Aniridia is a bilateral, panocular disorder presenting with abnormalities in the cornea, anterior chamber angle, iris, lens, optic nerve, macula, and retina. All patients with congenital aniridia have foveal hypoplasia which leads to various degrees of nystagmus and reduced visual acuity; however this is fixed and does not lead to progressive loss of vision. The most common causes of progressive visual decline in aniridic patients are cataracts, LSCD and glaucoma. Most patients have a visual potential in the 20/100 to 20/200 range. In this case, the main reason for the progressive visual changes is LSCD. This is based on the characteristic opaque late staining conjunctival epithelium extending into the visual axis.

Aniridic keratopathy (AK) is actually a manifestation of LSCD and can be observed in about half of aniridia patients under age 10, but reaches nearly 100% in adulthood. AK/LSCD is caused by a combination of factors: developmental abnormalities and progressive loss of the limbal stem cell niche with subsequent conjunctivalization of the cornea. AK is highly variable and asymmetric. Signs of keratopathy appear in the first decade of life, with peripheral superficial opacity (e.g., conjunctival epithelium). However over the years, it slowly progresses and involves the central cornea. The peak age for the development of near total LSCD is 30–40, but some may be sooner and some later. Clinically, we suspect that prolonged use of eye drops, namely, glaucoma medications, may lead to faster progression of the epithelial disease in aniridia.

Holland et al. described the progression of AK to LSCD in five distinct stages [4]. Neovascularization may be present at any point during disease development and is not a sensitive indication for severity or prognosis:

Staging of the disease is important in determining progression and timing of intervention. Stromal scarring which begins in Stage IV highlights the potential of these changes becoming permanent. If the patient develops stromal scarring, then they may no longer qualify for a limbal stem cell transplant alone and thus require additional procedures for therapeutic restoration of the corneal clarity.

About two-thirds of aniridia cases are inherited while the rest are sporadic. Most aniridia cases are due to a heterozygous mutation in the PAX6 gene (all sporadic cases should be screened at birth for gene deletions which if present will require screening for Wilms’ tumor in the first 5 years of life). The PAX6 gene plays a vital role in the regulation of genes/proteins that are crucial during eye development as well as normal tissue homeostasis. Previous studies have not found a significant correlation with the type of mutation (or deletion) in the progression of the disease since most of them lead to loss of function. The issue is likely a dosage effect, where having only one functional copy of PAX6 leads to reduced level of PAX6 protein which leads to abnormal development and function of the limbal niche.

It is worth noting that aniridic keratopathy may present in the absence of other classic stigmata of aniridia and be associated with minimally affected irides. These patients often have mutations in PAX6 and once identified can be counseled appropriately [5]. Previously, this condition used to be called by names such as autosomal dominant keratitis, but a more appropriate and encompassing name is PAX6-related keratopathy [5].

Management of mild AK (Stage I) includes mainly preservative-free lubricants. In moderate keratopathy (Stage II), measures that can improve the health of the epithelium include topical steroids, autologous serum drops, and amniotic membrane transplant. Most of these measures are aimed at improving the health of the ocular surface and enhancing the survival and expansion of surviving limbal stem cells; however, they are temporary and not a long-term solution. Another temporizing measure which can help improve the visual function is RGP/scleral lenses, which help correct the optical irregularities on the surface.

In more advanced disease (Stage III or later), limbal stem cell transplant is recommended. Penetrating keratoplasty as a primary procedure is contraindicated given the inevitable recurrence of LSCD in the graft. Finally another option is keratoprosthesis. It is best not to wait until Stage V since that would necessitate a keratoplasty as well.

There are several issues that need to be considered: First, is whether the patient is a candidate for systemic immunosuppression. At the time of presentation of total LSCD, most aniridics tend to be younger and healthy and thus are good candidates for immunosuppression. Older patients (above 60), or those with systemic comorbidities such as diabetes may not be good candidates. A patient who is not a candidate for immunosuppression is best managed with keratoprosthesis. In patients who are good candidates for immunosuppression, limbal allograft is the most reasonable first choice. Previously, we used cadaveric tissue (KLAL) for all such patients; however, in recent years we consider lr-CLAL to be the first choice—given the lower risk of rejection—and cadaveric tissue is used only when a first-degree relative is not available.

Another issue that must be considered is whether the eye has had previous transplant surgeries. It is not uncommon that an aniridic patient may have previously undergone a penetrating keratoplasty in the past which has subsequently failed due to recurrent LSCD and/or rejection. In these cases, since the eye has already been sensitized immunologically, the risk of future rejection is significantly higher and therefore our preference is to use a keratoprosthesis, namely, Boston type I.

Another issue is the severity of the glaucoma. A patient with very advanced glaucoma that requires close monitoring of IOP is not a very good candidate for keratoprosthesis since the IOP cannot be measured accurately.

The final issue that must be considered is the status of the stroma and endothelium. When conjunctivalization is not accompanied by deep stromal scarring and fibrosis, then a limbal transplant (as a non-penetrating procedure) is definitely the most appropriate choice since it avoids the need for more invasive interventions. In the case of stromal scarring, a limbal transplant followed by anterior lamellar keratoplasty is also preferred over Kpro. However, in the case of endothelial compensation, especially due to a tube shunt, going straight to Kpro may be more appropriate given the high likelihood of subsequent endothelial failure after keratoplasty.

First, it is important to specifically request KLAL tissue from the eye bank. We ask for tissue that is from a donor younger than 50, that is less than 5 days old, and has at least 3 mm of conjunctival skirt. We punch the tissue with a 7.5–8 mm trephine—leaving at least 1.5 mm of peripheral cornea. The tissue must then be thinned before it can be transplanted. Our preferred technique for thinning the tissue is to make a single cut in the limbal ring and then using a few drops of medical-grade cyanoacrylate glue to secure the graft to a flat surface (epithelial side up). Once the tissue is secure, we perform a controlled lamellar dissection (using a crescent knife) starting from the conjunctival side (Fig. 19.2b). The last part of the dissection is carried out with a Vannas scissor. The resulting tissue can be secured to the host limbal area with fibrin glue alone (after 360 peritomy and superficial keratectomy). Because the tissue is thin, there is no need to create a “bed,” and also there is minimal step off. Dr. Holland’s technique is similar except that he uses three pieces of 180° grafts that are secured at the anterior corneas with interrupted 10-0 nylon sutures, while the posterior aspects of the graft are secured to the sclera with fibrin glue.

She underwent a right KLAL involving 3 × 180 pieces, which were secured using fibrin glue only (Fig. 19.2b, c ). She was prescribed prednisolone acetate 1% QID, gatifloxacin, and Restasis while continuing her current drops (latanoprost, brimonidine). She was started on systemic immunosuppressive medications on the day of surgery: prednisolone (1 mg/kg), mycophenolate (1000 mg BID), and tacrolimus (4 mg BID). Patient was not started on any systemic antimicrobial prophylaxis given her low-risk status. Patient noted improved vision and by 1 month demonstrated clear cornea and grafts with resolving post-op inflammation and hemorrhage.

The most widely used protocol is the one developed in Cincinnati (EJH). Management of systemic immunosuppression is best done in collaboration with an organ transplant team given their familiarity with prescribing and monitoring of the medications. The Cincinnati protocol is summarized in Fig. 19.3 and consists of: