Bilateral Atypical Granular Corneal Dystrophy Associated with Unilateral Keratoconus in a Male Child.

A 14-year-old male presented with decreased vision. Slit lamp examination indicated multiple anterior corneal stromal opacities with clear intervening spaces accompanied with superficial subepithelial lines arranged in a quasi-whorl-like fashion bilateral with greater prominence in the right eye. Corneal steepening associated with thinning was noted only in the right eye. Genetic analysis confirmed a mutation suggestive of granular corneal dystrophy. Here, we describe a rare case of an atypical granular dystrophy associated with unilateral keratoconus in a male child.

INTRODUCTION

Typical stromal corneal dystrophies are not uncommon in clinical practice. The most common stromal corneal dystrophies described are granular dystrophy, lattice dystrophy, and macular dystrophy.1 Other less commonly described stromal dystrophies include Schnyder's crystalline dystrophy, Fleck corneal dystrophy, central cloudy dystrophy of Francois, posterior amorphous corneal dystrophy, congenital hereditary stromal dystrophy, and pre-Descemet corneal dystrophy.2

A subgroup of patients with corneal dystrophies presents with a combination of features of different dystrophies as typified by Avellino dystrophy.3 In this case report, we present a rare case of bilateral atypical granular corneal dystrophy (GCD) associated with unilateral keratoconus in a male child.

CASE REPORT

A 14-year-old male presented with complaints of defective vision bilaterally for 2 years duration. His visual acuity was 20/80 in the right eye improving to 20/40 with − 5.0 DS/−1.50 D Cyl at 180° and 20/40 in the left eye improving to 20/20 with − 0.50 DS. There was no history of any systemic illness or medication. Diffuse slit lamp examination revealed mild papillary reaction of the palpebral conjunctiva bilaterally. Examination of the cornea in both eyes indicated multiple subepithelial lines in a pseudovortex pattern extending from the inferior paracentral cornea with some of the lines crossing the pupillary axis. The lines were coarser in the right eye. In addition, isolated discrete white crumb-shaped opacities of varying sizes were present in the anterior stroma of both the corneas. The intervening corneal stroma was clear and the peripheral cornea was not involved [Figure 1a and b]. Optical section illumination demonstrated subepithelial location of the linear opacities and a slightly deeper anterior stromal location of the crumb-shaped opacities [Figure 1c]. The right eye had mild corneal steeping in the inferior paracentral region, and the corneal curvature in the left eye appeared clinically normal. The corneal endothelium appeared normal. The rest of the anterior and posterior segment findings were normal.

Figure 1

(a) Right eye. Diffuse illumination image of cornea depicting the patterned linear opacities along with crumb-shaped opacities. (b) Left eye. Diffuse illumination image showing patterned linear opacities with a fewer crumb-shaped opacities. (c) In vivo laser confocal microscopy showing linearly arranged hyper-reflective opacities (white arrowheads) along with denser and discrete granular deposits (yellow arrowhead). (d) Optical section slit lamp image showing the anterior stromal location of granular crumb-shaped opacities. (e) Anterior segment optical coherence tomography showing opacities limited to the anterior 140 microns of the cornea

In vivo laser confocal microscopy (Heidelberg Retina Tomograph 2 Rostock Cornea Module) revealed the subepithelial lesions as linear hyper-reflective “vertebra”- shaped silhouetted structures at a depth of 50–80 microns. The crumb-shaped opacities were denser, discrete, present in the region from 60 to 140 microns and more prominent in the right cornea [Figure 1d]. Spectral domain anterior segment optical coherence tomography (Spectralis) confirmed the depth of the crumb opacities to 140 microns [Figure 1e].

Corneal topography (Pentacam; Oculus Optikgerδte GmbH, Wetzlar, Germany) of the right eye showed steepening in the vertical meridian which was more exaggerated in the inferior paracentral region. The maximum anterior curvature was 57.8 D around the 3 mm zone inferiorly. Optical pachymetry indicated a central corneal thickness of 450 microns. There was a significant elevation of the posterior float of the cornea. The Belin/Ambrósio Enhanced Ectasia display indicated keratoconus. Corneal topography of the left eye showed the maximum anterior curvature of 45.2 D around the 3 mm zone inferiorly and the central corneal thickness of 522 microns, which were unremarkable.

The patient was the only child born out of a nonconsanguineous marriage. Slit lamp biomicroscopic examination of his mother and paternal grandfather did not reveal any corneal abnormality.

Genetic analysis was performed using 5 ml of the peripheral blood after obtaining additional informed consent. The study protocols adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board. Controls were selected from healthy South Indian volunteers without any family history of disease. The coding sequence and splice site junctions of TGFBI (BIGH3) gene were amplified from the genomic DNA of the patient and controls, and the mutation was identified by direct DNA sequencing of the samples.

We observed one reported missense mutation p.Arg555Trp456 and three previously reported polymorphisms (p.Lue269Phe, p.Val327Val, and p.Phe540Phe).45 R555W mutation has been reported in various ethnic populations,45 and this mutation indicates the hot spot specificity and pathogenicity for GCD.

DISCUSSION

Keratoconus can have both systemic and ocular associations. Common systemic associations include Downs’ syndrome, atopic disease, connective tissue, and collagen disorders such as Ehlers-Danlos syndrome, osteogenesis imperfecta, and Marfan's syndrome.7 Common ocular associations include retinitis pigmentosa, Leber's congenital amaurosis, vernal conjunctivitis, lattice, and granular dystrophies.7 The association of keratoconus with a corneal dystrophy is comparatively rare. However, there are published reports of bilateral keratoconus associated with typical GCD.68

Our patient had distinctly different characteristics than what has been described in the literature. The patient presented with an atypical form of GCD with unilateral keratoconus. Typical deposits of varying sizes and hues seen in GCD were interspersed with more superficial subepithelial lines arising from a zone in the inferior paracentral cornea and branching out in a whorl-like fashion. These lines were distinctly different than the lattice lines described in Avellino dystrophy.3 The genetic analysis confirmed a mutation in TGFBI (BIGH3) gene suggestive of GCD. Keratoconus was present only in the right eye, which had a significantly increased presence of the stromal lesions. It would be interesting to follow the natural course of the lesions in the left eye and to periodically screen for development of keratoconus in the left eye.

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Conflicts of interest

There are no conflicts of interest.