Fig. 19-36  Central corneal opacity in Peter’s anomaly.

Other ocular abnormalities have been associated less frequently and include strabismus, cataract, retinal detachment, macular degeneration, hypoplasia of the optic nerve, and chorioretinal colobomata.

When the ocular abnormalities are associated with dental, facial, or other systemic abnormalities, the term Rieger’s syndrome is applied. Dental and facial anomalies (see Fig. 19-34B) are most common and include hypodentia, microdentia, and occasional anodentia; malar hypoplasia; hypertelorism; redundant periumbilical skin, and hypospadias. Other systemic anomalies include short stature, heart defects, neurologic problems, empty sella syndrome, deafness, and mental deficiency.

Because there may be overlap of the phenotypic presentations of Rieger’s and Axenfeld’s syndromes in the same family,264 they

are sometimes treated as a single but protean syndrome called the Axenfeld-Rieger’s syndrome.17,260,265 Linkage studies reveal a

heterogeneous genetic picture; for example, the Rieger’s anomaly does not always map consistently to the 4q chromosome, as does Rieger’s syndrome.266 This suggests either the two phenotypic Rieger’s phenomena are genetically distinct despite their clinical similarities, or that multiple genetic defects can cause both Rieger’s

anomaly and Rieger’s syndrome.9 The cytogenetics and molecular genetics of these disorders are complex and evolving.265,267

Glaucoma in the Axenfeld-Rieger’s syndromes occurs in approximately 50% of affected individuals. The glaucoma may occur in infancy due to trabeculodysgenesis, but is usually delayed into the first or second decade of life. In infants, a goniotomy or trabeculotomy is the indicated surgical procedure. In older children, medical therapy should be tried before any surgical procedures. If surgery is necessary, the surgeon can choose a trabeculectomy with anti­ metabolite,189 combined trabeculectomy-with-trabeculotomy,268 or glaucoma tube procedure.269

Peter’s anomaly

Peter’s anomaly (Fig. 19-36) manifests as bilateral central corneal opacification with adhesions of the central iris to the posterior surface of the cornea. Frequently, these iris attachments arise from the collarette and attach to the cornea, where there is an absence of Descemet’s membrane and thinning of the posterior corneal stroma.270 In extreme cases, the lens can adhere to the corneal endothelium, with a cataract present. One classification distinguishes Peter’s eyes with normal lenses (type I) from a type with abnormal lenses (type II).271 This condition has also been called anterior chamber cleavage syndrome.2

Approximately half of the patients with Peter’s anomaly have ocular defects, and 60% have systemic defects.272 The ocular findings in Peter’s anomaly include microphthalmos, myopia, aniridia, and cataract.273 It has been genetically linked to the same mutation at the PAX6 locus as the aniridia gene in one study, although overlap of phenotypic expression is not prominent.9 Retinal detachment occurs spontaneously in up to 10% of patients.274

Systemic findings include developmental delay, congenital heart disease, congenital ear anomalies and hearing loss, genitourinary defects, cleft palate, and spinal defects.274 The ‘Peter’s-plus syndrome’ includes Peter’s anomaly, short stature, small hands, mental retardation, abnormal ears, and cleft lip and palate; it is inherited as an autosomal recessive and is the same as Kivlin syndrome.275

Glaucoma occurs in up to 50% of Peter’s anomaly eyes and may be present even when the anterior chamber angle appears grossly normal, although trabeculodysgenesis may be present. The glaucoma may be first seen in infancy or later in life. When glaucoma exists in infants, goniotomy, trabeculotomy, and trabeculectomy have been used, with the preferred procedure individualized to each patient. Medical therapy is important in older children and

should be attempted before any surgical procedure. If surgery is necessary, a trabeculotomy or trabeculectomy is indicated.

