Secondary Congenital Glaucoma Clinical Presentation

Updated: Jul 27, 2020
  • Author: Inci Irak Dersu, MD, MPH; Chief Editor: Hampton Roy, Sr, MD  more...
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Axenfeld-Rieger syndrome

Distinct iris and pupil abnormalities are noticed by parents at an early age.

Peters anomaly

Most cases are clinically recognizable in infancy with the loss of corneal clarity due to edema or scar.


Neurofibromatosis (von Recklinghausen disease): Patients seek medical attention for skin or eyelid lesions or eye enlargement.

Sturge-Weber syndrome (encephalofacial angiomatosis): The characteristic presentation is a red facial lesion since birth and is shown in the image below.

Female infant with Sturge-Weber syndrome. Facial p Female infant with Sturge-Weber syndrome. Facial port-wine nevus involves the left eyelid, associated with ipsilateral buphthalmos.

von Hippel-Lindau (retinal angiomatosis)

Patients usually present in their 20s or 30s with benign and malignant tumors in multiple organs.


Most patients present a few months after birth with pupillary abnormalities.

Obtain a full family history, and perform an ocular examination of parents and other relatives. Most cases of aniridia are familial, and it has an autosomal dominant transmission.

Decreased vision, photophobia, nystagmus, and strabismus are the most common clinical manifestations. Because glaucoma develops later in life, enlargement of the cornea is not part of the presentation.


Nanophthalmos is a developmental retardation of the globe after the closure of embryonic fissure. It is usually bilateral. It may be sporadic or transmitted in an autosomal dominant or recessive pattern. The eye is normal in shape but reduced in volume, and the sclera is remarkably thick. Young patients have high hyperopic refraction.



Ocular examination findings for associated conditions are described below.


Decreased visual acuity, pendular nystagmus, corneal pannus, microcornea, focal lens opacity, or lens subluxation may be noticeable.

Intraocular pressure (IOP) is elevated.

Foveal and optic nerve hypoplasia are frequent findings and partially the cause of poor visual acuity.

Gonioscopic examination reveals rudimentary iris, even if there is no visible iris during regular slit lamp examination.

The angle may be closed with peripheral anterior synechiae.

Axenfeld-Rieger syndrome

A prominent, anteriorly displaced Schwalbe line is seen as a white line with slit lamp microscopy.

Microcornea, macrocornea, and corneal opacity may be observed in certain cases.

Iris examination reveals polycoria, corectopia (shown in the image below), and ectropion uvea.

Axenfeld-Rieger syndrome with iris atrophy, corect Axenfeld-Rieger syndrome with iris atrophy, corectopia, and pseudopolycoria.

Iris strands and high insertion of iris (especially in patients with glaucoma) are prominent in gonioscopy.

IOP is elevated when glaucoma develops. In association, strabismus, cataract, macular degeneration, and coloboma may be found.

Peters anomaly

Corneal findings vary from minimal corneal edema to dense corneal leukoma. In some cases, corneal edema may regress with leaving residual scar behind.

Iridocorneal adhesions more commonly are located temporally.

Fifty percent of patients have glaucoma.

Associated anomalies may be present, as follows: anterior polar cataract, microphthalmia, microcornea, sclerocornea, or Axenfeld anomaly.

Neurofibromatosis (von Recklinghausen disease)

Patients have characteristic café au lait spots, plexiform neurofibroma of the upper eyelid, and axillary freckles. If plexiform neurofibroma is present, a 50% chance of developing glaucoma exists.

Glaucoma is always unilateral, usually exists at birth or shortly after, and presents as buphthalmos with or without corneal edema.

Buphthalmos may occur in the absence of elevated pressure due to regional hypertrophy. Buphthalmos is shown in the image below.

Female patient with plexiform neurofibroma (NF-1). Female patient with plexiform neurofibroma (NF-1). Upper right eyelid involvement, associated with ipsilateral buphthalmos. In Image A (left), patient is aged 8 months; in Image B (right), patient is aged 8 years.

Congenital ectropion uvea sometimes occurs with neurofibromatosis, and it is more likely to be associated with glaucoma.

Lisch nodules (bilateral, yellow greenish, dome-shaped iris elevations) usually appear after patients are 3 years and more frequently as the patient ages.

