INTRODUCTION — Glaucoma is a heterogeneous group of eye diseases that are characterized by a progressive optic neuropathy, manifested by cupping of the optic disc (picture 1) and usually, but not always, associated with increased intraocular pressure (IOP). Glaucoma can lead to optic nerve damage and consequent visual loss. Peripheral vision loss occurs first, but if glaucoma is untreated, central vision loss and complete blindness can occur [1]. In infants and toddlers, additional damage to the visual system, including large and potentially asymmetric refractive error, corneal edema or scarring, astigmatism, strabismus, and amblyopia, may occur. Early diagnosis and referral are crucial to ensuring optimal visual outcome.
An overview of the causes, presentation, and treatment of pediatric glaucoma will be presented here. Primary infantile glaucoma and glaucoma in adults are discussed separately. (See "Primary infantile glaucoma" and "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis" and "Angle-closure glaucoma".)
ANATOMY — The angle of the eye is the recess formed by the iridocorneal juncture. The scleral spur, trabecular meshwork, and Schwalbe's line lie within this angle. The trabecular meshwork is a fenestrated structure that transmits aqueous fluid to Schlemm's canal, from which it drains into the venous system (figure 1A). When the drainage of aqueous fluid from the anterior chamber is compromised, a new steady state develops with abnormally high intraocular pressure (IOP) (figure 2).
CLASSIFICATION
●Open-angle versus angle-closure glaucoma – Glaucoma can occur as open-angle or angle-closure forms. Each form may present in childhood, and each form may be either acute or chronic.
•Open-angle glaucoma – Open-angle glaucoma is an optic neuropathy characterized by progressive peripheral visual field loss followed by central field loss in a typical pattern. It is usually but not always in the presence of elevated intraocular pressure (IOP). This is the most common form of glaucoma in both for children and adults. (See "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis", section on 'Pathogenesis'.)
Open-angle glaucoma implies that the pathway to the angle structures and trabecular meshwork are "open," meaning the obstruction to aqueous outflow is at the level of the trabecular meshwork or distal. When viewed directly via gonioscopy, the trabecular meshwork is visible without evidence of obstruction.
•Angle-closure glaucoma – Angle-closure glaucoma is characterized by narrowing or closure of the anterior chamber angle. Although a myriad of mechanisms of closure are possible, most involve rotational closure from the iris (figure 1A-B). (See "Angle-closure glaucoma", section on 'Pathogenesis'.)
In angle-closure glaucoma, the path to the trabecular meshwork is blocked, usually by the iris, but sometimes by neovascularization. When viewed directly by gonioscopy, the angle structures and trabecular meshwork are obscured.
●Primary versus secondary – Both open-angle and angle-closure glaucoma can be classified into primary and secondary types to provide a framework for the evaluation and management of individual patients (table 1).
•Primary glaucoma – Primary glaucomas are those with isolated angle malformations (trabeculodysgenesis) [2]. Primary glaucoma may have onset at birth, in the first few years of life, or later in life (congenital, primary infantile, and juvenile glaucoma, respectively). The age at which symptoms first appear probably is related to the severity of angle dysgenesis. Although congenital, infantile, and juvenile glaucoma appear to represent three points on the spectrum of one disease, juvenile glaucoma traditionally is treated as a separate entity because it has a different clinical presentation and one that is more similar to primary open-angle glaucoma in adults. (See 'Primary glaucoma' below and "Primary infantile glaucoma".)
•Secondary glaucoma – Secondary glaucoma either is acquired or related to an underlying ocular abnormality; it can occur at any age and may be present at birth. (See 'Secondary glaucoma' below.)
PRIMARY GLAUCOMA
Primary infantile glaucoma — Primary infantile glaucoma is a rare disease, with onset in the first years of life. A distinction sometimes is made between glaucoma that is present at birth (true congenital glaucoma) and glaucoma that has onset in the first two to three years of life (infantile glaucoma) because the prognosis differs [3]. The later the onset, the less severe the structural anomaly and the more likely the glaucoma will respond to treatment. Primary infantile glaucoma is discussed in detail separately. (See "Primary infantile glaucoma".)
