retinopathy of prematurity
Introduction
Introduction to retinopathy of prematurity Retinopathy of prematurity (ROP), formerly known as posterior lens fibrosis (RLF), is closely related to premature birth, low birth weight, and high concentration of oxygen. It is due to the retinal blood vessels in premature infants that have not yet fully developed. Due to the proliferation of new blood vessels and fibrous tissue, posterior lens fibrosis is a late scar change of severe ROP. In 1984, the World Ophthalmology Society officially named the disease as retinopathy of prematurity. basic knowledge The proportion of illness: 0.001% - 0.007% Susceptible people: premature infants Mode of infection: non-infectious Complications: cataract
Cause
Causes of retinopathy of prematurity
(1) Causes of the disease
The exact cause of ROP remains unclear. Currently recognized risk factors include low birth weight, premature birth, oxygen therapy, and other hypercapnia, hypernatremia, hypoglycemia, hypotension, acidosis, anemia, blood transfusion, and high Bilirubinemia, sepsis, light, hypothermia, periventricular hemorrhage, patent ductus arteriosus, application of beta blockers.
Premature birth low birth weight
Immature retinal development is the root cause of ROP. The lower the birth weight, the smaller the gestational age, the higher the incidence of ROP, the more serious the condition. Some people have a fundus examination on 76 high-risk newborns who have successfully rescued. There is no case in full-term infants. ROP occurred, 12 cases of ROP were all premature, with an average gestational age of 31.75 weeks.
2. Oxygen therapy
In recent years, the birth rate of very low birth weight infants (VLBW) and ultralow birth weight infants (ELBW) has increased compared with the previous ones. Most of these children have used different methods of oxygen therapy. Animal models have confirmed that 7 weeks after birth, the mice are 75%. Living in a high-oxygen environment for 5 days, a model similar to human ROP can be successfully prepared. The longer the oxygen therapy time, the higher the inhaled oxygen concentration, the higher the arterial oxygen partial pressure, the higher the incidence of ROP, the more severe the condition, oxygen The treatment is closely related to ROP. The incidence of ROP with CPAP or mechanical aerator is higher than that of hood oxygen. It may be due to higher FiO2 during CPAP or mechanical ventilation. Patients usually have excessive oxygen in the incubator after birth. History, the longer the oxygen inhalation time, the higher the incidence rate, but it is also thought to be stopped by the high concentration of oxygen, which makes the tissue relatively hypoxia, and has nothing to do with the shortness of oxygen inhalation time (Jacobson, 1992), no suction. Oxygen history, may also be due to the sudden increase in oxygen saturation of fetal hemoglobin (fetal hemoglobi), fetal oxygen partial pressure (fetal PO2) into the neonatal oxygen partial pressure (neonatal PO2) when the acute stimulation changes, etc., in addition to , maternal anemia and multiple fetuses, etc. One of the causes of illness.
However, not all oxygen-absorbing premature low birth weight infants have ROP, and proper oxygen supply may not occur ROP. Some scholars have suggested that the production of ROP is related to "relative hypoxia", that is, the rapid suspension of oxygen after high concentration of oxygen will cause tissue. Relative to hypoxia, which promotes ROP production, suggesting that fluctuations in arterial oxygen partial pressure play an important role in ROP progression.
3. Other
(1) Race: The incidence of white ROP is higher than that of black people. The condition is heavy and the cause is unclear. It may be because the black pigment epithelium and choroid of the black people contain more melanin, which can protect against oxygen free radical damage.
(2) -blockers: It has been reported that prenatal natal beta-blockers can increase the incidence of ROP. Beta-blockers can enter the fetus through the placenta, increase choroidal vascular tone, and promote ROP. development of.
(3) Arterial blood carbon dioxide partial pressure (PaCO2): PaCO2 is too low can cause cerebral vasoconstriction, and can also cause retinal vasoconstriction leading to retinal ischemia, eventually forming ROP.
