Childhood Glaucoma

Educational Objectives

The goal of this lecture is to improve the diagnosis and treatment of childhood glaucoma. After hearing and assimilating this lecture, the clinician will be better able to:

1. Diagnose pediatric glaucoma.

2. Accurately measure intraocular pressure in children.

3. Manage primary congenital glaucoma in children.

4. Select appropriate medical treatments for children with glaucoma.

5. Summarize the current state of knowledge regarding genes implicated in pediatric glaucoma.

Summary

Pediatric glaucoma: defined as intraocular pressure (IOP)-related damage to eye; recognized by optic nerve (ON) damage and stretching of globe; criteria for diagnosis 2 of 5 features including IOP >21 mm Hg, cupping of optic disc, corneal findings, progressive myopia or myopic shift with increased ocular dimensions, and reproducible visual field (VF) defect consistent with glaucoma

Classification: glaucoma primary or secondary; secondary types acquired or nonacquired; nonacquired glaucoma ocular or systemic; secondary glaucoma open (≥50% of angle open) or closed (<50% open)

Clinical presentation: cornea and sclera of young eye soft and distensible; many features of early-onset glaucoma due to ocular stretching; large eye (buphthalmos) has increased corneal diameter, deep anterior chamber (AC), stretched or hyperplastic iris, lens dislocation, axial myopia, myopic fundus, and staphylomas; splits in Descemet membrane lead to Haab striae (HS); ON may show cupping; sclera remains distensible until ≈10 yr of age; increasing or asymmetrical myopia may indicate high IOP; acute, high IOP in older children painful, but chronic elevations (as in juvenile open-angle glaucoma [JOAG]) may present with clear cornea and no symptoms; patients with JOAG often myopic, with thin central corneal thickness (CCT)

Intraocular pressure: factors affecting assessment include type of tonometer, cooperation (struggling, breath holding, and lid squeezing temporarily increase IOP), eye movements (IOP should be measured in primary position of gaze), pharmacologic dilation, anesthesia (inhaled agents and propofol lower IOP, but midazolam, ketamine, and chloral hydrate do not), intubation, ventilation, use of speculum, corneal and biomechanical properties, and CCT; corneas thinner until ≈12 yr of age and in buphthalmic eyes; IOP in children should not be adjusted for CCT; Goldmann applanation tonometry reference standard for IOP; Perkins tonometer allows recumbent applanation during examination under anesthesia (EUA); Tono-Pen, pneumatonometer, and Icare overestimate IOP and may be affected by CCT; Icare requires no anesthetic drops

Other measurements: due to challenges of measurement, IOP cannot be relied on when monitoring younger children with glaucoma; serial measurements of corneal diameter and axial length may be taken during EUA; axial length approximated by refraction; A-scan sonography determines length of eye; in older children, IOLMaster can measure axial length but overestimates IOP if fovea not fixed

Optic nerve: glaucoma associated with deeper, steeper cup than in adults and concentric (rather than focal) thinning of rim; older children may have focal disc thinning and defects in nerve fiber layers; stereo photographs useful but difficult to obtain in children; optical coherence tomography used, but no normative database for children exists; B-scan sonography detects cupping when media opaque

Visual acuity (VA): causes of poor VA include amblyopia, glaucomatous VF loss, corneal decompensation, ocular morbidity, cataracts, aphakia, and surgical complications

Visual field: matures with age; Goldmann VF isopters slightly constricted in children but reach adult dimensions at ≈12 yr of age; in young children, VF damage may appear as reduction in sensitivity rather than focal defect; Goldmann perimetry easier for children than automated perimetry

Gonioscopy: angle continues to mature after birth; primary congenital glaucoma (PCG) characterized by deep AC, high iris insertion, flat approach, absence of angle recess, peripheral iris hyperplasia with scalloped insertion, and possibly Barkan membrane; gonioscopy can reveal congenital adhesions in Axenfeld-Rieger syndrome (ARS), peripheral anterior synechiae (PAS), uveitis, aniridia, cicatricial retinopathy of prematurity, neovascularization, rudimentary iris, iris strands, blood in canal of Schlemm suggesting elevated episcleral venous pressure (EVP), and effects of previous surgery; gonioscopy crucial for identifying mechanism of glaucoma, which guides management

