Premature Baby-Retinopathy of Prematurity.
At about 16 weeks of pregnancy, the retina, at the back of the inside of the eye, begins to develop blood vessels which provide nourishment and oxygen to the eye. Over time, this network of vessels gradually grows forward, eventually covering the entire surface of the retina. The process is usually complete at the end of term, or about 40 weeks gestation.
Prematurity can interfere with the development of these blood vessels. This condition is called retinopathy of prematurity (ROP) and it affects many premature babies. As with other conditions, the risk of developing ROP increases with the degree of prematurity. For example, about 80% of extremely premature baby, those of less than 26 weeks gestational age, have ROP whereas only about 15% of mildly premature babies, more than 30 weeks gestational age, do. A premature baby is at highest risk for ROP when born very prematurely or when the premature baby has a very low birth weight of 1500 g or less.
Although most cases are mild and treatable, ROP can permanently affect vision. Depending on the severity, ROP may cause minor vision impairments or, in more rare cases, blindness, especially if the condition in premature babies goes untreated.
Blood vessels generally grow from areas of high oxygenation, where the vessels already exist, to areas of low oxygenation, where the vessels have not yet formed. In this way, the retina is gradually and evenly covered in blood vessels that grow from the back of the eye towards the front like a wave approaching the shoreline.
The oxygen level of the premature baby’s environment is an important factor for the progress of normal blood vessel development. When the premature baby is in the womb, the concentration of oxygen in its blood stream is kept relatively steady and is lower than the levels that will occur after birth. In comparison, after a premature baby is born, oxygen levels in the bloodstream are kept in the desired range by adding oxygen to the air surrounding the premature baby; this helps the premature baby’s breathing. This rapid change in the level of oxygen in the premature baby’s bloodstream has an important effect on the regulation of blood vessel development. Moreover, if the premature baby is having other complications that affect the regular flow of oxygenated blood, this too can interfere with the normal growth and spreading of the blood vessels.
There are many factors that contribute to the development of ROP. The knowledge that oxygen levels have an effect came in the 1940s. At that time, many premature babies were given supplemental oxygen whether they were having breathing problems or not. At this time it was discovered that the premature babies who were given high concentrations of oxygen had a much higher incidence of ROP than premature babies who were not given oxygen. Although supplemental oxygen is often essential for a premature baby’s survival, especially those with the more severe form of lung and breathing complications, the level of supplemental oxygen must be carefully monitored and adjusted to keep oxygen levels in the bloodstream in the desired range. Following this adjustment, the frequency of ROP has gone down but not disappeared.
Stages of ROP
ROP is graded, or classified into stages of severity, from Stage 1, the mildest case, to Stage 5, the most severe. At what stage ROP is graded depends not only on the extent of the abnormal blood vessel growth but where in the eye the growth has taken place.
Fortunately, most cases of ROP are mild and resolve spontaneously. However, when ROP is severe and does not resolve with maturation of the baby, if left untreated these abnormal blood vessels can continue to grow on the surface of the retina and result in formation of fibrous tissue. This in turn can pull on the retina and may lead to partial or full detachment of the retina.
All premature babies are screened for ROP. If a problem is identified, screening will continue at regular intervals. If treatment is deemed necessary, surgery, usually with laser photocoagulation or cryotherapy, a kind of freezing, is performed.
Diagnosis of Retinopathy of Prematurity (ROP)
The retina of the eye is like the film in a camera. It lines the inside of the eye. At about 16 weeks of pregnancy, the retina begins to develop blood vessels. The blood vessels generally grow from areas of high oxygenation, where the vessels already exist, to areas of low oxygenation, where the vessels have not yet formed. In this way, the retina is gradually and evenly covered in blood vessels.
Fluctuation of oxygen levels in the developing retina is an important factor in the regulation of the growth of blood vessels. Moreover, if the premature baby is having other complications that affect the regular flow of oxygenated blood, this too can interfere with the normal growth and spreading of the blood vessels. If the blood vessels grow abnormally as a result, this is called retinopathy of prematurity (ROP).
Since development of retinal blood vessels is incomplete until about 35 to 37 weeks gestation, the retina is vulnerable to injury. Abnormal blood vessels can deliver either too much oxygen to the eye or too little. Hypoxemia, an insufficient oxygen supply in the blood, leads to local tissue damage called ischemia, or scarring. Hyperoxemia, which is too much oxygen, reduces the normal stimulus for development of the blood vessels; this will later result in loss of some of the developing blood vessels and ultimately lead to ischemia.
