Juvenile Glaucoma

Juvenile glaucoma is a rare juvenile-onset open-angle glaucoma (JOAG) often found associated with myopia that shows autosomal dominant transmission. This entity is one of a group of pediatric glaucomas known as primary developmental glaucoma.

Differential diagnoses of the primary developmental glaucomas

Primary congenital glaucoma

• Newborn primary congenital glaucoma

• Infantile primary congenital glaucoma

• Late-recognized primary congenital glaucoma

Autosomal-dominant juvenile open-angle glaucoma

Primary angle-closure glaucoma

Primary glaucoma associated with systemic abnormalities

• Sturge-Weber syndrome

• Neurofibromatosis (NF-1)

• Stickler syndrome

• Oculocerebrorenal (Lowe) syndrome

• Rieger syndrome

• SHORT syndrome

• Hepatocerebrorenal (Zellweger) syndrome

• Marfan syndrome

• Rubinstein-Taybi syndrome

• Infantile glaucoma associated with retardation and paralysis

• Oculodentodigital dysplasia

• Open-angle glaucoma associated with microcornea and absent sinuses

• Mucopolysaccharidosis

• Trisomy 13

• Duplication 3q syndrome

• Trisomy 21 (Down syndrome)

• Cutis marmorata telangiectatica congenita

• Warburg syndrome

• Kniest syndrome (skeletal dysplasia)

• Michel syndrome

• Nonprogressive hemiatrophy

• PHACE syndrome

• Sotos syndrome

• Linear scleroderma

• GAPO syndrome

• Roberts pseudothalidomide syndrome

• Wolf-Hirschhorn (4p-) syndrome

• Robinow syndrome

• Nail-patella syndrome

• Cranio-cerebello-cardiac syndrome (3C syndrome)

• Brachmann-de Lange syndrome

• Rothmund-Thomson syndrome

• 9p deletion syndrome

• Phakomatosis pigmentovascularis (PPV)

Primary glaucoma associated with ocular abnormalities

• Congenital pupillary-iris-lens membrane syndrome

• Aniridia (congenital and acquired glaucoma)

• Congenital ocular melanosis

• Sclerocornea

• Iridotrabecular dysgenesis

• Peters syndrome

• Congenital iris ectropion syndrome

• Posterior polymorphous dystrophy

• Idiopathic or familial elevated episcleral venous pressure

• Anterior corneal staphyloma

• Congenital microcoria with myopia

• Congenital hereditary endothelial dystrophy

• Congenital hereditary iris stromal hypoplasia

• Axenfeld-Rieger anomaly

Secondary acquired glaucomas in the pediatric age group

Traumatic glaucoma

• Acute glaucoma (angle concussion, hyphema, ghost cell glaucoma)

• Late-onset glaucoma with angle recession

• Arteriovenous fistula

Glaucoma secondary to intraocular neoplasm

• Retinoblastoma

• Juvenile xanthogranuloma

• Leukemia

• Melanoma of ciliary body

• Melanocytoma

• Iris rhabdomyosarcoma

• Aggressive nevi of the iris

• Medulloepithelioma

• Mucogenic glaucoma with iris stromal cyst

Glaucoma secondary to chronic uveitis

• Open-angle glaucoma

• Angle-blockage glaucoma (synechial angle closure, iris bombé with pupillary block, trabecular endothelialization)

Lens-related glaucoma

• Subluxation-dislocation and pupillary block (Marfan syndrome, homocystinuria, Weill-Marchesani syndrome, axial subluxation with progressive high myopia)

• Spherophakia and pupillary block

• Phacolytic glaucoma

Glaucoma following lensectomy for congenital cataracts

• Pupillary block

• Chronic open-angle glaucoma following infantile lensectomy

Steroid-induced glaucoma

Glaucoma secondary to rubeosis

• Retinoblastoma

• Coats disease

• Medulloepithelioma

• Familial exudative vitreoretinopathy

• Chronic retinal detachment

Secondary angle-closure glaucoma

• Cicatricial retinopathy of prematurity (ROP)

