Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Eye and Systemic Disease_Wright, Spiegel, Thompson_2006

One of the most challenging problems facing ophthalmologists who care for patients with EDS type VI and ocular fragility is the repair of the ruptured globe. Macsai et al.165 described an alternative to corneal transplantation and suturing in these patients. They performed a 360° conjunctival peritomy, removed the epithelium from the keratoglobus cornea, and sutured a ring of Descemet’s membrane and endothelium from a fresh donor corneoscleral ring to the patient’s sclera with 9-0 nylon suture. The conjunctiva was brought into position and tacked down over the edge of the donor graft. A full-thickness penetrating keratoplasty was performed 4 months later. This procedure was performed on both eyes with a final visual acuity OU of 20/100.

Marfan Syndrome

In its classical form, Marfan syndrome is characterized by the presence of abnormalities of the eye (ectopia lentis), aorta (dilatation of the aortic root and aneurysm of the ascending aorta and aortic aneurysm), and skeleton (dolichostenomelia, upper segment/lower segment ratio 2 SD below mean for age, pectus excavatum, and kyphoscoliosis).11,220 In addition to these three major criteria, auxiliary signs may be present, such as myopia, mitral valve prolapse, arachnodactyly, joint laxity, tall stature, pes planus, striae distensae, pneumothorax, and dural ectasia. The clinical diagnosis may be difficult in mild cases, and the spectrum of patients with connective tissue abnormalities simulating the Marfan syndrome is wide. The identification of fibrillin, a major component of connective tissue,242 as the defective gene in Marfan syndrome following the mapping of the disease to chromosome 15,56,57,133,289 has stirred up interest in this glycoprotein and its role in connective tissue diseases.

About 35% of patients with the Marfan syndrome do not develop lens subluxation.172 There have been reports of large families with Marfan syndrome without ectopia lentis in which the disease could not be linked to the fibrillin gene18 but maps to chromosome 3p24.2–p25.45 Marfan syndrome affects 1 in 20,000 persons.220

Ocular findings are present in at least 60% of patients with Marfan syndrome.4,50,172 A number of ocular histopathological studies have been published.60,67,223,296 The most characteristic and usually diagnostic ocular abnormality is subluxation of the crystalline lens (Fig. 5-3). The degree of subluxation varies from mild superior and posterior displacement, evident only on

FIGURE 5-3. Subluxated lens of a patient with Marfan syndrome. Note stretched zonules inferonasally.

maximal pupillary dilation, to significant subluxation placing the equator of the lens in the pupillary axis. Although superior and temporal displacement of the lens is most common, inferior, nasal, or lateral subluxation also occurs. Subluxation of the lens is slowly progressive in some patients and most noticeable in the first few years of life or in the late teens and early twenties; in most patients, however, no progression of the displacement is noted over the years. Total dislocation in the vitreous cavity is unusual early in life, but has been documented in older patients where it may, rarely, be complicated by phacolytic glaucoma. Lens dislocation into the pupil or the anterior chamber is characteristic of untreated homocystinuria.

In the Marfan syndrome, stretched zonular fibers can be seen through the dilated pupil. In places where zonules have ruptured, a straightening of the lens contour is noted and has been falsely labeled as a coloboma of the lens. Microspherophakia is present in about 15% of patients and results in high myopia. The cornea is flat with keratometric readings in the high 40s in about 20% of patients. Megalocornea (corneal diameter measuring more than 13.5 mm) may be present in some patients. The iris has a thin velvety texture, and the pupil is difficult to dilate in the more severely affected patients where there is atrophy of the dilator muscle fibers. Iridodonesis results from lens subluxation.

