Fundus photo showing ROP
Fundus photo showing large ridge and bleeding.
What is ROP and what causes it?
Retinopathy of Prematurity (ROP) is a retinal condition that affects premature infants who usually are
under a birth weight of 1,500 grams and/or have a gestational age (time at when they were born) of 32
weeks or less (normal gestational age is 38-43 weeks). The retina is the back portion of the eye which
captures light and sends signals to the brain, creating the ability to see. A tiny, highly complex system of
blood vessels supply the retina with oxygen and nutrients and these blood vessels begin to develop at 1618 weeks after conception, with full maturity occurring prior to normal birth. Premature birth disrupts the
development of the retina vasculature and leaves some of the retina without blood vessels, which causes
an anatomical and physiological change within the eye. Oxygen levels play an important role in the
normal formation of retinal blood vessels and in the development of Retinopathy of Prematurity.
When a baby is in the womb, oxygen saturation in the blood is around 80%. This relatively low oxygen
level signals the retina to grow new blood vessels and is essential for the normal development of the
vascular network. When a baby is born during the full gestational period, the lungs are fully developed,
which raises the oxygen saturation level to the high 90%. This higher oxygen level arrests blood vessel
growth within the retina, which is good since the retinal vasculature in fully mature. However, for a
premature infant, this vascular growth arrest is not a good thing. When a baby is born prematurely, often
they are put on a ventilator since the lungs are typically underdeveloped, though sometimes they will have
near normal lung function and will not need to be on a ventilator (rarely). Either way, this also raises the
oxygen saturation to near the high 90%, which also arrests retinal vascular growth. In these babies
however, the retinal vascular network is not fully developed and creates an area of avascular (no blood
vessels) tissue. A ridge is visibly noticeable at the boundary between the vascularized tissue and avascular
tissue and can be easily seen during an exam or on pictures of the retina (see above). The area of the
retina without any blood vessels still has a demand for oxygen and nutrients and releases a hormone
called Vascular Endothelial Growth Factor to stimulate the growth of blood vessels to that area. However,
because normal development was interrupted, any new blood vessels that grow after this interruption
grow without direction and are unable to cross the ridge between the vascular and avascular tissue. These
abnormal new blood vessels tend to be very fragile and often leak into either the retina, the vitreous (the
jelly like substance that fills the eye) or both. When this occurs, urgent treatment is needed.
How common is ROP and who should be screened?
Since ROP only affects premature infants, it is a fairly uncommon disease within the population of the
United States. However, of all the infants born prematurely, around 17% of them will develop ROP to
some extent. It is important to note that the lower the birth weight and/or gestational age, the higher the
risk of ROP forming. According to statistics from 2009 released by the National Eye Institute, around
16,000 premature infants develop ROP each year. Within the United States, ROP is the second leading
cause of blindness in infants, with 600 becoming blind each year. It is the standard of care to screen all
premature infants who:
1. Are less than or equal to 1,500 grams, and/or
2. Have a gestational age of less than or equal to 32 weeks, and/or
3. Have had an unstable clinical course.
What are the risk factors for the development of ROP?
The two biggest risk factors for the development of ROP are birth weight and gestational age. Though
over-all around 17% of premature infants develop ROP, around 70% of infants weighing under 750 grams
and 67% of infants with a gestational age of 26 weeks develop ROP. The graphs below show the relation
between these two risk factors and the development of ROP. Other risk factors for ROP include
intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, or patent ductus
arteriosus.
Graph showing association between birth weight and incidence of ROP
Graph showing association between gestational age and incidence of ROP
How is ROP diagnosed?
The doctor will perform a dilated exam with an indirect ophthalmoscope to determine the stage and what
part of the retina is affected by ROP. To minimize discomfort, several numbing drops will be placed in
the eye immediately before the exam. If there are any suspicious looking vessels or leakage within the
retina, the doctor will perform a Fluorescein Angiogram to determine the extent of the ROP.
Fluorescein Angiography is a test that documents blood circulation in the retina using fluorescein
dye which luminesces under blue light. Fluorescein is injected into a vein using an IV line and digital
fundus pictures are taken afterwards for around 5 minutes. These pictures show the exact location and
extent of leakage and if there are any abnormal blood vessels present. The doctor will explain these
pictures to you in more detail.
Fluorescein angiography showing abnormal blood vessels
Fluorescein angiography showing leakage at ridge
How is ROP classified?
ROP is classified along three catagories: zone, stage, and presence of plus disease.
Zone:
Stage:
Refers to the clinical appearance at the vascular/avascular junction. There are 5 stages:
•
Stage 1: A small demarcation line is present indicating the vascular/avascular junction. No new,
abnormal blood vessels are present.
•
Stage 2: A definite ridge is present. New, abnormal blood vessels may either be present or
absent.
•
Stage 3: New, abnormal blood vessels are growing from the ridge into the vitreous. Intraretinal
and/or vitreous bleeding is frequently present
•
Stage 4: The presence of partial retinal detachment.
• Stage 4a- A partial retinal detachment is present which does not involve the macula.
• Stage 4b- A partial retinal detachment is present which does involve the macula.
•
Stage 5- The presence of total retinal detachment.
• Stage 5 open- retina is not adherent to itself.
• Stage 5 closed- retina is adherent to itself.
Stage 1 ROP
Stage 2 ROP with visible ridge
Plus disease:
Plus disease describes the presence of venous dilation and arteriolar tortuosity within the retina. Plus
disease can occur at any stage and usually indicates that the ROP is increasing in severity. The presence
of plus disease is usually associated with generally poorer outcomes.
Fundus photo showing plus disease (white arrow)
Fundus photo showing large amounts of plus disease
How is ROP treated?
The best treatment is prevention. A growing body of evidence is showing that in low gestational aged
infants, the use of low oxygen levels (82-92%) during the first several weeks after birth decreases the risk
of ROP. The cut-off for what gestational age low oxygen levels should be used is still being debated,
however around 32 weeks seems to the most accepted age as of now. Some studies have reported that
increasing the oxygen saturation after the first several weeks also helps reduce the risk of ROP, though
these studies are less conclusive. The use of low oxygen saturation early after birth and higher oxygen
saturation later, and when exactly they should be used requires more study. If ROP progresses to the point
of requiring treatment, several options are available.
1. Laser therapy using Pan-Retinal Photocoagulation (PRP) is the standard treatment for ROP
and multiple studies have shown laser to be a very effective treatment for preventing the
progression of ROP. The laser is used to destroy the avascular retinal tissue, stopping it from
releasing Vascular Endothelial Growth Factor (VEGF-the hormone responsible for growing new
blood vessels). However, if a large amount of VEGF is already present in the eye, or if there is a
large amount of avascular retina, laser may not be completely effective.
2. Intravitreal injection of Avastin is used in patients who are non-responsive to laser treatment
alone. Avastin is a medication that irreversibly binds with Vascular Endothelial Growth Factor
(VEGF), preventing it from signaling the growth of new blood vessels. Studies have shown it to
be very effective, however since the cells that produce VEGF are not destroyed with this
treatment, VEGF is continuously produced by the eye. More than one injections may be
necessary to reduce the amount of VEGF in the eye to normal levels.
3. Pars Plana Vitrectomy is used to remove the vitreous from the eye, completely eliminating all
the VEGF in the eye. Vitreous hemorrhage and fibrovascular membranes pulling on the retina
causing a tractional retinal detachment are also removed during the surgery. Pars Plana
Vitrectomy is the only treatment for infants with stage 4 or stage 5 (retinal detachment is present)
ROP.
Fundus photo showing PRP spots (top of picture)
Intravitreal injection of Avastin