• Microphthalmos

• Nanophthalmos

• Retinoblastoma

• Persistent hyperplastic primary vitreous

• Congenital pupillary-iris-lens membrane

• Topiramate therapy

• Ciliary body cysts

• Following laser therapy for ROP

Malignant glaucoma

Glaucoma associated with increased venous pressure

• Cavernous or dural A-V shunt

• Orbital disease

Glaucoma secondary to intraocular infection

• Acute recurrent toxoplasmosis

• Acute herpetic iritis

• Endogenous endophthalmitis

• Maternal rubella infection

Glaucoma secondary to undetermined etiology

• Iridocorneal endothelial syndrome (ICE)[1]

Increased intraocular pressure (IOP) is caused by impaired outflow of aqueous humor through the trabecular meshwork into the Schlemm canal. On clinical examination with gonioscopy, the filtration tissues within the anterior chamber angle appear normal in persons with juvenile glaucoma.[2] Pathologic examination has found thickened tissue and abnormal deposit of extracellular tissue in the trabecular meshwork between the anterior chamber and the Schlemm canal.

Following recognition of linkage of the gene for juvenile glaucoma on chromosome 1 (band 1q21-q31), the gene itself was identified and related to mutations found in the trabecular meshwork inducible glucocorticoid response (TIGR) gene in patients with juvenile glaucoma. This gene, now called myocilin, codes for the glycoprotein myocilin that is found in the trabecular meshwork and other ocular tissues. The normal function of myocilin and its role in causing glaucoma is undetermined. In studies of consanguineous populations, Khan et al concluded that mutation in CYP1B1 rather than mutation in MYOC can sometimes underlie familial primary juvenile glaucoma.[3, 4, 5]

Frequency

United States

Juvenile glaucoma has an estimated occurrence of 1 per 50,000 persons. It is rare when compared in frequency to other types of childhood glaucoma.

Mortality/Morbidity

No risk of mortality exists with juvenile glaucoma. Loss of vision is possible without early diagnosis and treatment.

Race

Juvenile glaucoma has been observed in Japanese, French, French Canadian, Caucasian-American, Asian-American, Hispanic-American, African-American, Panamanian, German, English, Irish, Danish, Italian, and Spanish families.

Young black patients with juvenile glaucoma, especially when myopic, are more susceptible to glaucomatous damage than are whites.[6]

Sex

Juvenile glaucoma probably occurs with equal frequency and severity in males and females.

Age

Patients with juvenile glaucoma show no evidence of congenital or infantile glaucoma. When candidate children are monitored carefully in families with a history of glaucoma, the onset of abnormal eye pressures occurs in children aged 5-10 years. In sporadic patients or those with no known family history of juvenile glaucoma, recognition of this glaucoma has occurred more often in adolescence or during the early adult years.

With an early diagnosis of glaucoma, the prognosis is excellent for retention of vision in patients.[7, 8]

Family members of patients with juvenile glaucoma must be informed of their risk and the risk of glaucoma in offspring.

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Because patients with juvenile glaucoma are often asymptomatic, the diagnosis is sometimes made on routine ophthalmological examination when optic nerve abnormalities are noted. Symptoms of visual loss and headache may lead to discovery of the disease.

A family history of glaucoma with occurrence over 2 generations or in a parent and sibling often is responsible for an early diagnosis of juvenile glaucoma. Patients are asymptomatic until glaucoma is advanced. Myopia is present in 50% of persons with juvenile glaucoma.

General physical examination findings are normal.

• Eye examination

  • Elevated eye pressures - Both eyes

  • Myopia

  • Optic disc damage (cupping)

  • Visual field loss

  • Slit lamp examination - Normal

  • Gonioscopy - Normal, open angles, occasionally prominent uveal processes

Juvenile glaucoma is caused by a genetically determined defect in the trabecular meshwork with autosomal dominant transmission (see Pathophysiology).

Physical examination of the visual system may include elevated intra-ocular pressures, optic nerve atrophy or cupping, asymmetry of the optic nerve heads, and visual field loss.

Mutational analysis of the myocilin gene at chromosomal region 1q21-q31 can be performed. More than 50% of disease-causing alleles may be screened by restriction enzyme analysis.

Glaucoma assessment - Field testing, fundus photography, and retinal tomography

See Physical.

