Ординатура / Офтальмология / Английские материалы / Pediatric Ophthalmology Current Thought and A Practical Guide_Wilson, Saunders, Trivedi_2008

24.3.1Signs and Symptoms of Glaucoma in Infancy and Early Childhood

Infants and young children with glaucoma (from any cause) usually present for ophthalmologic evaluation because the pediatrician or parents have noted something unusual about the appearance of the child’s eyes or behavior. Corneal opacification and/or enlargement are the most common initial signs of glaucoma and both may progress over the first 2 years of life if

IOP remains elevated (Figs. 24.1–24.3). “Buphthalmos” is a term applied to describe the abnormal enlargement of an infant’s eye secondary to elevated

IOP; in extreme cases these eyes are vulnerable to

lens subluxation and even rupture with minor trauma (Fig. 24.4). The “classic triad” of findings: epiphora, photophobia, and blepharospasm [29] result from corneal edema often with associated breaks in Descemet’s membrane called Haab’s striae. The occurrence of Descemet’s membrane breaks appears to be confined to the first 2 years of life; they leave permanent evidence of early-onset glaucoma, and vary with respect to the associated corneal distortion and scarring (Fig. 24.5). Breaks with more vertical orientation may be seen associated with forceps delivery

[22].

Additional non-specific signs of glaucoma in early life include the presence of a deep anterior chamber and optic nerve cupping. In the absence of optic atrophy, the optic cup may decrease greatly in size

Fig. 24.1  Corneal enlargement bilaterally, with clear corneas. This infant was 2 months old at diagnosis, and responded initially to angle surgery, but subsequently required aqueous drainage device implantation in both eyes

Fig. 24.3  Newborn-onset congenital glaucoma with severe bilateral corneal edema and opacification. Despite reduction of IOP after surgery, central corneal opacification did not completely clear

Fig. 24.2  Corneal opacification of the right eye in a 1-month-old infant with primary congenital glaucoma

Fig. 24.4  Six-year-old boy with bilateral primary congenital glaucoma. The right eye responded well to angle surgery, while the left eye was more severely affected, became buphthalmic, and required multiple surgeries. Vision is poor in the left eye due to residual corneal scarring, and dense amblyopia

with IOP reduction, and will enlarge again if control of IOP is lost. Optic atrophy which may result from chronic or severe IOP elevation is irreversible.

24.3.2Signs and Symptoms

of Glaucoma in Older Children

Older children are typically evaluated because of decreased vision (usually from induced myopia, but sometimes from severe optic nerve damage) or circumstances in which secondary glaucoma might be suspected. While optic nerve cupping does not itself represent a reliable indicator of glaucoma, its presence should prompt thorough evaluation of that possibility in a child of any age (Fig. 24.6). Older children infrequently present with acute glaucoma inducing nauseating eye pain, headaches, and even colored haloes around lights (e.g., secondary to trauma

Fig. 24.5  Haab’s striae seen in retroillumination in an 8-year-old boy with unilateral congenital glaucoma diagnosed at the age of 9 months, and treated with goniotomy surgery. Note the curvilinear pattern of the Descemet’s membrane break, which fortunately spared the visual axis, and caused very little astigmatism in this eye. The vision in this eye is 20/25, and the IOP is normal without medications

Fig. 24.6  Severe optic nerve cupping in a 13-year- old girl whose juvenile open-angle glaucoma was diagnosed 3 years after she began wearing glasses for myopia. Intraocular pressures were 40 mmHg in both eyes, and responded to medications and trabeculectomy

or angle closure as with cicatricial retinopathy of prematurity).

Loss of vision from infant and childhood glaucoma occurs secondary to pathologic changes in the eye such as corneal opacification and optic nerve damage. Poor vision may also occur secondary to the development of unilateral or bilateral refractive errors, which in turn produce amblyopia, often with associated strabismus.

