FocalPoints - Pediatric Ophthalmology · MaRcH 2012 (MODULE 3 OF 3) Reviewers and Contributing Editor c. Gail Summers, MD, Editor for Pediatric Ophthalmology and Strabismus Edward

Pediatric GlaucomaTammy L. Yanovitch, MD, MHSc

Sharon F. Freedman, MD

VOLUME XXX NUMBER 3

MaRcH 2012 (MODULE 3 OF 3)

Reviewers and Contributing Editor

c. Gail Summers, MD, Editor for Pediatric Ophthalmology and Strabismus

Edward L. Raab, MD, JD, Basic and Clinical Science Course Faculty, Section 6

Sara S. O’connell, MD, Practicing Ophthalmologists Advisory Committee for Education

FocalPoints

Consultants

Teresa c. chen, MD

alana L. Grajewski, MD

Clinical Modules for Ophthalmologists

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ting

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ii F o C a l P o i n t s : M o d u l E 3 , 2 0 1 2

Focal Points Editorial Review BoardGeorge a. Stern, MD, Missoula, MT

Editor in Chief; Cornea and External Disease

D. Michael colvard, MD, FacS, Encino, CA

Cataract Surgery

Bradley S. Foster, MD, Springfield, MA

Retina and Vitreous

Syndee J. Givre, MD, PhD, Raleigh, NC

Neuro-Ophthalmology

Ramana S. Moorthy, MD, FacS, Indianapolis, IN

Ocular Inflammation and Tumors

Eric P. Purdy, MD, Fort Wayne, IN

Oculoplastic, Lacrimal, and Orbital Surgery

Steven I. Rosenfeld, MD, FacS, Delray Beach, FL

Refractive Surgery; Optics and Refraction

M. Fran Smith, MD, Gainesville, FL

Glaucoma

c. Gail Summers, MD, Minneapolis, MN

Pediatric Ophthalmology and Strabismus

Focal Points StaffSusan R. Keller, Acquisitions Editor

Kim Torgerson, Publications Editor

Clinical Education Secretaries and StaffGregory L. Skuta, MD, Senior Secretary for Clinical Education,

Oklahoma City, OK

Louis B. cantor, MD, Secretary for Ophthalmic Knowledge,

Indianapolis, IN

Richard a. Zorab, Vice President, Ophthalmic Knowledge

Hal Straus, Director of Print Publications

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F o C a l P o i n t s : M o d u l E 3 , 2 0 1 2 1

IntroductionPediatric glaucoma is a disease occurring in infants and children that is characterized by optic nerve damage secondary to increased intraocular pressure (IOP). It rep-resents a heterogeneous group of rare disorders with a variety of presentations and underlying etiologies. Like adult- onset glaucoma, treatment requires the preven-tion of optic nerve damage by lowering IOP. In addition, ophthalmologists must address problems unique to the pediatric population such as corneal scarring secondary to corneal edema and Haab striae, and amblyopia result-ing from anisometropia and strabismus. Due to the wide range of management challenges, treating children with glaucoma often requires a team approach that includes

ContentsIntroduction 1

classification 2

Signs and Symptoms 2•Infancy 2

•Childhood 2

Evaluation 2•History 2

•Ocular Examination 2

Differential Diagnosis 6

Primary childhood Glaucoma 6•Primary Congenital/Infantile Open- Angle

Glaucoma 6

•Juvenile Open- Angle Glaucoma 7

•Primary Pediatric Glaucoma Associated With Other Ocular Abnormalities 7

•Aphakic (Pseudophakic) Glaucoma 8

Treatment 8•Medical Management of IOP 8

•Surgical Management of IOP 9

•Secondary Management Issues 12

conclusion 13

clinicians’corner 14

Financial Disclosures

The authors, reviewers, and consultants disclose the following

financial relationships. D. Michael Colvard, MD, FACS: (C) Abbott

Medical Optics, Bausch + Lomb; (P) OASIS Medical. Sharon F.

Freedman, MD: (C) Pfizer. Alana L. Grajewski, MD: (L) Alcon

Laboratories, Allergan; Steven I. Rosenfeld, MD, FACS: (C) Inspire

Pharmaceuticals; (L) Allergan. C. Gail Summers, MD: (C) McKesson,

(L) BioMarin Pharmaceutical, (S) NOAH (The National Organization for

Albinism and Hypopigmentation). Tammy L. Yanovitch MD, MHSc:

(S) National Eye Institute.

The following contributors state that they have no significant financial

interest or other relationship with the manufacturer of any commer-

cial product discussed in their contributions to this module or with the

manufacturer of any competing commercial product: Teresa C. Chen,

MD; Bradley S. Foster, MD; Syndee J. Givre, MD; Susan R. Keller;

Ramana S. Moorthy, MD; Sara S. O’Connell, MD; Eric P. Purdy, MD;

Edward L. Raab, MD, JD; George A. Stern, MD; M. Fran Smith, MD;

Kim Torgerson.

C = Consultant fee, paid advisory boards or fees for attending a

meeting

L = Lecture fees (honoraria), travel fees or reimbursements when

speaking at the invitation of a commercial sponsor

P = Patents and/or royalties that might be viewed as creating a

potential conflict of interest

S = Grant support for the past year (all sources) and all sources used

for this project if this form is an update for a specific talk or manu-

script with no time limitation

Learning ObjectivesUpon completion of this module, the reader should be able to:

•Recognize the common manifestations of pediatric glaucoma

•Demonstrate an understanding of the methods of diagnosing and treating glaucoma in infants and children, including newer technologies and medications

•Distinguish pediatric glaucoma from adult- onset glaucoma and identify unique management challenges

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2 F o C a l P o i n t s : M o d u l E 3 , 2 0 1 2

ophthalmologists with subspecialty training in pediatric ophthalmology, glaucoma, and cornea, as well as a pedi-atric low vision specialist.

The field of pediatric glaucoma is changing rapidly with the application of new technologies for diagnosis and treatment. Examples of recent advancements in the field include rebound tonometry, optical coherence tomography (OCT), ultrasound biomicroscopy (UBM), prostaglandin analogues, and fiber optic–guided trabecu-lotomy. Another important development has been use of the Internet to facilitate communication among special-ists managing these rare conditions. A better understand-ing of genetic associations with pediatric glaucoma is also emerging. These advances will likely result in improved patient outcomes for this potentially blinding disease.

This module reviews the classification, signs and symptoms, evaluation, and management of pediat-ric glaucoma and incorporates information on recent advances in the field.

ClassificationNumerous classification systems have been proposed for pediatric glaucoma. Most of these systems are based on the underlying mechanism of disease. This type of classification system provides a structure that is clini-cally useful in terms of diagnosis and treatment. In pri-mary glaucoma, there is a developmental abnormality of the anterior chamber angle causing aqueous outflow obstruction. In contrast, in secondary glaucomas the mechanism of aqueous outflow obstruction is caused by processes such as inf lammation or neoplasia in a nor-mally developed angle. Primary glaucomas can be sub-grouped by their association with ocular and/or systemic abnormalities. Table 1 describes such a classification sys-tem. With this classification system, some cases of pedi-atric glaucoma have both primary and secondary causes (ie, infantile- onset glaucoma in Sturge- Weber syndrome, neurofibromatosis, and aniridia). Future classification systems will likely incorporate genetic information with the current phenotypically driven diagnostic labels.

Signs and SymptomsThe signs and symptoms of pediatric glaucoma vary with the age of onset and degree of IOP elevation.

