membrane involving the visual axis and anisometropia. Although the amount of myopia that is induced by the stretching of the infant globe can be neutralized by the flattening of the cornea, this myopia is often significant. Irregular astigmatism also is evident in many cases. A cycloplegic refraction should be performed as soon as possible and should be followed by frequent adjustments in lens power as the anisometropia changes. Appropriate occlusion therapy must be started as soon as amblyopia is recognized. Even brief periods of corneal clouding can cause deprivation amblyopia. Thus coordination of eye care with ophthalmologists interested in pediatric management can often maximize the child’s visual rehabilitation.

Long-term medical therapy in children can be difficult to maintain because of side effects and compliance problems. Moreover, few antiglaucoma medications have been studied in children, and they are mostly used either in a presurgical context or as an adjunct to partially successful surgery.

-Blockers, such as timolol 0.25%, are well tolerated in most patients who do not have asthma or heart disease.110,111 Selective 1-

adrenergic antagonists, such as betaxolol, may further decrease the incidence of pulmonary side effects. Newer topical agents, such as the agonists, prostaglandins, and topical carbonic anhydrase inhibitors, can also be used, but possible side effects must be monitored.As noted above, brimonidine should be avoided in children under 5 years of age. Coordination of the glaucoma medical regimen with the child’s pediatrician is advised. Generally, if an increasing number of topical drops is required for IOP control, further surgery may be indicated.

Patients with primary congenital glaucoma require regular

examinations throughout life. Increases in IOP, corneal edema, and retinal detachment165,166 can occur at any time and must be

detected as soon as possible and treated appropriately. The long-

term prognosis for IOP control in successfully treated cases of primary congenital glaucoma appears excellent,113,167 although late

relapses have been observed up to 15 years later.116 Most patients with primary congenital glaucoma successfully treated in infancy have maintained good pressure control with stable optic nerves and fully functional visual fields into adulthood.

Late developing primary congenital glaucoma

Late developing primary congenital glaucoma occurs in children whose IOP becomes elevated after the age of approximately 3, when corneal enlargement or significant symptoms no longer occur. The angle may have the appearance of isolated trabeculodysgenesis with a flat or concave insertion, or the angle anomaly may be indefinite with a partial development of the angle recess. Some authors group this presentation of glaucoma in the ‘juvenile’ category.13 This disorder may be difficult to distinguish from early developing primary open-angle glaucoma.

Initially, medical treatment should be attempted. Innovative laser treatments of the angle have been described,168,169 but they are not

widely available. In the event that surgery is required, a trabeculotomy ab externo is the initial surgical procedure of choice in children this age.

pupillary sphincter, trabeculodysgenesis, and glaucoma; this has also been referred to as iridogoniodysgenesis.The anterior stroma of the iris is markedly hypoplastic, and the pupillary sphincter is obvious as a tan distinct ring around the pupil. Glaucoma may occur at any time from birth until late adulthood; the striking iris appearance correlates with eventual glaucoma in 100% of cases. Childhood cases respond well to goniotomy or trabeculotomy. Cases with later onset have been managed successfully with medical therapy, argon laser trabeculoplasty, trabeculotomy, or trabeculectomy.

Its hereditary pattern is autosomal dominant.172 Early studies had found genetic linkage of iris hypoplasia to the Rieger’s syndrome locus at 4q25,173 but others considered this association inconsistent.174 A recent comprehensive review of the literature identifies a total of three causative loci (4q25, 6p25, and 13q14) and persuasively argues for retaining the broader clinical term ‘AxenfeldRieger syndrome’ to embrace a wide range of phenotypic subtypes (viz.,Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis­ anomaly, iridogoniodysgenesis syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia).175 This illustrates that there may be a significant difference in the clinical classification of the developmental glaucomas (i.e., autosomal dominant iris hypoplasia and autosomal dominant juvenile glaucoma share a common clinical presentation but different chromosomal defects) and the genetic associations discovered by molecular biology (i.e., iris hypoplasia and Rieger’s syndrome are linked on chromosome 4, but may appear very different from one another).9 From the patient’s vantage, any of these genetic aberrations or phenotypic expressions confer a 50% greater chance of developing glaucoma than would otherwise be recognized.