24.4 Ocular Examination

While the complete pediatric eye examination best evaluates a child with suspected glaucoma, there are specific goals of the glaucoma-related examination:

(a) confirming or excluding the diagnosis of glaucoma, (b) determining the etiology of the glaucoma (if present), and (c) gathering information (including any prior glaucoma interventions) vital to planning the optimal treatment. Examination under anesthesia may be avoided if the diagnosis of glaucoma can be confidently excluded (in an infant or young child) or if an older child would benefit from a medication trial. When indicated, the examination under anesthesia provides a one-stop opportunity for more detailed

gonioscopy and optic nerve head evaluation, as well as measurements such as corneal diameter and pachymetry, axial length measurement, and then any needed surgical intervention.

24.4.1Vision Testing

(Acuity and Visual Fields)

Optimal vision testing methods will vary with the patient’s age and cognitive function; fixation behavior and absent nystagmus are encouraging in infants, while older children should perform optotype testing. Automated visual field testing, applicable primarily to help assure the stability of older children with known glaucoma and glaucomatous field loss, often proves challenging for younger children, and children with nystagmus or poor vision. Even confrontation visual fields can often verify suspected severe nasal field loss in children with severe glaucoma and poor vision. Newer, faster testing algorithms may allow younger children to perform automated (Humphrey) visual field testing more reliably [31].

24.4.2 External Examination

External examination helps identify evidence of associated abnormalities (e.g., neurofibromatosis), buphthalmos (especially asymmetry between the eyes), photophobia, or nasolacrimal obstruction.

24.4.3 Tonometry

Measurement of the IOP (tonometry), critical to the diagnosis and treatment of children with glaucoma, belongs as part of the both the office and operating room routine. Portable applanation tonometers, such as the Perkins applanation tonometry and the TonoPen (a Mackay-Marg-type tonometer), prove very useful for IOP measurement in infants and young children [68, 115] whose size and attention precludes the gold-standard slit-lamp-mounted Goldmann applanation technique.

Intraocular pressure measurements are variably lowered by sedatives, narcotics, and inhalation anesthetic agents [30, 78, 125], and elevated by endotrachealintubation[29].Ketamineanesthesia,previously reported to elevate IOP[8], has recently compared favorably with sevoflurane anesthesia in terms of minimally altering measured IOP over several minutes after induction [14]. Chloral hydrate conscious sedation, effective only in small children and with careful monitoring, reportedly minimally affects awake IOP readings [53].Although IOPmeasurements taken in a sedated or anesthetic state are often less reliable than those in a calm, awake child, high preoperative IOP measurements generally remain in an abnormal range, and asymmetric IOPs between the two eyes usually remain so and often signal abnormality. Special care must be taken to avoid spuriously high IOP measured in the anesthetized child who is in laryngospasm, or

“light” with eyes rolled either upward or downward compared with the midline. The normal IOP in childhood, ranging from about 10 to 22 mmHg [29], rises from infancy to reach normal adult levels by middle childhood [90].

24.4.4 Anterior Segment Examination

Anterior segment findings provide key information in the evaluation of the pediatric glaucoma patient. The cornea should be inspected and measured (holding a ruler in the frontal plane in the office, and using a caliper and ruler during anesthetized examination).

Corneal changes resulting from elevated IOP often assist in diagnosing glaucoma with infant-onset, while other abnormalities may provide clues to the type of glaucoma (e.g., Peters syndrome, Axenfeld-

Rieger syndrome, etc.).

Acute severe IOP elevation produces corneal enlargement, frequently accompanied by tears in Descemet’s membrane (Haab’s striae) than initially manifest as corneal edema/opacification, later producing variable permanent scarring and refractive errors. Moderate IOP elevation insufficient to produce noticeable corneal opacity, gradually enlarges the infant’s corneas, sometimes proceeding unnoticed if symmetric, while concurrent optic nerve damage progresses to severe degrees. While the normal newborn corneal diameter ranges from 9.5 to 10.5 mm (mean

10 mm), reaching about 11.5 mm by the child’s second birthday, corneal diameters of 12–12.5 mm are suggestive of glaucoma in an infant less than 12 months of age, and a measurement of 13 mm or more in childhood strongly suggests abnormality, as does asymmetry in corneal diameter between eyes

[13, 29, 56, 98].