Wheatley and coworkers studied the distribution of fibrillin in normal ocular tissues and found the glycoprotein to be ubiquitous in the cornea, sclera, anterior chamber angle, uvea, zonules, lens capsule, and optic nerve septae.306 They concluded that ocular abnormalities in the Marfan syndrome could be correlated to the pattern of distribution of fibrillin in the eye. Further studies of sections and/or flat mounts of lens capsules from normal autopsy eyes, and surgical capsulotomy specimens from patients with senile cataracts and from patients with the Marfan syndrome, showed three distinct and adjacent zones in the equatorial and periequatorial regions of the normal lens capsule: zone I, a 0.75-mm-wide peripheral ring of the anterior capsule that contained radial bundles of fibrillin fibers which appeared to suspend the central part of the capsule; zone II, a 1- mm-wide meshwork of fibrillin-rich fibers that encircled the equator and served as an insertion platform for zonular fibers; and zone III, composed of radial, 0.1-mm-wide bands arranged in a periodic fashion in the most peripheral part of the posterior capsule. Fibrillin fibers were abnormal and disrupted in all three zones in patients with the Marfan syndrome.185 From these observations and a later study by Traboulsi et al.,287 it was concluded that fibrillin is a major constituent of the peripheral and equatorial areas of the lens capsule, that it may play a role in the ability of the lens to change its configuration during accommodation, and that the observed qualitative and quantitative abnormalities in fibrillin expression in the lens capsule of patients with the Marfan syndrome support a causal relationship to lens abnormalities in these patients.185,287

Strabismus is more common in the Marfan syndrome than in the general population of the United States.124 Exotropia occurs in about 10% of patients and esotropia in 2%. Strabismic or anisometropic or ametropic amblyopia should be suspected in all patients with reduced visual acuity, especially if the reduction is asymmetrical. In many cases, amblyopia responds surprisingly well to treatment despite years of uncorrected high errors of refraction. Open-angle glaucoma is significantly more common in patients with the Marfan syndrome in all age groups as compared to the general population and becomes more prevalent in this disease with increasing patient age.123 Pupillary block is unusual but has been documented. Phacolytic glaucoma has been noted in older patients with mature dislocated lenses and carries a guarded prognosis because of the complex vitreoretinal surgery needed to extract the hard cataractous lenses. Retinal

skeleton, ears, eyes, teeth, skin, and joints.160,228 Osteogenesis imperfecta is caused by abnormalities of the alpha1 or alpha2 chains of type I collagen. There is failure of type I collagen fibers to mature to their normal diameter. Mutations in the COL1A1 (chromosome 17) and COL1A2 genes (chromosome 7) account for most cases in all four types. The location of the mutation in the gene seems to determine the clinical phenotype.27,305 The diagnosis of osteogenesis imperfecta is based on clinical, dental, and radiologic criteria. Individuals with OI type I have bright blue sclerae that remain intensely blue throughout life (Fig. 5- 4). In types III and IV, the sclerae may be blue at birth, but the intensity of the color decreases such that by adolescence or early adulthood the sclera appear normal. The blue coloration results from the visualization of the underlying choroid through a thin sclera. Ocular rigidity was found to be reduced in a group of 16 patients with different types of OI.134 The perilimbal region is often whiter than the remaining sclera, resulting in the so-called Saturn’s ring. Electron microscopy reveals reduction in the

abnormalities in the form of microspherophakia and ectopia lentis.226 The incidence of this disease is about 1 in 100,000 individuals. Patients are of normal intelligence. One parent is usually short with or without stubby hands and no ocular abnormalities, indicating that the gene for this disorder is not completely recessive. Family members in previous generations may also be identified as carriers based on stature.98,143

Ocular abnormalities are only present in homozygotes.128 The microspherophakic lens tends to move into the pupillary area, leading to pupillary block and glaucoma.309 Total dislocation into the anterior chamber may occur. Myopia is most often caused by the spherophakia, but may be axial, and ranges from 3 to more than 20 diopters. Lenticular diameter may be as small as 6.75 mm, and the sagittal diameter of the lens may be increased by 25%.178 A peripheral iridectomy relieves pupillary block in most patients, but lens extraction may be necessary to control intraocular pressure elevation. Mydriatics are preferred over miotics for the relief of pupillary block; cycloplegics, however, have been reported to induce pupillary block in these patients.311