Developmental glaucoma with anomalous superficial iris vessels

Irregularly wandering superficial iris vessels with distortion or absence of the superficial iris stroma and distortion of the pupil are commonly seen in newborn children with glaucoma (see Fig. 19-8).The cornea usually is hazy, and the vessels may be difficult to see.These vessels can be differentiated easily from the normal radial

Glaucoma associated with other congenital anomalies

Familial hypoplasia of the iris with glaucoma

Familial hypoplasia of the iris with glaucoma (Fig. 19-23)170,171 is characterized by hypoplasia of the anterior iris stroma, a prominent

Fig. 19-23  Familial hypoplasia of iris with glaucoma. This patient’s mother and son have the same iris appearance and glaucoma. Anterior iris stroma is absent with the exception of a few strands nasally. The sphincter is a prominent ring contrasted against the dark slate-gray appearance of the peripheral iris.

Fig. 19-24  Edge of lens seen in aniridia shows absence of iris. Epithelial keratopathy is clearly visible in lower nasal portion, and a dense cataract is dislocated superiorly.

iris vessels, which are straight and have no associated distortion of the iris tissue.The normal radial iris vessels frequently are visible at birth, before the anterior stroma and its pigmentation have developed completely.

Superficial anomalous iris vessels in children are usually bilateral and resistant to therapy. Early trabeculotomy offers the most hope. Goniotomy can be performed in the least cloudy eye during the same surgery. If the cornea has not cleared dramatically, trabeculotomy or goniotomy should be repeated after 3 or 4 weeks.

Most of these eyes require multiple surgeries and long-term medical therapy. With aggressive management, many can be saved, although vision is rarely normal.

Aniridia

Aniridia (Fig. 19-24) is a bilateral congenital anomaly in which there is profound hypoplasia of the iris in frequent association with multiple ocular anomalies, such as peripheral corneal pannus and keratopathy, foveal hypoplasia, diffuse retinal dysfunction as seen on electroretinography, impaired acuity with nystagmus, cataract and ectopia lentis, and optic nerve hypoplasia.176 Recent studies using ultrasonic biomicroscopy have also documented ciliary body hypopalasia.177 The combination of these defects usually causes a formidable barrier to normal visual function. In addition, 50–75% of aniridics develop glaucoma.178

Two-thirds of patients with aniridia have an affected parent (autosomal dominant form) and one-third represent isolated new mutations.9 The autosomal dominant form without systemic abnormalities accounts for nearly 85% of cases. In the sporadic cases, approximately 20% of patients have been found to have Wilms tumor as part of the multisystem WAGR syndrome (Wilms’ tumoraniridia genitourinary anomalies retardation).173 Thus aniridic children without a family history require co-management with a pediatrician for surveillance of neoplasm and other complications.

The genetic locus of this syndrome for both the sporadic and

familial forms is a mutation of the PAX6 gene on the 11p13 chromosome.179,180 Curiously this is the same defective gene seen in

one case of Peter’s anomaly, although the two clinical syndromes are usually distinct and show little overlap.9,181

Although the defective iris is readily apparent at birth, in most cases glaucoma does not develop until later childhood or early

adulthood, and sometimes does not develop at all.182 In the less frequent infantile-onset cases, the glaucoma is thought to be due to a trabeculodysgenic anomaly of the anterior chamber angle. Because large corneas are rarely seen in aniridic glaucoma, the IOP elevation is presumed to occur at a later developmental stage, usually after age 5 and often into adolescence.Walton178 directly correlates the severity of the glaucoma with the extent of progressive synechial angle closure by the pulled-up residual iris stump.183

The iris is never completely absent; it may vary from being fairly well developed in some areas to being only a rudimentary stump in others. Most commonly, the anterior stroma sweeps up and over the meshwork like concave trabeculodysgenesis.

