What is Retinopathy of
Prematurity? Retinopathy of prematurity (ROP)
is an eye disease which results from abnormal development of the
retina (the light sensitive lining of the eye) in premature
babies. Not all premature infants develop
retinopathy of prematurity. And for many, it resolves
without treatment in early stages. But for those babies in
whom ROP progresses, treatment is necessary. It generally
occurs in both eyes, but may be worse in one eye compared to the
other. t s very rare that t occurs n one eye only. The
two critical factors for predicting which children are most likely
to develop ROP are:
- Birth weight of less than 1,500 grams (3 lbs
5 oz).
- Gestational age at birth (i.e. length of
pregnancy) of less than 32 weeks.
Although much has been written about the
association of the high oxygen requirements of these children and
the development of retinopathy of prematurity, oxygen is not the
cause of retinopathy of prematurity - prematurity is. Even
so, oxygen levels are still carefully monitored to ensure that
these infants are given only the amount of oxygen absolutely
necessary.
Infants weighing less than 1,000 grams (2 lbs 3
oz) at birth and who are born at 23 to 28 weeks gestational age
have a particularly high chance of developing retinopathy of
prematurity.
Infants are not born with retinopathy of
prematurity. They are born with immaturity of the retina
(i.e. incomplete development of the retinal blood supply).
The information 'contained in this article' is
intended to help you understand the eye, the disease, and the
treatment of ROP.
Structure and Function of the Eye
The adult eye is a sphere about 1 inch in
diameter. The wall of the eye has three layers:
- Outer fibrous layer - the sclera
- Middle vascular layer, containing blood
vessels - the choroid
- Inner nerve-containing layer - the retina
The cornea forms the front most part of
the eye. It's transparent and curved to focus incoming light
rays. The sclera, commonly called the "white of
the eye," forms an opaque and fibrous coat that protects the
eye. The conjunctiva is an extension of the inner
layer on the eyelid that forms a thin transparent membrane over
the front of the eye.
Many blood vessels and pigment (color) are
contained in the choroid. An extension from the front
section of the choroid forms the iris, or the colored part
of the eye. The center of the doughnut-shaped iris is called
the pupil. Just behind the iris is another extension
from the choroid that contains muscles and ligaments that hold the
lens in place and change its shape, from squashed for near
vision to stretched for far vision.
The eye has two segments: The anterior
segment is from the lens forward, includes the iris and is
bound by the cornea at the front. Aqueous humor, a
watery fluid, constantly flows into and out of the anterior
segment. The posterior segment lies behind the lens
and contains a gelatinous substance called vitreous humor.
Vitreous humor is formed during the eye's development and, unless
removed surgically, remains permanently in the eye.
Together, aqueous and vitreous humor give the eye sufficient
pressure, known as intraocular pressure, to keep it firm
and spherical.
The retina forms the inner coat of the
posterior segment and is comprised of two layers - a nerve-containing
layer resting on top of a pigmented layer which is
attached to the underlying choroid. The nerve containing
retina is physically attached to the pigmented retina only at the
front of the eye, just behind the lens and at the back of the eye,
at the optic nerve. When one suffers a detached
retina it is the nerve containing layer detaching from the
pigmented retina, not the entire retina. The nerve layer
contains cells - photoreceptors - that detect light rays
and pass the impulse via the optic nerve, to the brain, which
translates them into images. The central part of the retina
- the macula - is responsible for central vision and is
directly behind the lens. At the macula's center is the fovea,
which is the area of sharpest vision. The retina outside the
macula is known as the peripheral retina which allows
peripheral vision.
There are two kinds of photoreceptors in the
retina - rods and cones. Rods are much more sensitive
to light and so allow night vision, which is colorless vision and
provides only general outlines and objects. Rods predominate
in the periphery of the retina, but are completely absent from the
fovea. Cones, on the other hand, detect color and
allow sharp vision. The cones are most concentrated in the
fovea, but decrease in concentration in areas away from the
macula.