Juvenile glaucoma
Pathogenesis — Primary glaucoma diagnosed after four to five years of age usually is referred to as juvenile glaucoma. The pathogenesis of juvenile glaucoma is similar to that of infantile glaucoma (angle dysgenesis), and the disorder sometimes is called late-onset primary infantile glaucoma [4]. The age at which symptoms first appear probably is related to the severity of angle dysgenesis [5].
A subset of patients with juvenile glaucoma have juvenile-onset open-angle glaucoma (JOAG), a form of primary open-angle glaucoma (POAG) that presents in childhood to early adulthood without ocular enlargement. JOAG is commonly inherited in an autosomal dominant fashion [6,7]. Molecular defects causing JOAG and POAG have been identified on the long arm of chromosome 1, including mutations in the myocilin gene (MYOC, also known as trabecular meshwork-induced glucocorticoid response gene [TIGR]) [8-13]. There is considerable overlap between JOAG, POAG, and normal phenotypes, even with the same mutation. Within affected families, the age of onset is usually fairly consistent. (See "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis".)
Clinical features — Although the pathogenesis of infantile and juvenile glaucoma is similar, the presenting signs and symptoms differ. The presentation of juvenile glaucoma is insidious. Patients usually are asymptomatic, and optic nerve damage is occult. In patients with JOAG, a strong family history is often present, given its autosomal dominant inheritance pattern. (See 'Pathogenesis' above.)
In contrast to infantile glaucoma, which typically presents in the first few years of life when the cornea and sclera are more elastic, juvenile glaucoma is not associated with enlarged cornea or buphthalmos. Corneal edema, tearing, photophobia, headache, and eye pain are also uncommon since intraocular pressure (IOP) increases insidiously. IOP is always elevated, often severely. Because other symptoms are often lacking, elevated IOP may go unrecognized unless optic nerve cupping (picture 1) is noticed [14]. Vision loss may be the presenting symptoms. Peripheral vision is affected first, and if left untreated, central vision loss and blindness may occur.
Diagnosis — The diagnosis is established based upon characteristic findings of nerve damage on fundus examination (picture 1 and picture 2), typically in the presence of elevated IOP and visual field deficit. Often, the diagnosis is suspected because of a positive family history [1]. Once the diagnosis is made, children and adolescents with juvenile glaucoma are followed with IOP measurements in the office, optical coherence tomography, and/or serial automated visual field testing. The frequency of follow-up depends upon individual case severity.
Treatment — As with infantile glaucoma, surgical intervention is the mainstay of therapy, and medications are used as an adjunct. Angle surgery (ie, goniotomy or trabeculotomy) is the first-line surgical intervention. Surgical treatment of pediatric primary glaucoma is discussed in greater detail separately. (See "Primary infantile glaucoma", section on 'Surgery'.)
SECONDARY GLAUCOMA — Secondary glaucoma can occur in many different conditions (table 1). Some of the causes of secondary glaucoma have associated angle anomalies. In others, glaucoma may become an important complication, although it is not usually considered a primary manifestation of the disorder. Secondary glaucoma is usually suspected because of coexisting ocular and/or systemic disease. The diagnosis is confirmed with fundus examination, tonometry (ie, measurement of the intraocular pressure [IOP]), and visual field testing.
Angle anomalies — Glaucoma occurs secondarily in several disorders that have associated angle anomalies (table 1). Sturge-Weber syndrome (SWS), aniridia, and neural crest disorders are three of the most common disorders with secondary glaucoma, and they are discussed briefly below. For many of the other disorders listed in the table, detailed descriptions are provided separately. (See appropriate topic reviews.)
The pathogenesis of angle-anomaly glaucoma is similar to that of primary infantile and juvenile glaucoma. For this reason, the treatment strategies are similar. Surgical therapy is almost always necessary to control intraocular pressure (IOP) and preserve vision. Medical therapy is adjunctive. (See "Primary infantile glaucoma", section on 'Treatment'.)