The limbus may be dramatically stretched and thinned by ocular stretching in an infant eye with glaucoma, and the anterior chamber often deepens. Abnormalities of the iris and lens may signal primary anomalies or those secondary to other eye diseases

(e.g., aniridia, Axenfeld-Rieger syndrome, ectropion uvea).

24.4.5 Gonioscopy

Gonioscopy, providing vital anatomic information about the mechanism of glaucoma in a given eye, can be performed both in the office and under anesthesia.

Indirect gonioscopy with a Zeiss or Sussman gonioprism proves simple to perform at the slit lamp in the older child, while Koeppe (direct) gonioscopy is useful for infants and in the operating room, facilitating detailed inspection of the iris, angle structures (and optic nerve head using a direct ophthalmoscope). In contrast to the normal adult angle, the normal infant’s angle demonstrates a trabecular meshwork which appears almost as a smooth, homogeneous membrane extending from peripheral iris to Schwalbe’s line.

This trabecular meshwork becomes coarser and often increasingly pigmented over time [120].

In the eye with infantile glaucoma, the iris often demonstrates an insertion more anterior than normal, with altered translucency of the angle face producing an indistinct ciliary body band, trabecular mesh, and scleral spur. This translucent angle tissue has historically been dubbed “Barkan’smembrane”[10].Theangle structures may reveal other features suggestive of the glaucoma etiology. For example, in glaucoma after cataract surgery, an open-angle configuration suggests trabecular meshwork dysfunction which might be amenable to initial medical therapy, while a closed angle and pupillary block may require urgent surgical intervention. An abnormally prominent Schwalbe’s line, and iris adhesions to the angle structures may alternatively confirm Axenfeld-Rieger syndrome or

other anterior segment dysgenesis, while peripheral anterior synechiae may reveal the cause for IOP elevation in chronic uveitis. The eye with juvenile openangle glaucoma often has a normal-appearing open angle, with a prominent, lacy uveal meshwork.

Taken together with other findings of anterior examination (above), the adequacy of the angle view and its findings are important guides to the appropriate surgical intervention that may be needed.

24.4.6Optic Nerve and Fundus Examination

The optic nerve head appearance is usually the focus of the fundus examination in an eye with glaucoma, although abnormalities may help confirm the glaucoma type (e.g., a stalk in persistent fetal vasculature, foveal hypoplasia in aniridia, choroidal hemangioma in Sturge-Weber syndrome, etc.), or provide useful information for surgical planning (e.g., peripheral retinal pathology or vitreous stranding may suggest vitrectomy/peripheral laser along with aqueous drainage device placement in aphakia). Large optic nerve cups and/or asymmetry between the cupping of the two eyes suggests but does not confirm glaucoma in an infant or child. Shaffer and Heatherington reported that most eyes with primary infantile glaucoma had a cup/disc ratio larger than 0.3 (68% of 126 eyes) [102], while Richardson noted this degree of cupping in only 3% of 936 eyes of normal newborn infants [96]. Marked optic cup asymmetry was noted in only 0.6% of normal eyes in the latter series, contrasted with 89% noted for infants with monocular glaucoma.

Indirect ophthalmoscopy with a 28or 30-diopter lensmayminimizeapparentopticnerveheadcupping, better appreciated in the older child using binocular viewing at the slit lamp, or with a 14-diopter indirect lens or direct ophthalmoscope through a Koeppe gonioscopy lens under anesthesia. In infants and young children optic nerve cupping can occur rapidly with elevated IOP, while reversal of cupping can help confirm adequate IOP reduction, provided permanent optic nerve atrophy has not yet occurred. The older child’s optic nerve cupping may also decrease with long-standing IOP reduction, but improved visual function unfortunately does not occur.