Infancy

In infants, parents or pediatricians often note ocular abnormalities such as tearing and/or enlarged corneas

(Figure 1). Elevated IOP leads to enlargement of the globe, called buphthalmos. As the cornea stretches, edema, clouding, and tears in Descemet membrane (Haab striae) develop. Corneal opacification results in the classic triad of symptoms of congenital glaucoma— epiphora, blepha-rospasm, and photophobia.

childhood

Older children typically present with decreased vision or have conditions associated with glaucoma such as Sturge- Weber syndrome, aniridia, or pseudophakia/aphakia. Decreased vision is the result of induced myo-pia or, less commonly, end-stage optic nerve cupping. Although elevated IOP does not lead to corneal enlarge-ment or Haab striae after the age of 2 to 3 years, it does cause scleral stretching that leads to progressive myopia in children up to 10 years of age. Acute glaucoma rarely occurs in children, but when it does, the symptoms are similar to those in adults, including nausea and vomit-ing associated with eye pain, headaches, and/or colored haloes around lights.

EvaluationObjectives of the pediatric glaucoma evaluation include confirming/excluding the diagnosis of glaucoma, identi-fying the cause of glaucoma (if present), and gathering information vital to optimal management. Frequently, in infants and young children, an examination under anes-thesia (EUA) is required to accomplish these objectives.

History

The history obtains information about diagnostic signs and symptoms. This includes any indication of eye pain, light sensitivity, lid closure, and/or epiphora. The par-ents might indicate that the eyes appear asymmetric or have other anterior segment abnormalities. Because of the association with systemic abnormalities, past medi-cal history should be queried for developmental issues and other systemic findings. Lastly, family history of pri-mary congenital glaucoma, glaucoma, anesthetic prob-lems, and other ocular and systemic disorders should be elicited.

Ocular Examination

Visual acuity and Visual Field Testing. As with all pedi-atric patients, the method of optimal visual acuity test-ing depends on the patient’s age and cognitive function. In infants and young children, observations regarding nystagmus and “fix and follow” behavior give a rough

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i. Primary glaucomasa. Congenital open-angle glaucoma

1. newborn glaucoma (iridotrabeculodysgenesis)2. infantile glaucoma (trabeculodysgenesis)3. late-diagnosed glaucoma

B. Juvenile (open-angle) glaucomaC. associated with ocular abnormalities (anterior segment

developmental abnormality)1. iridodysgenesis

a. aniridiab. Congenital iris ectropion syndromec. iridotrabecular dysgenesis (iris hypoplasia)

2. Corneodysgenesis (or iridocorneodysgenesis)a. axenfeld-Rieger anomalyb. Peters anomalyc. Congenital microcornea with myopiad. sclerocorneae. Congenital hereditary endothelial dystrophyf. Posterior polymorphous dystrophy g. Megalocornea

d. associated with systemic abnormalities1. Chromosomal disorders

a. trisomy 13 (Patau syndrome)b. trisomy 15c. trisomy 18 (Edward syndrome)d. trisomy 21 (down syndrome)e. turner syndrome (Xo)

2. Connective tissue abnormalitiesa. Marfan syndromeb. stickler syndromec. others (see under secondary glaucomas)

3. Phakomatosesa. sturge-Weber syndrome (isolated vs with central

nervous system involvement)b. neurofibromatosis type ic. nevus of ota (ocular melanosis)d. von-Hippel-lindau syndrome

4. othera. Hepatocerebrorenal syndrome (Zellweger syndrome)b. Kniest dysplasiac. Hallerman-streiff syndromed. Michel syndromee. nail-patella syndromef. oculodentodigital dysplasiag. Prader-Willi syndromeh. Rubinstein-taybi syndromei. Waardenburg syndromej. Walker-Warburg syndromek. Cutis marmorata telangiectasia congenital

ii. secondary glaucomasa. traumatic glaucoma

1. acute glaucoma2. late-onset glaucoma with angle recession3. arteriovenous fistula

B. secondary to intraocular neoplasm1. Retinoblastoma2. Juvenile xanthogranuloma

3. leukemia4. Melanoma5. Melanocytoma6. iris rhabdomyosarcoma7. aggressive nevi of the iris

C. secondary to uveitis1. open-angle glaucoma2. angle-blockage glaucoma

a. synechial angle closureb. iris bombé with pupillary blockc. trabecular endothelialization

d. lens-induced glaucoma1. subluxation-dislocation and pupillary block

a. Marfan syndromeb. Homocystinuriac. Weill-Marchesani syndrome d. Ectopia lentise. Hyperlysinemia

2. spherophakia with pupillary block3. Phacolytic glaucoma

E. after surgery for congenital cataract1. lens tissue trabecular obstruction2. Pupillary block (angle closure)3. Chronic open-angle glaucoma associated with angle

abnormalitiesF. steroid-induced glaucomaG. secondary to rubeosis

1. Retinoblastoma2. Coats disease3. Familial exudative vitreoretinopathy4. Medulloephithelioma5. Chronic retinal detachment

H. secondary angle-closure glaucoma 1. Retinopathy of prematurity 2. Persistent fetal vasculature 3. Microphthalmos 4. nanophthalmos 5. iris stromal cysts 6. Ciliary body cysts 7. Congenital pupillary iris-lens membrane 8. Retinoblastoma 9. Cystinosis10. Central retinal vein occlusion11. topiramate-induced

i. Malignant glaucomaJ. Glaucoma associated with increased episcleral venus or

venous pressure1. sturge-Weber syndrome (isolated vs central nervous

system involvement)2. Cavernous or dural-venous fistula3. orbital disease

K. secondary to maternal rubellal. secondary to intraocular infection

1. acute recurrent toxoplasmosis2. acute herpetic iritis

Table 1. Classification Scheme for Pediatric Glaucoma

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Perkins and the Tono- Pen (Reichert Ophthalmic Instru-ments; Depew, New York) instruments, are very useful for IOP measurement in infants and young children who cannot cooperate with slit-lamp- mounted Gold-mann applanation tonometry (the “gold standard”). The newer Icare (Icare Finland Oy; Helsinki, Finland) rebound tonometer shows promise for both clinic and home tonometry in children (Figure 4).

Obtaining IOP measurements in infants or young children often requires an EUA. Sedatives, narcotics, and inhaled anesthetic agents usually variably decrease measured IOP, while endotracheal intubation increases it. In addition, laryngospasm or upward drift of the eyes often causes spuriously high IOP readings. Despite these

assessment of visual acuity. Preferential looking tests provide a quantitative estimate of visual acuity in infants and pre- verbal children. Optotype testing with pictures, HOTV matching, and/or letters quantifies the minimum resolvable acuity in older children. As with visual acuity, the method of optimal visual field testing depends on the patient’s age and cognitive function. Testing by confron-tation to distraction in infants and young children helps reveal gross visual field defects. Older children may be able to perform perimetry in order to identify and quan-tify field loss. The Humphrey SITA-fast program and frequency- doubling technology methods are typically reliable in children 8 years of age and older.

External Examination. This examination includes inspection of the head and face for a port-wine stain, pto-sis due to a lid mass, or other unusual features. A char-acteristic facial or systemic feature may help identify glaucoma associated with chromosomal abnormalities, metabolic disorders, connective tissue abnormalities, or phakomatoses (Figures 2 and 3).

Tonometry. Measuring IOP (tonometry) plays a criti-cal role in the diagnosis and management of pediatric glaucoma. Portable applanation tonometers, such as the

Figure 2 Port-wine stain in a boy with right-sided facial hemangioma and associated glaucoma. note the distribu-tion involving the upper and lower eyelids and the prominent redness of the right eye. the latter is the result of abnormal episcleral vessels in this eye, which also has a diffuse cho-roidal hemangioma.