Sturge-Weber syndrome — The classic triad of SWS includes facial port wine birthmark (picture 3A-B), intracranial angiomata, and glaucoma (picture 4). Individuals with SWS can develop glaucoma even if they do not have the classic triad [15,16]. Systemic manifestations may include seizures, intellectual disability, paresis, and cerebral calcifications. SWS is discussed in greater detail separately. (See "Sturge-Weber syndrome".)
SWS is a sporadic disorder, with only rare familial cases. Although the syndrome is rare, it is one of the more common causes of secondary glaucoma in children.
Glaucoma has been reported in 40 to 60 percent of patients with SWS [17,18]. Glaucoma is most often unilateral on the same side as the port wine birthmark. Patients who develop glaucoma usually have port wine birthmarks of both the upper and lower eyelids. The risk of glaucoma is highest in the first decade of life. Approximately one-half of patients with SWS have glaucoma at birth and present with enlargement of the globe and the other hallmarks of infantile glaucoma (tearing, photophobia, corneal enlargement). Occasionally, patients develop glaucoma in adulthood [19]. Thus, continued vigilance is needed, even in patients with initially normal IOP.
The pathogenesis of the glaucoma is variable, depending upon the age of onset [20]. Most cases that present early are due to a developmental angle anomaly that is indistinguishable from that in primary infantile glaucoma [21]. Other possible mechanisms for later-onset glaucoma include hypersecretion from an associated angioma of the choroid, elevated venous pressure associated with an episcleral hemangioma [20,22], or a combination of these abnormalities.
As is the case with primary pediatric glaucoma, surgery is the mainstay of treatment for glaucoma in patients with SWS [23,24]. However, some patients can be successfully managed medically [25]. (See "Primary infantile glaucoma", section on 'Surgery' and "Primary infantile glaucoma", section on 'Medical therapy'.)
The surgical success rate is generally lower and the complication rate higher in glaucoma associated with SWS, especially in those with an associated fundus hemangioma (picture 4).
Aniridia — Aniridia is a rare congenital abnormality caused by mutations in the PAX6 gene, which is involved in the early development of the eyes, brain, and central nervous system. The majority of cases are sporadic, with occasional familial cases. The familial cases are autosomal dominant and involve deletion of chromosome 11p13, a deletion that increases the risk of Wilms tumor (also known as the WAGR syndrome [Wilms tumor, aniridia, genitourinary anomalies, and mental retardation]) [4]. (See "Microdeletion syndromes (chromosomes 1 to 11)", section on '11p13 deletion syndrome (WAGR syndrome)'.)
The ocular manifestations of aniridia are not limited to the iris, although it is nearly always affected. The iris may be almost completely absent, sometimes with only a small residual stump visible only on gonioscopy, or have only minor changes. Other ocular manifestations include foveal hypoplasia, nystagmus, optic nerve hypoplasia, glaucoma, and progressive corneal degenerative changes. Glaucoma often presents in infancy but can present at any time.
The pathogenesis of the glaucoma in aniridia is multifactorial. A minority of patients have an anomalous angle present from birth [26]. Others form iris adhesions within the anterior chamber angle and go on to develop chronic angle closure glaucoma. Thus, aniridic glaucoma can result from congenital or acquired structural angle anomalies. Patients with aniridia should be regularly monitored for the development of glaucoma. Evaluation should include assessment of corneal signs (eg, edema, enlargement), examination of the optic nerve, and measurement of IOP.
The treatment of aniridic glaucoma is difficult. Goniotomy appears to be a reasonable option for patients with an open angle. Some authors have suggested prophylactic goniotomy for patients with aniridia [27]; however, this is controversial [28]. Trabeculotomy or tube shunting may be best suited for patients with angle closure [29].
Anterior segment dysgenesis — Anterior segment dysgenesis refers to developmental defects of the anterior segment and iris that result in a spectrum of ocular and systemic manifestations.
