Ординатура / Офтальмология / Английские материалы / Pediatric Ophthalmology for Primary Care 3rd edition_Wright, Farzavandi_2008

Isolated Ocular Causes

Ectopia Lentis et Pupillae

This is an ocular anomaly that consists of lens subluxation and corectopia (displaced pupil). The pupil is often misshapen, either oval or slit like, and is difficult to dilate. Persistent pupillary membranes, with or without lenticular adhesions, may occur. Ectopia lentis et pupillae is frequently bilateral and is often associated with myopia, glaucoma, and retinal detachment.

Bibliography

1.Wright KW, Chrousos GA. Weill Marchesani syndrome with bilateral angle closure glaucoma. J Pediatr Ophthalmol Strabismus. 1985;22:129–132

Chapter 19

Retinopathy of

Prematurity

Retinopathy of prematurity (ROP) is a serious, sight threatening complica tion of premature birth. Once an infant is blind from ROP retinal damage, the visual loss is almost always permanent. These children never see their mother’s face, never experience the beauty of a sunset.

The incidence and severity of ROP are related to the degree of prema turity. The infants at greatest risk for severe ROP are the most immature infants, ie, extremely low gestational age neonates, born before 28 weeks’ gestation, or extremely low birth weight infants (<1,000 g). The incidence of severe ROP in these at risk premature infants varies widely from approxi mately 2% to 28% (Tin et al; Chow, Wright et al; Wright et al; Vander veen). Among infants with severe or threshold ROP treated with laser, more than half will never achieve driving vision (20/60), while those who receive cryotherapy fair even worse, as more than half will end up legally blind after treatment.

Severe ROP is a major cause of blindness in developed countries such as the United States and England. In emerging nations that are developing neonatal care units, blindness from ROP has reached epidemic proportions.

Thus, ROP is a global health issue and is one of the main causes of childhood visual disability and blindness.

History of Retinopathy of Prematurity

Neonatal units began using oxygen in the early 1940s, based on observations that increasing the fraction of inspired oxygen (FiO2) imparts a more regu lar breathing pattern to infants. Use of incubators in the late 1940s enabled maintenance of high oxygen concentrations for prolonged intervals. By the 1950s, blindness from retrolental fibroplasia (RLF) was an epidemic, occur ring in more than 10,000 premature babies (Figure 19 1) (Palmer et al).

In the mid 1950s, oxygen was implicated as a cause of blindness from RLF. A National Institutes of Health multicenter randomized control trial

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Figure 19 1.

Graph showing incidence of retinopathy of prematurity (ROP) over time from the 1940s to the 1990s. Note that around 1955 the incidence of cicatricial and active ROP dropped significantly, because this is the point in time when oxygen use was curtailed. In the late 1960s through the 1990s, survival of very low birth weight infants increased along with the incidence of active ROP (red area). Note that the incidence of severe cicatricial ROP remained relatively low during this period.

comparing “routine oxygen” to “curtailed oxygen” in babies weighing less than 1,500 g showed conclusively that the rate of cicatricial ROP was

reduced by two thirds with curtailed oxygen (Kinsey et al). Subgroup analy sis suggested the risk of eye damage was related to the duration of oxygen exposure, but no correlation was found with the level of FiO2. Nonetheless, an FiO2 of 40% was adopted as the upper limit of what was “safe.” Pulse oximetry was unavailable at the time, and bluish skin color of neonates was found to be an unreliable indicator of hypoxia. Blindness from RLF was reduced significantly with curtailed oxygen delivery, but the inability to monitor blood oxygen saturation resulted in increased infant morbidity and mortality.

Concern over the risks of increased mortality, and cerebral palsy with curtailed oxygen protocols, resulted in a liberalization of oxygen delivery in the 1960s. By the 1980s, a second ROP epidemic had developed that in part was related to increased survival of infants of very low birth weight infants, but increased oxygen delivery also was a factor. During this time cryother apy studies suggested that in some infants the disease is treatable. Unfortu nately, even when regression occurs with cryotherapy treatment, the visual

outcome is poor in a significant proportion of children (Cryotherapy for ROP Cooperative Group). Use of pulse oximetry has facilitated control of oxygen fluctuations and more targeted overall oxygen saturation in neonates. In the new millennium several reports have described a dramatic reduction of severe ROP by lowering supplemental oxygen and keeping oxygen satu ration between 80% and 93% (Tin et al; Chow, Wright et al; Wright et al; Vanderveen). The physiologic reduced oxygen protocol also results in good developmental and systemic outcomes (Deulofeut).

