February 2012 Online Photo Diagnosis
By William Townsend, OD, FAAO
The individual in this photo has aniridia, a rare, progressive condition with multiple ocular and systemic manifestations. Its name denotes iris involvement, in which the iris is deficient or absent, but it also encompasses the cornea, anterior chamber, lens, retina, macula, and optic nerve.1 The frequency of anirida is reported to be 1:64,000 to 1:100,000. The most common cause is a mutation of the PAX6 gene on band p13 of chromosome 11.2 Netland et all evaluated the frequency of disorders associated with anirida. They reported the following ocular conditions: nystagmus (83 percent), cataract (71 percent), dry eye (53 percent), glaucoma (46 percent), keratopathy (45 percent), foveal hypoplasia (41 percent), strabismus (31 percent), and retinal disease (5 percent).3
Systemic conditions associated with aniridia include dental abnormalities (35 percent), developmental delay (17 percent), musculoskeletal abnormalities (13 percent), asthma (12 percent), depression (12 percent), and infertility (11 percent). Obesity and increased body mass index were found to be twice as frequent in individuials who have aniridia compared to their siblings who did not have aniridia.2
Anirida is present at birth, but aniridia-related keratopathy (ARK) appears later in life. The corneas are clear in infancy and early childhood, but during the teenage years superficial vascularization presents and over time progresses; these changes typically result in opacification of the corneal stroma with accompanying reduction in vision. Corneal vascularization of the cornea is superficial, and histological studies reveal goblet cells and conjunctival cells replacing the normal corneal epithelium.
The underlying defect in ARK has been presumed to result solely from corneal limbal stem cell deficiency. To date there has not been a reliable means of identifying these cells. It may be that the pathogenesis of ARK is more complex. Ramaesh et al proposed that there are other mechanisms that contribute to this condition. They found that the Pax gene is crucial in the development and maintenance of corneal epithelium. It up regulates gelatatinase-B, a matrix metalloproteinase (MMP), and cellular adhesion molecules (CAMs). MMPs are important in wound healing and helping to maintain corneal clarity. CAMs promote adherence of cells to one another and to the basement membrane. Reduced PAX6 activity reduces CAMs and the activity of MMPs. The maintenance of corneal clarity depends on these processes, and if they are inhibited the ultimate result is corneal opacification.
Management of ARK is often complex and frustrating. Mild-to-moderate cases benefit from preservative-free ocular lubricants. More advanced cases may require amniotic membrane transplant, penetrating keratoplasty with immunosuppression, and limbal stem cell transplant.