Anatomy and Embryology
The iris is a structure composed of connective tissue and blood vessels that lies just anterior to the lens. The central opening in the iris forms the pupil. The color of the iris is determined by pigmented cells within the stroma. Pigment may accumulate in these cells during the first year of life, and the color of the iris often changes during this time. The posterior layer of the iris is deeply pigmented. It extends slightly onto the anterior surface at the edge of the pupil.
The size of the pupil is variable. It changes in response to neural input to the smooth muscles within the iris. The dilator muscle of the iris is stimulated by sympathetic pathways. The chain of neurons responsible for dilation begin in the hypothalamus and synapses in the thoracic vertebra (first-order neuron), then passes out of the spinal column, across the pulmonary apex to synapse in the superior cervical ganglion (second-order neuron), then along the internal carotid plexus and through the cavernous sinus to join with the ophthalmic division of cranial nerve V and travel to the dilator muscle (third-order neuron) (Figure 29–1). The iris sphincter muscle is innervated by the parasympathetic system. These neurons originate in the Edinger-Westphal subnucleus of the third cranial nerve and travel along the inferior division of the nerve to the ciliary ganglion (preganglionic fibers), then to the iris sphincter through the short ciliary nerves (postganglionic fibers). These pathways mediate pupil constriction to light and near.
The sympathetic pathway for iris dilator muscles (pupil dilation). The first-order neuron begins in the hypothalamus, travels through the spinal cord, and synapses in the thoracic vertebrae. The second-order neuron travels over the pulmonary apex and synapses in the superior cervical ganglion. The third-order neuron travels adjacent to the internal carotid artery, then through the cavernous sinus to reach the eye. Damage anywhere along this pathway may cause Horner syndrome.
At 6 weeks of gestation the iris begins to form in association with the tunica vasuculosa lentis. This is a network of blood vessels that extends through mesenchymal tissue on the anterior surface of the developing lens. The muscles of the iris sphincter begin to develop at around 3 months’ gestation, followed at 6 months by formation of the dilator muscles. The iris stroma forms from neural crest cells. The posterior pigmented epithelium and muscles form from neuroectoderm. Much of the iris remains incompletely formed at birth, including pigmentation of the anterior layer and formation of the dilator muscles. This is why the iris often appears somewhat hypoplastic, even in normal newborns. During normal embryogenesis the tunica vasulosa lentis resorbs in the pupillary opening by birth. Remnants of the membrane may be seen in premature infants (Figure 29–2).
Abnormalities of the iris in children are relatively uncommon.
Iris abnormalities are usually detected by an abnormal appearance. These include changes in shape or size of the pupil, iris color, or lesions on the iris. Some iris disorders affect vision, but many do not. The latter are first noted by families or physicians (during a penlight examination or by noting an abnormality of the red reflex).
The pupil may be abnormally small or large at birth. Microcoria describes a small pupil, typically less than 2 mm. Primary microcoria occurs as a result of dilator muscle insufficiency. Generally, pupil openings smaller than 1.5 mm do not allow for adequate image formation, and may require surgical enlargement. Microcoria may occur as an isolated finding, or may be associated with systemic disorders, including Lowe syndrome, Marfan syndrome, and congenital rubella (Figure 29–3A). If the pupillary opening is so small that visual images cannot be properly formed, surgery to enlarge the opening is indicated. In this surgery, the pupil is enlarged by making cuts through the margin of the pupil (Figure 29–3B).
Congenital mydriasis is a condition in which the pupils are large and poorly reactive at birth. This sometimes occurs in association with congenital cardiac disease. If there are significant symptoms (e.g., photophobia), treatment with iris constricting medication (pilocarpine) or surgical reduction of the pupillary opening may be indicated.
An abnormal shape of the iris is called corectopia. This may occur as a primary defect (Figure 29–4), or in association with lens subluxation.
