Retinopathy of prematurity
Encyclopedia
Retinopathy of prematurity (ROP), previously known as retrolental fibroplasia (RLF), is an eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...

 disease that affects prematurely-born babies. It is thought to be caused by disorganized growth of retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

l blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

s which may result in scar
Scar
Scars are areas of fibrous tissue that replace normal skin after injury. A scar results from the biological process of wound repair in the skin and other tissues of the body. Thus, scarring is a natural part of the healing process. With the exception of very minor lesions, every wound results in...

ring and retinal detachment. ROP can be mild and may resolve spontaneously, but it may lead to blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...

 in serious cases. As such, all preterm babies are at risk for ROP, and very low birth weight is an additional risk factor. Both oxygen toxicity
Oxygen toxicity
Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen at elevated partial pressures. It is also known as oxygen toxicity syndrome, oxygen intoxication, and oxygen poisoning...

 and relative hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...

 can contribute to the development of ROP.

Pathophysiology

Normally, maturation of the retina proceeds in-utero, and at term the mature infant has fully vascularized retina. However, in preterm infants, the retina is often not fully vascularized. ROP occurs when the development of the retinal vasculature is arrested and then proceeds abnormally. The key disease element is fibrovascular proliferation. This is growth of abnormal new vessels that may regress, but frequently progresses. Associated with the growth of these new vessels is fibrous tissue (scar tissue) that may contract to cause retinal detachment. Multiple factors can determine whether the disease progresses, including overall health, birth weight, the stage of ROP at initial diagnosis, and the presence or absence of "plus disease". Supplemental oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 exposure, while a risk factor
Risk factor
In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...

, is not the main risk factor for development of this disease. Restricting supplemental oxygen use does not necessarily reduce the rate of ROP, and may raise the risk of other hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...

-related systemic complications.

Other physicians have suggested that supplemental oxygen, specifically oxygen tents given to pre-term infants specifically causes ROP. The hypothesized mechanism involves the degradation and developmental cessation of blood vessels in the presence of excess oxygen. When the excess oxygen environment is removed, the blood vessels begin forming rapidly again and grow into the vitreous humor of the eye from the retina, sometimes leading to blindness. This does not preclude the dangers of hypoxic environments for premature infants.

Patients with ROP are at greater risk for strabismus
Strabismus
Strabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...

, glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

, cataracts and myopia
Myopia
Myopia , "shortsightedness" ) is a refractive defect of the eye in which collimated light produces image focus in front of the retina under conditions of accommodation. In simpler terms, myopia is a condition of the eye where the light that comes in does not directly focus on the retina but in...

 later in life and should be examined yearly to help prevent and treat these conditions.

Diagnosis

Following pupillary dilation using eye drops, the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

 is examined using a special lighted instrument (an indirect ophthalmoscope). The peripheral portions of the retina are sometimes pushed into view using scleral depression. Examination of the retina of a premature infant is performed to determine how far the retinal blood vessels have grown (the zone), and whether or not the vessels are growing flat along the wall of the eye (the stage). Once the vessels have grown into Zone 3 (see below) it is usually safe to discharge the child from further screening for ROP. The stage of ROP refers to the character of the leading edge of growing retinal blood vessels (at the vascular-avascular border). The stages of ROP disease have been defined by the International Classification of Retinopathy of Prematurity (ICROP).

Retinal examination with scleral depression is generally recommended for patients born before 30–32 weeks gestation
Gestation
Gestation is the carrying of an embryo or fetus inside a female viviparous animal. Mammals during pregnancy can have one or more gestations at the same time ....

, with birthweight 1500 grams or less, or at the discretion of the treating neonatologist. The initial examination is usually performed at 4–6 weeks of life, and then repeated every 1–3 weeks until vascularization is complete (or until disease progression mandates treatment).

In older patients the appearance of the disease is less well described but includes the residua of the ICROP stages as well as secondary retinal responses.

Differential diagnosis

The most difficult aspect of the differential diagnosis may arise from the similarity of two other diseases:
  • familial exudative vitreoretinopathy which is a genetic disorder that also disrupts the retinal vascularization in full-term infants.
  • Persistent Fetal Vascular Syndrome also known as Persistent Hyperplastic Primary Vitreous that can cause a traction retinal detachment difficult to differentiate but typically unilateral.

International classification of retinopathy of prematurity (ICROP)

The system used for describing the findings of active ROP is entitled The International Classification of Retinopathy of Prematurity (ICROP). ICROP uses a number of parameters to describe the disease. They are location of the disease into zones (1, 2, and 3), the circumferential extent of the disease based on the clock hours (1-12), the severity of the disease (stage 1-5) and the presence or absence of "Plus Disease". Each aspect of the classification has a technical definition. This classification was used for the major clinical trials. It has been revised in 2005
The zones are centered on the optic nerve. Zone 1 is the posterior zone of the retina, defined as the circle with a radius extending from the optic nerve to double the distance to the macula. Zone 2 is an annulus with the inner border defined by zone 1 and the outer border defined by the radius defined as the distance from the optic nerve to the nasal ora serrata. Zone 3 is the residual temporal crescent of the retina.

The circumferential extent of the disease is described in segments as if the top of the eye were 12 on the face of a clock. For example one might report that there is stage 1 disease for 3 clock hours from 4 to 7 o'clock. (The extent is a bit less important since the treatment indications from the Early Treatment for ROP)

The Stages describe the ophthalmoscopic findings at the junction between the vascularized and avascular retina.
  • Stage 1 is a faint demarcation line.
  • Stage 2 is an elevated ridge.
  • Stage 3 is extraretinal fibrovascular tissue.
  • Stage 4 is sub-total retinal detachment.
  • Stage 5 is total retinal detachment.