Figure 3 Plexiform neurofibroma of the right upper eyelid that presented in association with glaucoma at birth, before the diagnosis of neurofibromatosis type 1 in this 3-year-old child. Glaucoma occurs in 1% to 2% of neurofibromatosis cases.

a

b

Figure 1 Primary congenital glaucoma. a. Buphthalmos in an 8-month-old infant with primary congenital glaucoma. the infant presented with increased corneal diameter in the right eye. b. slit-lamp view of a horizontally oriented Haab striae and corneal edema.

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suggests, but does not confirm, glaucoma. While indi-rect ophthalmoscopy with a 28- or 30-diopter lens may underestimate optic nerve head cupping, slit-lamp bio-microscopy, or direct ophthalmoscopy through a Koeppe lens under anesthesia, enables a better appreciation of optic nerve head contour and cupping. In pediatric glau-coma patients without optic atrophy, the optic cup may decrease greatly in size with IOP reduction.

Other Diagnostic Tests. A refraction, looking for increas-ing myopia, aids in diagnosing pediatric glaucoma. It also is important for maximizing visual function of the child with glaucoma, as high myopia, astigmatism, and/or anisometropia is often the result of IOP- induced corneal scarring and/or ocular enlargement. Axial eye length, measured by A-scan ultrasonography, is an adjunct to serial corneal diameter measurements. Stabilization and even reduction of axial length often occurs with IOP reduction. B-scan ultrasonography assists in retinal assessment in eyes with opaque media and can confirm the presence of a f luid- filled bleb around aqueous drain-age devices. The average central corneal thickness (CCT) of normal children is similar to that of adults, as there is little effect of age on CCT. As in adults, normal black chil-dren have thinner CCT than normal white children. In infants with congenital glaucoma who have enlarged cor-neas without edema, CCT is thinner than normal; by con-trast, children with aniridia and aphakia/ pseudophakia usually have thicker CCT. One should not “adjust” the measured IOP based on CCT. Instead, children with thin-ner CCTs who are glaucoma suspects should be moni-tored more closely, perhaps with a lowered target IOP.

Fundus photography facilitates comparison of the optic nerve appearance over time in older children. OCT, a noninvasive imaging technique, measures the thick-ness of the peripapillary retinal nerve fiber layer, as well as macular thickness and volume (Figure 5). There is now normative data on the values for macular thickness, reti-nal nerve fiber layer (RNFL) thickness, and optic nerve topography in the healthy eyes of children 3 to 17 years of age. Unfortunately, the utility of time-domain OCT in children is somewhat limited by the need for a clear visual axis and steady fixation, although newer spectral domain OCT devices, with faster acquisition times, may expand the usefulness of this imaging in younger chil-dren and those with nystagmus. (A useful tip to allow the comparison of an older child’s OCT findings with the manufacturer’s internalized normative database for young adults is to enter a date of birth that makes the child 18 years of age.)

factors, IOP measurements taken immediately after the induction of general anesthesia with sevof lurane are typically comparable to those taken in the awake, calm infant or young child. The normal IOP in childhood, ranging from 10 to 22 mmHg, rises from infancy to reach normal adult levels by middle childhood.

anterior Segment Examination. Corneal enlargement and opacification often signify the onset of glaucoma in infants and young children. During corneal exami-nation, the presence of edema, Haab striae, and/or scar-ring suggest congenital or infantile glaucoma. Corneal measurement with a ruler or calipers verifies the pres-ence or absence of corneal enlargement. The normal newborn corneal diameter averages 10.0 mm, increas-ing to 11.5 mm by 2 years of age. The identification of other anterior segment abnormalities such as posterior embryotoxon, iridocorneal touch, and absence of the iris may help elucidate the underlying cause of glaucoma.

Gonioscopy. Examination of the angle structures pro-vides critical information regarding the underlying mech-anism of the glaucoma. During the EUA, direct gonioscopy with a Koeppe lens enables detailed inspection of the iris and angle structures, while indirect gonioscopy with a Zeiss or Sussman gonioprism can be used for older chil-dren at the slit lamp. Gonioscopic findings vary depend-ing on the underlying diagnosis. (See angle descriptions with corresponding diseases later in this module.)

Optic Nerve and Fundus Examination. Large optic nerve cups or asymmetry of the optic nerve cups

Figure 4 Rebound tonometry with the icare tonometer en-ables intraocular pressure measurement on young children in the clinic without the use of anesthetic drops.

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Differential DiagnosisPediatric glaucoma shares some clinical features with other ophthalmic conditions (Table 1). The identification of a coexisting nonglaucomatous disorder does not elimi-nate the possibility of glaucoma. For example, glaucoma

may complicate uveitis, Peters anomaly, and megalocor-nea; glaucoma can even occur concurrently with con-genital nasolacrimal duct obstruction.

Primary Childhood GlaucomaPrimary glaucoma occurs when the angle structures develop abnormally, resulting in aqueous outf low obstruction. Primary glaucoma may have associated ocu-lar or systemic abnormalities.

Primary congenital/Infantile Open- angle Glaucoma

Primary congenital glaucoma (PCG) presents within the first 3 years of life with the signs and symptoms of buph-thalmos, epiphora, lid closure, photosensitivity, and myopia. It is the most common form of primary pedi-atric glaucoma. Its incidence varies with ethnicity and ranges from as high as 1:1250 in Slovakian Roms to as low as <1:10,000 in Western populations. Most cases of PCG (65% to 80%) are bilateral. The majority of cases (>75%) are diagnosed within the first year of life. The signs and symptoms of PCG correlate with disease sever-ity. As a result, milder cases tend to go unrecognized for a longer time and, therefore, sometimes develop perma-nent visual loss. Primary care providers who are sensi-tive to the signs and symptoms of PCG facilitate prompt referral and diagnosis.

PCG occurs in both sporadic and familial patterns. Inheritance is usually autosomal recessive in familial cases. Three genetic loci—GLC3A [OMIM 231300], GLC3B [OMIM 600975], and GLC3C [OMIM 613085]—have been identified by linkage analysis in large, multigenerational pedigrees with multiple affected individuals. To date, two main causative genes have been reported, the cyto-chrome P450 subfamily I polypeptide 1 (CYP1B1) gene within the GLC3A locus, and the latent transforming growth factor beta binding protein 2 (LTBP2 gene), most likely within the GLC3C locus. The myocilin (MYOC) gene has also been implicated in a few PCG cases.

Although the pathogenesis of PCG is not fully under-stood, reduced outf low through the trabecular mesh-work may be the result of a developmental arrest of neural crest cell- derived anterior chamber angle tissue. Causes of outf low obstruction include compression of the trabecular meshwork beams by a high iris and ciliary body insertion and abnormal development of the trabec-ular meshwork itself. The defect in PCG is limited to the

a

b

Figure 5 ocular coherence tomography (oCt) allows for the measurement of the peripapillary retinal nerve fiber layer thickness and macular volume. the current oCt software from Zeiss does not include a normative database for chil-dren. a. Results of a stratus oCt scan RnFl 3.4 protocol (Carl Zeiss Meditec, inc, dublin, California) taken on a boy with juvenile open-angle glaucoma of the right eye. there is significant thinning of the peripapillary nerve fiber layer in the right eye. b. optic nerve head photos of the same boy. note the cupping and pallor of the optic nerve in the right eye.

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filtration tissue, with the typical gonioscopic abnormal-ity being diminished transparency of the tissue overly-ing the scleral spur and ciliary body band. This produces the appearance of a membrane (Barkan membrane), now thought to represent the thick, compacted trabecular meshwork.