Pulsating proptosis, choroidal lesions, optic nerve glioma, and optic nerve sheath meningioma are other ocular findings.

Sturge-Weber syndrome (encephalofacial angiomatosis)

Corneal enlargement with or without glaucoma is seen in about two thirds of cases.

IOP is elevated in glaucoma cases.

Conjunctival vessels are dilated.

Retinal vessels appear tortuous, and choroidal hemangioma presents with a tomato catsup appearance at the posterior pole.


Patients have deeply set eyeballs in addition to narrowing of the palpebral fissure. Narrowing of the anterior chamber angles occurs between the fourth and sixth decades due to the short axial length, small cornea, and forward rotation of the lens/iris diaphragm and ciliary body.

von Hippel-Lindau (retinal angiomatosis)

On retinal examination, an elevated globular mass and enlarged feeding artery and vein are seen next to the lesion.

Exudation from the mass causes retinal detachment. Intravitreal and intraretinal hemorrhage causes loss of vision.

Neovascular glaucoma is observed in long-standing cases.

Lowe syndrome (oculocerebrorenal syndrome)

Findings include microphthalmos, strabismus, nystagmus, miosis, and iris atrophy.

Persistent hyperplastic primary vitreous

Persistent hyperplastic primary vitreous (persistent fetal vasculature) consists of microphthalmos, cataract, glaucoma, and retinal detachment that results from persistence and growth of fibrovascular structure anteriorly.

Retinopathy of prematurity

Bilateral glaucoma is caused by a shallow anterior chamber due to contraction of retrolental mass and peripheral anterior synechiae.

Anterior chamber abnormalities, such as a prominent Schwalbe line, have been described.

Glaucoma occurs in late stages, usually after age 2 years.




A defect in the PAX6 gene on chromosome 11 has been identified as the cause of aniridia. It can be sporadic and familial. The sporadic type is associated with Wilms tumor.

Although the name aniridia indicates a total absence of the iris, some amount of the iris stump is commonly found.

The anterior chamber angle closes slowly as the iris strands from the stump progresses toward the angle, which causes clinical manifestations of glaucoma in late childhood or adolescence.

Axenfeld-Rieger syndrome

On postulated pathophysiologic mechanisms that have been abandoned, Axenfeld-Rieger syndrome also was known as anterior chamber cleavage syndrome and mesodermal dysgenesis of the cornea and iris. The basic pathology is the developmental arrest of the neural crest cells during gestation. Because these cells are the origin of facial bones and teeth, abnormalities of these structures are associated with ocular abnormalities.

In Axenfeld anomaly, a prominent, anteriorly (centrally) displaced Schwalbe line (posterior embryotoxon) and iris strands are present that reach to the angle.

When Axenfeld anomaly is associated with glaucoma, it is termed Axenfeld syndrome.

In Rieger anomaly, with or without posterior embryotoxon or iris strands, corectopia (displacement of pupil) is present due to iridocorneal adhesions that are associated with membrane covering angle; polycoria (multiple pupils) due to iris atrophy and hole formation; and ectropion uvea.

Small-sized teeth (microdontia) and decreased number of teeth (hypodontia) of anterior maxillary incisors are observed.

When the whole anomaly is associated with glaucoma, it is termed Rieger syndrome.

Lately, Axenfeld-Rieger syndrome has been used for all types of clinical presentations.

Peters anomaly

Peters anomaly is characterized by bilateral congenital central corneal opacity, which is associated with iridocorneal adhesions toward the defective area.

The peripheral cornea is clear, and the total cornea is of normal size in most cases.

Peters anomaly results from the absence or thinning of endothelium, Descemet membrane, posterior corneal stroma, and sometimes Bowman layer.

Large fibroblastic cells fill into this space and adhere to the counterpart iris section.

Several mechanisms have been proposed, as follows: anoxia, infection (eg, rubella), and a mechanism that is similar to Axenfeld-Rieger anomaly.

Most cases of Peters anomaly have a sporadic origin. A mutation in the PAX6 gene on chromosome 11 has been identified.

The mechanism of glaucoma is reported as a problem in differentiation from neural crest cells, causing trabecular meshwork anomalies, such as absence of the Schlemm canal.

