Clinical and molecular aspects of congenital aniridia – A review of current concepts

Abstract

Congenital aniridia is a pan ocular disorder characterized by partial or total loss of iris tissue as the defining feature. Classic aniridia, however, has a spectrum of ocular findings, including foveal hypoplasia, optic nerve hypoplasia, nystagmus, late-onset cataract, glaucoma, and keratopathy. The latter three are reasons for further visual compromise in such patients. This entity is often due to mutations in the PAX6 (Paired box protein Pax-6) gene. Recently, aniridia-like phenotypes have been reported due to non- PAX6 mutations as in PITX2, FOXC1, FOXD3, TRIM44 , and CYP1B1 as well wherein there is an overlap of aniridia, such as iris defects with congenital glaucoma or anterior segment dysgenesis. In this review, we describe the various clinical features of classic aniridia, the comorbidities and their management, the mutation spectrum of the genes involved, genotype-phenotype correlation of PAX6 and non- PAX6 mutations, and the genetic testing plan. The various systemic associations and their implications in screening and genetic testing have been discussed. Finally, the future course of aniridia treatment in the form of drugs (such as ataluren) and targeted gene therapy has been discussed.

Novel clinical presentation and PAX6 mutation in families with congenital aniridia

“…Generally, the incidences of each ocular presentation was comparable to that of other reports ( 23 , 25 , 29 ), except for keratopathy. The percentage of keratopathy was much smaller in our study, this may be resulted from that the enrolled patients were generally younger and aniridia-associated keratopathy is age-dependent ( 18 ). Our results also highlight the high phenotypic heterogeneity of aniridia ( Table 2 ).…”

“…The common morphological types of cataract include posterior polar, posterior subcapsular, and total cataract. Cataract surgery in aniridia is challenging, because of the poor ocular surface, corneal opacification, friable capsule and lens dislocation ( 18 ). Iris prosthesis implantation can also be considered in cataract surgery, although several complications may occur during or after the surgery.…”

“…Glaucoma occurs in 46–70% of cases ( 19 ). Several possible mechanisms, including maldevelopment of the anterior chamber angle, absence of Schlemm’s canal, and obstruction of the angle with a shapeless, homogenous avascular tissue, are implicated in the development of glaucoma ( 18 ). Although medical therapy remains the first line of treatment, most patients with glaucoma eventually require surgical therapy, such as goniotomy, trabeculotomy, trabeculectomy, glaucoma drainage devices implantation and cyclodestructive procedures ( 19 ).…”

“…Aniridia-associated keratopathy (AAK), characterized by gradual corneal pannus and opacification, is another common cause of progressive vision loss. AAK is resulted from the breakdown of the limbal stem cell niche, impaired wound healing, and neural deterioration and can occur as early as 2 years of age ( 18 ). The management of AAK depends on its severity.…”

“…Penetrating keratoplasty tends to fail eventually, owing to the underlying limbal stem cell deficiency. Even procedures attempting to restore or improve the limbal stem cell niche, such as amniotic membrane transplantation, limbal or keratolimbal allograft transplantation, cultivated limbal epithelial transplantation, cultivated oral mucosa epithelial transplantation, have a risk of surgery failure ( 18 , 19 ). Keratoprosthesis is an option in treatment of end-stage AAK.…”