Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition

6

Iris and Pupils

Alex V. Levin

Thomas W. Wilson

  1. Raymond Buncic

David Rootman

The iris is formed during ocular development by an extension of the optic vesicle (neuroectoderm) forward as the posterior pigmented and nonpigmented iris epithelium, and an influx of neural crest cells forming the iris stroma. The iris sphincter and dilator muscles differentiate from the epithelial layers. Mesoderm contributes the endothelial lining of the vessels.

Abnormalities of embryogenesis can lead to iris anomalies including coloboma, persistent pupillary membranes, aniridia, and Axenfeld-Reiger syndrome. Iris findings can often give clues to underlying systemic diseases including Down syndrome (Brushfield spots), neurofibromatosis type 1 (Lisch nodules), Williams syndrome (stellate iris), and Hirschsprung syndrome (sector iris heterochromia). Abnormalities of the iris are also associated with other ocular abnormalities in diseases such as aniridia, albinism, and coloboma. Iris abnormalities can be the first clues of an underlying systemic disease or genetic disorder.

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Figure 6.1 Aniridia

Aniridia is an autosomal dominant abnormality of ocular development caused by a defect in the PAX6 gene located at chromosome 11p13. The association of Wilms tumor, sporadic aniridia, genitourinary abnormalities, and mental retardation is termed WAGR syndrome and is due to contiguous gene deletion in this region. Patients with aniridia will often present with nystagmus, photophobia, and decreased vision. Clinical findings include complete or partial absence of the iris, keratitis, cataract, macular hypo- plasia, and optic nerve hypoplasia. Glaucoma is present in ap- proximately one third of patients with aniridia and cataracts in approximately 50%.

 

Figure 6.2 Aniridia—Glaucoma

Glaucoma is a common association with aniridia. One fourth to one third of patients with aniridia will develop angle closure glaucoma in the first decade of life. The possible mechanisms include aplasia of the Schlemm canal, goniodysgenesis, or migration of the rudimentary iris stump forward, as shown here, resulting in obstruction of the trabecular meshwork. Medical treatment is often not successful and glaucoma surgery is required to control the intraocular pressure.

 

Figure 6.3 Aniridia—Macular Hypoplasia

Aniridia is often associated with nystagmus and visual loss. The most common cause of vision loss in a patient with otherwise clear media is macular and optic nerve hypoplasia. This photograph shows abnormal macula throughout the deeply depressed light reflex centrally. The retinal blood vessels also do not respect the foveal avascular zone. The optic nerve in this photograph also appears hypoplastic.

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Figure 6.4 Gillespie Syndrome

Gillespie syndrome is the association of aniridia and cerebellar ataxia and mental retardation. Aniridia associated with Gillespie syndrome is not caused by mutations of the PAX6 gene, and is therefore not associated with Wilms syndrome. The disorder is autosomal recessive. Note the typical scalloped pupil margin and more robust iris stump as compared to classic aniridia (Fig. 6.1).

 

Figure 6.5 Congenital Iris-Lens- Pupillary Membrane Syndrome

This photograph demonstrates secondary congenital miosis from a traction band extending across the borders of the pupil. White fibrous material seen centrally represents a remnant of the tunica vasculosa lentis. This form of persistent fetal vasculature (Chapter 7: Lens,Fig. 7.2) is characterized by corectopia and a high risk for glaucoma. The membrane may also extend behind the iris. Surgical pupilloplasty would be necessary in cases where the visual axis is significantly obstructed.

 

Figure 6.6 Physiologic Anisocoria

To be considered physiologic, the relative difference in the pupil sizes should be the same in light and dark conditions. There should be full extraocular movements and no evidence of ptosis. Old photographs are often helpful to determine the chronicity of the anisocoria. Further workup including neuroimaging, cocaine testing, and evaluation for neuroblastoma should be considered with any other neurologic or associated ocular findings.

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Figure 6.7 Iris Pupillary Cysts

Congenital cysts of the iris pigment epithelium are commonly detected on red reflex testing by the pediatrician. This photograph shows a group of cysts that are not obscuring the visual axis. Glaucoma is not typically associated with these cysts. The cysts tend to be multiple and are not large enough to occlude the visual axis. The cysts may rupture or collapse over time. Chronic use of phospholine iodide can cause similar cysts and will resolve with discontinuation of the medication. Cysts that occlude the visual axis can be disrupted with neodymium YAG capsulotomy or anterior segment surgery.

