Author reply

granular dystrophy, characterized by confluent granules.4 We believe that the severe granular dystrophy in the patient Drs Moller and Ridgway described2 resembles superficial juvenile granular dystrophy caused by the homozygous R124H genotype rather than the placoid type of granular dystrophy caused by the homozygous R555W genotype. The patient’s parents had a mild granular dystrophy phenotype characterized by fewer large granules,2 which may be caused by a heterozygous R124H genotype. Moreover, we believe that all the other reported patients with severe phenotype also had the homozygous R124H genotype. In fact, an R124H kerato-epithelin mutation is much more common than an R555W mutation in our clinic (unpublished data). Our severe case of placoid type granular dystrophy associated with the homozygous R555W genotype appears to be extremely rare, not only in Japanese but also in other ethnic groups.

REFERENCES

1. Moller HU, Ridgway AEA. Granular corneal dystrophy Groenouw type I: a report of a probable homozygous patient. Acta Ophthalmol (Copenh) 1990;68:97–101. 2. Moller HU. Granular corneal dystrophy Groenouw type I: clinical and genetic aspects. Acta Ophthalmol (Copenh) 1991;69 (suppl 198): Ph.D. Theses. 3. Moller HU. Inter-familial variability and intra-familial similarities of granular corneal dystrophy Groenouw type I with respect to biomicroscopical appearance and symptomatology. Acta Ophthalmol (Copenh) 1989;67:669 – 677. 4. Moller HU. Granular corneal dystrophy Groenouw type I (GRI) and Reis-Bu¨cklers’ corneal dystrophy (R-B): one entity? Acta Ophthalmol (Copenh) 1989;67:678 – 684.

AUTHOR REPLY DR MOLLER HAS REVIEWED NUMEROUS REPORTS OF GRANU-

lar corneal dystrophy,1 including a discussion of the phenotypic variability of this disease. The most striking characteristic in such variability is the number of granules in the cornea. One phenotype has numerous small granules (over 100), whereas another phenotype has fewer large granules (less than 50). The former is caused by a heterozygous R555W mutation, and the latter is caused by a heterozygous R124H mutation in the ␤ig-h3 (kerato-epithelin) gene. Therefore, clinically diagnosed granular corneal dystrophy can be classified into two genotypic groups. Moreover, Dr Moller mentioned several reports of a severe phenotype of granular dystrophy in many countries.1,2 We reviewed these reports, and that of Dr Moller, and we believe that all these severe patients had confluent granules with parents who had 20 to 30 granules in their corneas. In addition, the severe phenotype of granular dystrophy has two possible genotypes, either homozygous R555W or homozygous R124H. The homozygous R555W genotype causes a placoid type of granular dystrophy [see Dr Okada’s article in the August 1998 issue] which resembles a geographic form of Reis-Bu¨cklers dystrophy,3 whereas the homozygous R124H genotype causes superficial juvenile

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AMERICAN JOURNAL

MASAKI OKADA, MD SHUJI YAMAMOTO, MD HITOSHI WATANABE, MD YOSHIKAZU SHIMOMURA, MD YASUO TANO, MD

Osaka, Japan

REFERENCES

1. Moller HU. Inter-familial variability and intra-familial similarities of granular corneal dystrophy Groenouw type I with respect to biomicroscopical appearance and symptomatology. Acta Ophthalmol (Copenh) 1989;67:669 – 677. 2. Moller HU, Ridgway AEA. Granular corneal dystrophy Groenouw type I: a report of a probable homozygous patient. Acta Ophthalmol (Copenh) 1990;68:97–101. 3. Okada M, Yamamoto S, Tsujikawa M, et al. Two distinct kerato-epithelin mutations in Reis-Bu¨cklers corneal dystrophy. Am J Ophthalmol 1998;126:535–542. 4. Okada M, Yamamoto S, Inoue Y, et al. Severe corneal dystrophy phenotype caused by homozygous R124H keratoepithelin mutations. Invest Ophthalmol Vis Sci 1998;39: 1947–1953.

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OPHTHALMOLOGY

MARCH 2000