Anterior segment dysgenesis represents an arrest in late gestational development that may result in retained primitive endothelium, failure of the peripheral iris to migrate posteriorly, and/or failure of the corneal endothelium to fully differentiate. Individual disorders within this spectrum include [30-32]:
●Posterior embryotoxon or anteriorly displaced Schwalbe's line.
●Axenfeld-Rieger syndrome, which includes disorders formerly known as Axenfeld anomaly, Axenfeld syndrome, Rieger anomaly, Rieger syndrome, and iridogoniodysgenesis.
●Posterior keratoconus.
●Peters anomaly, a central defect in the corneal endothelium with various degrees of adhesion of the iris and lens capsule to the central cornea, with a resultant corneal leukoma (whitish plaque).
Glaucoma occurs at some time in approximately 60 percent of patients with these disorders. It may occur during infancy or much later. The increased IOP appears to be related to developmental angle anomalies. Patients with anterior segment dysgenesis should be monitored regularly for the development of glaucoma. Evaluation should include assessment of corneal signs (eg, edema, enlargement), examination of the optic nerve, and measurement of IOP.
These disorders were formerly known as anterior chamber cleavage syndromes or mesodermal dysgenesis; however, these terms are no longer used because it is now known that neural crest cells, not mesoderm, are primarily responsible for anterior segment development and that the simple concept of anterior segment "cleavage" may not be valid.
Retinopathy of prematurity — Retinopathy of prematurity (ROP) is a developmental vascular proliferative disorder that occurs in the incompletely vascularized retina of premature infants. It is discussed in detail separately. (See "Retinopathy of prematurity (ROP): Risk factors, classification, and screening", section on 'Introduction'.)
Glaucoma is a severe, late complication of ROP. It can occur across the spectrum of visual acuity and at any time. Between one-quarter and one-third of patients with stage 5 ROP (complete retinal detachment) develop glaucoma as a complication [33]. Diminished visual acuity and/or pain (particularly in blind eyes) may suggest the diagnosis of glaucoma in patients with ROP.
The pathogenesis of glaucoma in ROP varies. Mechanisms include contraction of the retrolental membranes leading to anterior rotation of the lens-iris diaphragm and secondary angle closure [34-37], high iris convexity, anterior iris insertion, pigment clumping in the trabecular meshwork, and the appearance of a translucent matrix in the angle structures [33].
The treatment of glaucoma in ROP varies depending upon the underlying mechanism. If glaucoma is caused by forward displacement of the lens-iris diaphragm, lensectomy is the preferred procedure. Medications and/or surgery may be used in other cases. Although more common in those treated for ROP, there have been reports of secondary glaucoma in untreated patients with ROP patients as well [38].
Aphakia (due to cataract surgery) — Children who have undergone cataract surgery are at risk for developing secondary open-angle or angle-closure glaucoma [39]. The term "aphakic glaucoma" is used for this category since cataract surgery involves removal of the crystalline lens. Both children who have had cataract extraction without implantation of an intraocular lens (true aphakia) and those who have had cataract extraction with placement of an intraocular lens (either at time of cataract surgery or subsequently, both deemed pseudophakia) are placed in the aphakic glaucoma category. In one series, aphakic glaucoma accounted for 20 percent of cases of pediatric glaucoma presenting to a children's hospital over a 20-year period [40]. (See "Cataract in children", section on 'Postoperative complications'.)
●Prevalence – The prevalence of glaucoma as a complication of pediatric cataract surgery has changed as surgical techniques have evolved. Current irrigation/aspiration techniques for congenital cataract surgery, coupled with mechanical anterior vitrectomy, seem to have reduced the rate of postoperative glaucoma [41]. However, the exact prevalence is not known. In one study of 137 patients who had undergone congenital cataract surgery and were followed for a mean of 9.6 years, glaucoma developed in 12 percent of the eyes [42]. In a meta-analysis using individual patient data on 470 children who underwent cataract surgery in infancy, 80 (17 percent) developed glaucoma at a median follow-up of 4.3 years [43]. The risk was highest among patients who underwent surgery at ≤4 weeks of age. Microphthalmos is an important risk factor for developing glaucoma after cataract surgery. In general, younger age at surgery and degree of other eye malformations are strongly correlated with subsequent risk of glaucoma development [42].
