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.

Case Reports

Purpose. To report a rare case of keratoconus concurrent with granular dystrophy in a patient of Italian origin. It is the seventh case in the literature and the second histopathologically documented case.

Methods. Keratoconus combined with granular dystrophy developed bilaterally in a 15-year-old boy from Italy. The corneal host button of the left eye obtained during penetrating keratoplasty 8 years later was analyzed histologically, immunohistochemically, and ultrastructurally.

Results. Histologic evaluation showed characteristic features of keratoconus, such as breaks in Bowman's layer and typical electron-dense trapezoidal deposits ultrastructurally. Other corneal dystrophies, such as Avellino dystrophy, were excluded.

Conclusions. The concurrence of keratoconus and granular dystrophy raises the possibility of a genetic linkage of the diseases, although a chance association cannot be excluded. The diagnosis of keratoconus in patients with granular dystrophy is important because impairment of vision might be the result of keratoconus and could be treated with contact lenses instead of keratoplasty. In the future, the use of computerized corneal topography might help to detect more cases of keratoconus concurrent with granular dystrophy.

Author Information

From Wilmer Eye Institute (G.W., W.R.G.), Eye Pathology Laboratory, Baltimore, Maryland, U.S.A.; and Centro de Oftalmologia Barraquer (J.T.), Barcelona, Spain.

Submitted February 1, 2001.

Revision received July 21, 2001.

Accepted August 13, 2001.

Address correspondence and reprint requests to Dr. G. Wollensak, Universitätsaugenklinik Fetscherstr. 74, D-01307 Dresden, Germany.

Article Outline

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

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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.

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).

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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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1. Rabinowitz YS. Major review: keratoconus. Surv Ophthalmol 1998; 42: 297–319.
2. Yoshida H, Funabashi M, Kanai A. Histological study of the corneal granular dystrophy complicated by keratoconus. Folia Ophthalmol Jpn 1980; 31: 218–23.
3. Mitsui M, Sakimoto T, Sawa M, et al. Familial case of keratoconus with corneal granular dystrophy. J Jpn Ophthalmol Soc 1996; 100: 916–9.
4. Koomoto R, Koomoto M, Moriyama H. One case of granular corneal dystrophy associated keratoconus and esotropia. Folia Ophthalmol Jpn 1984; 35: 2002–7.
5. Vajpayee RB, Snibson GR, Taylor HR. Association of keratoconus with granular corneal dystrophy. Aust NZ J Ophthalmol 1996; 24: 369–71.
6. Sassani JW, Smith G, Rabinowitz YS. Keratoconus and bilateral lattice-granular corneal dystrophies. Cornea 1992; 11: 343–50.
7. Munier FL, Korvatska E, DjemaI A, et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nat Genet 1997; 15: 247–51.
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.

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

© 2002 Lippincott Williams & Wilkins, Inc.