Corneal dystrophy initially presents as a circumferential and peripheral opacification of the epithelial and subepithelial layers, with vessels advancing into these areas from the limbus. Over many years, this pannus can extend centrally and eventually completely opacify the cornea.

Cataracts develop in most aniridic patients; and the lens may be displaced, with a segmental absence of zonules. Foveal hypoplasia is present in most cases and is clinically appreciated by the appearance of meandering small retinal vessels in what should be the normal avascular zone of the macular region. Vision is usually limited to no better than 20/200, with an accompanying pendular nystagmus. Cases of families with aniridia but normal macular development, no nystagmus, and good vision do occur, implying that the foveal hypoplasia is genetically determined rather than acquired as a result of light damage from lack of iris tissue.184

If aniridic glaucoma occurs in infancy, a trabeculotomy is the procedure of choice because goniotomies are usually unsuccessful if applied after the onset of glaucomatous IOP elevation.178

Encouraging results with trabeculotomy alone,185 trabeculectomy with or without antimetabolites,186–188 or a combination of both

procedures have been reported.189 In mice and in some humans,

one of the defects associated with a Pax 6 mutation is absence of Schemm’s canal.189a We have seen one such infant in which

Schemm’s canal could not be found either clinically or by high resolution ultrasound biomicroscopy.189b This has significant implications for performing trabeculotomy. In older children, medical therapy is indicated as the initial treatment. Surgical complications include direct lens injury and lens or vitreous incarceration in filtration sites; these problems are considerably reduced with the use of intracameral viscoelastic at the time of surgery.

Preventive goniotomy to prevent progressive adherence of the peripheral iris to the trabecular meshwork has been proposed by Walton.190 With a follow-up of over 9 years in 55 eyes which underwent one or more goniotomies at age 3, 90% had normal IOPs without medications – in contrast to the 50% of untreated aniridic eyes expected to develop glaucoma in this time frame.191 This uniquely innovative approach, with its demands for impeccable prophylactic surgery and meticulous follow-up, has yet to be duplicated by other centers.

In cases of failed trabecular surgery, glaucoma implants (e.g.,

Ahmed)192 or ciliodestructive procedures have been used, often with more than two procedures per eye required.146b,193

The cornea may become sufficiently opaque so that penetrating keratoplasty is needed, although the visual results are marginal (one to two lines of improvement in Snellen acuity).194 Lens opacification may require cataract extraction. Before operating, however, the ophthalmologist should attempt refraction through the aphakic portion of the pupil if the lens is subluxated. Either extracapsular or phacoemulsification surgery may be used, depending on

the stability of the zonules. Cataract extraction can be difficult and often is accompanied by vitreous loss or further deterioration of the cornea. The use of intraocular lens (IOL) implants in children is an evolving field,195 and whether their alleged ‘protective effect’ in forestalling the additional burden of aphakic glaucoma196 in these aniridic eyes has yet to be determined.

Sturge-weber syndrome (encephalofacial angiomatosis, encephalotrigeminal angiomatosis)

Sturge-Weber syndrome197,198 is characterized by a flat facial hemangioma which follows the distribution of the fifth cranial nerve (Fig. 19-25). The genetic transmission of this disease is unclear. Intracranial abnormalities can produce a spectrum of neurological problems, including seizure disorders in the child.199 For example, the classic meningeal hemangioma may be associated with calcification seen on skull X-ray; other more subtle findings can be neuroimaged with a variety of new techniques.200 The facial hemangioma is usually unilateral but occasionally may be bilateral. Choroidal hemangiomas and episcleral hemangiomas are commonly seen, and leakage from the choroidal hemangioma may cause retinal edema (Fig. 19-26). Such ocular abnormalities can be seen with indocyanine green angiography.201,202

