Albrecht v. Graefes Arch. klin. exp. Ophthal. 208, 25 31 (1978)

Graefes Archiv fur klinische und experimentelle

Ophthalmologie �9 by Springer-Verlag 1978

Reis-Biickler's Dystrophy

Y. Pouliquen, J.P. Giraud, and M. Savoldelli

Laboratoire de la Clinique Ophtalmologique de l'H6tel Dieu, 1, place du Parvis Notre Dame, F-75181 Paris Cedex 04, France

Summary. A case of Reis-Btickler's dystrophy in a 36-year-old man is reported. Its clinical aspect is compared with its histological and ultrastructural features. The slight reticular opacities situated superficially in the central part of the cornea, immediately beneath the epithelium, correspond to dark, irregular deposits. These replaced the basal membrane and Bowman's membrane and are composed of granular material, glycogen granules, and short fibers. These short, curved, osmiophilic fibers whose diameter is approximately 130A are also located inside the anterior stromal lamellae. These deposits seem to be the characteristic feature of this particular and rare dystrophy, stated as by Hogan. Their nature and origin are discussed.

Reis-Bfickler's dystrophy is a rare, familial condition. It was first described by Reis (1917) and individualized by Bfickler (1949). It is characterized by symmetric, central, superficial corneal lesions, first localised in the epithelium, later in Bowman's membrane and in the superficial stromal layers. It begins early in life and increases slowly. In childhood, the condition is discovered by recurrent epithelial erosion crises. Later, visual acuity deteriorates so that keratoplasty may become necessary.

Many clinical studies have been reported about Reis-Btickler's dystrophy, and its histological aspect is well known. Electron microscopic studies are less numerous [1,2,4], however, Hogan [3] recently summarized the main characteristics of the condition. In 1977 we had the opportunity to observe a case of Reis-B/ickler's dystrophys It has been the purpose of this paper to report its histologic aspect.

Case History

Our patient was born in 1942. He has known his corneal abnormality for many years. At school, he suffered from slight impairment of visual acuity and rare, recurrent epithelial erosions. His family

This paper was presented in part at the Sixth Annual Meeting of the European Club for Ophthalmic Fine Structure in Paris, France on March 31 and April 1, 1978

0065-6100/78/0208/0025/$01.40

26 Y. Pouliquen et al.

Fig. 1. Clinical aspect of Reis-Bfickler's corneal dystrophy

showed marked involvement with this condition: his mother, two sisters of his mother and his grand mother had all been affected.

The patient showed the following findings: Slight reticular, linear opacities situated superficially in the central cornea, immediately beneath the epithelium, the surface of which was irregular; the stroma was quite normal (Fig. 1). The lesions were symmetrical. There was no vascularisation, and the corneal sensibility was undisturbed. Visual acuity was 3/10 and P 4 for the right eye, and 1/20 and P 8 for the left eye. Intraocular pressure was normal. The retina looked normal, but the optic disc was pale due to an alcoholic intoxication in the past.

In November 1977 an 8 mm lamellar keratoplasty (4/I0 mm thick) was performed on the left eye. One half of the excised piece of cornea was fixed for 30 min in Bouin solution and embedded in paraffin. The other half was fixed in glutaraldehyde 1.5 % for 90 min and rinsed with phosphate buffer 0.1 M at pH 7.4. A second fixation was performed in 1% buffered osmium tetroxide. The tissue was then dehydrated and embedded in Araldite. Thin and ultrathin sections were cut on a Reichert ultramicrotome OMU2. They were observed with a Philips EM 300 electron microscope.

Resul ts

Light Microscopy

O n th in sect ions, the c o r n e a l c o n d i t i o n a f fec ted on ly the superf ic ia l layers o f the

co rnea , i.e. ep i the l ium, B o w m a n ' s m e m b r a n e a n d the a n t e r i o r p a r t o f the s t roma . T h e e p i t h e l i u m was i r regular . I ts th ickness was var iab le . I n s o m e areas it was

l imi ted to 3 o r 4 s u p e r i m p o s e d cells whe rea s in o t h e r a reas it a p p e a r e d qu i te n o r m a l ,

i.e. 7 o r 8 rows o f cells. Super f ic ia l a n d i n t e r m e d i a t e cells s eemed to be

m o r p h o l o g i c a l l y n o r m a l but , the basa l cells d id n o t h a v e thei r n o r m a l r egu la r

d i spos i t ion . In the th icker pa r t s o f the e p i t h e l i u m there were g r o u p s o f clear , h igh basa l cells, wh ich were o the rwi se no d i f fe ren t f r o m n o r m a l ones, whe reas in the

t h inne r zones o f the e p i t h e l i u m the basa l cells were r o u n d , m a l f o r m e d , a n d m i x e d

wi th d a r k cells ( p r o b a b l y d e a d cells). T h e b a s e m e n t m e m b r a n e a p p e a r e d th ick and

Reis-Biickler's Dystrophy 27

Fig. 2. Semi-thin section, Toluidin blue staining. There is an abundance of dark subepithelial deposits. Bowman's membrane is absent

irregular. In the central cornea Bowman's membrane was missing while in the corneal periphery it was delaminated. In the superficial stromal layers, we observed discrete linear deposits which appeared to be localized between the stromal lamellae. The density of the deposits was greatest immediately beneath the epithelium.