Frequently the glaucoma is difficult to control in these patients and may require insertion of a synthetic drainage device or ciliodestructive procedures. Rarely is the vision in the glaucomatous eye

better than 20/400, and as many as 50% of glaucomatous eyes are blind within the first decade of life.276,277

Penetrating keratoplasty and cataract extraction may be required to provide a clear visual axis, and the surgical obstacles to success are formidable.278 More advanced forms of this disorder may demonstrate varying degrees of corneal thinning. Severe cases show actual full-thickness holes through the cornea, with flat anterior chambers and adherence of the lens to the posterior cornea. The visual prognosis of glaucoma with extensive corneal disease is grim, although exceptions have been reported.279

Lowe syndrome (oculocerebrorenal syndrome)

The oculocerebrorenal syndrome of Lowe is an X-linked disorder of the OCRL1 gene, with clinical manifestations that include con-

genital cataracts, mental retardation, and progressive renal tubular dysfunction.280–282 The inheritance pattern is sex-linked reces-

sive: 100% of males have cataracts, and 50% of affected males have ­glaucoma.43 Linkage analysis allows detection of carriers as well as prenatal diagnosis.283,284

Female carriers of the defect exhibit characteristic (though not pathognomonic) irrregular, radially arrayed anterior cortical lens opacities, sometimes with posterior capsular changes as well. The glaucomatous angle can have the appearance of isolated trabeculodysgenesis but rarely responds to goniotomy; filtering or tube surgery may be required. Possibly the early surgical removal of cataract introduces the complexities of aphakic open-angle glaucoma into the clinical picture.285

This syndrome must be distinguished from the Zellweger (hepatocerebrorenal) syndrome, a lethal peroxisomal biogenesis disorder that causes infantile hypotonia, seizures, and death within the first year. Ophthalmic manifestations include corneal opacification, ­cataract, glaucoma, pigmentary retinopathy, and optic atrophy.286

Microcornea syndromes

Microcornea is both an autosomal dominant defect,96 as well as a non-specific finding seen in a variety of disorders (rubella syndrome, persistent hyperplastic primary vitreous, Rieger’s anomaly, nanophthalmos, and microphthalmia). It can also be seen with miscellaneous systemic diseases, such as fetal alcohol syndrome, myotonic dystrophy, and achondroplasia,287 and a syndrome of absent frontal sinuses.288

The term generally refers to patients with microphthalmia in which the eye is hyperopic and has a corneal horizontal diameter less than 10 mm, but microcornea can occur in a normal size globe, often with peripheral sclerocornea. Shallow anterior chambers and narrow angles may contribute to acute angle-closure glaucoma; treatment is directed toward the angle-closure glaucoma. Microcornea is an important predictive risk factor for determin-

ing which children operated on for congenital cataracts will go on to develop pediatric aphakic open-angle glaucoma.289,290 This risk

exists for either anterior or pars plana removal of the lens (without

IOLs).291,292

Fig. 19-37  Rubella retinopathy with anomalous pigmentation.

Rubella

Congenital rubella syndrome has a wide variety of severe ophthalmic and systemic complications.A worldwide rubella epidemic from 1963 to 1965 affected thousands of infants, many of whom continue to be seen as adults. Ocular disease was the most commonly noted disorder (78%), followed by sensorineural hearing deficits (66%), psychomotor retardation (62%), cardiac abnormalities (58%), and mental retardation (42%). Multiorgan disease was typical (88%).293

Glaucoma, cataract, microcornea, keratitis, uveitis, and a pigmented retinopathy (Fig. 19-37) are the most common ocular manifestations of congenital rubella infection.294 There is no correlation with gestational age of infection and a specific ophthalmologic defect.293

Rubella keratitis, often of relatively short duration, causes deep corneal clouding in either a diffuse or disciform pattern.This must not be confused with corneal edema resulting from glaucoma. The glaucoma may present in infancy and have the appearance of isolated trabeculodysgenesis.This form is best managed by goniotomy.

Glaucoma can also arise from iridocyclitis. These patients respond poorly to goniotomy and should be treated with aqueous suppressants, anti-inflammatory therapy, and cycloplegics during the acute phase, which frequently subsides over several weeks. Later onset glaucoma is commonly seen in rubella eyes with microcornea and cataract extraction under the age of 1 year.289

Chromosome abnormalities

Increasing numbers of chromosomal defects (Fig. 19-38) are associated with congenital glaucoma in its isolated or syndrome

forms,9a,69 including trisomy 21295; trisomy 13–15; trisomy 17– 18296,297; Turner’s syndrome; trisomy 3q; chromosome 6 and its

associations with both iridocorneodysgenesis and oculodentaldigital anomalies252,298,299; and trisomy 2q.300 Multiple ocular and systemic

defects may be evident, with a large variation in their presentations. The necessity for surgical or medical management must be individualized to each patient because some of these patients have a limited life expectancy. If isolated trabeculodysgenesis is evident on examination, a goniotomy would be the initial procedure.