The eyeball is held in place in the orbit of the
skull by six muscles. Each muscle moves the eye in one
primary direction. A given eye movement may involve more
than one of the muscles.
Development of the Eye
The eye begins to form in the embryo's fourth
week of development. The last 12 weeks of a full-term
delivery, from 28-40 weeks gestation, are particularly active for
the growth of the eye of the fetus. At term a baby's eye is
almost half of the adult size and continues to develop over the
next two years.
The anterior segment, or front of the eye is
almost full size at term so most of the continued growth takes
place in the posterior segment, just behind the lens in the
periphery of the retina. Retinal surface area doubles
between 6 months (26 weeks) of gestation and full term with a
further 50% increase over the next two years.
The retina (the light-sensitive inner layer of
the eye), the iris and the optic nerve (which transmits impulses
received by the eye to the brain) all develop from the primitive
forebrain. The lens and cornea are derived from the original
surface "skin" of the head. (Both help to focus
the incoming light rays on the light-sensitive retina). The
embryonic layer between the brain and head gives rise to the
vascular (blood vessel-containing) layer, the choroid and the
outer fibrous layer, the sclera.
From about the sixth week of gestation a
temporary network of blood vessels supplies the front of the eye
via the hyaloid artery, which originates in the back of the
eye, passes through the middle of the vitreous humor (the gelatin
that fills the back segment of the eye) and wraps vessels around
both surfaces of the lens and iris. The hyaloid artery later
incorporates into the optic nerve behind the eye and disappears
from inside the eye by seven months of gestation. The
vessels around the lens usually disappear by 34 weeks gestation.
There are no blood vessels in the retina before
the 16th week of gestation. From then on primitive cells
extend out from the optic disc (where the optic nerve
enters the eye) and stimulate the growth of normal blood
vessels. Production of the new blood vessels is usually
coomplete on the nasal side (towards the nose) of the eye by 8
months (35 weeks) gestation. The blood vessel networks on
the temporal side of the eye (towards the side of the head or
temples) are not mature until 2-3 months after normal term
birth
Development of ROP
As discussed earlier, growth of the blood supply
to the retina begins at 16 weeks of gestation and proceeds until a
little after a full term birth. If the retinal blood supply in the
premature infant continues its development just as if the baby
were still in the uterus, then retinopathy of prematurity does not
develop.
ROP occurs when abnormal blood vessels and scar
tissue form at the edge of the normal retinal blood supply.
The disease is caused by the abnormal retina's demand for
oxygen. As it has no blood supply, the abnormal retina is
starved for the oxygen needed for normal function. If the
disease progresses to the stage requiring treatment, the initial
treatment is to kill the abnormal retina and so eliminate its
damaging demand for oxygen.
If retinopathy of prematurity develops, it
usually appears between 35 and 45 weeks of conceptive age.
That is if the infant is born at 30 weeks gestation, and if
retinopathy of prematurity were to occur, it would appear when the
infant is between 5 and 15 weeks old. In the majority of
infants who develop ROP, the disease resolves spontaneously and
the retinal blood supply develops normally. If retinopathy
of prematurity regresses, the disease has usually lasted about 15
weeks.
However, ROP can progress to a serious, and
potentially blinding, eye problem which is estimated to result in
the blindness of approximately 500 infants in the United States
per year.
Classification of ROP
In the 1980's an international standard
classification of retinopathy of prematurity (known as ICROP) was
developed by a team of 23 experts from around the world. It
defines the disease by location relative to the optic nerve and
macula, by extent of disease around the circumference of the eye,
and by stages of progressive disease.
Location
Blood vessel development in the
retina occurs from the optic nerve out towards the periphery, that
is, from the back of the eye towards the front. The location
of the disease is referred to by the ICROP classification and is a
measure of how far this normal progression of blood vessel
development has progressed before the disease takes over.
Generally Zone II disease is more severe than Zone III
disease and Zone I disease is the most dangerous of all
since progression to extensive scar tissue formation and total
retinal detachment is most likely in this location.