Surgery is the definitive treatment for PCG. Medical therapy is reserved for brief, initial treatment to lower IOP and to help clear the cornea to facilitate surgery, as well as when postoperative IOP is not reduced to a nor-mal or targeted IOP. Angle surgery (goniotomy or trabec-ulotomy) successfully controls IOP in 70% to 80% of PCG cases. Surgical success is lower for cases that present at birth or after 1 to 2 years of age. Surgical options for PCG cases refractory to angle surgery include antimetabolite- augmented filtration surgery, aqueous drainage device implantation, and cycloablation. Reports of the suc-cess of these procedures vary. Visual prognosis in PCG depends on timely diagnosis and IOP reduction. Other factors affecting the final visual outcome in PCG include optic nerve damage, refractive error, corneal scarring, cataract, amblyopia, and strabismus.

Juvenile Open- angle Glaucoma

Juvenile open- angle glaucoma (JOAG) is primary open- angle glaucoma characterized by the onset of marked bilateral IOP elevation between the ages of 4 to 35 years. Children with JOAG often remain undiagnosed unless their family history prompts surveillance or the child presents with decreased distance vision secondary to induced myopia. Most cases of JOAG are familial with a dominant inheritance pattern, while some cases are sporadic. In several families with multiple affected indi-viduals, genetic studies have identified mutations of the myocilin (MYOC)/trabecular meshwork inducible gluco-corticoid response (TIGR) gene within the GLC1A locus [OMIM 137750]. The function of the myocilin protein is not known. Patients with JOAG have a normal appear-ing angle with gonioscopy. Treatment is difficult, often beginning with medication, and proceeding to filtration or aqueous drainage device surgery, although angle sur-gery may be helpful in some early- onset cases.

Primary Pediatric Glaucoma associated With Other Ocular abnormalities

Several of the primary pediatric glaucomas have associ-ated ocular abnormalities. Infantile- onset glaucoma may occur in many of these conditions; later- onset glaucoma due to secondary angle outf low obstruction may also develop (ie, aniridia).

aniridia. Aniridia is a developmental, bilateral disor-der characterized by congenital hypoplasia of the iris. Aniridia is commonly associated with other ocular abnor-malities, including small cornea with limbal abnormali-ties, cataracts, macular and optic nerve hypoplasia, and angle abnormalities. Progressive trabecular blockage by movement of the residual iris towards the trabeculum leads to glaucoma in 50% of aniridia cases; congenital onset glaucoma occurs infrequently but may be due to a primary drainage angle abnormality. Two-thirds of aniridia cases have autosomal dominant inheritance with the remaining one-third being sporadic. Aniridia is the result of a mutation in the paired box 6 (PAX6) gene [OMIM 607108]. Patients with sporadic aniridia may have large chromosomal deletions that include the Wilms tumor (WT1) gene [OMIM 607102], thus increasing their risk of Wilms tumor. Progressive angle narrowing and closure in aniridic infants with a strong family history of glaucoma may respond to prophylactic goniosurgery in selected cases. Once aniridic glaucoma develops, it is difficult to treat. Angle surgery is appropriate for early- onset cases, while trabeculectomy may be successful in older children. Aqueous drainage device implantation and cycloablation may be needed for refractory cases.

axenfeld-Rieger (a-R) Syndrome. A-R syndrome is a spectrum of anterior segment developmental abnormal-ities. There is usually incomplete formation of the ante-rior chamber. Findings may include hypoplasia of the anterior stromal leaf, iridotrabecular and iridocorneal processes, and posterior embryotoxon. Corectopia may also occur. Regardless of the ocular appearance, patients with A-R syndrome share the same features: a bilateral developmental disorder of the eyes, a family history of the disorder with an autosomal dominant inheritance pattern, no sex predilection, frequent systemic devel-opmental defects (dental anomalies, skull and skeleton dysplasia, and umbilical abnormalities), and glaucoma, occurring in more than 50% of cases, often in middle or late childhood although congenital onset does occur.

A-R syndrome and related phenotypes have been associated with 3 loci on chromosomes 4q25, 6p25 and 13q14. The genes on chromosome 4q25 and 6p25 have been identified as PITX2 and FKHL7, respectively. Because of genotypic and phenotypic overlap, some experts argue that Axenfeld anomaly, Rieger anomaly, Rieger syndrome, iridogoniodysgenesis anomaly, irido-goniodysgenesis syndrome, iris hypoplasia, and familial glaucoma iridogoniodysplasia should be considered one condition with variable phenotypes.

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Peters anomaly. This anterior segment developmental abnormality is usually bilateral and sporadic. Findings include a defect of Descemet membrane associated with localized corneal opacity and variable attachment of the iris to the periphery of the corneal leukoma. Cataract and/or lens adherence to the posterior corneal defect is common in this condition. Angle abnormalities often accompany Peters anomaly, and glaucoma occurs in at least 50% of cases. Although Peters commonly occurs as an isolated ocular disorder, there is a wide range of asso-ciated systemic and other ocular anomalies. Causative mutations of PAX6, PITX2, CYP1B1, and FOXC1 genes have been identified.

Glaucoma management in Peters anomaly is extremely difficult because of the presence of corneal opacity, cat-aract, and shallow or absent anterior chamber. When angle surgery is not possible, therapy starts with medica-tion. Commonly used surgical interventions in this con-dition include aqueous drainage device implantation or judicious cycloablation. Repeat glaucoma interventions are usually required.

aphakic (Pseudophakic) Glaucoma

Glaucoma often occurs after removal of congenital or developmental cataracts. The reported incidence ranges from 3% to 41%. This aphakic or pseudophakic glau-coma represents a serious cause of late visual loss in eyes after cataract removal. Aphakic or pseudophakic glaucoma is usually of the open-angle type, asymptom-atic, and delayed in onset for many years after cataract removal (median postsurgical onset is 5 years). Risk factors associated with aphakic or pseudophakic glau-coma include cataract removal in the first year of life, microphthalmia, and coexistence of persistent fetal vas-culature. The pathogenesis of open-angle glaucoma after cataract removal remains unknown.

When angle- closure glaucoma occurs in an aphakic or pseudophakic eye, prompt peripheral iridectomy (and sometimes synechialysis or anterior vitrectomy, or both) is mandatory and often curative. By contrast, medical therapy is the first-line treatment in aphakic or pseudophakic eyes with open-angle glaucoma; the angle, though open, often has peripheral anterior syn-echiae. When medical therapy does not control apha-kic or pseudophakic glaucoma, angle surgery usually has disappointing results. In some cases of early-onset glaucoma, a 360° trabeculotomy may decrease IOP. Tra-beculectomy with antiproliferative agents should be used with extreme caution in aphakic or pseudophakic eyes, because of the high risk of bleb scarring and endo-phthalmitis. Moderate success has been reported with

glaucoma drainage- device surgery, and cycloablation in selected refractory cases. Unfortunately, intraocular lens implantation, either primary or secondary, does not pro-tect against this type of glaucoma.

TreatmentThe main objective of managing pediatric glaucoma is to lower IOP and prevent optic nerve damage. Other objectives include addressing secondary issues such as refractive error, amblyopia, strabismus, and cor-neal opacification/scarring. Children with severe visual impairment may require low vision services to maximize use of their remaining visual function.

Medical Management of IOP

Many medications are available for the treatment of glaucoma. Although FDA approved for adult use, the safety and efficacy of many of these drugs have not yet been established in children. Under the guidance of the FDA, several pharmaceutical companies have initiated studies to address this issue.

Medical management provides an important adjunct to surgical treatment in PCG. Medical management can be initiated prior to surgery to lower the IOP and clear the cornea for better visualization or after sur-gery to provide further lowering of the IOP. In addition, increased IOP caused by juvenile and aphakic open-angle glaucoma, as well as most cases of secondary open-angle glaucoma, typically responds to medical management. The main issues with medical management in pediatric glaucoma include side effects and compliance.