Etiology and Pathophysiology

In utero, a fetus is normally in a state of physiologic hypoxia with between 22 and 25 mm Hg. This low oxygen environment is important because physi ologic hypoxia stimulates production of vascular endothelial growth factor (VEGF), which in turn stimulates normal vessel growth throughout the body and specifically the retina (Table 19 1). Retinal vessels grow out of the optic disc into the peripheral retina with the retina being almost fully vascularized at full term (40 weeks’ gestation) (Figure 19 2). When a fetus is born pre maturely, the retinal vessels have not had time to grow into the periphery, so there is an peripheral area of avascular retina (Figure 19 3A). The more premature the infant, the larger the area of peripheral avascular retina. Preterm birth of a fetus exposes the immature developing retina to higher oxygen levels than those present in the intrauterine environment. If the premature infant

is exposed to high oxygen, the hyperoxic state will down regulate VEGF and retinal vessel growth will stop. Severe hyperoxia can not only stop vessel growth, but can cause vaso obliteration of existing immature retinal vessels

Table 19-1. Pathogenesis of Retinopathy of Prematurity

1. Premature birth, so there is incomplete vascularization of retina, with avascular periph-

eral retina.

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2. Hyperoxia after birth down-regulates VEGF and causes arrest of normal vascular growth

and even vaso-obliteration of existing vessels.

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3. Avascular retina becomes hypoxic after several weeks, causing rebound overproduc-

tion of VEGF.

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4.Overproduction of VEGF stimulates shunts and in severe cases neovascularization, which is “active ROP.”

cicatricial ROP (total retinal detachment), who had birth weights greater than 1,500 g. These children had not been monitored and had received uncurtailed oxygen for prolonged periods of time.

Other than hyperoxia and low birth weight, other risk factors include gestational age, respiratory distress syndrome, infections, intracranial hem orrhage, and blood transfusions (Table 19 3). Blood transfusions increase ROP risk because adult hemoglobin dissociates oxygen more easily than fetal hemoglobin, providing increased retinal oxygen dose.

Table 19-3. Retinopathy of Prematurity Risk Factors

Birth weight

Hyperoxia

Respiratory distress syndrome

Intracranial hemorrhage

Gestational age

Blood transfusions

Classification of Retinopathy of Prematurity

The first phase that initiates ROP is vaso obliteration (Figure 19 3B). This occurs as VEGF is down regulated in response to hyperoxia. The active phases of ROP occur later, usually between 34 and 36 weeks’ gestational age.

The international classification of ROP uses 3 parameters: (1) zone of the disease (how posterior is the ROP), (2) clock hours of involvement (circum ferential extent of ROP), and (3) stage (degree of abnormal vasculature). In general, ROP is more severe in the superior temporal periphery because this is the last area to be vascularized and has the widest avascular zone.

Normal immature retina is not truly ROP, but represents avascular peripheral retina. Immature retina must be watched closely through serial retinal examinations. Immature retina in Zone III usually has a good prognosis.

Zones of Retinopathy of Prematurity

Figure 19 4 shows the various zones of ROP. Zone I is the most posterior zone, demarcated by a circle centered on the optic nerve that extends twice the distance from the disc to the fovea. Zone II is a circle centered on the optic nerve, with the radius being the distance from the optic nerve to the

nasal ora serrata. Zone III is the temporal crescent of peripheral retina not included in zones I and II. Therefore, if ROP is present nasally, it has to be in Zone I or II.

Active Stages of Retinopathy of Prematurity

The active stages of ROP represent the spectrum of severity of retinal shunt vessel overgrowth secondary to a rebound up regulation of VEGF released from the hypoxic avascular peripheral retina (Figure 19 3 C and D, Table 19 4). The vascular shunt is an arteriolar venous shunt at the border between the vascular retina and the avascular retina (Figure 19 5). There are 3 active stages that describe the extent of the shunt, and a condition of posterior ves sel dilation called plus disease. Active stages 1 and 2 indicate a relatively small vascular shunt within the retina. In stage 1 the shunt is flat, while stage 2 has an elevated ridge. Stage 3 represents neovascularization with new vessels growing off the surface of the retina and is a sign of severe disease (Figure 19 6). Plus disease is tortuosity and dilation of posterior retinal vessels close to the optic disc (Figure 19 7). This is a sign of severe disease and may coexist with stage 2 or 3 ROP. Plus disease has been found to be the most important risk factor indicating the need for laser treatment

Cicatricial Retinopathy of Prematurity

Cicatricial ROP is a type of regression that presents as scarring secondary to severe active ROP, usually stage 3, Zone I or II. The degree and severity of cicatricial ROP depends on the severity of the active disease and is quite variable. The hallmark of cicatricial ROP is retinal fibrosis, scarring, and

Figure 19 4.

International classification of retinopathy of prematurity zones. Zone I is the circumferential area around the optic nerve with a radius twice the distance from the optic nerve to the fovea (dark red area). Zone

II has a diameter from the optic nerve to the nasal retina (pink zone). Zone III is the temporal crescent of retina not covered by Zone I or Zone II (light pink area).