Anterior segment: conjunctiva — may be injected or scarred, or show bleb or dilated episcleral vessels; sclera — may show pigmentation, scleromalacia, or surgical scarring; corneal signs — include HS, large diameter, edema, hydrops, posterior embryotoxon, peripheral iris adhesions or PAS, pigment, penetrating keratoplasty (PKP) or other surgeries, opacification, or posterior polymorphous dystrophy (PPD); AC — may be deep or shallow, or asymmetric with other eye; may contain cells, blood, or pigment; iris — may show hyperplasia, aniridia, pseudopolycoria, corectopia, ectropion uveae, PAS, pupillary block, or iris bombe; lens — may feature coloboma, cataract, subluxation, spherophakia, adhesions to cornea, and Peters anomaly (PA); posterior segment — may exhibit vitreous hemorrhage or persistent fetal vasculature (PFV); other signs include tumors (eg, retinoblastoma), myopia, staphyloma, and foveal hyperplasia

Orbits and adnexal tissue: globe may be small (microphthalmia) or large; lids and periorbital skin may show hemangiomas, pigmentation, or tumor (eg, neurofibromatosis type 1 [NF-1]); NF-2 not associated with glaucoma

Systemic diseases: include rubella, Rubinstein-Taybi, ARS, Peters plus syndrome, and sequelae of maternal illness during pregnancy

Differential diagnosis: glaucoma should be considered in child with other conditions; epiphora — associated with obstructed nasolacrimal duct, conjunctivitis, foreign body, and chorioepithelial defect; photophobia — associated with uveitis, albinism, and cataract; enlarged cornea — may indicate axial myopia, megalocornea, or connective tissue disorder; appearance — elongated eye seen in axial myopia and retinal dystrophies; proptosis in shallow orbit may appear buphthalmic; cornea — clouding suggests keratitis due to herpes, rubella, or syphilis; corneal malformations include PA, dermoids, and skin disorders (eg, congenital ichthyosis); HS associated with birth trauma and PPD; disc — glaucoma mimicked by coloboma, morning glory syndrome, pits, and hyperplasia; iris — atrophy seen in iridocorneal endothelial syndrome (ICE; usually late in onset and unilateral); atrophy caused by surgery, trauma, inflammation, autosomal recessive disorders, and aniridia

Examination: Tono-Pen and gonioscopy used in neonates; child should not be restrained; progressive eyeball growth greater than expected or increasing cupping usually glaucoma; in older child, Icare or slit lamp examination possible

Surgical treatment: childhood glaucoma surgical disease; medications play supporting role; angle surgery procedure of choice for PCG; infants presenting at birth often have most severe disease; those presenting after 2 yr of age may not benefit from angle surgery; options are goniotomy and trabeculotomy; trabeculotomy may be performed in eye with cloudy cornea, but good view of angle needed for goniotomy; goniotomy spares conjunctiva and sclera for future trabeculectomy; complications of angle surgery include hyphema, PAS, cataract, hypotony, iris prolapse or incarceration, iridodialysis, cyclodialysis clefts, Descemet membrane stripping, corneal decompensation, lens subluxation, vitreous loss, endophthalmitis, and suprachoroidal hemorrhage; filtering surgery — creates alternative drainage; options are trabeculectomy with or without trabeculotomy and drainage devices; trabeculectomy often fails in children because of scarring around scleral flap, which necessitates careful technique and antimetabolites; buphthalmic eyes prone to leaks and hypotony; previous surgery risk factor for failure; hypotony, bleb leak, blebitis, endophthalmitis, and rupture must be treated promptly; trabeculectomy not suitable for children prone to trauma or if maintenance of hygiene or access to ophthalmologist questionable; however, it offers lower IOP, which may be important in children with severe corneal disease and advanced glaucoma; drainage devices — tube surgery less prone to bleb-related complications; tube can erode through conjunctiva or sclera, which causes epithelial ingrowth and infection, or retract into AC; high, encapsulated bleb or interference with extraocular muscles can cause strabismus; other complications include progressive corectopia, corneal endothelial damage, and corneal decompensation; deep insertion of tube safer; tubes do not lower IOP as much as trabeculectomy, but topical aqueous suppressant may be added; tubes allow use of contact lenses and survive better in eyes with previous surgeries; cyclophotocoagulation (CPC) — laser-induced destruction of cells of ciliary processes performed via external or internal approach; CPC proinflammatory and not advised in setting of uveitis; may promote cataracts; overtreatment may cause phthisis