Beta-adrenergic antagonists (Beta Blockers). Beta blockers decrease IOP by suppressing aqueous produc-tion. Although well tolerated from an ocular standpoint, these drugs can produce dangerous systemic side effects in infants (especially those with a history of prematu-rity) and in children prone to bronchospasm (asthma) or cardiac problems. Despite these warnings, topical beta blockers play an important role in treating children with glaucoma and serve as a first-line drug for those without contraindications. When used in children younger than 2 years of age, the dose should be low (ie, timolol 0.25%) and punctal occlusion should be used.

carbonic anhydrase Inhibitors (caIs). CAIs also decrease IOP by reducing aqueous production. Both top-ical (dorzolamide and brinzolamide) and systemic (acet-azolamide) forms are available. Acetazolamide lowers

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IOP (35%) more than its topical counterparts (25%). The pediatric dose for acetazolamide is 10 to 20 mg/kg/day. It has numerous side effects that include metabolic acido-sis, diarrhea, diminished energy levels, perioral and fin-ger tingling, and loss of appetite and weight. Therefore, it is reserved for refractory or high-risk cases. The topi-cal CAIs have minimal risk of systemic side effects and serve as excellent second-line drugs in many children with glaucoma (and first-line drugs in those unable to tolerate beta blockers).

Miotic Drugs (cholinergic Stimulators). Cholinergic stimulators lower IOP by increasing aqueous outf low through the trabecular meshwork. These drugs have largely been supplanted by newer medications. Pilocar-pine retains its usefulness to induce and maintain miosis before and after goniotomy or trabeculotomy for PCG.

adrenergic agonists (alpha agonists). Alpha agonists limit aqueous production and enhance uveoscleral out-f low, resulting in decreased IOP. In infants, brimoni-dine has produced life- threatening systemic side effects, including bradycardia, hypotension, hypothermia, hypo-tonia, and apnea. It also causes somnolence in toddlers. All children on brimonidine should be monitored for somnolence and treated with the lowest possible dose. Apraclonidine helps minimize bleeding with angle sur-gery and may be better tolerated than brimonidine for selected younger children requiring lower IOP. Thus, apraclonidine is helpful in children intolerant to beta blockers, or after pediatric corneal transplant (where topical carbonic anhydrase inhibitors have a relative contraindication).

Prostaglandin analogues. Prostaglandin analogues lower IOP by enhancing uveoscleral outf low. Both latanoprost and travoprost have been shown to lower IOP in selected children, especially those with JOAG. These drugs have excellent systemic safety profiles in children. However, they do produce thick, dark, long eye-lashes (Figure 6), and travoprost often causes some con-junctival redness and periocular pigmentation.

Surgical Management of IOP

Surgical intervention is the preferred treatment for PCG, angle- closure glaucoma, and other cases of pediatric glaucoma when medical therapy fails to adequately con-trol IOP. While most experts recommend angle surgery for PCG, there is disagreement about the optimal surgi-cal algorithm for the treatment of refractory PCG and other pediatric glaucomas. Glaucoma surgery in children

presents additional challenges to those encountered in adults due to the buphthalmic eye with stretched and distorted anatomy, and to the difficulties of postopera-tive evaluation and care. Repeat surgery is often neces-sary, and it is important to develop a long-term surgical strategy specifically designed to preserve subsequent options and prolong visual and ocular survival.

Pediatric glaucoma surgery can be divided into several broad categories (Table 2): angle surgery (goniotomy and trabeculotomy ab externo), filtering surgery (trabeculec-tomy with or without antifibrotics), aqueous drainage device surgery, cycloablation (cryotherapy or endoscopic laser) and others (peripheral iridectomy, combined trabeculectomy- trabeculotomy). In cases of blind, disfig-ured, and painful eyes, enucleation with prosthesis fit-ting may be appropriate treatment.

angle Surgery-Goniotomy/Trabeculotomy ab Externo. Goniotomy and trabeculotomy ab externo are the pre-ferred procedures for most PCG cases. The procedures are thought to be equally effective. While goniotomy involves the incision of the uveal trabecular meshwork under direct visualization (Figure 7), trabeculotomy does not require visualization of the angle structures. During trabeculotomy, Schlemm canal is cannulated with a tra-beculotome, a suture, or an illuminated catheter, which then tears through the trabecular meshwork (Figure 8). Both procedures decrease IOP by opening the trabecular meshwork.

If the cornea is clear, goniotomy has advantages over trabeculotomy, including no conjunctival scarring, ana-tomic precision, less trauma to adjacent tissues, and shorter operating times. In contrast, the microsurgeon

Figure 6 thickening and elongation of the lashes of the right upper eyelid in an infant with aphakic glaucoma who had undergone previous aqueous drainage device surgery and was using travoprost as adjunct therapy. other less common side effects in children include ocular redness and irritation.

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experienced in adult glaucoma surgery may find tra-beculotomy a more familiar procedure than goniotomy; moreover, trabeculotomy is not dependent on a clear cornea and can be directly converted to trabeculec-tomy if Schlemm canal is not found or is inadequately cannulated.

Innovations in the trabeculotomy procedure include the use of a 6-0 Prolene suture instead of a trabeculo-tome. The suture is pulled taut after being threaded into Schlemm canal for 180° or 360°, opening the respective angle. One of the dangers of this procedure is misdirec-tion of the suture into subretinal/suprachoroidal space. The use of the fiber optic–guided microcatheter and imaging system by iScience Interventional (Menlo Park,

California) enables visualization during the procedure and reduces the likelihood of this complication.

Combined trabeculotomy and trabeculectomy have been advocated in cases resistant to goniotomy, or in select populations in which glaucoma is present at birth, corneas are severely opaque, and success with primary trabeculotomy is unlikely.

Peripheral Iridectomy. A peripheral iridectomy is indi-cated for treatment of pupillary block. Although rare in children, pupillary block can occur after childhood cataract extraction or in association with intraocular inf lammation or advanced cicatricial retinopathy of prematurity.

Table 2. Surgical Interventions Used in the Management of Pediatric Glaucoma

P R o C E d u R E d E s C R i P t i o n i n d i C at i o n ( s )

angle surgery

Goniotomy incision of the uveal trabecular meshwork under direct visualization

Primary congenital glaucoma and other primary glaucomas

Chronic anterior uveitis-associated glaucoma

trabeculotomy ab externo Cannulation of schlemm canal and tearing through the trabecular meshwork

same as goniotomy; can be done in eyes with corneal clouding that impairs view for goniotomy

Filtration surgery

trabeculectomy (with or without antifibrotics)

Removal of a segment of the peripheral clear cornea +/– angle tissue under a partial-thickness scleral flap, creating a filtering “bleb”

Glaucoma in an eye with ioP uncontrolled on medications after angle surgery failure (or unlikely success with angle surgery) that has reasonable visual potential and unscarred conjunctiva

Combined trabeculectomy/trabeculotomy

Creation of filtering “bleb” and canalization of the schlemm canal with tearing through the trabecular meshwork

Glaucoma in an eye in which trabeculotomy cannot be completed (failure to cannulate schlemm canal) or in which angle surgery alone has failed or is unlikely to succeed

aqueous drainage device implantation

Placement of a flexible tube into the eye to conduct aqueous humor posteriorly to a reservoir (plate) sewn against the sclera