 

Figure 6.8 Congenital Iris Ectropion Uvea

Congenital ectropion uvea is an abnormal migration of posterior pigment epithelial into the anterior iris surface. The patient will often present with concerns regarding anisocoria or iris pigmentation. Clinical examination shows an irregular pigmented mass on the anterior surface of the iris with distortion of the pupil and corectopia. Secondary glaucoma will commonly present, requiring surgical treatment. The disorder is almost always unilateral and nonheritable. Histology shows a residual contractile cellular lining attached to the leading edge of the ectropion and possibly covering the trabecular meshwork.

 

Figure 6.9 Polycoria

Polycoria is a rare congenital abnormality with more than one pupil. True polycoria must have two completely separate iris margins. Pseudopolycoria is more common and caused by defects in the iris stroma or traction bands dividing the normal pupillary opening.

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Figure 6.10 Corectopia

Corectopia is a pupil that is not centered within the iris stroma. Mild corectopia as seen in this photograph will not affect the visual development; however, it may lead to the misdiagnosis of esotropia. On the Hirschberg light reflex test, the patient will have a light reflex on temporal iris, indicating a possible esotropia. Cover testing will determine the presence of an underlying strabismus. Severe corectopia may be associated with ectopia lentis and is referred to as ectopia lentis et pupillae (Chapter 7: Lens, Fig. 7.18). If the lens is not dislocated, these patients will often have no visual problems. A cosmetic contact lens could be used in this patient if there are cosmetic concerns.

 

Figure 6.11 Iris Coloboma

Iris colobomas are abnormalities of ocular development due to incomplete closure of the optic cup. Incomplete closures anteriorly lead to iris colobomas and incomplete closures posteriorly lead to choroidal and optic nerve colobomas. Colobomas are typically located inferonasally, which corresponds to the location of the embryonic fissure of the developing optic cup. Several syndromes have associated coloboma. CHARGE association is the combination of coloboma, heart defects, atresia choanae, retarded growth and development, genitourinary abnormalities, and ear anomalies. Partial trisomy 22 (cat eye syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edwards syndrome) are all associated with iris coloboma.

 

Figure 6.12 Persistent Pupillary Membrane

Persistent pupillary membrane is a common finding on careful slit-lamp examination. Persistent membranes are the result of incomplete regression of the primitive vascular supply in the developing eye with failure of dissolution of the surrounding neural crest derived iris stroma that normally covers the pupil in utero. The annular vessel within the optic cup provides the vascular supply for the anterior lens surface. If this vascular network does not involute completely, a resultant pupillary membrane will form. Pupillary membranes vary greatly in size, configuration, and severity. Even more severe membranes, as shown in the right image, may prove to be visually insignificant and dissolve with time, presumably due to the normal contraction and dilation of the pupil with changes in ambient light. Topical phenylephrine 2.5% can stretch the membrane and open the visual axis dramatically in some patients as shown on the left.

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Figure 6.13 Persistent Pupillary Membrane with Cataract

There can be attachment of the pupillary membrane to the anterior lens surface with a small cataract in the area of the attachment. This type of cataract is usually eccentric to the visual axis and rarely visually significant. Growth is uncommon. Note that the base of the iris strands are arising from the iris collarette, thus distinguishing this from posterior synechia (Fig. 6.24), where the attachment is to the pupil margin.

 

Figure 6.14 Iris Hypoplasia

Iris hypoplasia is characterized by a flat underdeveloped anterior iris leaflet with thin stroma. The iris sphincter is bared and easily identified around the pupil. Iris hypoplasia is associated with glaucoma and inherited as an autosomal dominant disorder. It can be caused by mutations in the PITX2 gene at 4q25. Patients identified with iris hypoplasia require periodic screening for early detection of glaucoma.

 

Figure 6.15 Axenfeld-Rieger Syndrome

Axenfeld-Rieger syndrome is a rare congenital anomaly of the iris and anterior chamber angle structures. It is typically bilateral and inherited as an autosomal dominant trait. Approximately 50% of the patients will develop secondary glaucoma. Clinical manifestations include a prominent Schwalbe line with iris strands extending from the Schwalbe line to the iris surface. As seen in this photograph, there may be significant thinning of the iris stroma and formation of iris defects.

 

Figure 6.16 Axenfeld-Rieger Syndrome

The glaucoma seen in approximately 50% of patients with Axenfeld-Rieger syndrome typically presents in early childhood and is the most likely caused by iridogoniodysgenesis rather than blockage of the trabecular meshwork by the iridocorneal strands seen here on gonioscopy. Medical management is often unsuccessful and surgery is often required. Several theories have been proposed to explain pathogenesis. This is an autosomal dominant developmental disorder of neural crest migration and may be due to mutations in the FOXC1 gene at 6p25 or PITX2 gene at 4q25. Another locus on chromosome 13q14 is also known.

