Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Retinal Disease_Wright, Spiegel, Thompson_2006

CLINICOPATHOLOGICAL CORRELATION OF ROP STAGES

Stage 1: Demarcation Line

This stage represents a thickened exaggeration of the line of normal advancing vasculature and comprises two distinct zones.54,56 The anterior vanguard zone is formed by a sheet of spindle-shaped cells that are the precursors of the differentiated vascular endothelium. It corresponds to the primitive mesenchyme (spindle cells) seen in normal fetal development, but the cells are hyperplastic, causing the demarcation line to be clinically visible (Fig. 10-9). Behind the proliferating spindle cells is a rear guard zone comprised of endothelial cells that have differentiated from the vanguard mesenchymal cells and are forming a primitive capillary meshwork. This zone is not clinically discernible until stage 2.

Stage 2: Ridge

The ridge represents a further thickening of the line in stage 1 because of continued proliferation of spindle cells in the vanguard zone.54–56 In addition, a thin white line behind the vanguard is separated by a lucent line of approximately the same width. The white line (ridge) is the predominant feature of this stage and histologically corresponds to proliferation of the endothelial cells of the rear guard zone (Fig. 10-10). The ridge has increasing height, width, and volume and extends up out of the plane of the retina. The ridge may turn from white to pink, which corresponds to an arteriovenous shunt of primitive vascular channels that has been shown clinically to leak fluorescein dye by Flynn et al.53 The retinal lesions in stage 1 and 2 regress in most cases, leaving few, if any, residual signs.

Stage 3: Ridge with Extraretinal

Fibrovascular Proliferation

Stage 3 involves neovascular proliferation of vessels that are continuous with the posterior aspect of the ridge and that extend into the vitreous perpendicular to the plane of the retina.54–56

Foos56 referred to these new vessels as “extraretinal vascular-

FIGURE 10-9A,B. (A) ROP, stage 1: macroscopic demarcation line (asterisk) represents a thickened exaggeration of normal vanguard. Vasodilation is evident posterior to the demarcation line. (From Foos RY. Retinopathy of prematurity: pathologic correlation of clinical stages. Retina 1987;7:260–276, with permission.) (B) ROP, stage 1: microscopic demarcation line demonstrates thickening of retina that is related to proliferation of spindle cells in vanguard (V). H&E, 300. (From Foos RY. Retinopathy of prematurity: pathologic correlation of clinical stages. Retina 1987;7:260–276, with permission.)

ization” and described three fairly distinct forms: placoid, polypoid, and pedunculated. The placoid form is the most common and has a circumferential orientation because of its occurrence in the region of the ridge (Fig. 10-11). It is also the most impor-

from the retina behind the ridge. Foos55,56 has demonstrated microscopically proliferation of solid cords of endothelial cells from the region of the rear guard (ridge) through the retinal surface into the vitreous cavity. Based upon Factor VIII preparations, Foos56 confirmed that these vessels are derived from proliferating endothelial cells, not from vasoformative mesenchymal cells, as in normal retinal angiogenesis. Serous exudate may accumulate under the retina during stage 3, and alterations of the vitreous also become evident. The changes in the vitreous body take two major forms: synchysis and condensation. Foos56 suggested that synchytic destruction of the vitreous body was related to the release of lytic substances by incompetent vessels within the retina or vitreous body and that condensation of the vitreous body over the ridge was related to depolymerization of hyaluronic acid and collapse of the collagenous framework into optically visible structures.

Stage 4: Subtotal Retinal Detachment

The retina begins to buckle and fold at the ridge and is drawn anteriorly toward the lens margin by vitreous condensation (Fig. 10-12). Although tractional forces are predominant, the detachment may have a serous component. Commonly, radial tractional forces limited to the temporal quadrants draw the nasal retina temporally, resulting in a meridional fold extending from the region of the disc to the temporal periphery. The contraction process may be so strong that finally all vessels will pass in a straight line from the optic nerve head toward the temporal periphery and nasal retina may overlie the nerve head.