An isolated report by Tawara and Inomata found an abnormal compact trabecular meshwork in patients with juvenile glaucoma.[9]

Treatment of juvenile glaucoma involves lowering of intra-ocular pressure pharmacologically or/and surgically.

Glaucoma medications may temporally control IOP. Often, a rising eye pressure over 1-3 years may become resistant to all medications and dictate a need for eye surgery.

Operations found useful for adult-onset open-angle glaucoma are useful in juvenile glaucoma. In addition, goniotomy is an effective procedure for this disease in both children and adults.

Consultation with an ophthalmologist familiar with this rare type of  glaucoma  may be helpful.

No limitations on activity are necessary. When vision remains only in one eye, protection of the remaining seeing eye is mandatory.

Repetitive regular eye examinations are indicated indefinitely after the diagnosis of juvenile glaucoma.

Reexamination of the eyes is indicated for those candidate children with a family history of juvenile glaucoma or with myopia and borderline IOPs.

Careful observation is indicated after glaucoma surgery.

As dictated by IOPs, antiglaucoma medications may be indicated.

The goals of pharmacotherapy are to reduce morbidity (visual loss due to optic nerve damage). These are applied topically to the eye.

Class Summary

For reduction of IOP in patients intolerant to other IOP-lowering medications or who have failed to respond optimally to other IOP-lowering medications.

Latanoprost (Xalatan, Xelpros)

May increase the outflow of aqueous humor. Patients should be informed about possible cosmetic effects to the eye/eyelashes, especially if uniocular therapy is to be initiated.

Bimatoprost (Latisse, Lumigan)

This agent is a prostamide analogue with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Bimatoprost ophthalmic solution is used to reduce IOP in open-angle glaucoma and ocular hypertension. Applied topically once a day prior to bed.

Travoprost ophthalmic (Travatan Z)

This agent is a prostaglandin F2-alpha analogue (FP). It is a selective FP prostanoid receptor agonist that is believed to reduce IOP by increasing uveoscleral outflow. Travoprost ophthalmic solution is used to treat open-angle glaucoma and ocular hypertension. Applied topically once a day prior to bed.

Tafluprost (Zioptan)

Tafluprost is a topical, preservative-free, ophthalmic prostaglandin analogue that is indicated for elevated IOP associated with open-angle glaucoma or ocular hypertension. The exact mechanism by which it reduces IOP is unknown, but it is thought to increase uveoscleral outflow. Applied topically once a day prior to bed.

Latanoprostene bunod ophthalmic (Vyzulta)

A 0.024% concentration of a prostamide analog used to lower intraocular (eye) pressure in patients with open-angle glaucoma or ocular hypertension.

Class Summary

These agents decrease aqueous production, possibly by blocking adrenergic beta receptors present in the ciliary body. Unfortunately, the nonselective medications in this class also interact with the beta receptors in the heart and lungs, causing significant adverse effects.

Timolol ophthalmic (Timoptic, Timoptic XE, Betimol, Istalol)

Timolol may reduce elevated and normal IOP, with or without glaucoma, by reducing the production of aqueous humor. Timolol gel-forming solution (Timoptic XE) usually is administered at night, unless it is used concurrently with latanoprost therapy. Used as 0.25% or 0.5% solution and applied topically to the eye 1-2 times per day.

Levobunolol (Betagan)

Levobunolol is a nonselective beta adrenergic blocking agent that lowers IOP by reducing aqueous humor production and possibly increasing the outflow of aqueous humor.

Metipranolol

Metipranolol is a beta adrenergic blocker that has little or no intrinsic sympathomimetic effect and membrane-stabilizing activity. It also has little local anesthetic activity. The drug reduces IOP by reducing the production of aqueous humor.

Class Summary

Alpha agonists work to both decrease production of fluid and increase drainage.

Brimonidine (Alphagan P)

Brimonidine is a relatively selective alpha2 adrenergic-receptor agonist that decreases IOP by dual mechanisms, reducing aqueous humor production and increasing uveoscleral outflow. Brimonidine has minimal effect on cardiovascular and pulmonary parameters. A moderate risk of allergic response to this drug exists. Caution should be used in individuals who have developed an allergy to Iopidine. IOP lowering of up to 27% has been reported. Applied topically 2-3 times a day.