Medications: prostaglandin analogs and α-adrenergics enhance outflow pathways and help keep iris away from angle incisions after angle surgery; most common volunteered side effect of carbonic anhydrase inhibitors is stinging on insertion; brinzolamide stings less than dorzolamide and therefore preferred in children; oral acetazolamide has more side effects; children should be monitored for acidosis and hypokalemia; central nervous system (CNS) depression most serious side effect of brimonidine; brimonidine contraindicated in children <8 yr of age; apraclonidine safer but can cause red eyes and follicular conjunctivitis; prostaglandin analogues — latanoprost safe; side effects include hypertrichosis, lash growth, and pigmentation of iris and skin; pilocarpine — may cause feeding problems and muscarinic side effects; steroids — increase IOP, especially in children; children should be monitored; choosing medications — babies with PCG usually treated first with low-dose β-blocker; next drug to add brinzolamide, followed by pilocarpine or apraclonidine, then acetazolamide; first-line medication for JOAG usually prostaglandin analogue or β-blocker, followed by carbonic anhydrase inhibitor, then apraclonidine; when many medications required, surgery should be considered; prostaglandins should be used with caution in patients with uveitis; pilocarpine not recommended in inflammatory glaucoma; carbonic anhydrase inhibitors should be used cautiously in corneal disease; principles — include using lowest dose, selective β-blockers, preference for apraclonidine over brimonidine, using punctal occlusion or lid closure, and reviewing side effects

Primary congenital glaucoma: usually sporadic; recessive inheritance possible; associated with mutation in CYP1B1; usually bilateral; children presenting at <3 mo of age or >2 yr of age have poor prognosis; buphthalmos usually present; high IOP associated with classic triad of photophobia, blepharospasm, and lacrimation; PCG not associated with other ocular defects; treated with angle surgery, and sometimes with trabeculectomy or drainage device

Juvenile open-angle glaucoma: not associated with other anomalies or syndromes; develops at 4 to 35 yr of age; 10% to 30% of cases inherited (autosomal dominant); associated with mutation in MYOC; angle may appear normal; signs include poorly defined landmarks, peripheral iris atrophy, high IOP, myopia, and strabismus; many children need surgery to control IOP

Glaucoma associated with nonacquired ocular anomalies: includes ARS, Peters plus syndrome, ectropion uvae, congenital iris hyperplasia, aniridia, PFV, ocular dermal melanocytosis (nevus of Ota), PPD, microphthalmus, microcornea, and ectopia lentis; ARS — variable phenotype; may involve angle, meshwork, and iris; mutations identified in PITX and FOXC; bilateral presentation distinguishes ARS from ICE; sexes equally affected; inheritance usually autosomal dominant; glaucoma develops in ≈50%; findings include posterior embryotoxon, adhesions between peripheral iris and line of Schwalbe, hypoplastic iris, corectopia, polycoria, dental anomalies, maxillary hypoplasia, hypertelorism, redundant umbilical skin or hernia, pituitary abnormalities, deafness, hypospadias, and cardiac defects; angle surgery contraindicated; treated with trabeculectomy or drainage device; PA — associated with triad of central corneal opacity, defects in posterior cornea, and lenticulocorneal or iridocorneal adhesions; PA type I involves cornea and iris; PA II also involves lens; 60% of cases bilateral; Peters plus syndrome has systemic features; PA associated with mutations in PITX, FOXC, CYP1B1, and PAX6; ocular manifestations variable (aniridia, iris coloboma, corectopia, PFV, and microcornea); glaucoma develops in ≈50% of cases; many children need PKP or corneal grafting; features of Peters plus syndrome include short stature, brachydactyly, limb shortening, cleft palate, dysmorphic facial features, and cardiac, genitourinary, and CNS abnormalities; visual prognosis poor; in young children, corneal grafting often unsuccessful; if corneal lesion small, optical iridectomy may be better option than PKP

Aniridia: varies from no iris to subtle hypoplasia; two-thirds of cases inherited (usually autosomal dominant); sexes equally affected; condition bilateral; 50% to 75% develop glaucoma in late childhood or adulthood; associated ocular defects include limbal stem cell deficiency leading to keratopathy, microcornea, thick cornea, PFV, cataracts, ectopia lentis, and hypoplasia of fovea and ON; systemic associations include Wilms tumor and WAGR syndrome (Wilms tumor, aniridia, genitourinary malformation, and retardation); Gillespie syndrome autosomal recessive disorder of aniridia, cerebellar ataxia, and mental retardation; angle surgery appropriate for early cases with goniotrabecular dysgenesis; most patients have secondary angle closure; trabeculectomy or tube preferred treatment