Iris colobomas occur as a result of incomplete closure of the embryonic fissure during formation of the eye. Because the inferonasal quadrant is the last area of the fissure to close, this is the typical location of iris colobomas (Figure 29–5). Colobomas may be isolated to the iris, or may be associated with colobomas of the lens, retina, or optic nerve. Large colobomas are often associated with underdevelopment of the entire eye (microphthalmos), and may be accompanied by lens subluxation (Figure 29–6). Iris colobomas may occur in association with many systemic abnormalities, including Trisomy 13 and CHARGE syndrome (Coloboma, Heart defects, Atresia of nasal choanae, growth Retardation, Genitourinary and Ear anomalies).
During embryological development, the normal network of vessels in the pupillary opening usually regresses by the time of birth. Residual vessels may be seen in normal infants who are born prematurely (Figure 29–2), and small remnants are visible in many normal individuals (Figure 29–8). Very prominent vessels are sometimes present at birth, which may regress spontaneously (Figure 29–7A and B). Larger bands of tissue may extend from the iris and attach to the lens capsule, causing distortion of the iris. Rarely, these remnants are large enough that they may interfere with vision (persistent pupillary membrane), in which case surgical removal may be indicated (Figure 29–9A and B).
The color of the iris is determined by pigment cells within the stroma. During the first year of life, pigment accumulation may change the color. In most people, the 2 pupils have the same color. Heterochromia is present if the color of the 2 irises is different (Figure 29–10). This may occur in association with a number of ocular or systemic conditions (Table 29–1). These include Waardenburg syndrome (Figure 29–11), hypomelanosis of Ito, and congenital Horner syndrome. Waardenburg syndrome is also associated with focal areas of decreased hair pigmentation and hearing loss. Hypomelanosis of Ito is a sporadic disorder characterized by an unusual whorl-like pattern of skin pigmentation (Figure 29–12). Central nervous system and limb anomalies occur in some patients. Ocular abnormalities include heterochromia, cataracts, and abnormal retinal pigmentation. Iris nevi are relatively common in children, and present as focal areas of increased pigment against the lighter normal iris stroma (Figure 29–13). The size is variable, and large lesions may mimic heterochromia. Iris nevi are almost always benign in children, but evaluation may be required if they change (similar to nevi on the skin). Iris heterochromia has been reported in association with Hirschsprung disease. This association is thought to be due to a shared perturbation of neural crest cell development.
Aniridia is a congenital, bilateral condition in which the iris is severely underdeveloped. The term aniridia is a misnomer, because almost all affected patients have at least a rudimentary stump of iris tissue, although this may not be visible without gonioscopy. On examination, the entire lens is visible (Figure 29–14A and B). On casual inspection the edge of the lens may be mistaken for the pupillary opening. With slit lamp magnification, the fine suspensory fibers that attach the lens to the ciliary body may be visualized.
(A) Aniridia. The edge of the lens is visible for 360° (long arrow). A small cataract is present in the center of the lens (short arrow). (B) Gonioscopic view in aniridia. The ciliary processes (short arrow) are visible adjacent to the edge of the lens. The tan stripe (long arrow) is the normal trabecular meshwork.
Aniridia has important ocular and systemic associations. Ocular abnormalities that occur commonly in aniridia include corneal surface disease, cataracts, optic nerve and foveal hypoplasia, and glaucoma. The vision is usually significantly decreased. Infants develop nystagmus early in life.
Aniridia is caused by mutations of the PAX6 gene (chromosome 11p13), and may occur in heritable and nonheritable forms. Approximately two-thirds of cases are transmitted as an autosomal dominant disorder, and one-third are sporadic. Wilms tumor occurs in approximately one-third of sporadic cases, because the Wilms tumor gene (WT1) is contiguous with the aniridia gene. Mutations of this location may also produce the WAGR complex (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation). If genetic testing of children with sporadic aniridia identifies tumors in the WT1 gene, regular monitoring for Wilms tumor with renal ultrasonography is indicated.