Elsevier

Ophthalmology

Volume 119, Issue 9, September 2012, Pages 1803-1810
Ophthalmology

Original article
Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

https://doi.org/10.1016/j.ophtha.2012.02.043Get rights and content

Objective

To document the clinical and morphologic corneal findings in the early stages of congenital aniridic keratopathy in Swedish families.

Design

Prospective, observational, comparative case series.

Participants

A total of 16 eyes of 16 subjects with congenital aniridic keratopathy and a clear central cornea, and 6 eyes from 6 healthy controls (unaffected relatives). Nine of the 16 eyes with aniridia came from 5 families with a documented familial history of aniridia.

Methods

Detailed ophthalmic examinations included best spectacle-corrected visual acuity (BSCVA), tear film production, tear break-up time (BUT), corneal touch sensitivity, intraocular pressure measurement, ultrasound pachymetry, slit-lamp biomicroscopy, and laser scanning in vivo confocal microscopy (IVCM).

Main Outcome Measures

Confirmed stage of aniridic keratopathy, clinical parameters of cornea and tear film (visual acuity, sensitivity, corneal thickness, tear production, and BUT), and the morphologic status of corneal epithelium, sub-basal nerves, and limbal palisades of Vogt.

Results

In early-stage aniridic keratopathy, BSCVA and tear BUT were reduced relative to controls (P < 0.001 for both), and corneal thickness was increased (P=0.01). Inflammatory dendritic cells were present in the central epithelium in aniridia, with significantly increased density relative to controls (P = 0.001). Discrete focal opacities in the basal epithelial region were present in 5 of 11 aniridia cases with an otherwise clear cornea. Opacities were associated with dendritic cells and harbored structures presumed to be goblet cells. Sub-basal nerves were extremely dense in 3 aniridia cases, and a prominent whorl pattern of nerves and epithelial cells was observed in 1 case. Normal limbal palisade morphology was absent in aniridia but present in controls.

Conclusions

Early-stage aniridic keratopathy is characterized by the development of focal opacities in the basal epithelium, altered sub-basal nerves, infiltration of the central epithelium by dendritic cells, tear film instability, and increased corneal thickness and degradation of limbal palisade architecture. These findings may help to elucidate the pathogenesis of aniridic keratopathy.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Study Criteria and Subjects

All subjects with aniridia had participated in a previous study of congenital aniridia in Sweden and Norway.4, 5 In that study, a total of 124 patients with aniridia (79 in Sweden and 45 in Norway) were traced and recorded. From the Swedish cohort, 16 subjects were recruited for the present study, based on a practical limitation of those residing in regions surrounding the 2 academic hospitals where full examinations could be conducted. Subjects were specifically selected to study early-stage

Patient Characteristics

The pedigrees of the 5 families examined are shown in Figure 2 (available at http://aaojournal.org). Results of the clinical examinations, indexed by a code indicating pedigree position, are given in Table 2 (available at http://aaojournal.org). Because of light sensitivity or ocular surface irritation in some subjects with aniridia, noncompliance during examination resulted in incomplete clinical data. The mean age was 31 years (range, 18–52 years) in subjects with aniridia and 37 years

Discussion

The goal of this study was to document clinical and morphologic corneal findings in the early stages of aniridic keratopathy. In an earlier study, slit-lamp examination showed absence of palisades of Vogt and superficial corneal vascularization in 16 of 16 aniridic eyes, 9 of which had clear central cornea.19 On the basis of this result and findings in other studies,5, 25, 26 we believe that under careful examination, most if not all cases of congenital aniridia can be found to have some degree

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    Manuscript no. 2011-1617.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    A European Union Marie Curie Fellowship (to N.L.). Funding support from Crown Princess Margareta's Foundation for the Visually Impaired, the Swedish Eye Fund, Carmen and Bertil Regnérs Foundation, and David and Beth Dahlins Foundation to UE. Support from King Gustav V and Queen Victoria's Freemasons Foundation, the County Council of Östergötland, and the Association of the Blind in Östergötland (to P.F.). The funding organizations had no role in the design or conduct of this research.

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