(4) Hypoxia caused by various factors, acidosis (pH<7.25), anemia, blood transfusion, hyperbilirubinemia, hypernatremia, hypoglycemia, hypothermia <35.6 °C, patent ductus arteriosus, ventricle Internal bleeding, sepsis, light, application of jaundice drugs, etc., are all related to the occurrence of ROP.
(two) pathogenesis
The true pathogenesis has not yet been elucidated. The immature retinal blood vessels are extremely sensitive to oxygen. High concentrations of oxygen cause the retinal vessels to contract or block, causing hypoxia in the retina. Angiotensin-producing factors are produced due to hypoxia, which stimulates retinal neovascularization. Occurred in the peripheral part of the retina, especially in the peripheral part of the temporal side. First, the neovascularization occurs in the inner layer of the retina. The blood vessels gradually grow from the inside of the retina to the surface, and then extend into the vitreous. The neovascularization is accompanied by fibrous tissue hyperplasia, fibrovascular membrane. Growing along the front of the vitreous, the fibrous membrane is formed behind the lens. The contraction of the membrane pulls the peripheral retina toward the center of the eyeball, causing traction retinal detachment, which eventually leads to atrophy of the eyeball and blindness.
Neovascularization
It plays a leading role in the development of ROP, and a variety of substances have been found to be involved in angiogenesis:
(1) Vascular Endothelial Growth Factor (VEGF): is a vascular endothelial-specific growth factor. A large number of studies have shown that it plays a central role in the process of angiogenesis and is the most important and most effective substance necessary for initiating neovascularization.
(2) Angiopoietin (ANG): It is also a vascular endothelial-specific growth factor, which functions as a blood vessel remodeling function, thickens blood vessels, stabilizes blood vessel walls, reduces exudation, and further matures blood vessels.
(3) Others: basic fibroblast growth factor (bFGF), human epidermal growth factor (EGF), human platelet-derived vascular endothelial growth factor (PD-VEGF), beta-transformed growth factor (-TGF), hepatocytes Growth factor (HGF), pigment epithelial-derived factor (PEDF), and the like.
The formation of new blood vessels is a complex interaction between many vascular factors, and the result of mutual regulation, under normal circumstances, when the angiogenic substance and anti-angiogenic substances reach equilibrium, the "switch" of angiogenesis is closed; if this balance Being broken, the pro-angiogenic material predominates, the "switch" opens, and the blood vessels are formed.
2. Mechanism of oxygenation-induced ROP
In addition to neovascularization, there is a possible cause, that is, the oxygen free radical theory, excessive oxygen can form a large number of oxygen free radicals, the anti-oxidation defense mechanism in the tissue can not be detoxified synchronously, resulting in damage of retinal tissue, the presence of antioxidant system in premature infants Defects, susceptible to oxygen free radical damage.
Prevention
Prevention of retinopathy of prematurity
Strict restriction of oxygen for early children is the only effective preventive measure. Unless there is a risk of life due to cyanosis, 40% oxygen can be given, and the time should not be too long. In addition, vitamins may have a preventive effect in early high-dose applications. Early detection, timely implementation of condensation or laser photocoagulation, has been successfully reported to prevent further deterioration of the lesion.
In order to prevent the occurrence of secondary glaucoma, severe cases of active period must be often dilated to avoid post-irisal adhesions. The mydriatic agent is suitable for 2% omatropine, one can avoid atropine poisoning, and the other is to prevent pre-adhesion of the peripheral part of the iris due to long-term continuous pupil dilation.
Complication
Complications of retinopathy of prematurity Complications cataract
When the vascular membrane is hyperplasia after the lens, the posterior capsule of the lens can be ruptured to form a cataract. The most serious complication is blindness.
