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Case Reports

Keratoconus Associated With Corneal Granular Dystrophy in a Patient of Italian Origin

Wollensak, Gregor M.D.; Green, William R. M.D.; Temprano, José M.D.

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Keratoconus is a noninflammatory progressive corneal thinning leading to inferior conical ectasia with irregular astigmatism, scarring, and impairment of vision as early as the second decade of life. It is mostly bilateral, and its incidence is approximately 1 in 2,000. 1 Corneal granular dystrophy is a rare autosomal dominant condition with focal white, snowflake-like opacities in the stroma of the cornea, which seldom impair vision significantly before the fifth decade of life.

We report a rare case of keratoconus combined with corneal granular dystrophy. The first case was reported from Japan in 1980. 2 This is the seventh case in the literature 2–5 and the second histopathologically documented case. 2


A 15-year-old boy was referred for corneal consultation from Italy to the Barraquer Institute in Barcelona, Spain, with slowly progressive loss of vision in the left eye because of corneal dystrophy. Slit-lamp examination showed relatively mild bilateral granular dystrophy with a few well-circumscribed deposits in the central anterior stroma in both eyes (Fig. 1), which could not explain the reduced vision in the left eye. Keratometry showed keratoconus in the left eye, and a contact lens was fitted. No other family members were affected. At the age of 21, keratoconus also developed in the right eye (keratometry reading OD: 49.00 D/52.75 D at 3°). At the age of 23, penetrating keratoplasty had to be performed in the left eye because of progressive irregular astigmatism (keratometry reading OS: 52.50 D/60.16 D at 19°). A Fleischer ring and Vogt striae were present. The preoperative best-corrected vision was 20/60 (−14.00 −6.00 × 140) in the left eye respectively 20/40 using contact lenses and 20/30 (−3.00 −2.00 × 50) in the right eye respectively 20/25 using contact lenses.

FIG. 1.
FIG. 1.:
A: Macrophotograph of left eye with some scattered crumb- and ring-shaped corneal deposits in the superficial stroma. B: Slit-lamp view showing corneal protrusion and thinning of the left eye.

Histopathologic examination of the left host corneal button showed typical features of keratoconus, with breaks in Bowman's layer, a thin subepithelial pannus, focal scarring of the anterior stroma, and marked thinning of the central stroma to 230 μm in thickness (Fig. 2A and B). In addition, several foci of granular deposits were identified in the superficial stroma, which were nonbirefringent, negative for amyloid with Congo red stain, and negative for acid mucopolysaccharides with alcian blue stain. The immunoperoxidase technique for IgG, IgA, IgM immunoglobulins and cytokeratin (AE1/AE3) showed negative staining reaction for the deposits. Ultrastructurally, the deposits were composed of typical electron-dense, angular, trapezoidal structures with random orientation (Fig. 2C).

FIG. 2.
FIG. 2.:
A: Histopathology of the left eye cornea with a superficial granular deposit (small arrow) and a break in Bowman's layer (large arrow). B: Marked central thinning of the corneal stroma consistent with keratoconus. C: Electron micrograph with electron-dense, trapezoidal granular deposits.


This is the second histopathologic description of a concurrence of keratoconus and granular dystrophy. 2 The histopathologic analysis confirmed our clinical diagnosis and excluded especially immunoglobulin deposits or Avellino dystrophy, whose concurrence with keratoconus has also been described in a family from Avellino in Italy. 6

The association of keratoconus with a relatively rare disorder like granular dystrophy, 1 especially when present in two generations, 2,3 suggests that there may be a genetic linkage between the two diseases. Therefore, chromosome 5, which has been identified for granular, lattice type 1 and Avellino dystrophy, 7 may be a possible gene locus for at least one form of hereditary keratoconus as has already been shown for chromosome 21, 8 although a chance association cannot be excluded.

The incidence of combined keratoconus and granular dystrophy may be higher than suggested by the few case reports because early stages of keratoconus can be overlooked on routine examination. Computerized corneal topography should help to reveal more cases and to further elucidate its pattern of inheritance. 9

From a clinical point of view, this case shows the importance of excluding additional keratoconus in granular dystrophy because this disorder can be the main reason for the decreased vision and can often be treated with contact lenses so that keratoplasty can be at least delayed or even avoided in these cases. Conversely, excimer laser treatment, which can be used in some cases with granular dystrophy, 10 should be applied with caution because of the corneal thinning caused by additional keratoconus.


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8. Rabinowitz YS, Zu L, Yang Y, et al. Keratoconus: nonparametric linkage analysis suggests a gene locus near the centromere of chromosome 21. Invest Ophthal Vis Sci 1999; 40: S564.
9. Rabinowitz YS, Garbus J, McDonnell PJ. Computer-assisted corneal topography in family members of patients with keratoconus. Arch Ophthalmol 1990; 108: 365–71.
10. Stark WJ, Chamon W, Kamp MT, et al. Clinical follow up of 193-nm ArF excimer laser photokeratectomy. Ophthalmology 1992; 99: 805–12.

Electron microscopy; Genetic linkage; Granular dystrophy; Keratoconus; Light microscopy

© 2002 Lippincott Williams & Wilkins, Inc.