Primary congenital and aphakic glaucoma that has failed angle surgery

Glaucoma in an eye with failed trabeculectomy with intraoperative mitomycin C and reasonable visual potential; high risk for complications with trabeculectomy (ie, sturge- Weber syndrome, aphakia); or high risk for failure with trabeculectomy from scarring (ie, after multiple conjunctival surgeries)

cycloablation

Cyclocryotherapy Freezing of the ciliary processes from an external approach

Reserved for extremely severe cases of glaucoma in which altered anatomy makes laser cycloablation unlikely to succeed

transscleral laser cyclophotocoagulation

laser ablation of the ciliary processes from an external approach

Glaucoma that is refractory to medical or other surgical interventions

Endoscopic laser cyclophotocoagulation

application of laser energy to the ciliary processes under direct visualization

Glaucoma that is refractory to medical or other surgical interventions and amenable to endoscopy

Enucleation Removal of the eye Glaucoma resulting in a blind, painful eye

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ba

Figure 8 trabeculotomy ab externo is a procedure in which a trabeculotome, polypropylene suture, or fiber- optic catheter is placed in schlemm canal and then pulled into the anterior chamber. this figure illustrates a 360° suture trabeculotomy in an in-fant with primary congenital glaucoma. a 6-0 Prolene suture was threaded in schlemm canal for 360°. the ends of the suture are then pulled, causing the suture to “cheesewire” through the trabecular meshwork for its entire circumference. a. the blue arrows indicate the force applied to the sutures being pulled. b. the blue suture is visible crossing the anterior chamber over the iris.

a

b

Figure 7 Goniotomy is a procedure in which the anterior trabecular meshwork is incised with a needle or knife to improve aqueous outflow. this procedure is most often used for infants with primary congenital glaucoma who have a clear cornea. a. an infant’s angle during the goniotomy procedure. a gonioscopy lens modified for use in surgery has been placed on the cornea to enable visualization of the angle structures. the 25-gauge needle has been inserted at the limbus into the anterior chamber and guided over the iris to engage and then incise the anterior trabecular meshwork. the assistant gently rotates the eye left and right to facilitate extension of the incision. Yellow arrows highlight the newly formed cleft. b. Closer view of a cleft following the goniotomy procedure. the pink arrows indicate the cleft.

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Filtering Surgery/Trabeculectomy. Filtering surgery is indicated when angle surgery fails or—as is the case in some primary and many secondary pediatric glaucomas—is unlikely to succeed. Trabeculectomy pro-motes filtration of aqueous humor by removing a seg-ment of angle tissue (or peripheral clear cornea) under a partial- thickness scleral f lap, creating a filtering “bleb” (Figure 9). The use of antifibrotic therapy (usually intra-operative mitomycin C) greatly improves trabeculec-tomy success rates in children. Recently, some surgeons have advocated a fornix (rather than limbus- based) con-junctival f lap in order to obtain better bleb morphology with reduced incidence of cystic avascular blebs prone to later leaks and infection. Trabeculectomy has a low success rate in infants younger than 2 years of age, and in aphakic eyes. All children are at risk for bleb scarring/ failure and serious bleb- related infection. Alternatives to mitomycin- enhanced trabeculectomy should be consid-ered, especially in infants, children with aphakic eyes, and children at a high risk for infection.

aqueous Drainage Device (Tube Shunt) Surgery. Aque-ous drainage device surgery is indicated for PCG cases that fail with angle surgery and other types of pediat-ric glaucoma that have failed or are not appropriate for trabeculectomy surgery. This surgery involves the place-ment of a f lexible tube into the anterior chamber (or pars plana), which drains aqueous humor posteriorly to a reservoir sewn against the sclera. This reservoir becomes encapsulated to form a bleb from which trapped f luid exits into the surrounding tissues. Several implants have been used in children, including the following glaucoma

devices: Molteno (Molteno Ophthalmic, Dunedin, New Zealand), Baerveldt (Abbott Medical Optics, Santa Ana, California), and Ahmed (New World Medical, Rancho Cucamonga, California; Figure 10). Reported success and complication rates vary. Common complications include tube malposition or blockage, corneal damage, pupil abnormalities, cataract, motility disturbance, and encapsulation with elevation of IOP. Rarer complications include retinal detachment (usually limited to aphakic eyes), epithelial down-growth, and infection. The final IOP achieved after aqueous drainage device surgery is often not as low as after successful trabeculectomy. The specific devices and techniques used to implant aqueous drainage devices in pediatric glaucoma cases should be individualized to the size of the eye, immediacy of the need for IOP reduction, and type of glaucoma.

cycloablation. A cycloablative procedure is indicated for refractory cases in which medical and other surgi-cal means have been exhausted or have proven inad-equate. These procedures reduce IOP by damaging the ciliary processes and thereby decreasing aqueous pro-duction. The results are often unpredictable and com-plications occur frequently. However, cycloablation may be especially helpful as an adjunct after aqueous drainage device placement with inadequate IOP reduc-tion. Cycloablative procedures include cyclocryother-apy, transscleral cyclophotocoagulation, and endoscopic cyclophotocoagulation.

Secondary Management Issues

Secondary management issues related to pediatric glau-coma include refractive error, strabismus, cataract, cor-neal opacification/scarring, and amblyopia.

Figure 9 trabeculectomy is a procedure in which a section of peripheral clear corneal and angle structures are removed under a partial-thickness scleral flap to create a filtering bleb. this photograph was taken of a filtering bleb in a child with juvenile open-angle glaucoma who underwent trabecu-lectomy with mitomycin C.

Figure 10 a girl with traumatic glaucoma underwent lens extraction and aqueous drainage device implantation. an ahmed tube was placed pars plana following vitrectomy.

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Refractive Error. Elevated IOP in children often causes myopia and/or anisometropia. In addition, Haab striae and corneal scarring can induce astigmatism. Children with refractive errors require spectacle correction. Even in the absence of refractive error, children with glau-coma and buphthalmos, and those who are visually mon-ocular, should wear glasses with polycarbonate safety lenses for eye protection.

Strabismus. Children with glaucoma may develop stra-bismus as a result of glaucoma surgery or secondary to sensory vision loss. These children may need eye muscle surgery in order to improve ocular alignment and per-haps binocular function. In these cases, strabismus sur-gery requires careful planning as it may be complicated by the presence of a tube shunt reservoir or filtering bleb, and care should be taken to minimize scarring to facilitate possible future glaucoma surgeries.

cataract. Glaucoma surgeries, including goniotomy, trabeculotomy, and tube shunt placement, can be com-plicated by cataract formation. Cataract extraction in children with glaucoma requires careful attention to controlling postoperative inflammation and IOP. Intra-ocular lens placement is reasonable in anatomically suit-able eyes. Selected eyes may benefit from concurrent placement of a glaucoma drainage device at the time of cataract removal with intraocular lens implant.

corneal Opacification/Scarring. Corneal opacification in PCG often clears with adequate IOP control. However, in some cases, the cornea remains cloudy and requires transplantation. Corneal transplantation in children is more difficult than in adults because the eye is less rigid and the risk of rejection is higher. The partial- thickness approach, improved immune response modulation, and a multidisciplinary approach may help improve out-comes in these cases.

amblyopia. Amblyopia commonly accompanies pediat-ric glaucoma, especially in those children with unilateral

disease or dense corneal scarring. Appropriate treat-ment involves correction of the underlying cause of amblyopia—refractive error, strabismus, cataract, and corneal scarring/opacification—coupled with patching of the better seeing eye.

ConclusionChildren with glaucoma require life-long follow-up for IOP control and secondary issues. Loss of IOP control, as well as complications in eyes with filtering blebs and aqueous drainage devices, may occur at any time. Chil-dren with glaucoma who have controlled IOP should be followed up at least every 6 months, and young chil-dren, or those whose IOP has been controlled for less than 2 years, should be evaluated every 3 to 4 months. In addition, young children with glaucoma often face vision- threatening difficulties, such as corneal scarring, anisometropia, and resultant amblyopia even after IOP control has been achieved.

