Aniridia is the absence of the iris, usually involving both eyes. It can be congenital or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular and optic nerve hypoplasia, cataract, and corneal changes. Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract. Aniridia in some individuals occurs as part of a syndrome, such as WAGR syndrome, or Gillespie syndrome.
The AN2 region of the short arm of chromosome 11 includes the PAX6 gene, whose gene product helps regulate a cascade of other genetic processes involved in the development of the eye. This PAX6 gene is around 95% similar to the pax gene found in zebrafish, a creature whose ancestors diverged from human evolutionary development around 400 million years ago. Thus the PAX6 gene is highly conserved across evolutionary lineages. Defects in the PAX6 gene cause aniridia-like ocular defects in mice. Aniridia is a heterozygous disorder, meaning that only one of the two chromosome 11 copies is affected. When both copies are altered, the result is a uniformly fatal condition with near complete failure of entire eye formation. In 2001, two cases of homozygous aniridia patients were reported; the fetuses died prior to birth and had severe brain damage. In mice, homozygous small eye defect leads to loss of the eyes and nose and the murine fetuses suffer severe brain damage.
Types
Aniridia may be broadly divided into hereditary and sporadic forms. Hereditary aniridia is usually transmitted in an autosomal dominant manner, although rare autosomal recessive forms have also been reported. Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma. These patients often also have genitourinary abnormalities and intellectual disability. Several different mutations may affect the PAX6 gene. Some mutations appear to inhibit gene function more than others, with subsequent variability in the severity of the disease. Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have foveal hypoplasia, and retain relatively normal vision. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder phenotype.
In May 2018, the U.S. Food and Drug Administration approved the CustomFlex Artificial Iris, the first synthetic iris for use in adults and children with congenital aniridia or iris defects related to other conditions, such as albinism, traumatic injury, or surgical removal due to ocular melanoma. The artificial iris is a surgically implanted device made of thin, foldable, medical-grade silicone and is custom-sized and colored for each individual patient. The prosthetic iris is held in place by the anatomical structures of the eye or, if needed, by sutures.