Symptom
Symptoms of retinopathy of prematurity Common symptoms Retinal hemorrhage Corneal opacity Visual disorder Bradycardia Unilateral fundus appears... Pigmentation
With the advancement of ROP treatment technology, the prognosis of children who have been treated early is greatly improved, and the fundus examination is performed as soon as possible, which is the key to the diagnosis and treatment of the disease. According to the development process of the disease, it is clinically divided into acute activities. Period, period of retreat and scar period.
Acute activity period
According to the International Classification of ROP (ICROP), there are three basic concepts in the active phase of the disease: according to regional positioning, the lesion range is recorded by clock hour, and it is divided into I to V according to the severity of the disease.
(1) Division: The retina is divided into 3 zones, zone I: the inner circle with the radius of the optic disc as the center and the distance from the optic disc to the fovea of the macula. The ROP occurs in the zone most seriously, and the zone II: The optic disc is centered, with the radius from the optic disc to the nose side of the serrated edge, the inner area of the circle outside the I zone, and the semi-moon area of the third side of the III area: the second side of the II area, which is the area where the ROP is the highest.
(2) Staging: divided into 5 stages, stage I, stage of vascular change: as seen in the early stage of the disease, the arteries and veins have tortuous expansion, and the venous diameter is sometimes more than 3 to 4 times larger than the normal diameter. The tip is visible like a brush-like capillaries, and a white flat subdivision line appears between the vascular region of the posterior pole of the retina and the surrounding avascular region. Stage II, retinopathy stage: the lesion develops further, the vitreous appears turbid, and the fundus is more The anterior iliac crest, the retinal neovascularization, mostly located near the equator, can also be seen in the anterior or posterior pole of the equator. The retina of this area is obviously bulged, and there are blood vessels crawling on the surface, often accompanied by retinal hemorrhage of varying sizes, white dividing line. Further widening and increasing, forming a ridge-shaped bulge higher than the surface of the retina, stage III, early stage of proliferation: hyperplastic vascular cords appearing at the localized retinal ridges, and develop into the vitreous, causing the periphery of the fundus (most) Or the posterior pole (a few) retinal small-scale detachment, the squat-shaped bulge is more prominent, and pink, indicating that the new blood vessels not only grow into the sputum And developed to the sputum, this stage with fibrosis, and into the vitreous, stage IV, moderate proliferative stage: the detachment range is extended to more than half of the retina, part of the retinal detachment, and is divided into A and B 2, IVA is the peripheral retinal detachment Irradiated with the macula, IVB is the retinal detachment involving the macula, retinal detachment is mostly traction, but also exudative, V stage, extreme hyperplasia stage: full retinal detachment, sometimes also a large amount of blood in the vitreous cavity, retinal detachment It is often funnel-shaped and can be divided into a wide funnel, a narrow funnel, a front width and a narrow width, and a front narrow and a wide width. In this period, there is extensive connective tissue hyperplasia and mechanical membrane formation, resulting in RLF.
(3) Special lesions:
1 additional lesions (plus): the posterior pole retinal vessels appear violent, distorted, or the anterior iris blood vessels are highly dilated, and the additional lesions are indications of ROP activity, once it appears to mean a poor prognosis.
2 Threshold ROP: ROP stage III, in zone I or zone II, neovascularization occupies 5 clock ranges continuously; or lesions are discontinuous, but accumulate up to 8 clock ranges, accompanied by plus, this period is early The critical period of treatment.
3 Prethreshold ROP: including 2 cases, if the lesion is limited to area I, ROP can be stage I, II, III; if the lesion is located in area II, there are 3 cases: stage II ROP with plus; III Period ROP is not accompanied by plus; stage III ROP with plus, but new blood vessels occupy less than 5 consecutive clock ranges or discontinuously accumulate 8 clock ranges.
4Rush lesions: ROP is confined to the I region, the neovascularization is straight, and the Rush lesion develops rapidly. Once medical personnel find it, they should be vigilant.
2. Regression period
Most of the children with the growth of ROP naturally stop, enter the degenerative phase, this period is characterized by the upper iliac vessels continue to grow into normal retinal capillaries in the avascular zone, the sputum gradually subsides, the peripheral retina gradually becomes transparent, leaving no sequelae, but still 20% to 25% of the children progress and enter the scar stage.