From the "flattened"
retina in the figure above you can see that:
-
Zone I is a small area around
the optic nerve and macula at the very back of the eye.
-
Zone II extends from the edge
of Zone I to the front of the retina on the nasal side of the
eye (i.e. nose side) and part way to the front of the retina
on the temporal side of the eye (i.e. temple side, or side of
the head).
-
Zone III is the remaining
crescent of retina in front of Zone II on the temporal side of
the eye.
Extent of Disease
Think of the eye as in time
sections of a twelve hour clock. The extent of ROP is
defined by how many clock hours of the eye's circumference is
diseased. The numbers around the "flattened"
retina in the figure show the hours of the clock for each
eye. For example, 3 o'clock is to the right, which is on the
nasal side for the right eye and temporal side for the left
eye. Often the disease is not present around all twelve
clock hours, so a description may often refer to "x"
number of clock hours of disease (e.g. nine clock hours would mean
that three quarters of the circumference of the retina is
involved).
Stages of the Disease
Retinopathy of prematurity is a
progressive disease. It starts slowly, usually anywhere from
the fourth to the tenth week of life, and may progress very fast
or very slowly through successive stages, from Stage 1 through
Stage 5. Or it may stop at Stage 1, Stage 2 or mild Stage 3
and disappear completely.
Stage 1 ROP is characterized
by a demarcation line separating the clearly normal retina from
the undeveloped retina. This line is typically white and
there is sharp contrast between the normal retina and the abnormal
retina.
Stage 2 ROP displays a
rolled ridge of scar tissue in place of the white demarcation line
in Stage 1. It may be limited to a small area of the retina
or it may encircle the entire inside of the eye like a belt around
the middle of the eye.
Stage 3 ROP is characterized
by the development of abnormal "new blood vessels" and
fibrous tissue (like scar tissue) on the edge of the ridge seen in
Stage 2 and extending into the vitreous (the back cavity of the
eye). Stage 3 is further divided into:
-
"Mild" - with only a
limited amount of abnormal tissue,
-
"Moderate" - with
significant amounts of abnormal tissue infiltrating into the
vitreous, or
-
"Severe" - massive
amounts of abnormal tissue infiltrate into the vitreous.
Statistically, eyes which reach
stage 3 moderate or severe have a 50% chance of proceeding to
Stage 4 or Stage 5 and possible blindness. Therefore, it is
at Stage 3 that treatment is instituted.
Stage 4 ROP is caused by the
scar tissue formed in Stages 1 through 3 pulling on the retina and
causing it to separate from the wall of the eyeball. The
detachment in Stage 4 is partial, occurring in one section of the
eye and, depending on its location, may or may not affect the
infant's vision.
Stage 4 is further categorized
depending on the location of the partial detachment:
-
Stage 4A is a partial
detachment outside the macula - the area of central vision -
in the preiphery of the retina. Therefore, the chance
for usable vision, if the retina reattaches, is relatively
good.
-
Stage 4B is partial detachment
involving the macula, usually with a fold extending out
through Zones I, II, and III. The involvement of the
macula severely limits the prospect for usable vision in this
eye.
Stage 5 ROP involves a
complete retinal detachment, with the retina assuming a closed or
partially closed funnel, from the optic nerve to the front of the
posterior cavity fo the eye, just behind the lens. Infants
with Stage 5 ROP have essentially no useful vision inthat
eye. Treatment at this stage involves surgery to relieve the
traction, causing the detachment, in an attempt to reattach the
retina.
Some vision may be recovered by
this surgery but the infant will most likely be legally blind in
the involved eye.
Plus Disease
Additional complications to those described in
Stages 1 through 5 may involve abnormal blood vessels in the iris
and engorgement and tortuosity of the normal blood vessels in the
retina. If these additional symptoms are particularly bad,
the plus ("+") designation is added to the Stage number,
e.g. Stage 2+.
If ROP is located in Zone I and there is plus
disease present, then progression of the disease may be
particularly rapid. This form is sometimes called Rush
Disease.