Neurofibromatosis (von Recklinghausen disease)

This is an autosomal disorder that is characterized by skin lesions in peripheral neurofibromatosis (NF-1) or by multiple nervous system tumors (eg, acoustic neurinoma, meningioma) in central neurofibromatosis (NF-2). Sporadic cases have been reported, especially in NF-1. Mutation of chromosome 17 in NF-1 and chromosome 22 in NF-2 has been described.

Pathology: Generally, abnormal neural crest cell proliferation is present. Glaucoma more likely occurs when the ipsilateral upper eyelid is involved with plexiform neurofibroma. It always is unilateral.

The exact mechanism of glaucoma is unknown, but developmental malformation of the angle, peripheral anterior synechiae, infiltration of angle with neurofibromatosis tissue, thickened choroid, and anteriorly extended ciliary processes are pathological findings.

Sturge-Weber syndrome (encephalofacial angiomatosis)

This nonhereditary neurocutaneous syndrome is characterized by facial cutaneous hemangioma (nevus flammeus or port wine stain) that affects first and second divisions of the trigeminal nerve and can result in seizures and mental deficiency.

Hemangiomas may occur bilaterally in 10-30% of cases.

Glaucoma may appear on both eyes, regardless of whether facial hemangioma is unilateral or bilateral.

Choroidal hemangioma (which grows slowly) occurs in 40% of cases and is a cavernous type of hemangioma. Calcification of cortex, especially of occipital lobe, is seen on CT scan of the head.

Mental deficits are observed in 60% of patients.

Hemianopsia and hemiparesis also are common.

The combination of elevated episcleral pressure secondary to small arteriovenous fistulas and developmental angle abnormality causes glaucoma.

von Hippel-Lindau (retinal angiomatosis)

This neurocutaneous disorder is autosomal dominant and is associated with hemangioblastoma of the retina and cerebellum. Renal cell carcinoma also develops later in life.

Average age of onset of the disease is 20-25 years.

Retinal angiomas consist of capillary proliferation, which leaks on fluorescent angiography. Iridocyclitis and neovascularization of the iris cause neovascular glaucoma.

Lowe syndrome (oculocerebrorenal syndrome)

This disorder is X-linked and is characterized by ocular and renal abnormalities and mental retardation.

Ocular disorders include congenital cataract and glaucoma, which are the earliest signs of the syndrome.

Pathology: Glaucoma is secondary to the microphakia and angle abnormalities.

Persistent hyperplastic primary vitreous (persistent fetal vasculature)

Glaucoma is secondary to shallow anterior chamber, which results from cataract formation or pulling of fibrovascular membrane lens-iris diaphragm forward.

Ciliary processes also are pulled forward.

Stickler syndrome

Also called hereditary arthro-ophthalmology, Stickler syndrome is transmitted in an autosomal dominant pattern. Besides glaucoma, other ocular findings include strabismus, amblyopia, high myopia, cataract, vitreoretinal degeneration, and retinal detachment. Glaucoma associated with Stickler syndrome usually responds well to medical treatment. Miotics should be avoided because of the risk of retinal detachment.



Complications include intractable glaucoma despite numerous interventions. Open-angle glaucoma can develop into angle-closure glaucoma or neovascular glaucoma. Eyes eventually can be phthisical.

Sturge-Weber syndrome (encephalofacial angiomatosis)

These eyes carry high risk for expulsive choroidal hemorrhage upon entering the eye causing sudden pressure change.

They are more likely to develop choroidal effusion from choroidal cavernous hemangioma.

Reducing the IOP as low as possible and performing posterior sclerotomies prior to entering the eye may reduce complications.

In a study by Iwach et al, intraoperative choroidal expansion was detected in 24% of patients who underwent trabeculectomy. [6]

In Agarwal's series of 18 patients with Sturge-Weber syndrome who underwent the trabeculotomy-trabeculectomy procedure, the following complications were noted: intraoperative hyphema (22.2%), vitreous loss (16.7%), and vitreous hemorrhage (5.6%). [5]

von Hippel-Lindau (retinal angiomatosis)

This condition consists of capillary proliferation that leaks on fluorescent angiography.

Iridocyclitis and neovascularization of the iris cause neovascular glaucoma.