Collaboration among providers often optimizes man-agement of these challenging patients. Use of the Inter-net facilitates collective decision- making in the care of these patients and may someday allow tele- diagnosis and management of pediatric glaucomas in remote global regions. Genetic studies promise new insights into the causes and cures for primary childhood glaucomas.

Tammy L. Yanovitch, MD, MHSc, is a Clinical Assistant Professor of Ophthalmology at Dean McGee Eye Institute and the University of Oklahoma Department of Ophthal-mology, Oklahoma City, Oklahoma.

Sharon F. Freedman, MD, is a Professor of Ophthalmol-ogy and Pediatrics, and Chief of the Pediatric Ophthal-mology and Strabismus Service at Duke University Eye Center, Durham, North Carolina.

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Clinicians’Corner

Clinicians’ Corner provides additional viewpoints on

the subject covered in this issue of Focal Points. Con-

sultants have been invited by the Editorial Review

Board to respond to questions posed by the Acade-

my’s Practicing Ophthalmologists Advisory Committee

for Education. While the advisory committee reviews

the modules, consultants respond without reading the

module or one another’s responses. –Ed.

1. What instrument do you use to determine IOP in children? How does the Icare tonometer (Icare Fin-land Oy, Helsinki, Finland) compare with the instru-ment that you use?

Dr. Chen: For babies and small children who will not sit at the slit lamp, the Perkins tonometer provides the most accurate IOP measurements. In addition to being most similar to our gold standard (ie, Goldmann applanation tonometry), the Perkins instrument also gives the doc-tor the best sense of whether an eye pressure reading is accurate. For example, the clinician can actually see the mires’ relative positions change as the baby takes a breath or relaxes in between screams or cries. The clini-cian then knows to use the pressure reading measured at the point that the baby is crying or squeezing the least.

The Icare tonometer, or any tonometer that has only momentary contact with the eye, is more subject to mea-surement error. Because eye pressures f luctuate signifi-cantly in a crying patient, these types of tonometers do not enable the doctor to determine if the eye pressure reading was measured during peak Valsalva or during relaxed moments. In contrast, the Perkins tonometer tip can be placed more easily with continual contact on the cornea surface until the baby relaxes, at which point the pressure measurement is recorded.

Dr. Grajewski: It depends on the setting. In the clinic, if I am able to obtain an applanation pressure with the Goldmann tonometer at the slit lamp, then I will tend to follow the IOP in that way. More likely, however, in a small child, I have better luck obtaining an IOP in the clinic with a Tono-Pen (Reichert Ophthalmic Instru-ments; Depew, New York) and now more often with the rebound tonometer, the iCare. However, if it looks like it would be impossible to obtain an IOP reading, I do not believe in struggling to obtain pressure measurements that I know are likely to be inaccurate. Tactile IOP may be helpful in unilateral or extreme cases, but in those cases, there are usually other signs of elevated pressure.

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Historically, the mean IOP, using only topical anesthe-sia with a Perkins (applanation) tonometer, and later with the Tono-Pen, in infants without glaucoma who were less than 4 months of age was reported to be around 11 mm Hg. In one study using inhalation anesthesia, the mean IOP for children measured approximately 8 mm Hg at age 1 year and increased gradually to about 12 mm Hg by age 5 years.

Overall, the clinical picture, along with the IOP, dic-tates the degree of suspicion. This includes when the IOP is taken (anesthesia, nursing, crying) and the examiner’s sense of whether or not the reading is accurate.

3. Do you find optical coherence tomography (OcT) helpful in managing children with glaucoma?

Dr. Chen: Imaging in babies and infants is often lim-ited by the fact that these patients usually present with cloudy corneas, which preclude good imaging. In addi-tion, even if such a patient were being examined under anesthesia, imaging is still limited by the fact these patients under anesthesia are often going to have goni-otomy surgery. Because goniotomy surgery requires a small pupil and imaging ideally requires a dilated pupil, portable OCT imaging is often not practical or ideal in these patients.

Imaging older children is often possible in the clinic. Nevertheless, using imaging in clinical decision- making for these older children is primarily limited by the lack of large normative databases for children and the lack of prospective longitudinal OCT studies in children with glaucoma. Further studies are needed to better deter-mine the role of spectral-domain OCT imaging in the management of the pediatric glaucomas.

Dr. Grajewski: When normative data for children are established, I am sure OCT will be used more frequently to follow young patients with glaucoma for signs of pro-gression. Presently I find OCT most helpful in children with large cups, borderline pressures, and a question of glaucoma. The presence of a robust nerve fiber layer is very reassuring and can be followed over time. Visual field testing in children supplements this information but is less reliable in the younger age groups.

In the operating room, I routinely use the Tono-Pen. I measure the IOP “early” after mask induction with the mask removed, if possible, and then “late” after induc-tion and intubation (either laryngeal airway LMA or endotracheal tube). I record these numbers along with the indication of “early” or “late” as each has its own set of pros and cons. This measurement then is just one of the data points used in the EUA to make a clinical deter-mination of whether intervention is needed.

With respect to the central corneal thickness (CCT), I do not recommend adjusting the IOP down to compen-sate for a thick cornea. I do follow the CCT as the cor-neal edema resolves to see if, in fact, the CCT is thin for future follow-up.

In the cooperative child in the clinic, I find the IOP using the iCare to be similar to the Tono-Pen. That being said, I think more children cooperate at an earlier age with the Icare than the Tono-Pen. The Icare seems to read the IOP a little higher compared to the Tono-Pen, but I would, in general, prefer to err on the side of a higher IOP. The one real drawback to the Icare, at this time, is the fact that the child needs to be upright. In the reclining or recumbent child, the Tono-Pen is bet-ter than trying to do a rebound measurement with the device that is currently available.

2. What IOP is considered abnormal in an infant sus-pected of having congenital glaucoma?

Dr. Chen: There is no absolute eye pressure number that enables a diagnosis of glaucoma, and the eye pressure should always be interpreted in the context of other clin-ical exam findings such as the optic nerve appearance. In general, if the baby is crying or squeezing during the entire exam, eye pressures in the mid- twenties may be “normal.” If the baby is sleeping or feeding during the pressure measurement, the eye pressure should not be elevated.

Dr. Grajewski: Oddly enough, this is not an easy ques-tion. The extremes are obvious, and large asymmetric IOP differences are obvious. There are so many consider-ations in obtaining the IOP measurement that it under-scores the significance of putting the IOP into the entire clinical picture. The clinical exam in total is more impor-tant than any single pressure value.

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Clinicians’Corner

4. When do you use medical management in children with glaucoma?

Dr. Chen: Medical management in children is often a temporizing measure prior to surgical intervention. In addition to protecting the optic nerve, medical treat-ment prior to surgery can often clear the cornea, which facilitates goniotomy surgery. Older children can often tolerate medical treatment for months to years, and this may stabilize the eye pressure long enough so that the success rate for the eventual glaucoma surgery is better.

Dr. Grajewski: I use medical management in primary infantile glaucoma while awaiting surgery. These are the children who I know will have a good chance of success with a low complication rate with angle surgery. Oth-erwise, I use medical management (short of oral medi-cation) for longer periods of time in children in whom I have already completed angle surgery (360°) and the next step is a glaucoma drainage device. I also use top-ical medications in patients with secondary glaucoma where surgery may carry a higher risk of complications and the surgical prognosis is poor. While most of these ultimately move on to further glaucoma surgery, if the child’s clinical exam is stable on medication, I will delay.