24.4.7 Other Useful Diagnostic Tests

24.4.7.1Refraction

Refractive error determination can not only suggest possible glaucoma (as when a myopic shift occurs rapidly after cataract removal, or asymmetric relative myopia occurs in the eye with higher IOP), but also serves a critical function in maximizing the visual function of the child with glaucoma, in whom high myopia, astigmatism, or anisometropia often result from IOP-induced corneal scarring and/or ocular enlargement.

24.4.7.2Axial Length (Ultrasound)

Measurement of the axial length (measured with ultrasound during examination under anesthesia) serves as an adjunct to serial corneal diameter determination for infants and young children being treated for glaucoma, since stabilization and even reduction in axial length can occur in the enlarged eye with stable IOP reduction [56]. This measurement also helps determine adequate size when aqueous drainage device surgery is contemplated (see Sect. 24.8). B-scan ultrasound helps confirm retinal status in eyes with opaque media, and can help confirm the patency of an aqueous drainage device (see Sect. 24.8).

24.4.7.3Central Corneal Thickness

Ultrasound pachymetry (to measure the central corneal thickness) has become standard in the evaluation of adults with open-angle glaucoma, since this variable seems to affect not only the accuracy of the measured IOP by applanation tonometry (elevated by an unusually thick central cornea, and vice versa) [6, 48], but also the potential susceptibility of an eye to glaucomatous vision loss at elevated IOP

[16, 59]. In children, the reported central corneal thickness ranges from ~540 μm (6–23 months) to ~550–560 μm for older children, with thinner central corneal thickness reported in white compared with black children [26, 27, 34, 47, 49, 52, 74], and stable measurements over at least 1 year in normal eyes and those on stable glaucoma treatment [75]. Central corneal thickness has been shown to be thinner in children with congenital glaucoma, and is probably

a function of the larger, stretched corneas of many of these children [47]. By contrast, eyes with aniridia have thicker than average central corneas [17], while those with aphakia, and particularly aphakic glaucoma, have thicker reported central corneas [76, 105, 106, 113], perhaps an acquired rather than a congenital feature [76].

The importance of central corneal thickness in the evaluation and management of children with glaucoma remains to be determined at the present time, and while this feature is worthwhile to measure and to consider when setting the target IOP, the clinician should avoid “adjusting” the measured IOP based on the pachymetry.

24.4.8Imaging Techniques: Fundus Photography,

Optical Coherence Tomography

Fundus photography of the optic nerve head has long been a mainstay in the evaluation of adults with glaucoma over time, and is useful in cooperative children with clear visual axes and without substantial nystagmus. Other imaging techniques which non-inva- sively image the optic nerve head (optical coherence tomography, for example, see below) may be useful in older children with glaucoma, primarily to document changes over time, rather than to diagnose glaucoma.

Optical coherence tomography, a non-invasive imaging technique able to measure the thickness of the peripapillary nerve fiber layer, as well as the macular area and volume, in adults and in children [2, 50, 97], may prove valuable to evaluate the thinning of these parameters in children with glaucoma [50, 72].At the present time, however, their utility is limited by the need for a clear visual axis and steady fixation, as well as a wide range of normal values, and lack of longitudinal data in children with glaucoma.

24.5 Differential Diagnosis

Many conditions may produce ocular changes that could initially suggest glaucoma (Table 24.2). When faced with ocular signs or symptoms suggestive of

Table 24.2  Differential diagnosis: infant and childhood glaucoma

1.Conditions sharing cornea enlargement (without other corneal pathology)

a.Megalocornea

b.Megalophthalmos

c.Axial myopia

2.Conditions sharing corneal edema or opacification

a.Birth trauma (with Descemet’s membrane ruptures)

b.Congenital corneal malformation (e.g., Peters syndrome, sclerocornea)

c.Corneal dystrophy (e.g., congenital hereditary endothelial dystrophy, posterior polymorphous dystrophy)

d.Metabolic disease (e.g., mucopolysaccharidoses, cystinosis, oculocerebrorenal/Lowe syndrome)

e.Infection (e.g., herpetic keratitis, phlyctenular)