In addition, Plus disease may be present at any stage. It describes a significant level of vascular dilation and tortuosity
Tortuosity
Tortuosity is a property of curve being tortuous . There have been several attempts to quantify this property. Tortuosity is commonly used to describe diffusion in porous media...

 observed at the posterior retinal vessels. This reflects the increase of blood flow through the retina. http://www.emedicine.com/oph/topic413.htm

Prognosis

Stages 1 and 2 do not lead to blindness. However, they can progress to the more severe stages. Threshold disease is defined as disease that has a 50% likelihood of progressing to retinal detachment. Threshold disease is considered to be present when stage 3 ROP is present in either zone I or zone II, with at least 5 continuous or 8 total clock hours of disease, and the presence of plus disease. Progression to stage 4 (partial retinal detachment), or to stage 5 (total retinal detachment), will result in substantial or total loss of vision for the infant.

Monitoring

In order to allow timely intervention, a system of monitoring is undertaken for infants at risk of developing ROP. These monitoring protocols differ geographically because the definition of high-risk is not uniform or perfectly defined. In the USA the consensus statement of experts is informed by data derived by clinical trials and published in Pediatrics 2006. They included infants with birthweights under 1500 grams or under 30 weeks gestation in most cases.

Treatment

  • Peripheral retinal ablation is the mainstay of ROP treatment. The destruction of the avascular retina is performed with a solid state laser photocoagulation
    Laser photocoagulation
    Laser coagulation or laser photocoagulation surgery is used to treat a number of eye diseases and has become widely used in recent decades...

     device, as these are easily portable to the operating room or neonatal ICU
    Intensive Care Unit
    thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...

    . Cryotherapy
    Cryotherapy
    Cryotherapy is the local or general use of low temperatures in medical therapy or the removal of heat from a body part. The term "cryotherapy" comes from the Greek cryo meaning cold and the word therapy meaning cure...

    , an earlier technique in which regional retinal destruction was done using a probe to freeze the desired areas, has also been evaluated in multi-center clinical trials as an effective modality for prevention and treatment of ROP. However, when laser treatment is available, cryotherapy is no longer preferred for routine avascular retinal ablation in premature babies, due to the side effects of inflammation and lid swelling.
  • Scleral buckling
    Scleral buckle
    A scleral buckle is one of several ophthalmologic procedures that can be used to repair a retinal detachment. Retinal detachments are usually caused by retinal tears, and a scleral buckle can be used to close the retinal break....

     and/or vitrectomy
    Vitrectomy
    Vitrectomy is a surgery to remove some or all of the vitreous humor from the eye. Anterior vitrectomy entails removing small portions of the vitreous from the front structures of the eye—often because these are tangled in an intraocular lens or other structures...

     surgery may be considered for severe ROP (stage 4 and 5) for eyes that progress to retinal detachment
    Retinal detachment
    Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...

    . Few centers in the world specialize in this surgery, because of its attendant surgical risks and generally poor outcomes.
  • Intravitreal injection of bevacizumab
    Bevacizumab
    Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....

     (Avastin) has been reported as a supportive measure in aggressive posterior retinopathy of prematurity.

In a recent clinical trial comparing bevacizumab with conventional laser therapy, intravitreal bevacizumab monotherapy showed a significant benefit for zone I but not zone II disease when used to treat infants with stage 3+ retinopathy of prematurity. (New England Journal of Medicine 2011 364(7):603-615)

History

A significant time in the history of the disease was between 1941–1953, when a worldwide epidemic of ROP was seen. Over 12,000 babies worldwide were not only born with the disease but blinded by it. Soul musician Stevie Wonder
Stevie Wonder
Stevland Hardaway Morris , better known by his stage name Stevie Wonder, is an American singer-songwriter, multi-instrumentalist, record producer and activist...

, actor Tom Sullivan
Tom Sullivan (singer)
Tom Sullivan is an American performer, author, and motivational speaker.-Personal life:Sullivan was born and raised in West Roxbury, Massachusetts, the son of Marie C. and Thomas J. Sullivan, who owned a saloon. His premature birth caused him to need oxygen treatment while in an incubator...

 as well as jazz singer Diane Schuur
Diane Schuur
Diane Schuur is an American jazz singer and pianist. Nicknamed "Deedles", she has won two Grammy Awards, headlined many of the world's most prestigious music venues, including Carnegie Hall and The White House and has toured the world performing with such greats as Quincy Jones, Stan Getz, B. B...

are a few famous people who have the disease.

The first case of the epidemic was seen on St. Valentine's Day in 1941, when a premature baby in Boston was diagnosed. Cases were then seen all over the world and the cause was, at that point, unknown. By 1951 a clear link between incidence and affluence became clear: many cases were seen in developed countries with organized and well-funded health care. Two British scientists suggested that it was oxygen toxicity that caused the disease. Babies born prematurely in such affluent areas were treated in incubators which had artificially high levels of oxygen. Studies on rats made this cause seem more likely, but the link was eventually confirmed by a controversial study undertaken by American pediatricians. The study involved two groups of babies. Some were given the usual oxygen concentrations in their incubators, while the other group had "curtailed" oxygen levels. The latter group was shown to have a lower incidence of the disease. As a result, oxygen levels in incubators were lowered and consequently the epidemic was halted.

External links

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