Diagnosis of ROP
Screening for ROP usually begins when the infant
is about 4 to 6 weeks of age. An eye doctor
(ophthalmologist), who specializes in either retinal disorders
(retinal specialist) or children's eye diseases (pediatric
ophthalmologist), uses a special instrument (an indirect
ophthalmoscope) which allows a view through its optic lens into
the back of the eye to examine the retina and determine whether
development of the blood vessels is occurring normally or not.
The infant is usually given some eye drops to
make the pupil dilate so that the viewing field is as wide as
possible. A light anesthetic, in the form of numbing eye
drops, may also be administered.
The examinations are usually performed in the
neonatal intensive care nursery where the neonatal staff can
continue to monitor the baby.
The infant will continue to be examined every 1
to 2 weeks until one of the following occurs:
- Development of the normal blood supply to the
retina is complete.
- Two successive 2-week exams show Stage 2 in
Zone III. Infants will then be examined every 4 to 6
weeks until the blood supply to the retina is fully developed.
- ROP is at "prethreshold", just
prior to requiring treatment. Follow-up exams will then
occur every week until either Threshold ROP occurs, which
requires treatment, or the retinopathy of prematurity
disappears.
- The ROP is disappearing.
After two successive 2-week exams have shown
regression, examinations should be continued every 4 to 6 weeks.
Once the normal blood supply to the retina is
completely developed, the infant will continue to be examined
every 6 to 12 months by a pediatric ophthalmologist or retinal
specialist to ensure that no further complications of ROP occur.
Treatment of ROP
Cryotherapy
The current standard for treatment
involves a freezing process, called cryotherapy. In the late
1980's a nationally organized clinical trial established that this
therapy improved the outcome of the disease for infants who had
reached Threshold Stage 3+ in 50% of cases. That is, half of
the treated eyes that would otherwise (i.e. without treatment)
have progressed to retinal detachment and possible blindness did
not do so.
The technique of cryotherapy
involves freezing the retina by touching a cold probe to the
outside of the eye and waiting to allow the freeze to reach the
abnormal retina (i.e. the retina without a blood supply) inside
the eye. The treatment kills the abnormal retina thus
eliminating its demand for oxygen. The abnormal blood
vessels disappear and the progression of scar tissue stops.
There are risks in performing
cryotherapy. Severe decreases in heart rate and breathing
rate may occur. For this reason heart rate and blood oxygen
are monitored constantly during the cryotherapy procedure.
Sometimes infants need to be placed back on a ventilator after the
procedure if they are having trouble breathing on their own.
Cryotherapy is performed under
either local anesthesia or general anesthesia. If local
anesthesia is used, this can be administered and the procedure
performed at the infant's bedside in the neonatal intensive care
nursery. Administration of general anesthesia may require
that the infant is transferred to the operating room.
Neonatal staff also accompanies the baby to ensure constant
monitoring of his or her condition. Some phsicians prefer to
give general anesthesia because they believe that cryotherapy is
such a painful procedure that it is in the infant's best interest
to be fully anesthetized.
After cryotherapy there is usually
a large amount of swelling around the eyes, bloody tears and
redness. These effects go away in approximately one week.
A newer therapy, laser treatment,
may achieve the same effects as cryotherapy with fewer
side-effects, but to date cryotherapy is the only treatment proven
in a large nationally-conducted clinical trial. Additional
trials are underway to clinically compare results of laser therapy
with results of cryotherapy.
Lasers
Lasers have been used to
successfully treat eye disorders in adults for over 20
years. Diabetic retinopathy is a retinal disease afflicting
diabetics which is like retinopathy of prematurity in that it
involves growth of abnormal blood vessels in the retina.
Treatment of diabetic retinopathy was revolutionized by the advent
of laser therapy. Prior to laser therapy there was no way to
prevent blindness in these people.