Stage 5: Total Retinal Detachment

As the retina becomes folded and progressively drawn anteriorly and centrally, it becomes pleated or rolled, like a scroll, resulting in foreshortening and progressive detachment of the posterior retina (Fig. 10-13). Subsequently the “V” or funnel shape of the detachment becomes altered in shape by both anterior and posterior closure. Machemer101 explains the pattern of the retinal detachment based on proliferation and contraction of tissue originating from the shunt area. When the shunt area forms a ring the pattern of the retinal detachment may vary according to whether the shunt area is anterior, equatorial, or posterior in location. For example, with equatorial or posterior

FIGURE 10-12. ROP, late stage 3: buckled and folded retina is being drawn anteriorly toward the lens margin by vitreous condensations emanating from the highly elevated ridge. 6. Insert: microscope features. H&E, 25. (From Foos FY. Chronic retinopathy of prematurity. Ophthalmology 1985;92:563–574, with permission.)

shunts the avascular peripheral retina stretches and stays attached forming a “trough” at its juncture with the detached nonstretchable vascularized retina. The vitreous undergoes further central synchysis and condensation of vitreous sheets on the retinal surface, but posterior vitreous detachment is rare. Extraretinal proliferation of nonvascular tissue is usually present at this stage, which includes retinal glial processes extending into the vitreous, epithelial membranes, and pigmented and nonpigmented retroretinal membranes.55,56

The vitreoretinal traction forces that cause the unique, progressive retinal detachment seen in ROP are poorly understood, especially because some features that characterize proliferative vitreoretinopathy associated with rhegmatogenous retinal detachment in adults are not conspicuous, for example, cellmediated proliferation along the surface of the detached posterior vitreous.56 However, the process is multifactorial and includes both intraretinal and extraretinal factors. Intraretinal factors may include contractile proteins in the vanguard cells, contraction of the rear guard endothelial cells, and astrogliosis of the superficial retina56 Extraretinal factors include contraction

of the extraretinal vasoproliferative tissue and synchytic destruction of the vitreous body, which provides a scaffold for growth of the extraretinal vessels.56

OCULAR FINDINGS IN REGRESSED ROP

Myopia, Astigmatism, and Anisometropia

Myopia is a common finding in the newborn premature infant even without ROP with a tendency toward less myopia by the latter half of the first year after birth.46,60,72a Myopia that is of higher degree and persists into later life is usually associated with prematurely born children afflicted with ROP.30 The incidence of myopia was determined in a large group of premature infants with birth weights of less than 1251 g followed as part of the multicenter study of Cryotherapy for Retinopathy of Prematurity.30 These eyes, which did not undergo cryotherapy, were refracted at 3, 12, and 24 months. Myopia was observed in approximately 20% of the children at each test age, and the percentage of high myopia ( 5 diopters) doubled from 2% to 4.6% between 3 and 12 months and remained stable thereafter. Lower birth weight and increasing severity of ROP were predictors of myopia and high myopia. In addition, anisometropia, astigmatism, and the presence of macular heterotopia and retinal folds also were associated with a higher incidence of myopia and high myopia. The exact mechanism of the myopia associated with ROP is unknown and may be due to an elongation of the globe, alteration of the lens or the corneal curvature, or a combination of all of these factors.30,34,46,81,140a More severe ROP results in a higher risk of myopia.82a,140a The degree of myopia at age 3 months predicts the presence of high myopia at 5.5 years; between 3 months and 1 year of age, a decrease in the proportion of eyes with hyperopia and an increase in the proportion with myopia occurs.140a Eyes with ROP treated with laser develop less myopia, on average, than do those treated with cryotherapy.85a Further animal model work, more studies of biometric measurements in the developing eye, and further observations on the effects of light on the developing eye may help clarify the factors underlying the development of abnormal refractive errors in infants with ROP.30