How ROP is diagnosed
All premature babies who fall within a screening protocol defined as birth weight less than 1500 g and gestational age of below 30 weeks are routinely examined for ROP. These premature babies will likely be examined initially at four to six weeks after birth. An eye doctor will use drops to dilate the pupils, which will allow for a better view of the inside of the eye.
Depending on the amount of abnormal blood vessel development, the premature baby’s condition will be graded and further examinations will be conducted every one to two weeks, depending on a variety of factors. These factors include the severity and location in the eye of ROP, and the rate of progression of blood vessel formation, called vascularization. In the majority of cases, even when ROP develops, it will resolve spontaneously with minimal effect on vision. However, a small percentage of premature babies screened for ROP, approximately 10%, will progress to the extent that it is no longer safe to wait for spontaneous resolution. For these babies, treatment will be offered to reverse the progression of ROP.
Stages of ROP
The severity of ROP is assessed by the area of retina that is involved, also referred to as the zone of vascularization, and the extent of the abnormal growth. The lower the number for the zone, the greater the area of the retina affected. The stages, or extent of the growth of abnormal blood vessels, are defined as follows.
Stage 1 ROP
In Stage 1 ROP, there is a thin line between the area with blood vessels and the area where blood vessels have not grown yet. At this stage, the vessels may grow normally on their own, but the condition must be watched.
Stage 2 ROP
In Stage 2 ROP, the line between the areas with and without blood vessels widens and thickens into a ridge. At this stage, the condition may still resolve, however, it may also progress to stage 3 ROP.
Stage 3 ROP
In Stage 3 ROP, new blood vessels begin to grow along the ridge and extend into the clear gel that fills the eye, called the vitreous body. These blood vessels can bleed and form scar tissue.
Stage 4A ROP
In Stage 4 ROP, the abnormal blood vessels and scar tissue pull on the retina, partially detaching it. In stage 4A, the centre of vision, called the fovea, is not involved.
Stage 4B ROP
In Stage 4B ROP, the retina is still only partially detached, but the fovea is affected usually leaving both the centre and peripheral vision impaired to some degree.
Stage 5 ROP
In Stage 5 ROP, the retina is completely detached, severely affecting vision.
Treatment of Retinopathy of Prematurity (ROP)
Retinopathy of prematurity (ROP) is an abnormal growth of blood vessels in the eye that can interfere with vision. Although usually mild, in its most severe form, ROP can cause a partial or complete detachment of the retina in premature babies. Treatment of ROP depends on the extent of the condition and its location in the eye. Since they are known to be at risk, all at risk premature babies are examined for ROP until the blood vessels reach the peripheral, or outer parts of the retina. If assessment shows any indication of ROP, assessment of the retina will continue at regular intervals. In a small number of cases, growth of normal vessels is prevented by the growth of abnormal vessel which may require treatment.
Surgical treatment of ROP
Treatment of ROP consists of laser surgery or, less frequently, criotherapy. The purpose of these surgical procedures is the same, in that they aim to stop the growth of abnormal blood vessels. Laser photocoagulation is done using a laser to remove parts of the retina which have not yet developed blood vessels. Cryotherapy uses freezing to accomplish the same goals.
Cases that do not resolve themselves and show signs of progression are usually treated by laser therapy to destroy the peripheral avascular retina, the area of the retina that has not developed abnormal blood vessels which is short of oxygen. This leads to the regression of abnormal blood vessels and allows normal vessels to grow.
It is possible for the disease process to continue in spite of treatment with laser or cryotherapy. In these cases, partial or full detachment of the retina may develop and in some cases this will require surgery. The severity of the detachment will be the major determining factor for long-term vision. Although surgical procedures can sometimes successfully reattach a retina, most premature babies will have some kind of visual impairment. Those few premature babies with a fully detached retina will likely be blind or nearly blind in that eye. In many cases, premature babies with a partial detachment will go on to have useful, though not perfect, vision in that eye.
Reviewed by Nasrin Najm-Tehrani, MSc, MD, MB, BCh, FRCS Ed (Ophthalmology)
Ophthalmologist, Ophthalmology and Vision Sciences
The Hospital for Sick Children
Assistant Professor, Ophthalmology and Vision Sciences
University of Toronto