5. What historical or clinical findings increase the risk of failure of angle surgery in glaucoma?

Dr. Chen: Primary congenital glaucoma is the most common developmental glaucoma. Primary congenital glaucoma can broadly be classified into two subtypes: newborn glaucoma and infantile glaucoma. This subclas-sification is based on both historical and clinical find-ings and was eloquently described by David Walton in his 2005 Chandler- Grant Lecture. Patients recognized at birth or in the first month of life are classified as “new-born primary congenital glaucoma.” Those presenting during their first 2 years of life have “infantile primary congenital glaucoma.” Patients diagnosed after 2 years of age may have “late recognized primary congenital glau-coma or juvenile glaucoma.”

Newborn primary congenital glaucoma is often recog-nized at birth because of the corneal opacification. Care-ful clinical exam may reveal abnormally large pupils and ectropion uveae. Gonioscopy often reveals iris insertion

on the anterior trabecular meshwork. This subtype of primary congenital glaucoma is important to recognize clinically, because these children often have an absent or hypoplastic Schlemm canal with unfavorable gonio-surgery results. In these babies, glaucoma drainage tube shunts should be considered as a possible initial surgical treatment. In contrast, the less severe infantile form of primary congenital glaucoma is characterized by more favorable results with goniosurgery.

Dr. Grajewski: In my experience, children who are at risk of failure with standard angle surgery are those with a diagnosis of anything other than primary infantile glau-coma or an obvious presentation of primary infantile glaucoma at birth.

6. are the parameters for performing transscleral cyclophotocoagulation in children different from those for adults?

Dr. Chen: Similar to adults, diode cyclophotocoagulation procedures should be considered as a last resort after other surgical procedures have been attempted. I do not use different laser parameters for children compared to adults.

Dr. Grajewski: I personally do not use this technique in children unless all other measures have failed. At that point in time the child is usually older, and I treat the eye sparingly but with similar parameters as in adults.

7. Do you ever perform prophylactic goniosurgery in patients with aniridia?

Dr. Chen: Glaucoma occurs in about half of patients with aniridia. Aniridic glaucoma typically occurs in late child-hood or early adulthood; aniridic glaucoma at birth is rare. The more common late-onset type of glaucoma is felt to occur because of progressive angle changes dur-ing the first two decades of life. These progressive angle changes are primarily comprised of increased confluence of iris stromal attachments onto the angle wall as well as tilting of the iris from a normal horizontal plane to a vertical plane that covers the angle wall. Prophylactic goniosurgery, as described by Morton Grant and David Walton, is indicated in select patients with aniridia who

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cannulate with a microcatheter. Certainly, if suture tra-beculotomy is determined to be the best initial surgical treatment in a particular patient, having the microcath-eter available may make the procedure safer, because the microcatheter would more easily allow the surgeon to know if the catheter or suture is inadvertently no longer in the canal.

Dr. Grajewski: Both of these newer technologies borrow some portion of the surgical procedure from standard pediatric angle surgery. The Trabectome is a trabecu-lotomy ab interno, although the approach is similar to a goniotomy. Theoretically, this device can be used for angle surgery but I have used it only in cases where there are multiple iris adhesions or an anteriorly dis-placed Schwalbe line, such as in Axenfeld- Rieger syn-drome, so that I am able to cauterize while I am cutting tissue. Otherwise, I see little advantage and the device feels large in these small eyes. As for canaloplasty, the fiber- optic element of the iScience device has provided us with anatomic certainty not previously realized for 360° trabeculotomy. Other than this use, I personally have no experience using canaloplasty for pediatric glaucoma.

Teresa c. chen, MD, is an Associate Professor of Oph-thalmology at the Harvard Medical School, Boston, Massachusetts. She is also on the full-time staff at the Massachusetts Eye and Ear Infirmary, where she is Chief Quality Officer.

alana L. Grajewski, MD, is a Professor of Ophthalmol-ogy at the University of Minnesota, and a Voluntary Pro-fessor of Ophthalmology and Co- Director of the Center for Pediatric Glaucoma, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida.

have documented progressive angle changes and who are thus at high risk for developing glaucoma. Prophylac-tic goniosurgery appears to significantly delay the onset of and decrease the severity of glaucoma in these select patients. Although more studies are needed, some stud-ies have suggested that prophylactic goniosurgery may prevent glaucoma entirely in some patients.

Dr. Grajewski: No. I do, however, perform an examina-tion under anesthesia with baseline measurements and gonioscopy but not surgery unless there is evidence that the angle and outflow is compromised.

8. What is the role of Trabectome technology (Neo-Medix, Tustin, california) and canaloplasty in the surgical management of congenital glaucoma?

Dr. Chen: Trabectome and canaloplasty are not necessary in the care of pediatric glaucoma patients, but their avail-ability may enhance glaucoma surgical treatment. Tra-bectome surgery is similar to goniotomy surgery, but Trabectome surgery may theoretically leave a wider final incision. For example, I have tried Trabectome surgery in pediatric uveitic glaucoma patients who have a poor prognosis for goniotomy surgery. These poor-prognosis uveitic glaucoma patients tend to be older than 10 years of age or have more than 180° of peripheral anterior syn-echiae. Although, in theory, leaving a wider final incision may increase the long-term success rates in these poor-prognosis eyes, further studies are needed to prove this.

Similarly, canaloplasty with microcatheter technol-ogy may facilitate cannulation of Schlemm canal for suture trabeculotomy, but experienced trabeculotomy surgeons can usually cannulate Schlemm canal without the microcatheter. Difficulty in cannulating Schlemm canal usually indicates an abnormally developed canal, which would not do as well with angle surgery in general and which would be difficult to thread with a suture or

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Suggested Reading

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Beck AD, Lynch MG. 360 degrees trabeculotomy for primary

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experience with the Ahmed Glaucoma Valve implant in

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latanoprost for the treatment of pediatric glaucoma. J AAPOS.

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glaucoma. Arch Ophthalmol. 1985;103:1163–1165.

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drainage device surgery in refractory pediatric glaucomas:

I. Long-term outcomes. J AAPOS. 2008;12:33–39.

O’Malley Schotthoefer E, Yanovitch TL, Freedman SF. Aqueous

drainage device surgery in refractory pediatric glaucoma:

II. Ocular motility consequences. J AAPOS. 2008;12:40–45.

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carbonic anhydrase inhibitor therapy for pediatric glaucoma.

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as adjunct chemotherapy with trabeculectomy in congenital

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and levobetaxolol in pediatric glaucomas: a randomized

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Wright TM, Freedman, SF. Exposure to topical apraclonidine

in children with glaucoma. J Glaucoma. 2009;18:395–398.

Yanovitch TL, Enyedi LB, Schotthoeffer EO, Freedman SF.

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Related academy Materials

Childhood glaucoma. In: Glaucoma. Basic and Clinical Science

Course, Section 10. 2011–2012

Sloan CF, Whitson JT. Recent advances in the treatment of

pediatric glaucoma. Current Insight. http://one.aao.org/CE/News/

CurrentInsight/Abstract.aspx?cid=476c4f19-be76-4e89-abbd-

aac2b5359729

Stuart A. Clinical update: pediatrics. The challenge of

diagnosing pediatric glaucoma. EyeNet. November/December

2009. http://www.aao.org/publications/eyenet/200911/

pediatrics.cfm

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FocalPoints - Pediatric Ophthalmology · MaRcH 2012 (MODULE 3 OF 3) Reviewers and Contributing Editor c. Gail Summers, MD, Editor for Pediatric Ophthalmology and Strabismus Edward