography was a safe procedure to perform in a pregnant woman, the response
was yes in 127, no in 83, and "unknown" in 310. When asked whether it was
safer to perform ICG angiography or IVFA in a pregnant woman, the response
was "IVFA" in 259, "ICG" in 24, "unknown" in 211, and no response was given
in 26.
COMMENT
Indocyanine green has a documented record of use for nonophthalmic purposes
and has been given to pregnant women without adverse effect on mother or fetus.
Before its present clinical use in ophthalmic angiography, ICG was used extensively
as a chromodiagnostic agent in the evaluation of hemodynamic changes that
occur during pregnancy. Indocyanine green clearance has been used to measure
apparent liver blood flow and cardiac output in pregnant women. In a study
by Robson and associates,7 ICG, 0.5 mg/kg of
body weight, was given intravenously to 12 women at 12 to 14, 24 to 26, and
36 to 38 weeks of pregnancy and then at 10 to 12 weeks after delivery. Intravenous
ICG, 0.5 mg/kg of body weight, has also been used in the assessment of hepatic
excretion in pregnant women afflicted with hyperemesis gravidarum.8
Evidence that ICG does not cross the placenta comes from 2 studies where
simultaneous measurements were made in the maternal and fetal blood after
intravenous administration in the mother. Rudolf and associates9
used intravenous ICG to characterize hepatic excretion function during the
course of a normal pregnancy. Intravenous boluses of ICG, 0.5 mg/kg, were
given to 168 pregnant women during all 3 trimesters of pregnancy and post
partum. No placental transfer of the dye could be detected by simultaneous
measurement of ICG in the maternal and fetal cord blood. Probst and associates10 studied the clearance and placental transfer of ICG
during labor. Eight of their 9 patients were given intravenous ICG, 5 mg/kg
of body weight. Although this dose represents many times the currently recommended
dose for ICG angiography, no ICG could be detected in fetal blood samples
that were obtained simultaneously with maternal blood or in umbilical vein
blood collected immediately after birth.
Recent improvements in digital video technology have led to increased
use of ICG for retinal angiography.11 The safety
of ICG is well established, with severe adverse effects occurring in 0.05%
or less.12-13 Despite the documented
safety of ICG when used for retinal angiography and the experience of using
intravenous ICG in pregnant women to measure hepatic blood flow, there is
still hesitation to use ICG for retinal angiography in pregnant women. Valluri
and associates4 reported the ICG angiographic
finding in 4 women with preeclampsia. However, the ICG angiography was withheld
until the postpartum period.
Both ICG and fluorescein are classified by the Food and Drug Administration
as pregnancy category C, indicating that studies have not been conducted and
therefore it is unknown whether fetal harm will result when administered to
a pregnant woman. This is important, because the results of this survey indicate
that 434 (83%) of the 520 responding vitreoretinal specialists have, during
the course of their careers, examined at least 1 pregnant patient who required
either IVFA or ICG angiography. Although the majority reported withholding
IVFA, nearly one quarter of the respondents also withheld ICG angiography.
The results support the impression that fear of teratogenic effects
in the fetus is the major reason for not performing angiography in pregnant
patients.4 However, fear of being sued was
almost as common a reason to withhold ICG angiography and IVFA. The ability
of many respondents to treat the patient without obtaining the test (25% for
IVFA and 10% for ICG angiography) raises the question of whether the test
was actually necessary.
Not surprisingly, the indications to perform ICG angiography in pregnancy
were quite different from the indications to perform IVFA. Diabetic retinopathy
and choroidal neovascular membrane were the most common indications for IVFA,
and choroidal neovascular membrane and choroidal tumor were the most common
indications for ICG angiography.
The overall safety of ICG angiography in pregnancy was unable to be
assessed by most respondents. When asked whether ICG angiography was a safe
procedure to perform in a pregnant woman, 60% of the respondents indicated
that they did not know. Only 24% indicated it was safe and only 16% believed
that it was not safe. Fifty percent of the respondents believed that IVFA
was safer than ICG angiography in the setting of pregnancy, and only 5% believed
that ICG was the safer of the two. A longer "track record" was noted by many
of the respondents as the reason to choose IVFA as the safer test.
The results of this survey suggest widespread hesitation to use ICG
for retinal angiography in pregnant women. A lack of awareness of the evidence
supporting the safety of ICG use in pregnancy for nonophthalmic indications
is the most likely explanation for these responses. Current practice patterns
regarding the use of ICG angiography in pregnant patients may be unnecessarily
restrictive.
AUTHOR INFORMATION
Accepted for publication August 5, 2000.
This study was supported in part by the Vitreoretinal Research and Education
Foundation, Philadelphia, Pa.
Corresponding author: Mitchell S. Fineman, MD, Retina Vitreous Consultants,
3501 Forbes Ave, Suite 500, Pittsburgh, PA 15213.
From Retina Vitreous Consultants, Pittsburgh, Pa (Dr M. Fineman); Retina
Service, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University,
Philadelphia, Pa (Drs Maguire and Benson); and Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, Mass (Dr S. Fineman).
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