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Figure 6.17 Axenfeld-Reiger Syndrome

This syndrome has associated systemic abnormalities, including facial and dental anomalies. Facial abnormalities include midfacial and maxillary hypoplasia with prominence of the lower lip as compared to the upper lip. Telecanthus with a flat nasal bridge is a common facial feature. Dental anomalies include a decreased number of teeth (hypodontia), decreased size (microdontia), and absence of teeth (anodontia) (left image). There is an increased rate of umbilical hernias or incomplete involution of the umbilicus, as seen in the right image. Deafness, structural cardiac anomalies, and cerebellar atrophy have been associated.

 

Figure 6.18 Iris Mamillations

Iris mamillations are formed elevations of normal iris tissue found on the anterior surface of the iris. They may be bilateral or unilateral and should be differentiated from Lisch nodules, which are more scattered, amorphous, and generally not the same color as the iris. Mamillations are always multiple and clustered with a decrease in the usual iris crypts and valleys. There is a rare association with glaucoma.

 

Figure 6.19 Iris Hemangioma

The left photograph is a localized hemangioma of the iris. Histopathologically, there may be capillary and cavernous configurations. Patients may present with a discoloration on the iris. Spontaneous hyphema (right image) may occur. Treatment for small solitary tumors would include surgical removal or systemic steroids. Diffuse iris hemangiomas occur in Sturge-Weber syndrome.

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Figure 6.20 Iris Nevus

Iris nevi are small areas of pigmentation on the anterior surface of the iris. They are nonprogressive in size and do not distort the pupil. They are well circumscribed and typically found in the first years of life. They may be single or multiple. Iris nevi may also be referred to as iris freckles.

 

Figure 6.21 Sector Iris Heterochromia

Sector iris heterochromia is often incorrectly referred to as sector iris nevus. Note that the iris architecture is normal throughout. Compare this to Figure 6.20, where the architecture changes in the location of the iris. Sector iris nevus is actually an abnormal migration of neural crest cells and thus a deficiency of melanocytes. The abnormal portion of the iris is the hypopigmented sector. This may be associated with other disorders of abnormal neural crest migration such as Hirschsprung disease (Chapter 17: Gastrointestinal,Fig. 17.4). Patients with sector iris nevus should specifically be asked about constipation and large stools.

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Figure 6.22 Horner Syndrome

Horner syndrome caused by sympathetic chain denervation of the pupil dilator muscle, Müeller muscle, and sweat glands of the face results in the classic triad of miosis, ptosis, and anhidrosis. Other clinical abnormalities can include a decreased amplitude of accommodation, lower intraocular pressure, and elevated lower lid (upside-down ptosis). The anisocoria is greater in dim illumination than bright. The amount of ptosis is typically small, between 1 and 2 mm. In the pharmacologic test of Horner syndrome, 4% cocaine drops fail to dilate the abnormal smaller pupil but do dilate the normal one. Hydroxyamphetamine testing fails to dilate the pupil in peripheral (third-order) lesions. Heterochromia in congenital cases reflects failure of the sympathetic supply to the neural crest cells for pigmentation, and may be very subtle. Causes include traumatic birthing traction on the brachial plexus (Klumpke palsy). Urinary homovanillic acid and vanillylmandelic acid are elevated in neuroblastoma. Congenital heart surgery, central venous line placement in the subclavian or external jugular vein, and other paravertebral anomalies are other causes.

 

Figure 6.23 Iris Melanoma

Iris melanoma is a rare uveal tumor in children. The tumors are slow growing and are unlikely to metastasize early in the disease. Patients may present with a noticeable brown mass on the iris or hyphema. These tumors are extremely rare in the black population. Differential diagnoses include iris nevi and ectropion uveae. The most common histologic form of iris melanoma is spindle cell. Other histopathologic cell types are mixed and epithelioid. Treatment remains controversial, but many experts advocate enucleation.

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Figure 6.24 Posterior Synechiae

Posterior synechiae are adhesions between the pupil margin and anterior lens capsule secondary to inflammation of the iris with adherence to the anterior capsule of the lens. The pupil is often restricted to one position, and iris bombe with pupillary block and acute angle closure glaucoma can occur. The risk of posterior synechiae can be reduced with control of the intraocular inflammation and daily mydriatic agents. This child also has a cataract due to his uveitis. The iris should be freed from the anterior lens capsule at the time of surgery.

 

Figure 6.25 Congenital Absence of the Pupil Sphincter and Dilator

This rare anomaly is usually an isolated unilateral or bilateral disorder but may also be seen in central hypoventilation syndrome (Ondine curse). The iris is fixed and middilated. Note that there is no collarette and the stroma is rather featureless. This is not visually significant, but hypoaccommodation may require optical correction and bifocals.