3. Scar stage
Because the disease can move from the active period to the scar stage quickly, the active period and the scar stage lesions often exist in the same case at the same time. Therefore, the period of irreversible change of the residual active disease is generally called the scar stage, and the scar is generally used. The period is divided into 5 degrees:
1 degree: no obvious change in the posterior pole of the fundus, slight scarring changes in the peripheral part (pigmentation, choroidal atrophy), most of the visual acuity is normal, the retinal blood vessels are narrow, the periphery of the retina is gray and turbid, and the irregular shape of the small pieces is irregular. Pigment spots, the nearby vitreous also has small turbidity, often accompanied by myopia.
2 degrees: the retinal blood vessels are pulled to the temporal side, the macula is biased to the temporal side, pigmentation is present, and opaque white tissue blocks are visible around. If the macula is healthy, the visual acuity is good; if the lesion involves the macula, different degrees of visual impairment will occur, and the periphery of the retina The organicized mass, the optic disc and the retinal blood vessels are pulled to one side by this pulling, and there is a pigment arc on the edge of the side disc, and the disc is faded.
3 degrees: retinal fold formation, and the vitreous membrane of the lesion heals and is wrapped by blood vessels, extending to the peripheral part and associated with the white tissue block, the visual acuity is below 0.1, the fiberized membrane pulls the retina to form one or several folds, each The wrinkles are connected with the membrane-like agglomerates of the retina. The folds 905 are located on the temporal side, 105 is located on the nasal side, and the lower side of the superior temporal iliac crest is rare. The retinal blood vessels are not distributed along this fold, and congenital Congenital retinal folds are different.
4 degrees: in the vitreous of the posterior part of the lens, it can be seen that the gray-white turbidity occupies part of the pupil collar. After the crystal, the fibrous membrane is visible or a part of the retina is removed. The pupil collar is obscured, and the ophthalmoscope is visible from the undetected ophthalmoscope. reflection.
5 degrees: fibrous tissue proliferation after lens, corneal opacity, cataract, often eyeball atrophy, loss of vision, the whole body is covered by fibrous membrane or detached mechanical retina, dilated examination, visible in the periphery of the pupil It has a zigzag-like elongate ciliary process, and the anterior chamber is very shallow. It often has adhesions before and after the iris. It can also cause corneal opacity due to secondary glaucoma or extensive pre-irisal adhesion. The eyeball is smaller than normal and invaginated.
4. Fundus examination
(1) The first inspection time: effective screening should detect the early ROP in time, and reduce the number of unnecessary inspections. At present, most scholars at home and abroad advocate premature birth with a gestational age <32 weeks and a birth weight <1500g. Children, starting a fundus examination 4 weeks after birth.
(2) follow-up examination: according to the results of the first examination, such as no lesions in both eyes or only stage I lesions, can be reviewed once every other week until the ROP is regressed, the retinal vessels grow to the serrated margin, if there is a stage II lesion Or pre-threshold lesions or Rush lesions should be reviewed once a week. If the degree of ROP decreases during follow-up, it can be checked every 2 weeks until the lesion is completely regressed. If stage III lesions occur, it should be reviewed 2 to 3 times a week. If the threshold level is reached, condensation or laser treatment should be performed within 72 hours of diagnosis.
(3) Inspection method: In the first half hour of the examination, the pupils of the Dolly Eyes are fully scattered, and the eyeballs are anesthetized with the eyeballs, and then the eyelids are separated by an opener, using an indirect ophthalmoscope and diopter 20~ The 30D lens is used for fundus examination. The examination process is best carried out by the cooperation of nursing staff, neonatal doctors and ophthalmologists. Vital signs should be monitored at the same time to prevent bradycardia caused by eye reflexes, in order to reduce milk inhalation. After 30 minutes to 2 hours after the examination, the food can be eaten. The smaller the body weight, the longer the fasting period, but to prevent the occurrence of hypoglycemia.
