There are several known or
suspected risk factors for the development of retinopathy of
prematurity. ROP seems to be a multifactorial disease, and many
different conditions or stimuli probably contribute to the risk of
developing this problem.
GESTATIONAL AGE AND LOW BIRTH
WEIGHT
The lower an infant's birthweight and gestational age at birth, the
more likely they are to develop ROP, and the more likely it is to
require treatment. The CRYO-ROP group found that 47% of infants with a
birth weight between 1000 and 1250 grams had some degree of ROP, as
compared with 90% of infants with a birthweight less than 750 grams.
The percentage of neonates with stage 3 ROP was 8% for the 1000-1250
gram group and 37% for the <750 gram group. A similar pattern was
seen for gestational age, with ROP occurring in 83% of infants born at
less than 28 weeks gestation and in 30% of infants born at more than
31 weeks gestation.
SUPPLEMENTAL OXYGEN
In the ROP epidemic of the 1950's, oxygen was shown to be a major
cause for the development of the disease. It was discovered that
infants on higher levels of supplemental oxygen were more likely to
have ROP, but infants on lower levels of oxygen were more likely to
die or have systemic complications of low oxygen. As arterial blood
oxygen monitoring became available, it was possible to monitor the
blood oxygen levels more precisely. With today's trancutaneous blood
oxygen monitoring, the use of oxygen can be very carefully titrated to
minimize the risk of ROP while avoiding the systemic complications of
having too little oxygen. Ironically, with the increasing skill and
technology available in NICUs, we are seeing an increase in ROP, since
more tiny babies are surviving that would have otherwise have died.
Although supplemental oxygen is a significant risk factor for ROP, the
careful control of oxygen levels in modern NICUs probably reduces this
risk as low as possible without compromising the infant's medical
status.
VITAMIN E DEFICIENCY
Because of its antioxidant properties, vitamin E has been evaluated as
a possible treatment or prophylaxis for ROP. Several controlled
clinical trials have been performed, but the results are difficult to
interpret. In 1986, the Institute of Medicine published a report in
which they stated that there was no conclusive evidence of either
benefit or harm from vitamin E administration. They did feel, however,
that there was enough evidence to support treatment for vitamin E
deficiency in premature infants.
RACE
There are some racial differences in the risk for developing ROP. In
the CRYO-ROP study, black infants were found to be less likely to
develop ROP and less likely to go on to threshold ROP than white
infants. Other racial groups appeared to have a similar risk of ROP as
compared with white infants.
My personal experience has been that hispanic infants tend to have a
slower course of ROP than white or black infants. While most infants
with ROP have gradually increasing retinopathy with regression over a
matter of 4-6 weeks, hispanic infants may have persistent stage 2 ROP
for 2-3 months before significant regression occurs.
INDOMETHACIN
Patent ductus arteriosus is the abnormal persistence of a small fetal
blood vessel leading from the pulmonary artery to the aorta that
normally closes spontaneously shortly after birth. The initial
treatment of this disorder is with indomethacin, a non- steroidal
anti-inflammatory agent similar to ibuprofen. One retrospective study
has shown that treatment with indomethacin is associated with an
increased risk of severe ROP, while another study was unable to
demonstrate a similar association.
SURFACTANT
The use of calf lung surfactant in the treatment of neonatal
respiratory distress syndrome has been a dramatic advance in the care
of premature infants. Surfactant therapy not only reduces mortality,
but also decreases the incidence of a chronic lung disease known as
bronchopulmonary dysplasia, or BPD. A retrospective study by Repka et
al in 1992 showed that surfactant treatment is associated with a
decreased risk of ROP (64% vs. 85% for any ROP; 3.4% vs. 10% for
threshold ROP) independent of birth weight or gestational age. This
effect is probably a result of the markedly improved pulmonary and
nutritional status in patients treated with surfactant rather than a
direct effect of the surfactant on the ROP process.
LIGHT LEVELS
The amount of ambient light reaching the premature eye may have an
effect upon the development of ROP. There are some theoretical reasons
to suspect that bright light may induce or worsen ROP. Many NICUs now
cover their isolettes or cribs with blankets or have less intense
lighting systems in an attempt to reduce the light exposure for their
infants. This has been suggested as a possible way to lower the risk
for ROP, and is presently the subject of a controlled clinical trial.
There has been some controversy recently concerning light as a risk
factor for retinopathy. PARADE magazine recently ran a
"scare" article about the dangers of fluorescent lights for
premature babies' eyes. Much of this controversy has been generated by
H. Peter Aleff, the father of a child who is blind because of ROP. His
"research" is summarized on a web page entitled Prevent
Blindness in Premature Babies The information at this site sounds
very scientific because of the numbers of articles from medical and
scientific journals that are cited as references. However, many of
these articles are misquoted or taken out of context, and very few of
the conclusions that he draws are valid. Fluorescent light is
certainly not the only or even the primary cause of ROP, since several
other unrelated risk factors have been strongly associated with the
disease. I also strongly disagree with Mr. Aleff's allegation that
NICU nurses and doctors know that lights cause ROP but don't care
enough about their patients to protect them. Hopefully, this fanatic
and unscientific approach will not detract from the serious research
being done in this area.
OTHER POTENTIAL RISK FACTORS
Many other possible risk factors for the development of ROP have been
postulated, including:
-
Elevated blood carbon
dioxide levels
-
Anemia
-
Blood transfusions
-
Intraventricular hemorrhage
-
Respiratory distress
syndrome
-
Chronic hypoxia in utero
-
Multiple spells of apnea or
bradycardia
-
Mechanical ventilation
-
Seizures
These factors may have a direct
effect on the risk of ROP, or they may simply be indicators of
smaller, "sicker" infants who are more likely to develop
many of the complications of prematurity, including retinopathy. More
study will be needed to further delineate the actual independent risk
potential for each of these factors.
The incidence of ROP appears to be independent of whether the patient
is male or female, and there is no difference in the incidence of ROP
for the right eye versus the left eye. It also does not appear to
matter whether the infant is a product of a single or multiple birth.
We have traditionally thought of
ROP as a disorder caused by exposure of premature infants to noxious
stimuli encountered after birth. However, we are learning that some of
the factors that precipitate ROP are not within our control, and may
occur before birth. Chronic hypoxia in utero and intrauterine growth
retardation are two prenatal conditions that seem to be related to the
development of ROP. Infants have been seen with full blown threshold
ROP within a day or two after birth, implying that the retinopathy was
already well under way prior to birth. It is suspected that as many as
one third of cases of ROP are caused by prenatal rather than postnatal
conditions.
The Country Hills Eye Center Home Page
Dr. Scott C. Richards Main Page
For information regarding the
Country Hills Eye Center phyician
specializing in retinal and diabetic eye diseases
www.countryhillseyecenter.eyemd.org
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