Whereas pediatric glaucoma in aniridia can occur as an infantile trabeculodysgenesis but is more likely to occur later as a secondary glaucoma (progressive angle closure), the glaucoma associated with Sturge-Weber syndrome is more likely to appear in infancy and less often manifests in late childhood or adolescence. SturgeWeber glaucoma is present when the facial hemangioma involves the lids or conjunctiva. Two different mechanisms are thought to be involved. If the glaucoma occurs in infancy, an isolated trabeculodysgenesis type of angle anomaly usually is assumed, described in one case as due to abnormalities in the canal of Schlemm and jux-

tacanalicular tissue.203 Some claim that this is sometimes responsive to goniotomy,204,205 with more than one procedure frequently

required. Medical therapy effectively controls the glaucoma in but

a third of pediatric cases.206

Other authors prefer trabeculotomies,178,207 combined trab-

eculectomy/trabeculotomy,208 or glaucoma tubes, such as an Ahmed valve209,210 or a two-staged Baerveldt procedure.211 As the child ages,

the elevated IOP is due to an elevation of episcleral venous pressure

that occurs as a result of arteriovenous shunts through the episcleral hemangiomas (Fig. 19-27).212,213 In older children, medical therapy

may be better tolerated and effective, with fewer side effects. If medical therapy is unsuccessful, either filtration or tube surgeries can be used.12 In the face of surgical failure, cyclodestructive procedures – cryotherapy,214 diode laser cyclophotocoagulation,157,215,216 or

Fig. 19-26  Hemangioma of the choroid is almost always present in eyes with Sturge-Weber syndrome. In this case, leakage reduced macular acuity.

Fig. 19-27  Note the dense episcleral anastomosis found in surgery. These were not visible until Tenon’s capsule was elevated. Anastomoses can

be cauterized easily and usually do not represent a significant bleeding problem at surgery.

endocyclophotocoagulation217 – can be performed, although more than one intervention is usually required, as is the case in many such difficult pediatric glaucomas.218

In approximately 20% of procedures which penetrate the anterior chamber, such as trabeculectomy, intraoperative or early postoperative choroidal detachment can occur from a rapid expansion of the choroidal hemangioma with effusion of fluid into the suprachoroidal and subretinal spaces (Fig. 19-28).216 Careful attention to maintaining a normal to high IOP during and after surgery

– through the use of an anterior chamber maintainer cannula for constant infusion, generous amounts of viscoelastic, and meticulous wound closure – may forestall intraand perioperative complications. Fortunately, such an event is usually not encountered,208 and prophylactic sclerostomies need not be routinely performed.219 However, the surgeon needs to anticipate such a precipitous event of sudden anterior chamber flattening, which may be impossible to re-form through the surgical site or paracentesis site. Posterior sclerotomy followed by anterior chamber reformation should be performed in an attempt to drain fluid from the suprachoroidal space. Extreme caution is advised: the choroid must not be penetrated, to avoid a catastrophic hemorrhage.

If these efforts are not fully successful, usually in a few days, the expansion subsides as the IOP increases. Repeat filtering surgery can be reconsidered at a later time because the choroidal hemangioma may scar, sometimes enabling the surgeon to successfully perform the procedure without recurrence of the expansion. In such reoperative circumstances, two or three posterior sclerotomies should be preplaced, to prevent this anticipated expansion. Alternatively, a glaucoma valve or shunt, inserting the tube into an eye in which IOP has been carefully maintained by an anterior chamber full of viscoelastic, may be considered after a failed filtering surgery.

There is a classification of neural crest disorders that involve episceral vascular malformations plus ocular hyperpigmentation groups together the Sturge-Weber syndrome, Klippel-Trénaunay- Weber syndrome, oculodermal melanocytosis (nevus of Ota), and phakomatosis pigmentovascularis (a combination of oculodermal melanocytosis and nevus flammeus that is found almost exclusively in Asians).220 When oculodermal melanocytosis and nevus flammeus (phakomatosis pigmentovascularis) occur together, with each extensively involving the globe, there is a strong predisposition for congenital glaucoma. When one or both are present with only

­partial globe involvement, elevated IOP could develop later in life, and long-term glaucoma surveillance is advised. The vascular malformations appear to play a more important role in the predisposition to glaucoma than the oculodermal melanocytosis.