3.Conditions sharing epiphora, and “red eye”

a.Congenital nasolacrimal duct obstruction

b.Conjunctivitis

c.Corneal epithelial defect

d.Inflammation (e.g., uveitis)

4.Conditions sharing optic nerve cupping (or abnormality)

a.Optic nerve pit

b.Optic disc coloboma

c.Optic nerve atrophy

d.Optic nerve hypoplasia

e.Physiologic cupping (diagnosis of exclusion)

glaucoma, the clinician must consider and rigorously rule out this diagnosis, cognizant that identification of a coexisting disorder does not by itself eliminate the possibility of glaucoma.

24.6 Primary Childhood Glaucoma

24.6.1Primary Congenital/Infantile Open-angle Glaucoma

The most common of the primary pediatric glaucomas, primary congenital glaucoma (PCG) has an estimated incidence of only 1 in 10,000–20,000 live births in Western countries, as opposed to a much higher incidence in the Middle East and Slovak Romany populations, where parental consanguinity may

play a role in the increased incidence of PCG [86].

Most cases (65–80%) are bilateral, without clear gender or racial/ethnic predilection, and >75% present in the first year of life. About 25% of PCG presents in the newborn, and more than 60% are diagnosed by age 6 months [21, 29]. Although PCG always occurs early in life, with typical corneal features of enlargement, Descemet’s membrane breaks, and resultant edema usually occurring during the first year of life, its phenotypic features vary greatly in severity (e.g., photophobia, corneal clouding and enlargement), so that its recognition may be delayed in milder cases, allowing time for often permanent visual loss to occur. Prompt diagnosis of glaucoma often relies on the sensitivity of parents and primary care providers to the significance of these signs and symptoms [121].

While the majority of primary infantile glaucoma cases are sporadic (no known family history), those which are familial usually show an autosomal recessive inheritance, with variable penetrance from 40% to 100% [93, 118]. Several genetic loci have been identified associated with PCG. Hence two loci,

GLC3A, linked to the 2p21 region, and GLC3B, linked to the 1p36 region, have been identified, and the presence of at least a third locus in the human genome responsible for congenital glaucoma is suspected. Mutations in the CYP1B1 (cytochrome P4501B1) gene have been identified in those cases of congenital glaucoma linked to GLC3A [99, 100], with a variety of CYP1B1 mutations found in families with congenital glaucoma worldwide [3, 54, 64, 65, 77, 80, 85, 95, 107, 109, 110, 117]. The CYP1B1 gene is hypothesized to play an important role in the developing eye [101]. The routine genetic testing of children with PCG, a laudable goal for the near future, must await better funding of the laboratories currently equipped to do such testing, which is consuming of time and resources.

Although the pathogenesis of PCG is not fully understood, the increased resistance to outflow through the trabecular meshwork in PCG may well result from a developmental arrest of neural crest cell-de- rived anterior chamber angle tissue, with subsequent aqueous outflow obstruction by one or more mechanisms. These may include compression of the trabecular meshwork beams by a high iris and ciliary body insertion as well as abnormal development of the trabecular meshwork itself [29, 58, 66]. The inherited defect of PCG is largely limited to the filtration tis-

sues, with typical gonioscopic abnormalities in this disease which include diminished transparency of the tissues overlying scleral spur and ciliary body band, producing the appearance of a membrane (Barkan’s membrane, see Sect. 24.4.5), now thought to represent the thick, compacted trabecular meshwork itself

[10].

Surgery constitutes the definitive treatment for

PCG, with medical therapy reserved as brief, initial therapy to help lower the IOP and clear the cornea to facilitate surgery, and as an adjunct in those patients where IOP reduction is incomplete after surgery. Angle surgery (usually goniotomy or trabeculotomy), usually the favored initial surgery, is successful in the majority of cases, especially those with presentation between 3 and 12 months of age; surgical success drops for those with presentation at birth or after age 1–2 years (see Sect. 24.8.2.1). In certain ethnic populations, simple angle surgery has lower reported success, and experienced surgeons therefore favor combined trabeculotomy–trabeculectomy [85, 93].

