ABSTRACT

Congenital aniridia is a rare condition affecting a wide range of ocular structures, from the ocular surface to the retina. We present the case of a 59-year-old woman with PAX6- and WT1-negative congenital aniridia who developed aniridia-associated keratopathy and progressive endothelial dysfunction with corneal decompensation after cataract surgery. The patient underwent successful ultrathin Descemet stripping endothelial keratoplasty. Despite the challenges faced with an unstable iridolenticular diaphragm, we were pleasantly surprised to see improvement not only of corneal edema and endothelial function but also of the whole cornea, including anterior corneal anatomy and appearance. In conclusion, endothelial transplantation in a patient with aniridia resulted in improvement of all the corneal structures from the endothelium to the stroma, epithelium, and possibly even the ocular surface.

Introduction

Congenital aniridia (CA) is a rare panocular condition with different inheritance patterns and phenotypic expression. The PAX6 gene on chromosome 11p13 is a crucial factor in its pathogenesis. The most common form is autosomal dominant CA, which involves only the eyes and has complete penetrance but variable expressivity. Sporadic cases are less frequent and are associated with a de novo mutation. This form of CA can correlate with Miller/WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome. Autosomal recessive CA is the least common variant and can be associated with cerebellar ataxia and mental retardation (Gillespie syndrome).¹

CA affects a wide range of eye structures, from the ocular surface to the cornea, iris, lens, optic nerve, and macula. The cornea and ocular surface are characteristically affected, and the term aniridia-associated keratopathy is used to describe the progressive ocular surface pathology that greatly contributes to the reduction of the visual acuity of these patients.²

Discussion

Patients with CA pose a great challenge for surgeons because it is a panocular condition with range of pathologies in most of the eye structures. The ocular surface is particularly and characteristically affected, termed aniridia-associated keratopathy. Most patients with CA have a mutation in the PAX6 gene. The remaining patients seem to have a slightly milder pathology and disease course, as in our patient.¹ Aniridia keratopathy is usually associated with superficial corneal alterations due to limbal stem cell insufficiency. Although endothelial dysfunction is not common, cases of histopathology-proven Descemet’s membrane/endothelial damage have previously been reported with subendothelial fibrous membrane present in some cases.⁵ Whether this was the case in our patient or the compromised endothelium was partly or totally associated with the previous cataract surgery cannot be ascertained.

DSEK is currently the preferred method for endothelial replacement in cases of aniridia as it offers minimal risk of posterior dislocation and easier manipulation compared to Descemet’s membrane endothelial keratoplasty.⁶

We noticed that in our patient, the corneal stroma and ocular surface showed improvement after DSEK despite being significantly affected preoperatively. This was associated with a marked improvement in BCVA from hand movements to 0.55 LogMAR, reduced fluorescein staining, and an increase in tear film break-up time to 5-6 seconds from 2-3 seconds preoperatively (Figure 4a,b). This great visual outcome and improvement in the appearance of the whole cornea was maintained throughout the 2-year follow-up period. Although this improvement could be related to the reduction of corneal swelling and epithelial edema after restoring corneal endothelial function, the extent of improvement in the corneal surface could not be fully explained.

This is the first reported case in which endothelial transplantation in a patient with aniridia resulted in improvement of the whole corneal appearance. CA is a complex pathology affecting all of the corneal (and other) structures. We observed improvement of the whole corneal appearance and function, including improved tear break-up time and superficial staining following successful TM-DSEK. A number of explanations for this can be suggested, but the mechanism remains to be elucidated. Interestingly, Zola et al.⁷ demonstrated improved corneal clarity and reduced density of anterior subepithelial fibrosis following endothelial keratoplasty in non-aniridic eyes. They proposed a cascade of corneal remodeling following resolution of stromal edema after Descemet stripping automated endothelial keratoplasty, amongst other factors, as a possible mechanism for this improvement, which suggests that a similar interaction could be the reason behind the great improvement seen in our case. Although the preoperative endothelial dysfunction may have contributed to the worsening of the ocular surface disease, the improvement noted after restoration of endothelial function cannot be fully explained. There may still be an underlying association or synergistic interaction between stromal keratocytes, limbal stem cells, and corneal endothelium that is responsible for the health of the whole cornea and hence of corneal integrity.