The implantation of an intraocular lens (pseudophakia) does not appear to decrease the incidence of glaucoma after cataract surgery [44,45]. (See "Cataract in children", section on 'Optical and visual rehabilitation'.)
●Pathogenesis – Several factors may contribute to the development of aphakic glaucoma [46,47]:
•An underlying anterior segment defect that contributed to the development of congenital cataract
•Subclinical angle anomalies
•Predisposition from the combination of cataract and microcornea
•Early exposure to intraocular inflammation from cataract extraction
The role of corneal thickness in these patients is uncertain. Many patients demonstrate abnormally thick corneas, which may artificially raise IOP measurements.
●Monitoring – Children who have undergone cataract surgery should be monitored for the development of glaucoma with periodic tonometry and examination of the optic nerve [48]. Most patients who develop aphakic glaucoma do so within four to six years of their cataract surgery, with an average of approximately one year postsurgery [49,50]. However, glaucoma can occasionally develop at >8 to 10 years after cataract surgery [41,51]. Thus, patients who have had infantile cataract surgery should be followed for life. Excessive loss of hyperopia (farsightedness), the induction of frank myopia (nearsightedness), or corneal clouding in the aphakic patient should raise immediate suspicion of glaucoma [52,53].
●Management – Aphakic glaucoma may respond to medical therapy. Thus, a trial of medical therapy usually is attempted before undertaking surgical intervention. Pharmacologic therapy consists of topical IOP-lowering agents that are commonly used in adults with glaucoma. (See "Open-angle glaucoma: Treatment", section on 'Pharmacologic therapies'.).
In addition, echothiophate can be used in this population since the aphakia (or pseudophakia) prevents the side effect of tonic accommodation.
Surgery is reserved for patients who are refractory to medical therapy. The outcome of surgery for aphakic glaucoma is less favorable than that for primary congenital glaucoma [4]. (See "Primary infantile glaucoma", section on 'Surgery'.)
Intraocular inflammation — Glaucoma can occur as a complication of inflammation or uveitis. The mechanism is similar regardless of age of onset: damage to and blockage of trabecular meshwork by inflammatory cells or scarring. The underlying cause of uveitis varies by age. Inflammatory glaucoma in children usually is a complication of juvenile idiopathic arthritis (formerly juvenile rheumatoid arthritis) or sarcoidosis or is idiopathic (often of viral etiology). (See "Uveitis: Etiology, clinical manifestations, and diagnosis".)
Control of inflammation is the mainstay of treatment. Acute trabeculitis, inflammatory obstruction, and pupillary block usually respond to corticosteroids and antiglaucoma medications. Goniotomy has been shown to be an effective procedure in children whose IOP remains elevated despite medical therapy [54,55]. Glaucoma from angle closure usually requires trabeculectomy or tube shunt surgery.
Tumors — Glaucoma can occur as a complication of ocular tumors, particularly retinoblastoma, but occasionally other types of tumors (eg, medulloepithelioma, juvenile xanthogranuloma, histiocytosis X, leukemia). (See "Retinoblastoma: Clinical presentation, evaluation, and diagnosis".)