Surgical options for cases of PCG refractory to angle surgery include antimetabolite-augmented filtration surgery [12, 40, 61, 104], aqueous drainage device implantation [25, 35, 39, 69, 71, 104], and cycloablation [79], with variable reported success, depending upon the reported series (see Sects. 24.8.4, 24.8.5, 24.8.6). Visual prognosis in PCG depends not only on the timely glaucoma diagnosis and IOP reduction, but also on the secondary corneal, refractive, and optic nerve changes produced by the initially elevated

IOP [29].

24.6.2 Juvenile Open-angle Glaucoma

By contrast to PCG, this rare disease is an autosomaldominant early-onset form of primary open-angle glaucoma, which has been linked in several families to mutations of the myocilin/trabecular meshworkinducible glucocorticoid response gene at the GLC1A locus on chromosome 1q21-q31 [111]. Characterized by onset of marked bilateral IOP elevation between ages 4 and 35 years, the optic nerve cupping and visual field loss caused by IOP elevation in juvenile open-angle glaucoma (JOAG) often remain asymptomatic unless family history prompts surveillance, or the child presents with myopia and decreased dis-

tance vision. Gonioscopy reveals normal-appearing angle structures. Treatment is difficult, often beginning with medication, and proceeding to filtration or aqueous drainage device surgery, although angle surgery may be helpful in some early-onset cases (see Sect. 24.8.1.5).

24.6.3Primary Pediatric Glaucoma Associated With Ocular Anomalies (Anterior Segment Dysgenesis)

There are a number of primary pediatric glaucomas that have associated ocular anomalies of the anterior segment (Table 24.1), involving neural crest mesenchymal tissue. Infantile-onset glaucoma may occur in many of these conditions (hence the designation primary glaucomas); later-onset glaucoma due to secondary angle outflow obstruction may also occur in some (e.g., aniridia). In some of these well-recog- nized disorders, systemic abnormalities may also occur (Table 24.1). Phenotypic classification schemes necessarily have significant overlap between the diagnostic categories, some of which probably share genetic abnormalities; a brief description of the features of more commonly noted diagnoses follows.

24.6.3.1Aniridia

Children with this bilateral developmental disorder, which is characterized by congenital absence of a normal iris, develop glaucoma in at least 50% of cases, often with onset delayed until middle or late childhood (Fig. 24.7). Aniridia is associated with multiple ocular defects (and sometimes also systemic abnormalities), variably manifesting from birth to later childhood or even adulthood. Aniridia is inherited in an autosomal dominant fashion with almost complete penetrance in about two thirds of cases, with the remaining cases sporadic. This disorder results from abnormal neuroectodermal development secondary to PAX6 gene mutations at chromosome 11p13 (locus symbolAN2) [84a]. Sporadic aniridia may be associated with Wilms’ tumor, genitourinary abnormalities, and mental retardation (WAGR) resulting from large

deletions of 11p13, which include both the PAX6 and the adjacent Wilms tumor locus [114].

Ocular anomalies congenitally associated with aniridia include a small cornea with limbal abnormalities, hypoplastic iris leaflet, cataracts, macular hypoplasia, and angle abnormalities. Eyes with aniridia experience progressive ocular abnormalities resulting in corneal opacification, lens opacification, and glaucoma secondary to increased filtration angle dysfunction. Most aniridic eyes with acquired glaucoma demonstrate progressive trabecular blockage by movement of the residual iris tissue in front of the trabeculum [44]. Careful gonioscopic monitoring of the angle by serial anesthetic examination is recommended in aniridic infants with a strong family history of aniridic glaucoma; progressive angle narrowing and closure in these young children has been treated with prophylactic goniosurgery by some surgeons [24].