Glaucoma associated with nonacquired systemic disease: includes trisomy 21, Marfan syndrome, Weill-Marchesani syndrome, Stickler syndrome, homocystinuria, Lowe syndrome, mucopolysaccharidoses, NF-1, Sturge-Weber syndrome (SWS), Klippel-Trenaunay-Weber syndrome, Rubinstein-Taybi syndrome, and congenital rubella; Sturge-Weber syndrome (SWS) — characterized by ipsilateral facial cutaneous hemangioma (port wine stain) and variable ocular involvement; usually unilateral; if onset in early neonatal or infantile period, condition may respond to angle surgery; second peak of onset late in childhood due to raised EVP, and treated with filtering surgery

Glaucoma after cataract surgery: in most cases, angle open; postulated mechanisms include angle anomalies associated with congenital cataract, postoperative inflammation, steroid response, noxious substances diffusing from vitreous, and anatomical changes after removal of lens; glaucoma develops in ≥20% of children within 5 yr after cataract surgery, but can also develop later, requiring lifelong follow-up; risk factors for glaucoma include younger age at cataract surgery, small corneal diameter, and PFV

Readings

Baig NB et al: Ultrasound evaluation of glaucoma drainage devices in children. J AAPOS 2015 Jun;19(3):281-4; Bayoumi NH: Surgical management of glaucoma after congenital cataract surgery. J Pediatr Ophthalmol Strabismus 2015 Jul- Aug;52(4):213-20; Beck A, Chang TCP: Glaucoma: definitions and classification. Available at: www.aao.org/pediatric-center-detail/glaucoma-definitions-classification. Accessed July 16, 2016; Beck AD et al: Surgical outcomes with 360-degree suture trabeculotomy in poor-prognosis primary congenital glaucoma and glaucoma associated with congenital anomalies or cataract surgery. J AAPOS 2011 Feb;15(1):54-8; Bohnsack BL, Freedman SF: Surgical outcomes in childhood uveitic glaucoma. Am J Ophthalmol 2013 Jan;155(1):134-42; Chen TC et al: Pediatric glaucoma surgery: a report by the American Academy of Ophthalmology. Ophthalmology 2014 Nov;121(11):2107-15; Comi AM: Sturge-Weber syndrome. Handb Clin Neurol 2015;132:157-68; Dosunmu EO et al: Intraocular pressure in children: the effect of body position as assessed by Icare and Tono-Pen tonometers. Am J Ophthalmol 2014 Dec;158(6):1348-1352.e1; Freedman SF et al: Glaucoma-related adverse events in the first 5 years after unilateral cataract removal in the Infant Aphakia Treatment Study. JAMA Ophthalmol 2015 Aug;133(8):907-14; Jayaram H et al: Long-term outcomes of trabeculectomy augmented with mitomycin C undertaken within the first 2 years of life. Ophthalmology 2015 Nov;122(11):2216-22; Khan AO: Genetics of primary glaucoma. Curr Opin Ophthalmol 2011 Sep;22(5):347-55; Kraus CL et al: Comparison of the effectiveness and safety of transscleral cyclophotocoagulation and endoscopic cyclophotocoagulation in pediatric glaucoma. J Pediatr Ophthalmol Strabismus 2014 Mar-Apr;51(2):120-7; Lee TE et al: Comparison of intraocular pressure measurements between Icare Pro rebound tonometer and Tono-Pen XL tonometer in supine and lateral decubitus body positions. Curr Eye Res 2015 Sep;40(9):923-9; Papadopoulos M et al: Childhood glaucoma surgery in the 21st century. Eye (Lond) 2014 Aug;28(8):931-43; Souzeau E et al: Occurrence of CYP1B1 mutations in juvenile open-angle glaucoma with advanced visual field loss. JAMA Ophthalmol 2015 Jul;133(7):826-33; Tung I et al: Second glaucoma drainage devices in refractory pediatric glaucoma: failure by fibrovascular ingrowth. Am J Ophthalmol 2014 Jul;158(1):113-7; Yu Chan JY et al: Review on the management of primary congenital glaucoma. J Curr Glaucoma Pract 2015 Sep-Dec;9(3):92-9; Zagora SL et al: Primary congenital glaucoma outcomes: lessons from 23 years of follow-up. Am J Ophthalmol 2015 Apr;159(4):788-96.

Disclosures

For this lecture, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Edmunds was recorded for the Audio Digest Ophthalmology Comprehensive Review, First Edition. For information on the Audio Digest Ophthalmology Comprehensive Review, please visit www.audio-digest.org. The Audio Digest Foundation thanks Dr. Edmunds for her cooperation in the production of this lecture.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OP541701

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.