Class Summary

By slowing the formation of bicarbonate ions, causing a reduction in sodium and fluid transport, these agents may inhibit carbonic anhydrase in the ciliary processes of the eye. This effect decreases aqueous humor secretion, reducing IOP. Carbonic anhydrase inhibitors typically have a weaker effect than beta blockers.

Dorzolamide (Trusopt)

Dorzolamide is a reversible carbonic anhydrase inhibitor that may decrease aqueous humor secretion, causing a decrease in IOP. Presumably, it slows bicarbonate ion formation, producing a subsequent reduction in sodium and fluid transport.

Systemic absorption can affect carbonic anhydrase in the kidney, reducing hydrogen ion secretion at the renal tubule and increasing renal excretion of sodium, potassium bicarbonate, and water. Dorzolamide is less stinging on instillation secondary to buffered pH. Applied 2-3 times per day.

Brinzolamide (Azopt)

Brinzolamide catalyzes a reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. It may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than 1 topical ophthalmic drug is being used, administer them at least 10 minutes apart. Applied 2-3 times per day.

Methazolamide (Neptazane)

Methazolamide reduces aqueous humor formation by inhibiting the enzyme carbonic anhydrase, which results in decreased IOP. Oral carbonic anhydrase inhibitors have significant adverse effects, including tiredness, malaise, and anorexia. Because of an increased incidence of adverse effects, it is rarely indicated for the treatment of ocular hypertension.

Class Summary

Combination solution may further decrease aqueous humor secretion compared to each solution used as monotherapy, while improving compliance. These agents have been approved by the FDA for children aged 2 years or older.

Brinzolamide/brimonidine (Simbrinza)

This combination product contains the carbonic anhydrase inhibitor brinzolamide and the alpha2 adrenergic receptor agonist brimonidine. It is indicated for reduction of elevated intraocular pressure in patients with primary open-angle glaucoma.

Timolol/brimonidine (Combigan)

Brimonidine is a selective alpha2 adrenergic receptor agonist and timolol is a nonselective beta-adrenergic receptor inhibitor. Each of these agents decrease elevated IOP, whether or not associated with glaucoma.

Timolol/dorzolamide (Cosopt)

Dorzolamide is a carbonic anhydrase inhibitor that decreases aqueous humor secretion, causing a decrease in IOP. This agent presumably slows bicarbonate ion formation with subsequent reduction in sodium and fluid transport. Timolol is a nonselective beta-adrenergic receptor blocker that decreases IOP by decreasing aqueous humor secretion.

Class Summary

By slowing the formation of bicarbonate ions, causing a reduction in sodium and fluid transport, these agents may inhibit carbonic anhydrase in the ciliary processes of the eye. This effect decreases aqueous humor secretion, reducing IOP. Carbonic anhydrase inhibitors typically have a weaker effect than beta blockers.

Acetazolamide (Diamox Sequels)

Acetazolamide is primarily used for the treatment of refractory POAG and secondary glaucomas.  Oral carbonic anhydrase inhibitors have significant adverse effects, including tiredness, malaise, and anorexia. Because of an increased incidence of adverse effects, it is rarely indicated for the treatment of ocular hypertension.

Methazolamide (Neptazane)

Methazolamide reduces aqueous humor formation by inhibiting the enzyme carbonic anhydrase, which results in decreased IOP. Oral carbonic anhydrase inhibitors have significant adverse effects, including tiredness, malaise, and anorexia. Because of an increased incidence of adverse effects, it is rarely indicated for the treatment of ocular hypertension.

Class Summary

Agents in this class may reduce intraocular pressure by increasing the outflow of aqueous humor through the trabecular meshwork route.

Netarsudil ophthalmic (Rhopressa)

Netarsudil ophthalmic solution 0.02% is a newly approved (2018) rho kinase inhibitor indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. It has not been evaluated for the treatment of juvenile glaucoma.

Latanoprost/netarsudil ophthalmic (Rocklatan)

Newly approved (2019) combination of a rho kinase inhibitor plus an ophthalmic prostaglandin analogue. It is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. It has not been evaluated for the treatment of juvenile glaucoma.