Retinopathy of prematurity

What is retinopathy of prematurity?

Retinopathy of prematurity refers to a disease affecting the retina of premature babies. Being born too early has the potential to disrupt the development of blood vessels in the retina of the eye, which form in the retina and may grow into the vitreous body where they deform the retina. Severe cases may progress to retinal detachment. If left untreated, children can lose their sight. However, this can usually be avoided with early detection and treatment of the disease. Retinopathy of prematurity is most commonly seen in very preterm babies and in preterm babies who require mechanical ventilation.

How does retinopathy of prematurity develop?

The retinal blood vessels of the eye develop between the 16th and 40th week of pregnancy. As a result, retinal blood vessel formation has not yet been completed in very premature infants at their time of birth.

Due to the onset of breathing after birth, the blood oxygen saturation of premature infants is higher than it was in the uterus. High oxygen saturation has consequences: Production of the growth factor VEGF (vascular endothelial growth factor), that would normally stimulate blood vessel formation, is inhibited. As a result, vessel development is slowed down. As the condition progresses, the preterm infants react to the lack of vessel and oxygen supply by producing excessive amounts of VEGF a few weeks before their expected due date (from the 32nd to 34th week after last menstruation). This leads to excessive formation of new blood vessels in the retina.

Not only do the new vessels sprout in the retina, they frequently grow into the vitreous body too. Blood vessels that have grown into the vitreous body pull on the retina. Consequently, the retina may become distorted or even peel off. The more immature the babies, the greater the risk of retinopathy of prematurity.

IGF -1 (insulin-like growth factor)is another growth factor that influences blood vessel development and is produced in the liver. IGF-1 is reduced in premature infants under some circumstances: malnutrition, poor weight gain, and conditions like necrotizing enterocolitis or sepsis. Such infants run an increased risk of developing retinopathy of prematurity.

What are signs of retinopathy of prematurity?

Retinopathy of prematurity first becomes noticeable several weeks after birth. The first signs are retinal changes which are visible during eye examinations. It is followed by an acute phase of the disease involving various stages.

During their development, blood vessels of the retina grow from its center to the periphery. Premature birth stunts the growth. This can be seen in the first stage of the disease: in its center, the retina has a good blood supply. This area is bordered by an outer zone with no blood vessels. The retina looks gray there. The larger the zone lacking blood vessels, the worse the prognosis. In stage two, there is a prominent ridge dividing the area with good blood supply from the area without blood supply. In stage three, new blood vessels have formed and already infiltrated the vitreous body. During stage 4, the retina is being pulled from its surface. Stage 5 involves complete detachment of the retina resulting in blindness of the affected eye.

Physicians speak of "plus disease" when the fundus of the eye shows a pathological widening of retinal vessels. The prognosis of retinopathy worsens as a result of this condition.

Not always will all stages of the disease be gone through. If retinopathy is mild, it comes to a stop by itself at an early stage so the retina can recover without treatment.

How is retinopathy of prematurity diagnosed?

All children born before 31 weeks of pregnancy should undergo an eye examination. In addition, those born before 37 weeks of pregnancy who required supplemental oxygen over a period of several days or who suffer from certain medical conditions are at an increased risk for retinopathy of prematurity and should be examined. Among these conditions are necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, or severe anemia.

Screening for retinopathy of prematurity is most commonly done six weeks after birth. After that, examinations should be repeated every one, two or three weeks, according to how severe the retinopathy is.

Eyedrops are applied for the examination in order to widen the pupil and to numb the eye surface. During the examination, a hook or retractor is used to keep the eyelids open. The physician can look through the dilated pupil at the fundus of the eye using an ophthalmoscope to evaluate the retina. The fundus of the eye is photographed using a camera with a wide angle lens.

Which treatment options are available?

The need for treatment is determined by the stage of the disease, how large the the area with proper blood supply is and if plus disease is present. Stages 1 or 2 often heal spontaneously and no treatment is necessary. If further worsening takes place, however, prompt therapy is essential. After all, when vessels grow into the vitreous body, retinal distortion and detachment may follow soon after.

Most commonly, retinopathy of prematurity is managed with laser coagulation or anti-VEGF therapy.

Laser coagulation to treat retinopathy of prematurity has been practiced for a long time. The physician obliterates the retina using a laser in the outer, non-vascularized area. This prevents retinal detachment.

Anti-VEGF therapy, on the other hand, is a relatively new treatment modality. It involves the injection of a medication into the eyeball which inhibits growth factor VEGF. In this way, excessive growth of new blood vessels is stopped.

In consultation with the parents, doctors choose the right therapy. Laser coagulation usually requires anesthesia and demands a physician with a high level of experience. Laser treatment creates scars in the outer areas of the retina so blood circulation is no longer possible here. In this border region, the retina will remain non-functional for the rest of the patient's life. This can lead to a restricted field of vision. Benefits of this method are that in most cases only one treatment session is necessary and the does not have to be cut open.

VEGF therapy can be done without anesthesia. The treatment does not damage the retina, which means that the so far non-vascularized region can form new blood vessels later on. The method has another advantage as it positively affects the progression of short-sightedness. In other words, preterm babies are less prone to develop severe short-sightedness with VEGF therapy. Profound short-sightedness is otherwise a common outcome of retinopathy of prematurity and Laser treatment does not influence it. Nevertheless, there is a risk of inflammation within the eyeball because VEGF inhibitors have to be injected into the eyeball. Over time, the effect of the treatment wears off, making more tightly schedules follow-up visits and perhaps additional treatment sessions necessary.

In later stages of the disease, when the retina has already detached, laser or anti-VEGF treatments are not enough. For this group of patients, surgery is required to reattach the retina to the wall of the eyeball: A vitrectomy is a procedure in which the vitreous body of the eye is taken out and as a replacement the eyeball is filled with a gas or silicone oil. In this way, the retina is pressed outwards against the wall.

Prognosis and long-term consequences

Prognosis is good if the disease comes to a halt by itself at an early stage. Severe forms of retinopathy of prematurity carry a much worse prognosis if left untreated, yielding an unfavorable outcome in 50 to 90 percent of cases.

With treatment, however, retinal detachment can usually be prevented. Treating severe forms at a later point in life lowers the chances of success.

Also a retinopathy of prematurity which has been effectively treated can lead to long-term consequences. Blood vessels as well as the macula, which represents the central area of the retina, may become deformed. This can result in the formation of holes in the retina even after many years. Retinal detachment may also appear years later.

In addition, children suffering from retinopathy of prematurity face an increased risk of becoming severely short-sighted.