Other studies34,89,91,98,147 performed in infants with regressed ROP have noted a higher incidence of strabismus, amblyopia,

anisometropia, and high refractive errors compared with control groups of infants who did not have ROP. Gallo et al.58 noted an increased incidence of refractive errors, strabismus, and retinal complications in children with regressed ROP. Microcornea and microphthalmos have also been associated with ROP.31,81

Foveal Avascular Zone

Ibayashi et al.74 studied vascular patterns using fluorescein angiography in patients aged 5 to 15 years with cicatricial retinopathy of prematurity and found a high incidence of incomplete development of avascular zones in the macula when compared to a control group. They concluded that underdevelopment of the foveal avascular zone was an important feature of cicatricial ROP and had a significant correlation with active disease but had no relationship to visual prognosis in most cases. Isenberg75 demonstrated a delayed macular development in infants with ROP, and he speculated that this possibly could engender amblyopia, which could lead to strabismus.

LATE COMPLICATIONS OF

REGRESSED ROP

Glaucoma

Kwitko94 estimated that secondary glaucoma developed in 30% of eyes with severe retinopathy of prematurity. Young infants or children with severe advanced ROP are most often affected; however, acute angle closure has been reported in adults.108,151 The mechanism most likely causing secondary angle-closure glaucoma is an anterior displacement of the lens–iris diaphragm secondary to contraction of a retrolental fibroglial mass.108 However, other mechanisms have been proposed. In adult eyes with ROP and no retrolental mass, possible mechanisms include both pupillary block and ciliary block.90,108 Increased lens thickness has been documented in ROP patients and may also play a role in a pupillary block mechanism.108 Progressive very high myopia maybe a sign that the large lens is crowding the angle, and glaucoma is a risk. Other mechanisms to explain secondary angle-closure glaucoma seen in ROP include inflammation93 and anterior segment neovascularization.108 Hartnett et al.68 prospectively examined the anterior segment of 27 eyes of 17 prema-

ture infants with stage 4 and 5 ROP to identify and classify structural characteristics that could predispose the premature infant with ROP to glaucoma. In addition to identifying pathological changes, for example, anterior and posterior synechiae, they noted changes that may have a developmental origin such as corneal dystrophy, Barkan’s-like membrane, and large tunica vasculosa-like vessels. Thus, abnormal development of the angle and inadequate outflow could possibly contribute to the pathogenetic mechanism of glaucoma seen in eyes with advanced ROP.68

The choice of therapy for secondary glaucoma in ROP may include medical or surgical measures and is based on the initial intraocular pressure and vision, degree of lens opacity and intumescence, presence of anterior segment neovascularization, and the gonioscopic appearance of the anterior chamber angle.108 Acute angle-closure glaucoma occurring in adults may respond to medical treatment, including miotic therapy. Following stabilization of intraocular pressure, laser iridotomy or surgical peripheral iridectomy can be performed.108,151 Kushner90 reported the successful relief of apparent ciliary block glaucoma in two children and one adult with cicatricial ROP using cycloplegic therapy after failure of miotic therapy. Two of these patients later required either lensectomy or vitreous aspiration. Pars plana lensectomy and anterior vitrectomy or lensectomy via the limbal approach has been advocated by Pollard135,136 to treat secondary angle-closure glaucoma with severe advanced cicatricial ROP. Most of these patients presented after the age of 2 years. Although patients had final vision of only light perception to hand motion, his rational was to retain a painfree eye and avoid enucleation. Kushner and Sondheimer93 treated seven children with cicatricial grade 5 ROP and secondary glaucoma with shallow anterior chambers with corticosteroids. They were able to control intraocular pressures and avoid enucleation. Inflammation in these eyes secondary to either phacolytic glaucoma, blood or blood breakdown products, or neovascular glaucoma responded to topical corticosteroids. Filtering surgery for lateonset acute or chronic angle-closure glaucoma may be necessary if intraocular pressure cannot be controlled with either medical treatment or peripheral iridectomy.108 Alloplastic tube shunt implantation may be the treatment of choice for neovascular- ization-induced secondary angle closure in eyes with useful vision potential.108 Ciliodestructive procedures are recommended for blind and painful eyes.108