October 2018

CORNEA

Presentation spotlight
Successful treatment of non-healing corneal epithelial defect in patient affected by congenital aniridia


by Stefanie Petrou Binder, MD, EyeWorld Contributing Writer


Aniridia-associated keratopathy before autologous serum

Aniridia-associated keratopathy after 2 weeks of autologous serum
Source (all): Chiara Bonzano, MD

 

Clinician shares her experience in the diagnosis and treatment of a patient with eye pain and reduced vision due to aniridia

Aniridia is a congenital, hereditary disease that affects an individual’s eyes bilaterally and is an extreme form of iris hypoplasia in which the iris appears to be absent on routine clinical examination. Gonioscopy reveals the presence of an iris root, however, and more extensive examinations can show the full disorder involving macular and optic nerve hypoplasia, cataract, and corneal changes, which all contribute to reduced visual acuity and the presence of nystagmus. The incidence of aniridia is estimated between 1:64,000 and 1:100,000, and the ocular surface in eyes with this congenital anomaly can often be affected by a progressive pathology known as aniridia-associated keratopathy (AAK) that is thought to contribute to impaired vision.

Recognizing congenital aniridia

A case report presented at the 22nd ESCRS Winter Meeting discussed a case of aniridia and the complexities of management. The case study report was presented by Chiara Bonzano, MD, FEBO, Policlinico San Martino, University of Genoa, Italy, who treated the patient in question, whose initial complaints were headaches and eye pain.
The patient was a 46-year-old female who was started on a regimen of topical broad spectrum antibiotic drops, as prescribed by an outside ophthalmologist, without symptomatic improvement. After an initial eye examination at the polyclinic, she was referred to the corneal department due to a persistent right-sided corneal epithelial defect that developed over a 9-week period. The patient had a history of cataract surgery with phacoemulsification and lens implantation, had undergone a null point surgery for nystagmus, and underwent right-sided ethylenediaminetetraacetic acid (EDTA) chelation treatment for calcified band keratopathy. The patient’s medical history was negative for diabetes, positive for mild hypertension, anxiety/depression, and congenital aniridia. Her relevant family history revealed that the patient’s father died of a stroke and her mother died of complications related to lung cancer. Otherwise, the patient was a non-smoker, and she did not drink alcohol or take drugs.
Dr. Bonzano began with a slit lamp examination, which revealed conjunctival hyperemia, an epithelial defect that stained positively with fluorescein, and an iris rudimentary stump imaged by gonio photography, in the patient’s right eye. She evaluated corneal sensitivity by using a corneal Cochet-Bonnet contact aesthesiometer, and it was decreased. The patient’s right-sided visual acuity was very low, perceiving hand movements. The left eye revealed the presence of an iris stump as well and the visual acuity on the left side was 20/200. Ocular motility exams showed bilateral nystagmus. The intraocular pressure was elevated in both eyes, 30 mm Hg in the right eye and 28 mm Hg in the left eye.

Treatment of epithelial defect and symptoms

Dr. Bonzano started the patient on preservative-free anti-glaucoma medication drops to reduce the IOP and considered her options for the management of the persistent epithelial defect, which along with the presence of bilateral rudimentary iris stumps suggested the existence of aniridia-associated keratopathy.
She prescribed preservative-free artificial tears in 2-hour intervals, prophylactic topical ofloxacin four times daily, and patched the patient’s eye with vitamin ointments at nighttime. After 7 days, the corneal defect improved but was not completely healed. To aid in the healing process and protect the eye, she opted to apply a soft therapeutic contact lens, which was removed due to fit issues. At this point, the treatment plan was switched to include the application of autologous serum 40% every 2 hours. After approximately 15 days, corneal healing was evident. The cornea markedly improved both visually and with respect to improvements in visual acuity, signifying a healed corneal epithelial defect. Despite the healing process, the best corrected visual acuity (BCVA) was improved but still limited by foveal hypoplasia. Both eyes achieved 20/200, and the IOP was reduced to 19 in the right eye and 18 in the left eye.
“In this case study, corneal epithelial metaplasia and tear stability improved significantly with treatment,” Dr. Bonzano said. “The patient’s visual acuity showed only a slight improvement, however, due to the foveal hypoplasia that was evident in this case. Autologous serum by providing epitheliotropic factors has proven to have a beneficial effect that was superior to conventional therapy, improving AAK and providing better subjective comfort.”
Genetic testing was positive for the paired box gene 6 (PAX6) mutation, a deletion involving chromosome 11p13, which is necessary for the production of a protein involved in early eye development. The PAX6 gene encodes a transcription factor that is involved in several developmental pathways, predominantly in the eye, brain, and pancreas. It is associated with aniridia, Peter’s anomaly, and keratitis.1 “The changes associated with PAX6 deletion are progressive and include a thickening and vascularization of the peripheral cornea,” Dr. Bonzano explained. “The PAX6 impaired function of basal limbal stem cells and basal corneal epithelial cells lead to a lowered expression of alpha-enolase, which is a marker of stem cell metabolism. We see an associated ingrowth of vessels due to increased levels of VEGF, leading to the development of AAK, an increased extent of apoptosis, disturbances in tear fluid lipidome, increased oxidative stress, generation of ROS, and increased inflammation.”
Further examinations such as corneal cytology revealed the presence of goblet cells and a renal ultrasound was negative for congenital urinary anomalies, which have been associated with PAX6 mutations in the context of WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation). Also, confocal imaging and slit lamp photographs of the patient’s eye revealed a thickening and vascularization of the peripheral cornea. White opacities in the corneal periphery were noted that are typical of aniridia associated keratopathy.
In an unrelated retrospective cohort study of 275 eyes of 138 patients, medical records of patients diagnosed with congenital aniridia between 1991 and 2006 were reviewed for the prevalence of central corneal opacity (CCO), which is present at birth, and AAK, which develops progressively with advancing age in these patients. The investigators found that 13% (35 eyes, 20 patients) had CCO. Twenty-five percent (68 eyes, 35 patients) developed AAK. AAK became prominent at a mean age of 21.6 years of age, and the severity progressed with age. The visual outcome was worse in patients with CCO than with AAK. Cataract frequently occurred in AAK patients (78%) who required cataract surgery at a mean age of 26.6 years of age. Glaucoma was more prevalent in the patients with CCO (74%) than in those with AAK (37%), the study showed.2

References

1. Davis LK, et al. Pax6 3’ deletion results in aniridia, autism and mental retardation. Hum Genet. 2008;123:371–8.
2. Lee HK, et al. Corneal abnormalities in congenital aniridia: congenital central corneal opacity versus aniridia-associated keratopathy. Am J Ophthalmol. 2018;185:75–80.

Editors’ note: Dr. Bonzano has no financial interests related to her comments.

Contact information

Bonzano: chiarabonzano@ymail.com

Successful treatment of non-healing corneal epithelial defect in patient affected by congenital aniridia Successful treatment of non-healing corneal epithelial defect in patient affected by congenital aniridia
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