On sections fixed with Bouin solution and imbedded in paraffin we found a weackly positive PAS reaction while Masson trichome, reticulin and thioflavin T staining was negative.

Electron Microscopy

The superficial and intermediate epithelial layers seemed to be normal, but the basal cells were seriously altered: Most of them had an abnormally clear, vacuolated cytoplasm, which was poor in cytoplasmic filaments, but rich in glycogen. Some of the cells were degenerated. While desmosomes were occasionally seen on the lateral aspect of the basal cell plasma membrane, hemidesmosomes facing the basement membrane were missing. Also the basement membrane itself was absent between epithelial cells and the stroma. It was replaced by dark, irregular deposits, which were made up of fine, granular material, glycogen granules and short fibers. Bowman's membrane was equally absent, at least in the central portion of the

Fig. 3. A The basement membrane subjacent to the clear epithelial cells is missing. Note the numerous intercytoplasmic glycogen particles and the electron dense subepithelial deposits. Mag. 15,080. B Detail of the subepithelial deposits. Microgranules (g), microfibrills (mJ), glycogen (gO. Mag. 50,160

Fig. 4. A View of the anterior corneal stroma. The deposits are scattered throughout the section. Note the normal appearance of the fibrocyte. Mag. 7980. B Typical appearance of the deposits Mag. 51,300

30 Y. Pouliquen et al.

cornea. The anterior stromal layers were infiltrated by large deposits made up of short, curved, osmiophilic fibrils located inside the stromal lamellae. The mean diameter of the fibrils was 130A. These deposits seem to be the characteristic feature of this particular dystrophy. They are accumulated between the collagen fibrils and form larger or smaller patches. They were found only in the anterior stroma. The deeper stromal layers were normal. While these deposits seemed to have no connection to fibroblasts an accumulation of an entirely different, slightly granular material was often observed close to the plasma membrane of fibroblasts.

Discussion

The case presented here clearly suffered from typical Reis-Btickler's dystrophy, which is a disease of the epithelium and of the superficial stromal layers. The epithelial disease is mainly confined to the basal cells and causes cell alterations with loss of cytoplasmic filaments, a loss of desmosomes and hemidesmosomes and an increase of glycogen granules inside and outside the cells. In the central cornea, basement membrane und Bowman's membrane are absent. Instead, there are characteristic subepithelial disposits which infiltrate the superficial stromal layers. The fact that Reis-Bfickler's dystrophy is primarily an epithelial disorder is confirmed by the clinical course of the disease: It appears very early in life and first leads to recurrent epithelial erosions which can be explained by the lack of adherence between basal cells and stromal tissue. The corneal opacities which increase during life can be considered a result of both destruction of Bowman's membrane and accumulation of deposits. The pathogenic mecanism of this dystrophy is probably based on both an epithelial protease activity against Bowman's membrane and a synthesis activity resulting in the production and accumulation of a specific material which is deposited beneath the epithelium and in the anterior stromal layers. In this context it is noteworthy that the primitive corneal ectoderm is able to secrete a fibrillar material.

The involvement of the fibroblasts is uncertain. They have signs of marked activity and their cytoplasm sometimes has a particular fibrillar aspect. However, we do not think that they are involved in the secretion of the deposits, because they are not located in the vicinity of the stromal cells. They are probably only involved in subepithelial stromal scar formation.

The nature of the deposits remains obscure. We are quite certain that they are not amyloid because they are morphologically different and react differently to staining. Also a collagenous nature is quite unlikely, since they are smaller (130A,) than collagen fibrils and show no periodic cross striation. They show no affinity for reticulin staining. Hogan [3] thinks that they represent procollagen fibrils. If they are, they still present a lot of questions: Are they secreted by epithelial cells, or are they original fibrils of Bowman's membrane modified by a cell protease activity? Are they the result of a specific collagen-like epithelial secretion, similar to the primary embryonic fibrils associated with a formation-defect of Bowman's membrane, or are they caused by secondary lysis of Bowman's membrane ? Further studies of the first stages of the disease will be necessary to answer these questions.

Reis-Bfickler's Dystrophy 31

References

1. Akiya, S., Brown, S.I.: The ultrastructure of Reis-Bfickler's dystrophy. Amer. J. Ophthal. 72, 549- 554 (1971)

2. Babel, J., Leuenberger, P.: Corneal dystrophy of Reis-Bfickler's. Ultrastructure study of two cases. Arch. Ophthal. Paris 33, 49-62 (1973)

3. Hogan, M.J.: Patogenia de la distrofia corneal de Reis-Bfickler. Arch. Soc. Esp. Oftal. 37, 109- (1977)

4. Kanai, A., Kaufmann, H.E., Polak, F.M.: Electron microscopic study of Reis-Biickler's dystrophy. Amer. J. Ophthal. 5, 953 (1973)

Received June 30, 1978