Cohen Syndrome

Cohen syndrome is characterized by congenital hypotonia, midchildhood truncal obesity, narrow hands and feet, and a typical facial appearance with a high nasal bridge, open mouth with prominent central incisors, short philtrum, and micrognathia.31,42,197,198 Some patients have delayed puberty but no documentable endocrinological abnormalities.7,54 Granulocytopenia may be present, and Warburg and coworkers299 postulated the existence of two types, type I (with granulocytopenia) and type II (without granulocytopenia). Cohen syndrome can be differentiated from Bardet–Biedl syndrome by the absence of polydactyly and hypogenitalism; both feature a progressive retinal dystrophy that is, however, much more severe in the Bardet–Biedl syndrome. Cohen syndrome is inherited in an autosomal recessive fashion,70,82,145 and the gene has been mapped to 8q22–q23.277

Night blindness with poor vision and constricted visual fields are universal. Downslanting of the palpebral fissures occurs in all patients. A pigmentary retinopathy with progressive chorioretinal atrophy develops as early as the first decade of life. The electroretinogram is nonrecordable, and bony spicules are seen in the retinal periphery. Progressive myopia is

one of the hallmarks of the disease and is present in the majority of patients.299 Cataracts develop in some patients in the fourth and fifth decades of life.196

No specific treatment is available. Despite the granulocytopenia, patients with Cohen syndrome do not seem prone to infection.299

Stickler Syndrome (Hereditary Progressive

Arthro-Ophthalmopathy)

This syndrome is a clinically heterogeneous group of dominantly inherited disorders of collagen.109,173,204,270,280,294 Four genetic loci have been identified. The most common type, STL1 or membranous vitreous type, is caused by mutations in the COL2A1 gene on 12q14.79,84 The other forms include STL2 or beaded vitreous type caused by mutations in COL11A1, STL3 or nonocular type caused by mutations in COL11A2, and an additional form whose locus has not be identified yet.264

The incidence of Stickler syndrome is estimated at 1 : 20,000. Optiz et al.204 believe that Stickler syndrome is more common than Marfan syndrome. Some features are common to more than one clinical subtype; these include sensorineural hearing loss in about 25% of patients, cleft palate in about 25%, and a progressive arthropathy that is often subtle early in life but becomes most pronounced in the fourth or fifth decade. Although most patients have increasing stiffness, soreness, and arthritic changes, some have hyperextensible joints. Flattening of the epiphyseal centers on X-rays is present early in life, and, together with congenital myopia, constitute the minimal diagnostic criteria for the Stickler syndrome. Mitral valve prolapse is present in 45% of patients.163

The ocular findings include congenital and sometimes stable high myopia, presenile cataracts, and vitreoretinal degeneration; Retinal detachment is common.144,266 In the most common STL1 type the vitreous is liquefied with midperipheral circumferential condensations or veils (Fig. 5-5). Radial perivascular patches of lattice degeneration are present in the posterior pole and midperiphery (Fig. 5-6). Glaucoma develops in about 5% of cases. Rarely, patients develop subluxation of the lens.

The management of patients with Stickler syndrome includes the prevention of retinal detachment through repeated careful ophthalmoscopic examinations and prophylactic treatment of retinal holes. Patients with cleft palate receive appro-

A

FIGURE 5-7A–C. Typical flat facial appearance of a patient with Kniest syndrome (A). Note enlarged interphalangeal joints (B) and knees (C).

in dominantly inherited myopia with or without retinal detachment and deafness. The diagnosis should also be suspected in dominantly inherited cleft palate, mild spondyloepiphyseal dysplasia, and in dominantly inherited mitral valve prolapse.

Kniest Dysplasia

Patients with this autosomal dominant bone dysplasia have short stature, prominent wide joints, short trunk with a broad thorax and protrusion of the sternum, and a flat midface with depressed nasal bridge (Fig. 5-7). Cleft palate is present in about 40% of patients and 75% of patients have hearing loss. X-rays demonstrate widening of the metaphyses and narrowing of joint spaces. The cartilage in growth plates has a “Swiss cheese” appearance on histopathological sections; this appearance is caused by the dilated endoplasmic reticulum complex in chondrocytes. The disorder results from mutations in COL2A1,308 the