Secondary glaucoma can result from:
●Tumor infiltration of the angle
●Inflammation of the angle
●Secondary hemorrhage into the angle [56]
●Angle closure, produced by anterior displacement of the iris-lens diaphragm by a bulky tumor (typical in retinoblastoma)
Trauma — Glaucoma can occur as an acute or late complication of blunt or penetrating ocular trauma. The mechanisms for traumatic glaucoma include:
●Hyphema, with blockage of the trabecular meshwork with red blood cells or debris
●Damage to the angle, leading to decreased outflow of aqueous (a late complication)
●Inflammation of the trabecular meshwork
●Damage to the lens
Glaucoma associated with hyphema requires urgent referral and management because IOP can rise rapidly to high levels, causing damage to the optic nerve and blood staining of the cornea. Surgical evacuation of the blood collection may be necessary if the IOP cannot be controlled. Modest elevation of IOP usually responds to temporary medical therapy. Patients with sickle cell disease can present with significant increases in IOP with minimal hyphema. They typically do not respond well to medical management and require early anterior chamber washout. (See "Traumatic hyphema: Management", section on 'Patients with intraocular hypertension' and "Traumatic hyphema: Management", section on 'Surgical clot evacuation'.)
Steroid-induced — Steroid-induced glaucoma is more common among adults but can occur in children. This form of glaucoma occurs most commonly in patients who use corticosteroid eye drops, although it has been observed infrequently in chronic and, to a lesser extent, acute systemic corticosteroid use [57,58]. The mechanism of steroid-induced glaucoma remains unknown. The condition usually subsides after discontinuation of steroids. (See "Major adverse effects of systemic glucocorticoids", section on 'Ophthalmologic effects'.)
SUMMARY AND RECOMMENDATIONS
●Definition – Glaucoma is a heterogeneous group of eye diseases that are characterized by a progressive optic neuropathy, manifested by cupping of the optic disc (picture 1) and usually, but not always, associated with increased intraocular pressure (IOP). (See 'Introduction' above.)
●Classification
•Open-angle versus angle-closure glaucoma – Glaucoma can occur in open-angle or angle-closure forms. Angle-closure glaucoma is characterized by narrowing or closure of the anterior chamber angle (figure 1A-B). (See "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis", section on 'Pathogenesis' and "Angle-closure glaucoma", section on 'Pathogenesis'.)
•Primary versus secondary forms – Both open-angle and angle-closure glaucoma can be classified into primary and secondary types (table 1). (See 'Classification' above.)
●Primary glaucomas – These are conditions in which there is an isolated angle malformation (trabeculodysgenesis). Onset may be at birth, in the first few years of life, or later in life. (See 'Primary glaucoma' above.)
Primary infantile glaucoma is a rare disease, with onset in the first years of life. It is discussed in greater detail separately. (See "Primary infantile glaucoma".)
Juvenile glaucoma refers to primary glaucoma diagnosed after four to five years of age. Patients are usually asymptomatic, and optic nerve damage is occult. The diagnosis is established based upon characteristic findings of nerve damage on fundus examination (picture 1 and picture 2), typically in the presence of elevated IOP and visual field deficit. Often, the diagnosis is suspected because of a positive family history. Surgical intervention is the mainstay of therapy, and medications are used as an adjunct. (See 'Juvenile glaucoma' above.)
●Secondary glaucoma – Secondary glaucoma can occur in many different conditions (table 1). Causes of secondary glaucoma include (see 'Secondary glaucoma' above):
•Angle anomalies (eg, Sturge-Weber syndrome (SWS), aniridia, anterior segment dysgenesis) (see 'Angle anomalies' above)
•Retinopathy of prematurity (ROP) (see 'Retinopathy of prematurity' above and "Retinopathy of prematurity (ROP): Risk factors, classification, and screening")
•Aphakia (due to cataract surgery) (see 'Aphakia (due to cataract surgery)' above and "Cataract in children", section on 'Postoperative complications')
•Intraocular inflammation (see 'Intraocular inflammation' above)
•Ocular tumors (see 'Tumors' above and "Retinoblastoma: Clinical presentation, evaluation, and diagnosis")
•Trauma (see 'Trauma' above and "Traumatic hyphema: Clinical features and diagnosis")
•Exposure to glucocorticoids (see 'Steroid-induced' above and "Major adverse effects of systemic glucocorticoids", section on 'Ophthalmologic effects')
Secondary glaucoma is usually suspected because of coexisting ocular and/or systemic disease. The diagnosis is confirmed with fundus examination, tonometry (measurement of IOP), and visual field testing.
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