A related syndrome called cutis marmorata telangiectatica congenita involves periocular vascular anomalies associated either with regional or generalized cutaneous marbling.221 It has also been associated with infantile trabeculodysgenic glaucoma222–225 and, in one report, with intraoperative suprachoroidal hemorrhage.194

Neurofibromatosis (von recklinghausen’s disease)

Neurofibromatosis (Fig. 19-29) is an autosomal dominant disorder with variable expressivity, affecting as many as 1 in 3000 people,226 and manifesting as anomalies of the neuroectoderm and the development of active hamartomas throughout the body.227 The most common form, neurofibromatosis type 1 (NF-1) (von Recklinghausen’s disease), has seven possible manifestations, requiring two for diagnosis: six or more large café-au-lait macules; plexiform neurofibromata; inguinal or axillary freckling; optic glioma; Lisch nodules (melanocytic hamartomas of the iris); distinctive osseous lesions of the sphenoid or long bones; and a first-degree relative with NF-1. (Curiously there is a report of a monozygotic twin with NF-1 and congenital glaucoma – indicating the complexity of genetic manifestation in the disease.)228

Neurofibromatosis type 2 (NF-2) is a rarer disorder associated with bilateral acoustic neuromas or other neural proliferative lesions, such as meningioma, schwannoma, and glioma. Although NF-2’s defining diagnostic criteria are in flux,229 the disease has a very high mortality by the third decade.230

The extensive literature on the ocular findings of NF-1 includes neurofibromatous nodules on the iris and eyelids, with ectropion uvea,231 optic nerve gliomas in as many as 15% of asymptomatic children under age 6,232 and a variety of complications resulting from mass-occupying lesions in the orbit, such as pulsating exophthalmos to sphenoid bone maldevelopment, herniation of brain tissue into the orbit, or proptosis resulting from optic nerve gliomas. Multiple retinal tumors can be seen, including large retinal astrocytic hamartomas, multiple retinal capillary hemangiomas and corkscrew anomalies,233 and combined hamartomas of the retina

and retinal pigment epithelium, resulting in rubeotic glaucoma, vitreous hemorrhage, and retinal detachment.234

A ‘real world’ context for what a general clinician might encounter, however, was suggested by a study of 211 NF-1 patients, whose diagnosis excluded ophthalmologic criteria, and who were then assessed by anamnestically masked observers, to determine the frequency of ophthalmic findings. The most common lesions, often together, were Lisch nodules (88%) and choroidal hamartomas (29%); but enlarged corneal nerves, plexiform neurofibromas, and symtomatic optic nerve gliomas were found in less than 5% of cases.235

Glaucoma may appear up to 50% of the time when neuro­ fibromas involve the upper eyelid or the eye itself (Fig. 19-30).The anterior chamber angle may take on several appearances.236 Isolated trabeculodysgenesis may be evident. Synechial closure caused by neurofibromatous tissue posterior to the iris or neurofibromatous infiltration of the angle itself, which may be accompanied by synechial closure, may be present. A sheet of avascular, opaque, dense tissue may arise from the periphery of the iris and extend anteriorly into the angle. Later onset glaucoma in neurofibromatosis can

be associated with unilateral ectropion uvea at the pupillary margin.178,237,238 Usually there is accompanying unilateral ptosis with-

out a palpable neurofibroma; the pupil appears larger due to the static iris hyperplasia of the central iris pigment epithelium. This form of iris ectropion glaucoma may also appear as a distinct form, independent of NF-1 or other anterior segment anomalies.239

Fig. 19-30  Plexiform neuroma of the upper lid in this patient with neurofibromatosis. Eye beneath plexiform neuroma had severe glaucoma that had not been diagnosed.

The preferred treatment in infants is usually goniotomy, with trabeculotomy recommended if iris adhesions are prominent. In older children, medical therapy should be tried first, followed by the surgeon’s choice of surgical interventions: trabeculotomy,