The vast majority of this disease occurs in premature infants, with a history of excessive oxygen in the incubator, which can be diagnosed accordingly.
Examine
Examination of retinopathy of prematurity
Vascular closure occurs during the period of excessive oxygen inhalation, and the earliest change in the active proliferative phase is: the endothelial proliferative nodules of capillaries appear in the retinal nerve fiber layer, and the blood vessels are often globular, with vibrating mesenchymal cells proliferating around them. As a result, the nerve fiber layer becomes thicker, sometimes there may be small hemorrhage and edema (Fig. 1). As the lesion develops, the nerve fiber layer is further thickened, and the new capillary bud penetrates the inner limiting membrane to reach the surface of the retina, and the severer can further enter. The vitreous body, in which it can continue to grow into a vascular fibrous membrane, producing bleeding or traction retinal detachment.
In the late stage, different degrees of vascular fiber membrane formation can be seen after the crystal. There are many fibrous cords connected between the membrane and the retina. The light can be free of retinal detachment. In severe cases, the whole retina can be detached and adhered to the posterior fibrous membrane. In addition, there may be peripheral anterior adhesions, posterior adhesions, pupillary membrane formation, and secondary glaucoma changes. In very advanced patients, it is difficult to diagnose tissue fibrosis only after tissue sectioning, which is often misdiagnosed as false. Glioblastoma, Coats disease, etc., but if no capillary area is found in the peripheral retina, it can be used as an important diagnostic basis.
Special auxiliary examination: fundus examination and ultrasound examination.
Diagnosis
Diagnosis and diagnosis of retinopathy of prematurity
Differential diagnosis
The vast majority of this disease occurs in premature infants, with a history of excessive smoking in the incubator. According to this, it can be diagnosed, in addition to the identification of organic compounds formed by congenital retinal folds, Coats disease, retinoblastoma, suppurative endophthalmitis and intravitreal blood, the following diseases should also be identified.
(1) Bloch-Sülzberger syndrome (incontinentia pigmenti) This syndrome is a family history of ectodermal system disease at birth or after birth. A small number of cases have a posterior crystal atrophy, which is different from this disease.
(2) Retinal dysplsia (retinal dysplsia) The disease also has a fibrous membrane after the presence of crystal. However, there are bilateral small eyeballs at the time of birth, adhesion after the iris, and family history and mental retardation, somatic dysplasia, cerebral edema, cardiovascular disease, multi-finger (toe) and other systemic diseases, and this disease is different.
(3) congenital encephalo-ophthalmic dysplasia (congerital encephalo-ophthalmic dysplasia) is also seen in premature infants, there are also fibrous posterior fibrous membrane and retinal hypoplasia and detachment. However, there are brain edema, ptosis, dysplasia of the cerebral cerebellum, etc., which can be distinguished from this disease.
(4) The original hyperthermia vitreous and the former pseudophacia fibrosa are also known as the persistent posterior fetal fibrovascular sheath of the lens. The crystal vascular membrane should disappear completely in the fetus for 8 and a half months. In the process, an obstacle occurs and remains permanently, and the vascular membrane remains after the congenital crystal is formed. Although there are also small eyeballs, secondary glaucoma and other changes, but the disease is seen in the full-term infants with no significant weight loss, monocular, pupil and crystal deviation, and many different points from the disease can be distinguished.
When the vascular membrane of the crystal is over-denatured, it is violently broken, causing cataract. While the cortex is absorbed, the mesodermal tissue invades and forms a connective tissue membrane called a fibrous pseudocrystal.
(5) familial exudative vitreoretinopathy (familial exudative vitreoretinopathy) seen in the fundus of the lesion, similar to this disease. However, most of them are autosomal dominant inheritance, and full-term neonates with spontaneous birth have no history of oxygen inhalation, which is different from this disease.