Due to a technical advance in the
last few years, laser therapy can now be administered to newborn
infants. The same instrument that the doctor uses to examine
the infant's retina - the indirect ophthalmoscope - can also
deliver the laser treatment beam into the eye. So if the
doctor sees abnormal retina with the indirect ophthalmoscope, it
can also be treated.
Laser treatment acts in the same
way as cryotherapy by killing the abnormal retinal tissue and so
eliminates the growth of abnormal blood vessels and ends the
progression of scar tissue formation.
The potential benefits of laser
treatment are:
-
Less need for anesthesia
-
Less pain
-
Less swelling after the
procedure
-
Less likelihood of damage to
the eye
-
Less chance of decreases in
heart and breathing rates during the treatment
The drawback of laser therapy is
that it has only been proven effective in a few small clinical
trials and not in a large nationwide trial. Early trials
indicate that laser therapy is at least as effective as
cryotherapy and potentially better at preventing many infants
progressing to retinal detachment. Currently a large
nationwide trial is being organized.
Traditional laser systems were
large, immobile units that required moving the infant to the laser
rather than bringing the laser to the baby. Newer lasers -
using semiconductors - are fully portable and can be taken to the
nursery and attached to an indirect ophthalmoscope for treating
ROP babies without disturbing their routine.
Surgery
If cryotherapy, or laser treatment
at Stage 3 is unsuccessful in preventing progression to retinal
detachment stages - Stage 4 and Stage 5 - there are some surgical
treatment options.
If the detachment is shallow (i.e.
there is not a lot of space between the retina and the eye wall) a
technique called scleral buckling may be effective.
This involves placing a belt around the outside of the eye and
tightening in until the retina is close enough to the wall to
reattach itself.
Some studies have shown this
technique to be effective in some cases of Stage 4a, Stage 4b and
mild Stage 5. Vision after successful scleral buckling tends
to be better than after the more invasive surgical procedures
discussed below.
If scleral buckling is not possible
or is unsuccessful a more direct technique for reattaching the
retina, called a vitrectomy, can be performed.
In this procedure the eye is opened
up, the lens is removed and some or all of the vitreous humor is
removed so the surgeon can access the detached retina. The
source of traction causing the detachment (i.e., the scar tissue
or membrane that is tugging at the retina) is cut away from the
retina and the retina is then laid back against the eye wall by
injecting a gelatin-like material to replace the vitreous that was
removed.
A vitrectomy is not always
successful in reattaching the retina and even if the retina is
reattached, only a fraction of the eyes achieve ambulatory vision,
the ability to recognize faces.
Late Complications of Retinopathy
of Prematurity
Most infants with mild retinopathy
of prematurity (Stages 1 to mild 3) that spontaneously resolves
itself will have no remaining scar tissue. However, some
infants who undergo regression may still suffer further
complications later in life. These later complications
include:
Strabismus and Amblyopia
Strabismus (crossed eyes)
and amblyopia (lazy vision in one eye) occur more
frequently in infants with even the mildest stages of regressed
ROP compared with premature infants who do not develop ROP.
Eye muscle surgery (for strabismus) and patching (for amblyopia)
are often necessary.
Myopia
Myopia (near-sightedness)
can occur with the mildest forms of regressed ROP. The
nearsightedness is usually more severe when a greater amount of
scar tissue remains from regressed ROP. Myopia is
correctable with glasses.
Glaucoma
Different forms of glaucoma
(increased pressure in the eye) may develop in eyes that have
regressed or treated ROP. Glaucoma may cause pain and does
damage vision. Laser, or other types of surgery, are
sometimes necessary to help the eye drain off the build-up of the
watery fluid (aqueous humor) that bathes the front of the eye and
causes the increased pressure.
Late-onset Retinal Detachment
Late Retinal Detachment may rarely
occur in the mid-teens or early adulthood as a result of traction
from scar tissue as the eye grows or as the vitreous gel shrinks,
pulling holes in the retina. Surgery is usually necessary
for repair.
Any person who experienced
retinopathy of prematurity should therefore see a retina
specialist and/or a pediatric ophthalmologist at least once a year
during childhood and early adult years.
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