Aniridic glaucoma is difficult to treat, once it develops. Medical therapy may delay the need for surgical intervention. While no specific surgical treatment has proven best for aniridic glaucoma, angle surgery may be appropriate for early-onset cases (trabeculotomy favored by many surgeons due to the shallow anterior chamber and unprotected crystalline lens in these eyes). Trabeculectomy may be successful in older children, but is particularly challenging due to the propensity of these eyes to develop postoperative flat anterior chambers. Aqueous drainage device implantation [7] and very careful cycloablation may be needed for particularly refractory cases [1, 119, 127].

Fig. 24.7  Aniridia in an infant undergoing examination under anesthesia to allow gonioscopic examination of the angle structures. Note the limited rim of iris, and the clear outer border of the crystalline lens, in this eye with normal IOP

Extreme caution is recommended when performing filtration surgery or aqueous drainage device surgery in cases of congenital-onset aniridic glaucoma, since hypotony can result in flat chambers with subsequent corneal and lenticular opacification. Surgical interventions should maximally protect the cornea, considering the vulnerability of the cornea to later decompensation, and the poor response to penetrating keratoplasty.

24.6.3.2Axenfeld-Rieger Syndrome

This condition represents a type of the so-called anterior chamber cleavage syndromes, in which there are variable abnormalities in the anterior segment often involving the cornea, angle, iris, and lens, and usually showing evidence of incomplete formation of the anterior chamber cavity. The collective term

Axenfeld-Rieger (A-R) syndrome includes all clinical variations within this spectrum of developmental anomalies[103].Regardlessofocularmanifestations, all patients with A-R syndrome share the same general features: (a) a bilateral, developmental disorder of the eyes; (b) a frequent family history of the disorder, with an autosomal dominant mode of inheritance; (c) no sex predilection; (d) frequent systemic developmental defects; and (e) a high incidence of associated glaucoma. The iris may show hypoplasia of the anterior stromal leaf, iridotrabecular and iridocorneal processes, and posterior embryotoxon (previously termed Axenfeld anomaly). Other deformities may occur in the iris, such as corectopia (Fig. 24.8).

Fig. 24.8  Right eye of a 22-year-old man with Ax- enfeld-Rieger syndrome in both eyes. Glaucoma became uncontrolled in high school, and was managed with 5-fluorouracil-augmented trabeculectomy

Glaucoma is a common complication, occurring in more than 50% of cases, often in middle or late childhood. Dental anomalies in the form of oligodontia and anodontia, dysplasias of the skull and skeleton, and umbilical abnormalities are common.

Regarding genetics, A-R syndrome and related phenotypes have been associated with three loci, on chromosomes 4q25, 6p25, and 13q14. The genes at chromosomes 4q25 and 6p25 have been identified as PITX2 and FKHL7, respectively [5]. Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis anomaly, iridogoniodysgenesis syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia all have sufficient genotypic and phenotypic overlap that they should, some authors feel, be considered one condition [5].

24.6.3.3Familial Hypoplasia of the Iris

There are some individuals demonstrating congenital hypoplasia of the iris without some of the other anterior segment abnormalities of the A-R syndrome. This autosomal dominant disorder (also termed iridogoniodysgenesis anomaly type I) demonstrates iris hypoplasia, goniodysgenesis, and early-onset glaucoma, and has been mapped to gene locus 6p26, and appears due to mutations in the gene FKHL7. A similar condition which includes non-ocular features (iridogoniodysgenesis type 2) may be allelic to A-R syndrome, mapping to 4q25, and resulting from mutations in the gene PITX2 [84b].

The risk of glaucoma in A-R and related disorders is estimated at 50–75%, with most cases presenting in childhood and early adulthood, rather than in infancy.

Outflow obstruction probably results from arrested maturation of angle structures. While medical therapy may initially provide IOP control, surgical intervention is often needed. Angle surgery, while reasonable in infant-onset disease, enjoys lower success than in PCG, and other modalities may be needed for refractory cases (see Sect. 24.8).

24.6.3.4Peters Anomaly

This congenital anomaly, usually bilateral and sporadic, a variation of the so-called anterior chamber